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FDA expands abemaciclib use in high-risk early breast cancer
Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.
The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.
At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.
“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.
A version of this article first appeared on Medscape.com.
Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.
The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.
At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.
“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.
A version of this article first appeared on Medscape.com.
Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.
The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.
At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.
“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.
A version of this article first appeared on Medscape.com.
Commentary: Looking at Treatment Regimens for HR+ Breast Cancer and Triple-Negative Breast Cancer, March 2023
A post hoc analysis of the ShortHER trial, including 784 patients with hormone-positive (HR+) and human epidermal growth factor receptor 2–positive (HER2+) early breast cancer who received adjuvant trastuzumab plus chemotherapy, showed that adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better outcomes than tamoxifen (TAM) or TAM and AI (TAM-AI) in this population. Disease-free survival rates at 8 years were 86.4% for AI vs 79.7% for the TAM/TAM-AI groups, with an absolute difference of 6.7% (log-rank P = .013). This effect was seen independently of menopausal status in a multivariate analysis.
In the exploratory analysis focusing on the premenopausal patients, the addition of gonadotropin-releasing hormone to ET was associated with a significantly better disease-free survival. This was also noted in an exploratory subgroup analysis of the SOFT trial,[1] which showed greater benefit from the addition of ovarian suppression to TAM, as compared with TAM alone, among women with HER2+ disease (hazard ratio 0.41; 95% CI 0.22-0.75).
It is important to note that not all patients in the ShortHER trial received the standard-of-care duration of adjuvant trastuzumab; half of them received only 9-week treatment as opposed to the standard 12 months of adjuvant therapy. It is unclear whether this difference in adjuvant therapy could have affected the results, although the disease-free survival multivariate analysis showed no significant effect of the treatment arm on the role of ET. More studies are needed to verify the optimal adjuvant ET for patients with HR+/HER2+ breast cancer, especially in premenopausal patients.
Contralateral Prophylactic Mastectomy Offers No Survival Advantage in Triple-Negative Breast Cancer
There is insufficient evidence that contralateral prophylactic mastectomy (CPM) improves survival in patients with unilateral triple-negative breast cancer (TNBC). A multi-institutional database study, including 796 patients with TNBC, of which 15.5% underwent CPM, showed that CPM did not offer survival benefit to patients with unilateral TNBC. Women who underwent CPM were more likely to be White (P < .001), younger (P < .001), and had had genetic testing performed (P < .001). While there was a borderline improvement in 5-year unadjusted overall survival for patients undergoing CPM compared with no CPM overall (95.1% vs 85.0%; P = .05), no significant improvement was observed for local recurrence-free survival (P = .40) or distant recurrence-free survival (P = .37). Very few (n = 15/673, 2.2%) of the no-CPM patients developed a new primary breast cancer; 3 of the 15 patients were known BRCA1 or BRCA2 mutation carriers. Among the genetic mutation carriers, 5-year overall survival was 97.2% for CPM vs 84.1% for no CPM (P = .35). This study did not demonstrate any statistically significant survival difference between CPM compared with no CPM, regardless of the presence of a BRCA mutation, although prior studies have shown improved outcomes for CPM in BRCA mutation carriers.[2] Larger prospective studies are needed to evaluate the potential benefit of CPM among patients with TNBC, especially patients with BRCA1/2 mutations.
Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy Beneficial in HER2+/HR+ Metastatic Breast Cancer
The current first-line standard of care for HER2+ metastatic breast cancer is dual anti-HER2 targeted therapy plus chemotherapy, with consideration for maintenance treatment with anti-HER2 therapy and ET for patients with HR+ and HER2+ metastatic breast cancer. The potential benefit of adding ET for patients with HR+/HER2+ metastatic breast cancer has been reported previously, but data overall are limited. This study analyzed the real-world data of 147 patients with HR+/HER2+ metastatic breast cancer from a prospective registry and who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET. The findings showed that adding ET resulted in a significant improvement in 5-year progression-free survival (PFS) (hazard ratio 0.59; P = .031) and overall survival (hazard ratio 0.52; P = .018) compared with not adding ET. No new safety concerns were identified when combining HER2+ targeted therapy and ET. While this is a small retrospective analysis, results are certainly encouraging and support the addition of ET to dual anti-HER2 therapy as maintenance therapy post chemotherapy in this subset of patients.
