Breast Cancer

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Persistent chemotherapy-related amenorrhea (CRA) after treatment for breast cancer was common and associated with worse long-term quality of life among premenopausal women in a large multicenter French cohort study.

The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.

At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.

In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).

Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).

The findings were published online November 16 in JAMA Network Open.

The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.

“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”

The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.

For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.

“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”

Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.

“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”

These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.

“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”

The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.

Persistent chemotherapy-related amenorrhea (CRA) after treatment for breast cancer was common and associated with worse long-term quality of life among premenopausal women in a large multicenter French cohort study.

The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.

At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.

In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).

Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).

The findings were published online November 16 in JAMA Network Open.

The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.

“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”

The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.

For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.

“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”

Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.

“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”

These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.

“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”

The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.

Persistent chemotherapy-related amenorrhea (CRA) after treatment for breast cancer was common and associated with worse long-term quality of life among premenopausal women in a large multicenter French cohort study.

The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.

At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.

In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).

Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).

The findings were published online November 16 in JAMA Network Open.

The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.

“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”

The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.

For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.

“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”

Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.

“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”

These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.

“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”

The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.

The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation.

To develop the 2023 recommendations, the Agency for Healthcare Research and Quality (AHRQ) conducted a systematic review assessing the latest clinical trial evidence, and ASTRO assembled an expert task force to determine best practices for using partial breast irradiation.

“There have been more than 10,000 women included in these randomized controlled trials, with 10 years of follow-up showing equivalency in tumor control between partial breast and whole breast radiation for appropriately selected patients,” Simona Shaitelman, MD, vice chair of the guideline task force, said in a news release.

“These data should be driving a change in practice, and partial breast radiation should be a larger part of the dialogue when we consult with patients on decisions about how best to treat their early-stage breast cancer,” added Dr. Shaitelman, professor of breast radiation oncology at the University of Texas MD Anderson Cancer Center in Houston.

What’s in the New Guidelines?

For patients with early-stage, node-negative invasive breast cancer, the updated guideline strongly recommends partial breast irradiation instead of whole breast irradiation if the patient has favorable clinical features and tumor characteristics, including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older.

In contrast, the 2017 guideline considered patients aged 50 and older suitable for partial breast irradiation and considered those in their 40s who met certain pathologic criteria “cautionary.”The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size.

The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40.

Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients.

For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40.

In addition to relevant patient populations, the updated guidelines also address techniques and best practices for delivering partial breast irradiation.

Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation.

Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry.

The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.

“We hope that by laying out the evidence from these major trials and providing guidance on how to administer partial breast radiation, the guideline can help more oncologists feel comfortable offering this option to their patients as an alternative to whole breast radiation,” Janice Lyons, MD, of University Hospitals Seidman Cancer Center, Cleveland, Ohio, and chair of the guideline task force, said in the news release.

The guideline, developed in collaboration with the American Society of Clinical Oncology and the Society of Surgical Oncology, has been endorsed by the Canadian Association of Radiation Oncology, the European Society for Radiotherapy and Oncology, and the Royal Australian and New Zealand College of Radiologists. Guideline development was funded by ASTRO and the systematic evidence review was funded by the Patient-Centered Outcomes Research Institute. Disclosures for the task force are available with the original article.
 

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation.

To develop the 2023 recommendations, the Agency for Healthcare Research and Quality (AHRQ) conducted a systematic review assessing the latest clinical trial evidence, and ASTRO assembled an expert task force to determine best practices for using partial breast irradiation.

“There have been more than 10,000 women included in these randomized controlled trials, with 10 years of follow-up showing equivalency in tumor control between partial breast and whole breast radiation for appropriately selected patients,” Simona Shaitelman, MD, vice chair of the guideline task force, said in a news release.

“These data should be driving a change in practice, and partial breast radiation should be a larger part of the dialogue when we consult with patients on decisions about how best to treat their early-stage breast cancer,” added Dr. Shaitelman, professor of breast radiation oncology at the University of Texas MD Anderson Cancer Center in Houston.

What’s in the New Guidelines?

For patients with early-stage, node-negative invasive breast cancer, the updated guideline strongly recommends partial breast irradiation instead of whole breast irradiation if the patient has favorable clinical features and tumor characteristics, including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older.

In contrast, the 2017 guideline considered patients aged 50 and older suitable for partial breast irradiation and considered those in their 40s who met certain pathologic criteria “cautionary.”The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size.

The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40.

Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients.

For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40.

In addition to relevant patient populations, the updated guidelines also address techniques and best practices for delivering partial breast irradiation.

Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation.

Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry.

The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.

“We hope that by laying out the evidence from these major trials and providing guidance on how to administer partial breast radiation, the guideline can help more oncologists feel comfortable offering this option to their patients as an alternative to whole breast radiation,” Janice Lyons, MD, of University Hospitals Seidman Cancer Center, Cleveland, Ohio, and chair of the guideline task force, said in the news release.

