Breast Cancer

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

A version of this article first appeared on Medscape.com.

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

A version of this article first appeared on Medscape.com.

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.² In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.³ These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.

Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.⁴ A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.

Additional References

1. Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586  
2. Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X  
3. Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
4. Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797

Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.² In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.³ These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.

Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.⁴ A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.

Additional References

1. Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586  
2. Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X  
3. Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
4. Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797

Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.² In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.³ These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.

Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.⁴ A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.

Additional References

1. Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586  
2. Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X  
3. Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
4. Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797

A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.

It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.

Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.

Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.¹ Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.

Additional Reference

1. Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266

A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.

It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.

Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.

Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.¹ Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.

Additional Reference

1. Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266

A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.

It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.

Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.

Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.¹ Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.

Additional Reference

1. Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.

The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?

A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.

In short, European investigators found that it’s safe to skip SLNBs in women with breast cancers no larger than 2 cm if preoperative ultrasounds of the axilla show no evidence of nodal disease.

At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.

Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.

The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.

Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
 

A case-by-case decision

The study included women of all ages, with a median age of 60 years.

Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.

The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.

Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.

However, it didn’t seem to make a difference in the overall study results.

Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).

Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.

“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.

The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.

Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.

The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.

METHODOLOGY:

• Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain. 
• To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
• The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
• Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women. 
• Results were adjusted for potential confounders, including age, race, and ethnicity.

TAKEAWAY:

• Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
• Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
• Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
• The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.

IN PRACTICE:

The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”

SOURCE:

The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.

LIMITATIONS:

The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.

DISCLOSURES:

The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

The risk of developing breast cancer in individuals with pathogenic cancer syndrome variants may be less elevated in those without a first-degree family history, according to findings from a large population-based cohort study.

Similar results were seen for patients with Lynch syndrome.

The findings suggest that a first-degree family history confers much of the risk that is associated with pathogenic variants associated with hereditary breast, ovarian, and colorectal cancers. Furthermore, to avoid overtreatment in those without a first-degree family history who undergo genetic testing, that history should be considered when discussing potential follow-up care, the investigators argue.

“This difference in penetrance in carrier individuals, if replicated in larger studies, could be sufficient to justify stratifying just individuals with a family history into high-risk groups currently eligible for specialist clinical care,” Leigh Jackson, PhD, of the University of Exeter College of Medicine and Health, Royal Devon and Exeter Hospital, England, and his colleagues noted.

To assess how population penetrance of familial cancer syndromes varies based on family history, researchers analyzed exome sequences and clinical data collected between March 2006 and June 25, 2021, from 454,712 UK Biobank participants with either breast or colorectal cancer, a self-reported family history of breast or colorectal cancer, and a pathogenic/likely pathogenic variant in the major genes associated with hereditary breast cancer or Lynch syndrome.

After researchers controlled for sex, death, recruitment center, screening, and prophylactic surgery, those with a pathogenic BRCA1 (n = 230) or BRCA2 (n = 611) variant had an increased risk of breast cancer, and the risk was higher in those with a first-degree family history (relative hazard, 10.3 and 7.8, respectively), than in those without a first-degree family history (relative hazard, 7.2 and 4.7), the investigators reported.

Penetrance to age 60 years was also higher in those with vs. without a first-degree family history (44.7% and 24.1% vs 22.8% and 17.9%, respectively).

Similarly, patients with Lynch syndrome and a pathogenic MLH1, MSH2, or MSH6 variant (n = 89, 71, and 421, respectively) had an increased risk of colorectal cancer, and that risk was higher in those with vs. without a family history (relative hazard, 35.6, 48.0, and 9.9 vs. 13.0, 15.4, and 7.2). Penetrance to age 60 was higher for those with a pathogenic MLH1 and MSH2 variant with vs. without a family history (30.9% and 38% vs. 20.5% and 8.3%).

The study results were published online in eClinicalMedicine, part of The Lancet Discovery Science.

“The findings of this study suggest that any universal policy of returning pathogenic cancer predisposing genetic variants found incidentally or through direct-to-consumer genetic testing of asymptomatic individuals should consider family history and other factors when counseling patients on the risks and benefits of follow-up care,” the investigators recommended. “It will be very difficult to counsel individuals as to their particular risk profile without further pedigree construction or investigations.

“If penetrance estimates from affected families are used, there is a danger of overmanagement of asymptomatic individuals with no family history of disease. These ‘patients-in-waiting’ may be exposed to unnecessary surveillance or more invasive prophylactic procedures,” they added.

This study was supported by an MRC grant. The authors reported having no competing interests.

The risk of developing breast cancer in individuals with pathogenic cancer syndrome variants may be less elevated in those without a first-degree family history, according to findings from a large population-based cohort study.

Similar results were seen for patients with Lynch syndrome.

The findings suggest that a first-degree family history confers much of the risk that is associated with pathogenic variants associated with hereditary breast, ovarian, and colorectal cancers. Furthermore, to avoid overtreatment in those without a first-degree family history who undergo genetic testing, that history should be considered when discussing potential follow-up care, the investigators argue.

“This difference in penetrance in carrier individuals, if replicated in larger studies, could be sufficient to justify stratifying just individuals with a family history into high-risk groups currently eligible for specialist clinical care,” Leigh Jackson, PhD, of the University of Exeter College of Medicine and Health, Royal Devon and Exeter Hospital, England, and his colleagues noted.