High PD-L2 Levels May Predict Worse Clinical Outcomes in ER+ Breast Cancer
Programmed cell death-1 ligand-2 (PD-L2) is a second ligand for programmed cell death-1 (PD-1) and inhibits T-cell activation. A retrospective study including patients with estrogen receptor–positive (ER+) breast cancer looked at PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, locoregional ER+ breast cancer in the main study cohort (n = 684) and in an independent validation cohort (n = 273), and correlated findings with PFS. High levels of PD-L2 protein were present in up to one third (33%) of ER+ tumors and were associated with shorter PFS in the entire cohort of patients with ER+ breast cancer (hazard ratio 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (hazard ratio 3.4; P < .001). A multivariable analysis showed that high levels of PD-L2 were an independent prognostic marker in ER+ patients. These findings suggest that high PD-L2 is associated with unfavorable prognosis in ER+ breast cancer and may be a potential biomarker of response to checkpoint inhibitors.
Additional References
- Francis PA, Pagani O, Fleming GF, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379:122-137. Doi: 10.1056/NEJMoa1803164
- Li X, You R, Wang X, et al. Effectiveness of prophylactic surgeries in BRCA1 or BRCA2 mutation carriers: A meta-analysis and systematic review. Clin Cancer Res. 2016;22:3971-3981. Doi: 10.1158/1078-0432.CCR-15-1465
A post hoc analysis of the ShortHER trial, including 784 patients with hormone-positive (HR+) and human epidermal growth factor receptor 2–positive (HER2+) early breast cancer who received adjuvant trastuzumab plus chemotherapy, showed that adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better outcomes than tamoxifen (TAM) or TAM and AI (TAM-AI) in this population. Disease-free survival rates at 8 years were 86.4% for AI vs 79.7% for the TAM/TAM-AI groups, with an absolute difference of 6.7% (log-rank P = .013). This effect was seen independently of menopausal status in a multivariate analysis.
In the exploratory analysis focusing on the premenopausal patients, the addition of gonadotropin-releasing hormone to ET was associated with a significantly better disease-free survival. This was also noted in an exploratory subgroup analysis of the SOFT trial,[1] which showed greater benefit from the addition of ovarian suppression to TAM, as compared with TAM alone, among women with HER2+ disease (hazard ratio 0.41; 95% CI 0.22-0.75).
It is important to note that not all patients in the ShortHER trial received the standard-of-care duration of adjuvant trastuzumab; half of them received only 9-week treatment as opposed to the standard 12 months of adjuvant therapy. It is unclear whether this difference in adjuvant therapy could have affected the results, although the disease-free survival multivariate analysis showed no significant effect of the treatment arm on the role of ET. More studies are needed to verify the optimal adjuvant ET for patients with HR+/HER2+ breast cancer, especially in premenopausal patients.
Contralateral Prophylactic Mastectomy Offers No Survival Advantage in Triple-Negative Breast Cancer
There is insufficient evidence that contralateral prophylactic mastectomy (CPM) improves survival in patients with unilateral triple-negative breast cancer (TNBC). A multi-institutional database study, including 796 patients with TNBC, of which 15.5% underwent CPM, showed that CPM did not offer survival benefit to patients with unilateral TNBC. Women who underwent CPM were more likely to be White (P < .001), younger (P < .001), and had had genetic testing performed (P < .001). While there was a borderline improvement in 5-year unadjusted overall survival for patients undergoing CPM compared with no CPM overall (95.1% vs 85.0%; P = .05), no significant improvement was observed for local recurrence-free survival (P = .40) or distant recurrence-free survival (P = .37). Very few (n = 15/673, 2.2%) of the no-CPM patients developed a new primary breast cancer; 3 of the 15 patients were known BRCA1 or BRCA2 mutation carriers. Among the genetic mutation carriers, 5-year overall survival was 97.2% for CPM vs 84.1% for no CPM (P = .35). This study did not demonstrate any statistically significant survival difference between CPM compared with no CPM, regardless of the presence of a BRCA mutation, although prior studies have shown improved outcomes for CPM in BRCA mutation carriers.[2] Larger prospective studies are needed to evaluate the potential benefit of CPM among patients with TNBC, especially patients with BRCA1/2 mutations.
Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy Beneficial in HER2+/HR+ Metastatic Breast Cancer
The current first-line standard of care for HER2+ metastatic breast cancer is dual anti-HER2 targeted therapy plus chemotherapy, with consideration for maintenance treatment with anti-HER2 therapy and ET for patients with HR+ and HER2+ metastatic breast cancer. The potential benefit of adding ET for patients with HR+/HER2+ metastatic breast cancer has been reported previously, but data overall are limited. This study analyzed the real-world data of 147 patients with HR+/HER2+ metastatic breast cancer from a prospective registry and who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET. The findings showed that adding ET resulted in a significant improvement in 5-year progression-free survival (PFS) (hazard ratio 0.59; P = .031) and overall survival (hazard ratio 0.52; P = .018) compared with not adding ET. No new safety concerns were identified when combining HER2+ targeted therapy and ET. While this is a small retrospective analysis, results are certainly encouraging and support the addition of ET to dual anti-HER2 therapy as maintenance therapy post chemotherapy in this subset of patients.