The guideline, developed in collaboration with the American Society of Clinical Oncology and the Society of Surgical Oncology, has been endorsed by the Canadian Association of Radiation Oncology, the European Society for Radiotherapy and Oncology, and the Royal Australian and New Zealand College of Radiologists. Guideline development was funded by ASTRO and the systematic evidence review was funded by the Patient-Centered Outcomes Research Institute. Disclosures for the task force are available with the original article.
 

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued an updated clinical practice guideline on partial breast irradiation for women with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). The 2023 guideline, which replaces the 2017 recommendations, factors in new clinical trial data that consistently show no significant differences in overall survival, cancer-free survival, and recurrence in the same breast among patients who receive partial breast irradiation compared with whole breast irradiation. The data also indicate similar or improved side effects with partial vs whole breast irradiation.

To develop the 2023 recommendations, the Agency for Healthcare Research and Quality (AHRQ) conducted a systematic review assessing the latest clinical trial evidence, and ASTRO assembled an expert task force to determine best practices for using partial breast irradiation.

“There have been more than 10,000 women included in these randomized controlled trials, with 10 years of follow-up showing equivalency in tumor control between partial breast and whole breast radiation for appropriately selected patients,” Simona Shaitelman, MD, vice chair of the guideline task force, said in a news release.

“These data should be driving a change in practice, and partial breast radiation should be a larger part of the dialogue when we consult with patients on decisions about how best to treat their early-stage breast cancer,” added Dr. Shaitelman, professor of breast radiation oncology at the University of Texas MD Anderson Cancer Center in Houston.

What’s in the New Guidelines?

For patients with early-stage, node-negative invasive breast cancer, the updated guideline strongly recommends partial breast irradiation instead of whole breast irradiation if the patient has favorable clinical features and tumor characteristics, including grade 1 or 2 disease, estrogen receptor (ER)-positive status, small tumor size, and age 40 or older.

In contrast, the 2017 guideline considered patients aged 50 and older suitable for partial breast irradiation and considered those in their 40s who met certain pathologic criteria “cautionary.”The updated guideline also conditionally recommends partial over whole breast irradiation if the patient has risk factors that indicate a higher likelihood of recurrence, such as grade 3 disease, ER-negative histology, or larger tumor size.

The task force does not recommend partial breast irradiation for patients with positive lymph nodes, positive surgical margins, or germline BRCA1/2 mutations or patients under 40.

Given the lack of robust data in patients with less favorable risk features, such as lymphovascular invasion or lobular histology, partial breast irradiation is conditionally not recommended for these patients.

For DCIS, the updated recommendations mirror those for early-stage breast cancer, with partial breast irradiation strongly recommended as an alternative to whole breast irradiation among patients with favorable clinical and tumor features, such as grade 1 or 2 disease and ER-positive status. Partial breast irradiation is conditionally recommended for higher grade disease or larger tumors, and not recommended for patients with positive surgical margins, BRCA mutations or those younger than 40.

In addition to relevant patient populations, the updated guidelines also address techniques and best practices for delivering partial breast irradiation.

Recommended partial breast irradiation techniques include 3-D conformal radiation therapy, intensity modulated radiation therapy, and multicatheter interstitial brachytherapy, given the evidence showing similar long-term rates of ipsilateral breast recurrence compared with whole breast irradiation.

Single-entry catheter brachytherapy is conditionally recommended, and intraoperative radiation therapy techniques are not recommended unless integrated into a prospective clinical trial or multi-institutional registry.

The guideline also outlines optimal dose, fractionation, target volume, and treatment modality with different partial breast irradiation techniques, taking toxicities and cosmesis into consideration.

“We hope that by laying out the evidence from these major trials and providing guidance on how to administer partial breast radiation, the guideline can help more oncologists feel comfortable offering this option to their patients as an alternative to whole breast radiation,” Janice Lyons, MD, of University Hospitals Seidman Cancer Center, Cleveland, Ohio, and chair of the guideline task force, said in the news release.

The guideline, developed in collaboration with the American Society of Clinical Oncology and the Society of Surgical Oncology, has been endorsed by the Canadian Association of Radiation Oncology, the European Society for Radiotherapy and Oncology, and the Royal Australian and New Zealand College of Radiologists. Guideline development was funded by ASTRO and the systematic evidence review was funded by the Patient-Centered Outcomes Research Institute. Disclosures for the task force are available with the original article.
 

A version of this article was first published on Medscape.com.

The American Society of Clinical Oncology (ASCO) has released guidance on how to prioritize use of key oncology drugs amid ongoing shortages.

As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.

The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.

The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology. 

In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.

And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.

The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.

The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.

More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.

In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”

Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.

In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.

“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
 

A version of this article appeared on Medscape.com.

The American Society of Clinical Oncology (ASCO) has released guidance on how to prioritize use of key oncology drugs amid ongoing shortages.