To assess how population penetrance of familial cancer syndromes varies based on family history, researchers analyzed exome sequences and clinical data collected between March 2006 and June 25, 2021, from 454,712 UK Biobank participants with either breast or colorectal cancer, a self-reported family history of breast or colorectal cancer, and a pathogenic/likely pathogenic variant in the major genes associated with hereditary breast cancer or Lynch syndrome.

After researchers controlled for sex, death, recruitment center, screening, and prophylactic surgery, those with a pathogenic BRCA1 (n = 230) or BRCA2 (n = 611) variant had an increased risk of breast cancer, and the risk was higher in those with a first-degree family history (relative hazard, 10.3 and 7.8, respectively), than in those without a first-degree family history (relative hazard, 7.2 and 4.7), the investigators reported.

Penetrance to age 60 years was also higher in those with vs. without a first-degree family history (44.7% and 24.1% vs 22.8% and 17.9%, respectively).

Similarly, patients with Lynch syndrome and a pathogenic MLH1, MSH2, or MSH6 variant (n = 89, 71, and 421, respectively) had an increased risk of colorectal cancer, and that risk was higher in those with vs. without a family history (relative hazard, 35.6, 48.0, and 9.9 vs. 13.0, 15.4, and 7.2). Penetrance to age 60 was higher for those with a pathogenic MLH1 and MSH2 variant with vs. without a family history (30.9% and 38% vs. 20.5% and 8.3%).

The study results were published online in eClinicalMedicine, part of The Lancet Discovery Science.

“The findings of this study suggest that any universal policy of returning pathogenic cancer predisposing genetic variants found incidentally or through direct-to-consumer genetic testing of asymptomatic individuals should consider family history and other factors when counseling patients on the risks and benefits of follow-up care,” the investigators recommended. “It will be very difficult to counsel individuals as to their particular risk profile without further pedigree construction or investigations.

“If penetrance estimates from affected families are used, there is a danger of overmanagement of asymptomatic individuals with no family history of disease. These ‘patients-in-waiting’ may be exposed to unnecessary surveillance or more invasive prophylactic procedures,” they added.

This study was supported by an MRC grant. The authors reported having no competing interests.

The risk of developing breast cancer in individuals with pathogenic cancer syndrome variants may be less elevated in those without a first-degree family history, according to findings from a large population-based cohort study.

Similar results were seen for patients with Lynch syndrome.

The findings suggest that a first-degree family history confers much of the risk that is associated with pathogenic variants associated with hereditary breast, ovarian, and colorectal cancers. Furthermore, to avoid overtreatment in those without a first-degree family history who undergo genetic testing, that history should be considered when discussing potential follow-up care, the investigators argue.

“This difference in penetrance in carrier individuals, if replicated in larger studies, could be sufficient to justify stratifying just individuals with a family history into high-risk groups currently eligible for specialist clinical care,” Leigh Jackson, PhD, of the University of Exeter College of Medicine and Health, Royal Devon and Exeter Hospital, England, and his colleagues noted.

To assess how population penetrance of familial cancer syndromes varies based on family history, researchers analyzed exome sequences and clinical data collected between March 2006 and June 25, 2021, from 454,712 UK Biobank participants with either breast or colorectal cancer, a self-reported family history of breast or colorectal cancer, and a pathogenic/likely pathogenic variant in the major genes associated with hereditary breast cancer or Lynch syndrome.

After researchers controlled for sex, death, recruitment center, screening, and prophylactic surgery, those with a pathogenic BRCA1 (n = 230) or BRCA2 (n = 611) variant had an increased risk of breast cancer, and the risk was higher in those with a first-degree family history (relative hazard, 10.3 and 7.8, respectively), than in those without a first-degree family history (relative hazard, 7.2 and 4.7), the investigators reported.

Penetrance to age 60 years was also higher in those with vs. without a first-degree family history (44.7% and 24.1% vs 22.8% and 17.9%, respectively).

Similarly, patients with Lynch syndrome and a pathogenic MLH1, MSH2, or MSH6 variant (n = 89, 71, and 421, respectively) had an increased risk of colorectal cancer, and that risk was higher in those with vs. without a family history (relative hazard, 35.6, 48.0, and 9.9 vs. 13.0, 15.4, and 7.2). Penetrance to age 60 was higher for those with a pathogenic MLH1 and MSH2 variant with vs. without a family history (30.9% and 38% vs. 20.5% and 8.3%).

The study results were published online in eClinicalMedicine, part of The Lancet Discovery Science.

“The findings of this study suggest that any universal policy of returning pathogenic cancer predisposing genetic variants found incidentally or through direct-to-consumer genetic testing of asymptomatic individuals should consider family history and other factors when counseling patients on the risks and benefits of follow-up care,” the investigators recommended. “It will be very difficult to counsel individuals as to their particular risk profile without further pedigree construction or investigations.

“If penetrance estimates from affected families are used, there is a danger of overmanagement of asymptomatic individuals with no family history of disease. These ‘patients-in-waiting’ may be exposed to unnecessary surveillance or more invasive prophylactic procedures,” they added.

This study was supported by an MRC grant. The authors reported having no competing interests.