High PD-L2 Levels May Predict Worse Clinical Outcomes in ER+ Breast Cancer
Programmed cell death-1 ligand-2 (PD-L2) is a second ligand for programmed cell death-1 (PD-1) and inhibits T-cell activation. A retrospective study including patients with estrogen receptor–positive (ER+) breast cancer looked at PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, locoregional ER+ breast cancer in the main study cohort (n = 684) and in an independent validation cohort (n = 273), and correlated findings with PFS. High levels of PD-L2 protein were present in up to one third (33%) of ER+ tumors and were associated with shorter PFS in the entire cohort of patients with ER+ breast cancer (hazard ratio 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (hazard ratio 3.4; P < .001). A multivariable analysis showed that high levels of PD-L2 were an independent prognostic marker in ER+ patients. These findings suggest that high PD-L2 is associated with unfavorable prognosis in ER+ breast cancer and may be a potential biomarker of response to checkpoint inhibitors.
Additional References
- Francis PA, Pagani O, Fleming GF, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379:122-137. Doi: 10.1056/NEJMoa1803164
- Li X, You R, Wang X, et al. Effectiveness of prophylactic surgeries in BRCA1 or BRCA2 mutation carriers: A meta-analysis and systematic review. Clin Cancer Res. 2016;22:3971-3981. Doi: 10.1158/1078-0432.CCR-15-1465
A post hoc analysis of the ShortHER trial, including 784 patients with hormone-positive (HR+) and human epidermal growth factor receptor 2–positive (HER2+) early breast cancer who received adjuvant trastuzumab plus chemotherapy, showed that adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better outcomes than tamoxifen (TAM) or TAM and AI (TAM-AI) in this population. Disease-free survival rates at 8 years were 86.4% for AI vs 79.7% for the TAM/TAM-AI groups, with an absolute difference of 6.7% (log-rank P = .013). This effect was seen independently of menopausal status in a multivariate analysis.
In the exploratory analysis focusing on the premenopausal patients, the addition of gonadotropin-releasing hormone to ET was associated with a significantly better disease-free survival. This was also noted in an exploratory subgroup analysis of the SOFT trial,[1] which showed greater benefit from the addition of ovarian suppression to TAM, as compared with TAM alone, among women with HER2+ disease (hazard ratio 0.41; 95% CI 0.22-0.75).
It is important to note that not all patients in the ShortHER trial received the standard-of-care duration of adjuvant trastuzumab; half of them received only 9-week treatment as opposed to the standard 12 months of adjuvant therapy. It is unclear whether this difference in adjuvant therapy could have affected the results, although the disease-free survival multivariate analysis showed no significant effect of the treatment arm on the role of ET. More studies are needed to verify the optimal adjuvant ET for patients with HR+/HER2+ breast cancer, especially in premenopausal patients.
Contralateral Prophylactic Mastectomy Offers No Survival Advantage in Triple-Negative Breast Cancer
There is insufficient evidence that contralateral prophylactic mastectomy (CPM) improves survival in patients with unilateral triple-negative breast cancer (TNBC). A multi-institutional database study, including 796 patients with TNBC, of which 15.5% underwent CPM, showed that CPM did not offer survival benefit to patients with unilateral TNBC. Women who underwent CPM were more likely to be White (P < .001), younger (P < .001), and had had genetic testing performed (P < .001). While there was a borderline improvement in 5-year unadjusted overall survival for patients undergoing CPM compared with no CPM overall (95.1% vs 85.0%; P = .05), no significant improvement was observed for local recurrence-free survival (P = .40) or distant recurrence-free survival (P = .37). Very few (n = 15/673, 2.2%) of the no-CPM patients developed a new primary breast cancer; 3 of the 15 patients were known BRCA1 or BRCA2 mutation carriers. Among the genetic mutation carriers, 5-year overall survival was 97.2% for CPM vs 84.1% for no CPM (P = .35). This study did not demonstrate any statistically significant survival difference between CPM compared with no CPM, regardless of the presence of a BRCA mutation, although prior studies have shown improved outcomes for CPM in BRCA mutation carriers.[2] Larger prospective studies are needed to evaluate the potential benefit of CPM among patients with TNBC, especially patients with BRCA1/2 mutations.
Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy Beneficial in HER2+/HR+ Metastatic Breast Cancer
The current first-line standard of care for HER2+ metastatic breast cancer is dual anti-HER2 targeted therapy plus chemotherapy, with consideration for maintenance treatment with anti-HER2 therapy and ET for patients with HR+ and HER2+ metastatic breast cancer. The potential benefit of adding ET for patients with HR+/HER2+ metastatic breast cancer has been reported previously, but data overall are limited. This study analyzed the real-world data of 147 patients with HR+/HER2+ metastatic breast cancer from a prospective registry and who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET. The findings showed that adding ET resulted in a significant improvement in 5-year progression-free survival (PFS) (hazard ratio 0.59; P = .031) and overall survival (hazard ratio 0.52; P = .018) compared with not adding ET. No new safety concerns were identified when combining HER2+ targeted therapy and ET. While this is a small retrospective analysis, results are certainly encouraging and support the addition of ET to dual anti-HER2 therapy as maintenance therapy post chemotherapy in this subset of patients.
High PD-L2 Levels May Predict Worse Clinical Outcomes in ER+ Breast Cancer
Programmed cell death-1 ligand-2 (PD-L2) is a second ligand for programmed cell death-1 (PD-1) and inhibits T-cell activation. A retrospective study including patients with estrogen receptor–positive (ER+) breast cancer looked at PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, locoregional ER+ breast cancer in the main study cohort (n = 684) and in an independent validation cohort (n = 273), and correlated findings with PFS. High levels of PD-L2 protein were present in up to one third (33%) of ER+ tumors and were associated with shorter PFS in the entire cohort of patients with ER+ breast cancer (hazard ratio 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (hazard ratio 3.4; P < .001). A multivariable analysis showed that high levels of PD-L2 were an independent prognostic marker in ER+ patients. These findings suggest that high PD-L2 is associated with unfavorable prognosis in ER+ breast cancer and may be a potential biomarker of response to checkpoint inhibitors.
Additional References
- Francis PA, Pagani O, Fleming GF, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379:122-137. Doi: 10.1056/NEJMoa1803164
- Li X, You R, Wang X, et al. Effectiveness of prophylactic surgeries in BRCA1 or BRCA2 mutation carriers: A meta-analysis and systematic review. Clin Cancer Res. 2016;22:3971-3981. Doi: 10.1158/1078-0432.CCR-15-1465
Commentary: Evaluating first-line regimens in breast cancer, March 2023
Treatment strategies designed to improve or maintain efficacy while minimizing toxicity are desired by both patients and healthcare providers. Neoadjuvant endocrine therapy (NET) represents a therapeutic option for certain patients with luminal breast cancers who may not be candidates for chemotherapy because of comorbidities or preferences to avoid certain treatments. Furthermore, studies have demonstrated tumor or nodal downstaging with NET, as well as the ability of genomic assays to predict clinical response to NET and its association with breast-conserving therapy (BCT).[4,5] The phase 2 ACOSOG Z1031 trial reported outcomes among 509 women with clinical stage II or III estrogen receptor (ER)–positive breast cancer who received an aromatase inhibitor (AI; exemestane, letrozole, or anastrozole) for 16-18 weeks before surgery. A total of 67.2% of patients had BCT, and of the patients thought to require mastectomy or have inoperable breast cancer at presentation (N = 226), 50.4% were able to have BCT. The pCR rate was low (1%); however, the 5-year cumulative incidence rate for local-regional recurrence was estimated at 1.53% (Hunt et al). This study supports the consideration of NET for select patients, demonstrating a favorable impact on surgery and local-regional recurrence rates. It is also thought-provoking in terms of identifying predictors of response to NET and other novel therapies that can be combined with endocrine therapy in the neoadjuvant space.