As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.

The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.

The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology. 

In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.

And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.

The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.

The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.

More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.

In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”

Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.

In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.

“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
 

A version of this article appeared on Medscape.com.

The American Society of Clinical Oncology (ASCO) has released guidance on how to prioritize use of key oncology drugs amid ongoing shortages.

As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.

The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.

The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology. 

In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.

And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.

The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.

The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.

More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.

In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”

Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.

In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.

“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.

Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.

Additional Reference

1. Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112

Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.

Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.

Additional Reference

1. Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112

Prior studies show inconsistent outcomes in patients with invasive lobular carcinoma (ILC) and data in premenopausal women is limited. The retrospective cohort study by Yoon and colleagues analyzed the data from three databases and included 225,938 premenopausal women with stage I-III ILC or invasive ductal carcinoma (IDC) in their study to evaluate survival trends in young women with ILC. In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed superior breast cancer severity score (BCSS) outcomes during the first 10 years after diagnosis (HR 0.73; P < .001); similar results were seen in the Asan Medical Center Research (AMCR) database (HR 0.50; 95% CI 0.29-0.86; P = .01). After 10 years, the trend reversed, and BCSS outcomes worsened by 80% in patients with ILC in the SEER database (HR 1.80; P < .001). This was also seen in both the Korean Breast Cancer Registry (HR 2.79; 95% CI 1.32-5.88; P = .007) and AMCR database (HR 2.23; 95% CI 1.04-4.79; P = .04). These findings remained consistent after adjusting for tumor characteristics including age, stage, tumor grade, hormone receptor status, and after controlling for treatment with chemotherapy and radiation. In addition, in the SEER database, the histologic type exerted a statistically significant time-dependent association with BCSS, with ILC showing decreasing BCSS over time (time interaction HR 1.93; 95% CI 1.78-2.10; P < .001). Furthermore, on annual hazard function analysis, the ILC annual peak event of BCSS occurred 5 years after diagnosis, whereas the IDC recurrence events peaked at 5 years before diagnosis, suggesting a higher late recurrence rate for ILC. These findings may have implications on the duration of endocrine therapy used in these patients given concern for worse long-term outcomes in premenopausal patients with ILC.

Oral selective estrogen receptor degraders (SERD) have recently emerged as a new therapeutic mechanism for patients with hormone receptor–positive breast cancer who have developed resistance to other endocrine therapies. Two of these agents, elacestrant and camizestrant, have demonstrated statistically significant progression-free survival benefit in these populations, particularly in tumors with ESR1 mutations. The efficacy of these agents in tumors with ESR1 wild-type subgroup remains uncertain. A meta-analysis by Wong and colleagues of individual patient data from four randomized clinical trials (ACELERA, AMEERA-3, EMERALD, and SERENA-2) included 1290 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer who received oral SERD or endocrine therapies (ET) of the physician's choice. In the overall cohort, oral SERD showed improved progression-free survival (PFS) outcomes compared with ET of the physician's choice (HR 0.783; 95% CI 0.681-0.900; P < .001). This was also noted in the subgroup of patients with ESR1 mutations (HR 0.557; 95% CI 0.440-0.705; P < .001); although no significant PFS benefit was observed with oral SERD in the ESR1 wild-type subgroup (HR 0.944; 95% CI 0.783-1.138; P = .543). These results suggest that the PFS benefit observed with oral SERD is mainly seen in patients with ESR1-mutated tumors, and, therefore, these drugs should be prescribed accordingly.

Additional Reference

1. Cold S, Cold F, Jensen M-B, et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022;114:1347–1354. doi: 10.1093/jnci/djac112

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

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

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

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

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

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

The US Preventive Services Task Force (USPSTF)¹ is comprised of an independent panel of preventive services clinician experts who make evidence-based recommendations, with the letter grade assigned based on the strength of the evidence, from A through D (TABLE 1), on preventive services such as health screenings, shared decision making patient counseling, and preventive medications.  Both A and B recommendations are generally accepted by both government and most private health insurance companies as a covered preventive benefit with no or minimal co-pays.

In 2002, the USPSTF released a Grade B recommendation that screening mammography for average-risk patients (with patients referring to persons assigned female at birth who have not undergone bilateral mastectomy) should take place starting at age 40 and be repeated every 1 to 2 years.² This was consistent with or endorsed by most other national breast cancer screening guidelines,  including the American College of Obstetricians and Gynecologists (ACOG), National Comprehensive Cancer Network (NCCN), the American Cancer Society (ACS), and the American College of Radiology. 

In 2009, the USPSTF changed this Grade B recommendation, instead recommending biennial screening mammography for women aged 50 to 74.³ The most significant change in the revised guideline was for patients aged 40 to 49, where the recommendation was “against routine screening mammography.” They went on to say that the decision to start “biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.” Other prominent national guideline groups (ACOG, NCCN, ACS) did not agree with this recommendation and maintained that patients aged 40 to 49 should continue to be offered routine screening mammography either annually (NCCN, ACS) or at 1-to-2-year intervals (ACOG).^4-6 The American College of Physicians and the American Academy of Family Practice endorsed the 2016 USPSTF guidelines, creating a disparity in breast cancer mammography counseling for averagerisk patients in their 40s.⁷

In 2016, the USPSTF revisited their breast cancer screening recommendation and renewed their 2009 recommendation against routine screening in patients aged 40 to 49, with the American College of Physicians and the American Academy of Family Practice again endorsing these guidelines.⁸ ACOG, ACS, NCCN, and ACR continued to recommend age 40 as a starting age for routine mammography screening (TABLE 2). As a result, over the past 14 years, patients aged 40 to 49 were placed in an awkward position of potentially hearing different recommendations from their health care providers, those differences often depending on the specialty of the provider they were seeing. 

In 2023. On May 9, the USPSTF released a draft of their latest recommendation statement stating that all patients at average risk for breast cancer should get screened every other year beginning at age 40, bringing most of the national guideline groups into alignment with regard to age to start mammographic screening.⁹ 

Why the change? 

To answer this question, we need to examine the relevant epidemiology of breast cancer. 

Continue to: Incidence...

Incidence

It is estimated that, in the United States in 2023, there will be 300,590 new cases of breast cancer, resulting in 43,700 deaths.¹⁰ From 2015–2019, there were 128.1 new breast cancer cases/100,000 population, which is the highest rate of cancer in the United States, regardless of sex.¹¹ Diagnoses among patients aged 40 to 49 are rising at a faster rate than previously, about 2% per year between 2015 and 2019. 

Racial and ethnic differences

In addition to the racial and ethnic epidemiologic differences in breast cancer, there are also disparities in breast cancer care and outcomes that need to be considered when making national guidelines/policy recommendations. 

Black women have high mortality rates from breast cancer. While non-Hispanic White patients have the highest rates of breast cancer (TABLE 3), non-Hispanic Black patients have the highest rates of death due to breast cancer.¹⁰ There appear to be several reasons for the estimated 40%-higher rate of mortality among Black women, including: 

• systemic racism in primary research, guidelines, and policy
• inequities in diagnostic follow-up and access to evidence-based cancer treatments
• biologic differences in breast cancer (ie, the incidence of triple-negative breast cancer (TNBC) is 2-fold higher in Black women compared with the other racial and ethnic groups in the United States).^12-14 

While prior studies have suggested that screening mammography might be less effective for patients with TNBC, a recent study demonstrated that patients who had mammography–screened-detected TNBC tumors were smaller and more likely to be node- negative compared with non-screened patients with TNBC.(14) Patients with screened-detected TNBCs were also more likely to undergo a lumpectomy instead of a mastectomy compared with non–screened detected TNBC (68.3% vs 46.1%; P = .002) (TABLE 4). These data strongly suggest that screening mammography is indeed effective in detecting TNBC at earlier stages, one of the best proxies for breast cancer mortality. 

Non-White patients have higher incidence rates of breast cancer in their 40s. A second factor to consider in racial differences is the relatively higher incidence of breast cancer in Hispanic, Black, and Asian patients in their 40s compared with non-Hispanic White patients. In a recent analysis of data from 1973 to 2010 from the Surveillance, Epidemiology, and End Results (SEER) Program, the median age of patients with breast cancer in the United States was 58.0 years (interquartile range [IQR], 50.0–67.0 years).¹⁶ Across all US demographic populations by age at diagnosis, more than 20% of patients will have their initial diagnosis of  breast cancer under the age of 50, and 1.55% (1 in 65) patients between ages 40 and 49 years will be diagnosed with breast cancer.4 However, among patients aged 50 and younger diagnosed with breast cancer, a significantly higher proportion are Black (31%), Hispanic (34.9%), or Asian (32.8%) versus White (23.1%) (P < .001 for all).¹⁶ So, for there to be similar racial and ethnic mammography capture rates with White patients, starting mammography screening ages would need to be lower for Black (age 47 years), Hispanic (and 46 years), and Asian (age 47 years) patients. Data from this study of the SEER database16 also demonstrated that more Black and Hispanic patients at age of diagnosis were diagnosed with advanced (regional or distant) breast cancer (46.6% and 42.9%, respectively) versus White or Asian patients (37.1% and 35.6%, respectively; P < .001 for all). 

These findings led the authors of the study to conclude that the “Current [2016] USPSTF breast cancer screening recommendations do not reflect age-specific patterns based on race.” The USPSTF stated that this is one of the reasons why they reconsidered their stance on screening , and now recommend screening for all patients starting at age 40. 