The CLEOPATRA trial has established a regimen of docetaxel/trastuzumab/pertuzumab as standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with superior progression-free survival (PFS) and overall survival (OS) compared with a docetaxel/trastuzumab regimen. Crosstalk between HER2 and ER signaling pathways has been implicated in resistance to anti-HER2 and endocrine therapies. Real-world data have shown that the addition of endocrine therapy to first-line dual anti-HER2-targeted therapy post chemotherapy in HER+/hormone receptor positive (HR+) metastatic breast cancer was associated with benefits in PFS and OS.[6] The phase 2 PERTAIN trial randomly assigned 258 patients with HER2+/HR+ metastatic breast cancer to receive pertuzumab/trastuzumab plus an AI or trastuzumab/AI, with induction chemotherapy given at the investigator’s discretion. At a median follow-up of > 6 years, the PFS benefit seen with the addition of pertuzumab was maintained (20.6 vs 15.8 months in the trastuzumab/AI arm; stratified hazard ratio 0.67; P = .006). Although there was not a statistically significant difference in median OS (60.2 months in the pertuzumab/trastuzumab/AI arm vs 57.2 months in the trastuzumab/AI arm; stratified hazard ratio 1.05; P = .78), the effect of pertuzumab was potentially amplified in those without induction chemotherapy (26.6 vs 12.5 months) (Arpino et al). These data provide further support for the addition of pertuzumab to trastuzumab in the first-line treatment setting for HER2+ metastatic breast cancer and suggest that some patients may benefit from dual HER2 blockade with endocrine therapy (without chemotherapy).
Additional References
- Schmid P, Cortes J, Pusztai L, et al, for the KEYNOTE-522 Investigators. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382:810-821. Doi: 10.1056/NEJMoa1910549
- Schmid P, Cortes J, Dent R, et al, for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
- Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: Clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30:1279-1288. Doi: 10.1093/annonc/mdz158
- Cao L, Sugumar K, Keller E, et al. Neoadjuvant endocrine therapy as an alternative to neoadjuvant chemotherapy among hormone receptor-positive breast cancer patients: Pathologic and surgical outcomes. Ann Surg Oncol. 2021;28:5730-5741. Doi: 10.1245/s10434-021-10459-3
- Iwata H, Masuda N, Yamamoto Y, et al. Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: The TransNEOS study. Breast Cancer Res Treat. 2019;173:123-133. Doi: 10.1007/s10549-018-4964-y
- Loft M, Lok SW, De Boer R, et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2+/HR+ metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74. Doi: 10.1007/s10549-022-06856-1
Treatment strategies designed to improve or maintain efficacy while minimizing toxicity are desired by both patients and healthcare providers. Neoadjuvant endocrine therapy (NET) represents a therapeutic option for certain patients with luminal breast cancers who may not be candidates for chemotherapy because of comorbidities or preferences to avoid certain treatments. Furthermore, studies have demonstrated tumor or nodal downstaging with NET, as well as the ability of genomic assays to predict clinical response to NET and its association with breast-conserving therapy (BCT).[4,5] The phase 2 ACOSOG Z1031 trial reported outcomes among 509 women with clinical stage II or III estrogen receptor (ER)–positive breast cancer who received an aromatase inhibitor (AI; exemestane, letrozole, or anastrozole) for 16-18 weeks before surgery. A total of 67.2% of patients had BCT, and of the patients thought to require mastectomy or have inoperable breast cancer at presentation (N = 226), 50.4% were able to have BCT. The pCR rate was low (1%); however, the 5-year cumulative incidence rate for local-regional recurrence was estimated at 1.53% (Hunt et al). This study supports the consideration of NET for select patients, demonstrating a favorable impact on surgery and local-regional recurrence rates. It is also thought-provoking in terms of identifying predictors of response to NET and other novel therapies that can be combined with endocrine therapy in the neoadjuvant space.
The CLEOPATRA trial has established a regimen of docetaxel/trastuzumab/pertuzumab as standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with superior progression-free survival (PFS) and overall survival (OS) compared with a docetaxel/trastuzumab regimen. Crosstalk between HER2 and ER signaling pathways has been implicated in resistance to anti-HER2 and endocrine therapies. Real-world data have shown that the addition of endocrine therapy to first-line dual anti-HER2-targeted therapy post chemotherapy in HER+/hormone receptor positive (HR+) metastatic breast cancer was associated with benefits in PFS and OS.[6] The phase 2 PERTAIN trial randomly assigned 258 patients with HER2+/HR+ metastatic breast cancer to receive pertuzumab/trastuzumab plus an AI or trastuzumab/AI, with induction chemotherapy given at the investigator’s discretion. At a median follow-up of > 6 years, the PFS benefit seen with the addition of pertuzumab was maintained (20.6 vs 15.8 months in the trastuzumab/AI arm; stratified hazard ratio 0.67; P = .006). Although there was not a statistically significant difference in median OS (60.2 months in the pertuzumab/trastuzumab/AI arm vs 57.2 months in the trastuzumab/AI arm; stratified hazard ratio 1.05; P = .78), the effect of pertuzumab was potentially amplified in those without induction chemotherapy (26.6 vs 12.5 months) (Arpino et al). These data provide further support for the addition of pertuzumab to trastuzumab in the first-line treatment setting for HER2+ metastatic breast cancer and suggest that some patients may benefit from dual HER2 blockade with endocrine therapy (without chemotherapy).