My current counseling approach

I encourage all racial and ethnic patients between the ages of 40 and 49 to undergo screening mammography because of the associated relative risk mortality reduction rates, which range from 15% to 50%. I also share that with my patients that, because of the younger average age of onset of breast cancer in Black, Hispanic, and Asian patients, they may derive additional benefit from screening starting at age 40.⁴ 

Impact of draft guidelines on breast cancer screening and mortality in younger patients

There is clear, unequivocal, and repeatable Level 1 evidence that screening mammography in the general population of patients aged 40 to 49 reduces breast cancer mortality. Breast cancer is the leading cause of cancer in the United States, the second leading cause of cancer mortality in patients, and 1 in 5 new breast cancer diagnoses occur in patients between the ages of 40 and 49. While recent efforts have been made to come to consensus on a screening starting age of 40 for patients at average risk for breast cancer, the USPSTF appeared to be an outlier with their 2016 recommendation to routinely start mammography screening at age 50 instead of 40.¹⁷ 

The USPSTF is a very important national voice in cancer prevention, and their 2023 (draft) revised guidelines to age 40 as the recommended starting screening age now agrees with the leading US guideline groups listed in Table 2. These guideline groups have gone through varying processes, and now have finally arrived at the same conclusion for age to start screening mammography in women of average risk. This agreement should come as a significant comfort to health care providers and patients alike. Changing the starting age to 40 years will result in thousands of lives and hundreds of thousands of life-years saved for patients aged 40 to 49. ● 

The US Preventive Services Task Force (USPSTF)¹ is comprised of an independent panel of preventive services clinician experts who make evidence-based recommendations, with the letter grade assigned based on the strength of the evidence, from A through D (TABLE 1), on preventive services such as health screenings, shared decision making patient counseling, and preventive medications.  Both A and B recommendations are generally accepted by both government and most private health insurance companies as a covered preventive benefit with no or minimal co-pays.

In 2002, the USPSTF released a Grade B recommendation that screening mammography for average-risk patients (with patients referring to persons assigned female at birth who have not undergone bilateral mastectomy) should take place starting at age 40 and be repeated every 1 to 2 years.² This was consistent with or endorsed by most other national breast cancer screening guidelines,  including the American College of Obstetricians and Gynecologists (ACOG), National Comprehensive Cancer Network (NCCN), the American Cancer Society (ACS), and the American College of Radiology. 

In 2009, the USPSTF changed this Grade B recommendation, instead recommending biennial screening mammography for women aged 50 to 74.³ The most significant change in the revised guideline was for patients aged 40 to 49, where the recommendation was “against routine screening mammography.” They went on to say that the decision to start “biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.” Other prominent national guideline groups (ACOG, NCCN, ACS) did not agree with this recommendation and maintained that patients aged 40 to 49 should continue to be offered routine screening mammography either annually (NCCN, ACS) or at 1-to-2-year intervals (ACOG).^4-6 The American College of Physicians and the American Academy of Family Practice endorsed the 2016 USPSTF guidelines, creating a disparity in breast cancer mammography counseling for averagerisk patients in their 40s.⁷

In 2016, the USPSTF revisited their breast cancer screening recommendation and renewed their 2009 recommendation against routine screening in patients aged 40 to 49, with the American College of Physicians and the American Academy of Family Practice again endorsing these guidelines.⁸ ACOG, ACS, NCCN, and ACR continued to recommend age 40 as a starting age for routine mammography screening (TABLE 2). As a result, over the past 14 years, patients aged 40 to 49 were placed in an awkward position of potentially hearing different recommendations from their health care providers, those differences often depending on the specialty of the provider they were seeing. 

In 2023. On May 9, the USPSTF released a draft of their latest recommendation statement stating that all patients at average risk for breast cancer should get screened every other year beginning at age 40, bringing most of the national guideline groups into alignment with regard to age to start mammographic screening.⁹ 

Why the change? 

To answer this question, we need to examine the relevant epidemiology of breast cancer. 

Continue to: Incidence...

Incidence

It is estimated that, in the United States in 2023, there will be 300,590 new cases of breast cancer, resulting in 43,700 deaths.¹⁰ From 2015–2019, there were 128.1 new breast cancer cases/100,000 population, which is the highest rate of cancer in the United States, regardless of sex.¹¹ Diagnoses among patients aged 40 to 49 are rising at a faster rate than previously, about 2% per year between 2015 and 2019. 

Racial and ethnic differences

In addition to the racial and ethnic epidemiologic differences in breast cancer, there are also disparities in breast cancer care and outcomes that need to be considered when making national guidelines/policy recommendations. 

Black women have high mortality rates from breast cancer. While non-Hispanic White patients have the highest rates of breast cancer (TABLE 3), non-Hispanic Black patients have the highest rates of death due to breast cancer.¹⁰ There appear to be several reasons for the estimated 40%-higher rate of mortality among Black women, including: 

• systemic racism in primary research, guidelines, and policy
• inequities in diagnostic follow-up and access to evidence-based cancer treatments
• biologic differences in breast cancer (ie, the incidence of triple-negative breast cancer (TNBC) is 2-fold higher in Black women compared with the other racial and ethnic groups in the United States).^12-14 

While prior studies have suggested that screening mammography might be less effective for patients with TNBC, a recent study demonstrated that patients who had mammography–screened-detected TNBC tumors were smaller and more likely to be node- negative compared with non-screened patients with TNBC.(14) Patients with screened-detected TNBCs were also more likely to undergo a lumpectomy instead of a mastectomy compared with non–screened detected TNBC (68.3% vs 46.1%; P = .002) (TABLE 4). These data strongly suggest that screening mammography is indeed effective in detecting TNBC at earlier stages, one of the best proxies for breast cancer mortality. 

Non-White patients have higher incidence rates of breast cancer in their 40s. A second factor to consider in racial differences is the relatively higher incidence of breast cancer in Hispanic, Black, and Asian patients in their 40s compared with non-Hispanic White patients. In a recent analysis of data from 1973 to 2010 from the Surveillance, Epidemiology, and End Results (SEER) Program, the median age of patients with breast cancer in the United States was 58.0 years (interquartile range [IQR], 50.0–67.0 years).¹⁶ Across all US demographic populations by age at diagnosis, more than 20% of patients will have their initial diagnosis of  breast cancer under the age of 50, and 1.55% (1 in 65) patients between ages 40 and 49 years will be diagnosed with breast cancer.4 However, among patients aged 50 and younger diagnosed with breast cancer, a significantly higher proportion are Black (31%), Hispanic (34.9%), or Asian (32.8%) versus White (23.1%) (P < .001 for all).¹⁶ So, for there to be similar racial and ethnic mammography capture rates with White patients, starting mammography screening ages would need to be lower for Black (age 47 years), Hispanic (and 46 years), and Asian (age 47 years) patients. Data from this study of the SEER database16 also demonstrated that more Black and Hispanic patients at age of diagnosis were diagnosed with advanced (regional or distant) breast cancer (46.6% and 42.9%, respectively) versus White or Asian patients (37.1% and 35.6%, respectively; P < .001 for all). 

These findings led the authors of the study to conclude that the “Current [2016] USPSTF breast cancer screening recommendations do not reflect age-specific patterns based on race.” The USPSTF stated that this is one of the reasons why they reconsidered their stance on screening , and now recommend screening for all patients starting at age 40. 

My current counseling approach

I encourage all racial and ethnic patients between the ages of 40 and 49 to undergo screening mammography because of the associated relative risk mortality reduction rates, which range from 15% to 50%. I also share that with my patients that, because of the younger average age of onset of breast cancer in Black, Hispanic, and Asian patients, they may derive additional benefit from screening starting at age 40.⁴ 

Impact of draft guidelines on breast cancer screening and mortality in younger patients

There is clear, unequivocal, and repeatable Level 1 evidence that screening mammography in the general population of patients aged 40 to 49 reduces breast cancer mortality. Breast cancer is the leading cause of cancer in the United States, the second leading cause of cancer mortality in patients, and 1 in 5 new breast cancer diagnoses occur in patients between the ages of 40 and 49. While recent efforts have been made to come to consensus on a screening starting age of 40 for patients at average risk for breast cancer, the USPSTF appeared to be an outlier with their 2016 recommendation to routinely start mammography screening at age 50 instead of 40.¹⁷ 

The USPSTF is a very important national voice in cancer prevention, and their 2023 (draft) revised guidelines to age 40 as the recommended starting screening age now agrees with the leading US guideline groups listed in Table 2. These guideline groups have gone through varying processes, and now have finally arrived at the same conclusion for age to start screening mammography in women of average risk. This agreement should come as a significant comfort to health care providers and patients alike. Changing the starting age to 40 years will result in thousands of lives and hundreds of thousands of life-years saved for patients aged 40 to 49. ● 

The US Preventive Services Task Force (USPSTF)¹ is comprised of an independent panel of preventive services clinician experts who make evidence-based recommendations, with the letter grade assigned based on the strength of the evidence, from A through D (TABLE 1), on preventive services such as health screenings, shared decision making patient counseling, and preventive medications.  Both A and B recommendations are generally accepted by both government and most private health insurance companies as a covered preventive benefit with no or minimal co-pays.

In 2002, the USPSTF released a Grade B recommendation that screening mammography for average-risk patients (with patients referring to persons assigned female at birth who have not undergone bilateral mastectomy) should take place starting at age 40 and be repeated every 1 to 2 years.² This was consistent with or endorsed by most other national breast cancer screening guidelines,  including the American College of Obstetricians and Gynecologists (ACOG), National Comprehensive Cancer Network (NCCN), the American Cancer Society (ACS), and the American College of Radiology. 