Additional References
- Schmid P, Cortes J, Pusztai L, et al, for the KEYNOTE-522 Investigators. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382:810-821. Doi: 10.1056/NEJMoa1910549
- Schmid P, Cortes J, Dent R, et al, for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
- Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: Clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30:1279-1288. Doi: 10.1093/annonc/mdz158
- Cao L, Sugumar K, Keller E, et al. Neoadjuvant endocrine therapy as an alternative to neoadjuvant chemotherapy among hormone receptor-positive breast cancer patients: Pathologic and surgical outcomes. Ann Surg Oncol. 2021;28:5730-5741. Doi: 10.1245/s10434-021-10459-3
- Iwata H, Masuda N, Yamamoto Y, et al. Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: The TransNEOS study. Breast Cancer Res Treat. 2019;173:123-133. Doi: 10.1007/s10549-018-4964-y
- Loft M, Lok SW, De Boer R, et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2+/HR+ metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74. Doi: 10.1007/s10549-022-06856-1
Treatment strategies designed to improve or maintain efficacy while minimizing toxicity are desired by both patients and healthcare providers. Neoadjuvant endocrine therapy (NET) represents a therapeutic option for certain patients with luminal breast cancers who may not be candidates for chemotherapy because of comorbidities or preferences to avoid certain treatments. Furthermore, studies have demonstrated tumor or nodal downstaging with NET, as well as the ability of genomic assays to predict clinical response to NET and its association with breast-conserving therapy (BCT).[4,5] The phase 2 ACOSOG Z1031 trial reported outcomes among 509 women with clinical stage II or III estrogen receptor (ER)–positive breast cancer who received an aromatase inhibitor (AI; exemestane, letrozole, or anastrozole) for 16-18 weeks before surgery. A total of 67.2% of patients had BCT, and of the patients thought to require mastectomy or have inoperable breast cancer at presentation (N = 226), 50.4% were able to have BCT. The pCR rate was low (1%); however, the 5-year cumulative incidence rate for local-regional recurrence was estimated at 1.53% (Hunt et al). This study supports the consideration of NET for select patients, demonstrating a favorable impact on surgery and local-regional recurrence rates. It is also thought-provoking in terms of identifying predictors of response to NET and other novel therapies that can be combined with endocrine therapy in the neoadjuvant space.
The CLEOPATRA trial has established a regimen of docetaxel/trastuzumab/pertuzumab as standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with superior progression-free survival (PFS) and overall survival (OS) compared with a docetaxel/trastuzumab regimen. Crosstalk between HER2 and ER signaling pathways has been implicated in resistance to anti-HER2 and endocrine therapies. Real-world data have shown that the addition of endocrine therapy to first-line dual anti-HER2-targeted therapy post chemotherapy in HER+/hormone receptor positive (HR+) metastatic breast cancer was associated with benefits in PFS and OS.[6] The phase 2 PERTAIN trial randomly assigned 258 patients with HER2+/HR+ metastatic breast cancer to receive pertuzumab/trastuzumab plus an AI or trastuzumab/AI, with induction chemotherapy given at the investigator’s discretion. At a median follow-up of > 6 years, the PFS benefit seen with the addition of pertuzumab was maintained (20.6 vs 15.8 months in the trastuzumab/AI arm; stratified hazard ratio 0.67; P = .006). Although there was not a statistically significant difference in median OS (60.2 months in the pertuzumab/trastuzumab/AI arm vs 57.2 months in the trastuzumab/AI arm; stratified hazard ratio 1.05; P = .78), the effect of pertuzumab was potentially amplified in those without induction chemotherapy (26.6 vs 12.5 months) (Arpino et al). These data provide further support for the addition of pertuzumab to trastuzumab in the first-line treatment setting for HER2+ metastatic breast cancer and suggest that some patients may benefit from dual HER2 blockade with endocrine therapy (without chemotherapy).
Additional References
- Schmid P, Cortes J, Pusztai L, et al, for the KEYNOTE-522 Investigators. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382:810-821. Doi: 10.1056/NEJMoa1910549
- Schmid P, Cortes J, Dent R, et al, for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
- Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: Clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30:1279-1288. Doi: 10.1093/annonc/mdz158
- Cao L, Sugumar K, Keller E, et al. Neoadjuvant endocrine therapy as an alternative to neoadjuvant chemotherapy among hormone receptor-positive breast cancer patients: Pathologic and surgical outcomes. Ann Surg Oncol. 2021;28:5730-5741. Doi: 10.1245/s10434-021-10459-3
- Iwata H, Masuda N, Yamamoto Y, et al. Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: The TransNEOS study. Breast Cancer Res Treat. 2019;173:123-133. Doi: 10.1007/s10549-018-4964-y
- Loft M, Lok SW, De Boer R, et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2+/HR+ metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74. Doi: 10.1007/s10549-022-06856-1
Who’s at higher risk for breast cancer recurrence?
New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.
“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.
The study was published online in Cancer.
Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.
Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.
The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease.
Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).
Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.
The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.
Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.
“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”
What might these results mean for practice and following patients over the long term?
According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”
Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.
Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.
“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.
The study was published online in Cancer.
Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.
Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.
The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease.
Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).
Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.
The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.
Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.
“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”
What might these results mean for practice and following patients over the long term?
According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”
Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.
Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.
“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.
The study was published online in Cancer.
Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.
Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.
The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease.
Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).
Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.
The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.
Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.
“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”
What might these results mean for practice and following patients over the long term?
According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”
Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.
Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANCER
Myths about smoking, diet, alcohol, and cancer persist
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Meta-analysis shows MRI as most effective supplemental BC screening tool
Key clinical point: Magnetic resonance imaging (MRI) proved to be the best supplemental breast cancer (BC) screening modality in women with dense breasts and who had a negative mammogram who were at an average or intermediate risk for the disease.
Major finding: Among the screened patients with dense breasts and a negative mammogram, 541 cases of BC were detected using supplemental modalities. The incremental cancer detection rate was highest with MRI (1.54 per 1,000 screenings) compared with other supplemental modalities (P < .001).
Study details: Findings are from a meta-analysis of 22 randomized clinical trials and prospective observational studies including 261,233 patients, of which 120,081 patients had dense breasts and a negative mammogram.
Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.
Source: Hussein H et al. Supplemental breast cancer screening in women with dense breasts and negative mammography: A systematic review and meta-analysis. Radiology. 2023;221785 (Jan 31). Doi: 10.1148/radiol.221785
Key clinical point: Magnetic resonance imaging (MRI) proved to be the best supplemental breast cancer (BC) screening modality in women with dense breasts and who had a negative mammogram who were at an average or intermediate risk for the disease.
Major finding: Among the screened patients with dense breasts and a negative mammogram, 541 cases of BC were detected using supplemental modalities. The incremental cancer detection rate was highest with MRI (1.54 per 1,000 screenings) compared with other supplemental modalities (P < .001).
Study details: Findings are from a meta-analysis of 22 randomized clinical trials and prospective observational studies including 261,233 patients, of which 120,081 patients had dense breasts and a negative mammogram.
Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.
Source: Hussein H et al. Supplemental breast cancer screening in women with dense breasts and negative mammography: A systematic review and meta-analysis. Radiology. 2023;221785 (Jan 31). Doi: 10.1148/radiol.221785
Key clinical point: Magnetic resonance imaging (MRI) proved to be the best supplemental breast cancer (BC) screening modality in women with dense breasts and who had a negative mammogram who were at an average or intermediate risk for the disease.
Major finding: Among the screened patients with dense breasts and a negative mammogram, 541 cases of BC were detected using supplemental modalities. The incremental cancer detection rate was highest with MRI (1.54 per 1,000 screenings) compared with other supplemental modalities (P < .001).
Study details: Findings are from a meta-analysis of 22 randomized clinical trials and prospective observational studies including 261,233 patients, of which 120,081 patients had dense breasts and a negative mammogram.
Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.
Source: Hussein H et al. Supplemental breast cancer screening in women with dense breasts and negative mammography: A systematic review and meta-analysis. Radiology. 2023;221785 (Jan 31). Doi: 10.1148/radiol.221785
ET duration: A risk factor for cognitive impairment in BC patients
Key clinical point: Duration of endocrine therapy (ET) is an important risk factor for cognitive function impairment in patients with breast cancer (BC).
Major finding: Duration of ET was a significant risk factor for overall cognitive decline (odds ratio 1.296; 95% CI 1.008-1.665), with the prolongation of ET further increasing the risk for cognitive decline (linear-by-linear association test statistic 5.872; P < .05).
Study details: Findings are from a prospective, interventional single-center study including 127 women with BC, of which 49 patients were classified into the cognitive decline group.