In 2009, the USPSTF changed this Grade B recommendation, instead recommending biennial screening mammography for women aged 50 to 74.³ The most significant change in the revised guideline was for patients aged 40 to 49, where the recommendation was “against routine screening mammography.” They went on to say that the decision to start “biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.” Other prominent national guideline groups (ACOG, NCCN, ACS) did not agree with this recommendation and maintained that patients aged 40 to 49 should continue to be offered routine screening mammography either annually (NCCN, ACS) or at 1-to-2-year intervals (ACOG).^4-6 The American College of Physicians and the American Academy of Family Practice endorsed the 2016 USPSTF guidelines, creating a disparity in breast cancer mammography counseling for averagerisk patients in their 40s.⁷

In 2016, the USPSTF revisited their breast cancer screening recommendation and renewed their 2009 recommendation against routine screening in patients aged 40 to 49, with the American College of Physicians and the American Academy of Family Practice again endorsing these guidelines.⁸ ACOG, ACS, NCCN, and ACR continued to recommend age 40 as a starting age for routine mammography screening (TABLE 2). As a result, over the past 14 years, patients aged 40 to 49 were placed in an awkward position of potentially hearing different recommendations from their health care providers, those differences often depending on the specialty of the provider they were seeing. 

In 2023. On May 9, the USPSTF released a draft of their latest recommendation statement stating that all patients at average risk for breast cancer should get screened every other year beginning at age 40, bringing most of the national guideline groups into alignment with regard to age to start mammographic screening.⁹ 

Why the change? 

To answer this question, we need to examine the relevant epidemiology of breast cancer. 

Continue to: Incidence...

Incidence

It is estimated that, in the United States in 2023, there will be 300,590 new cases of breast cancer, resulting in 43,700 deaths.¹⁰ From 2015–2019, there were 128.1 new breast cancer cases/100,000 population, which is the highest rate of cancer in the United States, regardless of sex.¹¹ Diagnoses among patients aged 40 to 49 are rising at a faster rate than previously, about 2% per year between 2015 and 2019. 

Racial and ethnic differences

In addition to the racial and ethnic epidemiologic differences in breast cancer, there are also disparities in breast cancer care and outcomes that need to be considered when making national guidelines/policy recommendations. 

Black women have high mortality rates from breast cancer. While non-Hispanic White patients have the highest rates of breast cancer (TABLE 3), non-Hispanic Black patients have the highest rates of death due to breast cancer.¹⁰ There appear to be several reasons for the estimated 40%-higher rate of mortality among Black women, including: 

• systemic racism in primary research, guidelines, and policy
• inequities in diagnostic follow-up and access to evidence-based cancer treatments
• biologic differences in breast cancer (ie, the incidence of triple-negative breast cancer (TNBC) is 2-fold higher in Black women compared with the other racial and ethnic groups in the United States).^12-14 

While prior studies have suggested that screening mammography might be less effective for patients with TNBC, a recent study demonstrated that patients who had mammography–screened-detected TNBC tumors were smaller and more likely to be node- negative compared with non-screened patients with TNBC.(14) Patients with screened-detected TNBCs were also more likely to undergo a lumpectomy instead of a mastectomy compared with non–screened detected TNBC (68.3% vs 46.1%; P = .002) (TABLE 4). These data strongly suggest that screening mammography is indeed effective in detecting TNBC at earlier stages, one of the best proxies for breast cancer mortality. 

Non-White patients have higher incidence rates of breast cancer in their 40s. A second factor to consider in racial differences is the relatively higher incidence of breast cancer in Hispanic, Black, and Asian patients in their 40s compared with non-Hispanic White patients. In a recent analysis of data from 1973 to 2010 from the Surveillance, Epidemiology, and End Results (SEER) Program, the median age of patients with breast cancer in the United States was 58.0 years (interquartile range [IQR], 50.0–67.0 years).¹⁶ Across all US demographic populations by age at diagnosis, more than 20% of patients will have their initial diagnosis of  breast cancer under the age of 50, and 1.55% (1 in 65) patients between ages 40 and 49 years will be diagnosed with breast cancer.4 However, among patients aged 50 and younger diagnosed with breast cancer, a significantly higher proportion are Black (31%), Hispanic (34.9%), or Asian (32.8%) versus White (23.1%) (P < .001 for all).¹⁶ So, for there to be similar racial and ethnic mammography capture rates with White patients, starting mammography screening ages would need to be lower for Black (age 47 years), Hispanic (and 46 years), and Asian (age 47 years) patients. Data from this study of the SEER database16 also demonstrated that more Black and Hispanic patients at age of diagnosis were diagnosed with advanced (regional or distant) breast cancer (46.6% and 42.9%, respectively) versus White or Asian patients (37.1% and 35.6%, respectively; P < .001 for all). 

These findings led the authors of the study to conclude that the “Current [2016] USPSTF breast cancer screening recommendations do not reflect age-specific patterns based on race.” The USPSTF stated that this is one of the reasons why they reconsidered their stance on screening , and now recommend screening for all patients starting at age 40. 

My current counseling approach

I encourage all racial and ethnic patients between the ages of 40 and 49 to undergo screening mammography because of the associated relative risk mortality reduction rates, which range from 15% to 50%. I also share that with my patients that, because of the younger average age of onset of breast cancer in Black, Hispanic, and Asian patients, they may derive additional benefit from screening starting at age 40.⁴ 

Impact of draft guidelines on breast cancer screening and mortality in younger patients

There is clear, unequivocal, and repeatable Level 1 evidence that screening mammography in the general population of patients aged 40 to 49 reduces breast cancer mortality. Breast cancer is the leading cause of cancer in the United States, the second leading cause of cancer mortality in patients, and 1 in 5 new breast cancer diagnoses occur in patients between the ages of 40 and 49. While recent efforts have been made to come to consensus on a screening starting age of 40 for patients at average risk for breast cancer, the USPSTF appeared to be an outlier with their 2016 recommendation to routinely start mammography screening at age 50 instead of 40.¹⁷ 

The USPSTF is a very important national voice in cancer prevention, and their 2023 (draft) revised guidelines to age 40 as the recommended starting screening age now agrees with the leading US guideline groups listed in Table 2. These guideline groups have gone through varying processes, and now have finally arrived at the same conclusion for age to start screening mammography in women of average risk. This agreement should come as a significant comfort to health care providers and patients alike. Changing the starting age to 40 years will result in thousands of lives and hundreds of thousands of life-years saved for patients aged 40 to 49. ● 

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0>
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi: 10.1093/annonc/mdx308

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308

Breast cancer in young women presents a unique set of challenges owing to life-stage at the time of diagnosis and treatment. Oncofertility, family planning, and pregnancy are essential issues to address at the time of initial consultation and throughout the survivorship setting. Various studies have provided supportive evidence regarding the safety of pregnancy after breast cancer diagnosis and treatment.³ HR+ breast cancer is associated with its own distinctive considerations related to pregnancy and its timing, including the use of endocrine therapy for 5-10 years, the role of female hormones during pregnancy, and late patterns of recurrence that characterize this subtype. A meta-analysis including eight eligible studies and 3805 women with HR+ early breast cancer investigated the prognostic impact of future pregnancy among these patients (Arecco et al). A total of 1285 women had a pregnancy after breast cancer diagnosis and treatment; there was no difference in disease-free survival (hazard ratio 0.96; 95% CI 0.75-1.24; P = .781) and better overall survival (OS; hazard ratio 0.46; 95% CI 0.27-0.77; P < .005) in those with vs those without subsequent pregnancy. Added to this body of data is the prospective POSITIVE trial, which showed that a temporary pause of endocrine therapy for an attempt at conceiving appears to be safe in young women with early HR+ breast cancer with short-term follow-up.⁴ Future research efforts investigating outcomes after assisted reproductive technologies in this population, those with germline mutations, and extended follow-up of studies, such as POSITIVE, will continue to inform guidance for and management of young women with breast cancer.

Guidelines favor the use of adjuvant chemotherapy for small, node-negative, triple-negative breast cancer (TNBC), specifically T1b and T1c tumors.⁵ However, high-quality data to inform this decision-making are sparse, and it is valuable to consider the magnitude of benefit weighed against possible risks and side effects of treatment, as well as patient comorbidities. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database including 11,510 patients (3388 with T1b and 8122 with T1c TNBC) evaluated the impact of adjuvant chemotherapy on OS and breast cancer–specific survival (BCSS) (Carbajal-Ochoa et al). The use of adjuvant chemotherapy was associated with improved OS (hazard ratio 0.54; 95% CI 0.47-0.62; P < .001) and BCSS (hazard ratio 0.79; 95% CI 0.63-0.99; P = .043) among T1c TNBC. For those with T1b tumors, adjuvant chemotherapy improved OS (hazard ratio 0.52; 95% CI 0.41-0.68; P < .001) but did not improve BCSS (hazard ratio 0.70; 95% CI 0.45-1.07; P = .10). A better understanding of the molecular drivers implicated in this heterogeneous subtype, and predictors of response and resistance, will aid in identifying those patients who have greater benefit and those who can potentially be spared chemotherapy-related toxicities.

Additional References

1. Anwar SL, Cahyono R, Prabowo D, et al. Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors. BMC Cancer. 2021;21:590. doi: 10.1186/s12885-021-08343-0
2. Sestak I, Distler W, Forbes JF, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28:3411-3415. doi: 10.1200/JCO.2009.27.2021
3. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
4. Partridge AH, Niman SM, Ruggeri M, et al for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi:10.1056/NEJMoa2212856
5. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700-1712. doi:10.1093/annonc/mdx308