Disclosures: This study was supported by Shanghai Science and Technology Innovation Action Plan and other sources. The authors declared no conflicts of interest.
Source: Yin Y et al. Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching. Front Med. 2023;10:1132287 (Jan 26). Doi: 10.3389/fmed.2023.1132287
Key clinical point: Duration of endocrine therapy (ET) is an important risk factor for cognitive function impairment in patients with breast cancer (BC).
Major finding: Duration of ET was a significant risk factor for overall cognitive decline (odds ratio 1.296; 95% CI 1.008-1.665), with the prolongation of ET further increasing the risk for cognitive decline (linear-by-linear association test statistic 5.872; P < .05).
Study details: Findings are from a prospective, interventional single-center study including 127 women with BC, of which 49 patients were classified into the cognitive decline group.
Disclosures: This study was supported by Shanghai Science and Technology Innovation Action Plan and other sources. The authors declared no conflicts of interest.
Source: Yin Y et al. Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching. Front Med. 2023;10:1132287 (Jan 26). Doi: 10.3389/fmed.2023.1132287
Key clinical point: Duration of endocrine therapy (ET) is an important risk factor for cognitive function impairment in patients with breast cancer (BC).
Major finding: Duration of ET was a significant risk factor for overall cognitive decline (odds ratio 1.296; 95% CI 1.008-1.665), with the prolongation of ET further increasing the risk for cognitive decline (linear-by-linear association test statistic 5.872; P < .05).
Study details: Findings are from a prospective, interventional single-center study including 127 women with BC, of which 49 patients were classified into the cognitive decline group.
Disclosures: This study was supported by Shanghai Science and Technology Innovation Action Plan and other sources. The authors declared no conflicts of interest.
Source: Yin Y et al. Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching. Front Med. 2023;10:1132287 (Jan 26). Doi: 10.3389/fmed.2023.1132287
Meta-analysis associates HER2-low expression with good prognosis in early BC
Key clinical point: Low expression of human epidermal growth factor receptor 2 (HER2) protein was associated with improved survival outcomes in patients with early breast cancer (BC).
Major finding: HER2-low expression vs HER2-zero BC was associated with a significant overall survival benefit in the entire population (hazard ratio [HR] 0.83; 95% CI 0.78-0.88) and in the subpopulations of patients with hormone receptor-positive BC (HR 0.83; 95% CI 0.77-0.89) and triple-negative BC (HR 0.78; 95% CI 0.70-0.87).
Study details: Findings are from a meta-analysis of 14 studies including 52,106 patients with early BC.
Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.
Source: Wei T et al. Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis. Front Oncol. 2023;13:1100332 (Feb 2). Doi: 10.3389/fonc.2023.1100332
Key clinical point: Low expression of human epidermal growth factor receptor 2 (HER2) protein was associated with improved survival outcomes in patients with early breast cancer (BC).
Major finding: HER2-low expression vs HER2-zero BC was associated with a significant overall survival benefit in the entire population (hazard ratio [HR] 0.83; 95% CI 0.78-0.88) and in the subpopulations of patients with hormone receptor-positive BC (HR 0.83; 95% CI 0.77-0.89) and triple-negative BC (HR 0.78; 95% CI 0.70-0.87).
Study details: Findings are from a meta-analysis of 14 studies including 52,106 patients with early BC.
Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.
Source: Wei T et al. Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis. Front Oncol. 2023;13:1100332 (Feb 2). Doi: 10.3389/fonc.2023.1100332
Key clinical point: Low expression of human epidermal growth factor receptor 2 (HER2) protein was associated with improved survival outcomes in patients with early breast cancer (BC).
Major finding: HER2-low expression vs HER2-zero BC was associated with a significant overall survival benefit in the entire population (hazard ratio [HR] 0.83; 95% CI 0.78-0.88) and in the subpopulations of patients with hormone receptor-positive BC (HR 0.83; 95% CI 0.77-0.89) and triple-negative BC (HR 0.78; 95% CI 0.70-0.87).
Study details: Findings are from a meta-analysis of 14 studies including 52,106 patients with early BC.
Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.
Source: Wei T et al. Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis. Front Oncol. 2023;13:1100332 (Feb 2). Doi: 10.3389/fonc.2023.1100332
HER2+/HR+ metastatic BC: Adding pertuzumab to trastuzumab+AI shows PFS benefit
Key clinical point: According to the PERTAIN trial’s final analysis, the progression-free survival (PFS) benefit associated with the addition of pertuzumab to trastuzumab+aromatase inhibitor (AI) persisted even after >6 years of follow-up in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC).
Major finding: After a median follow-up of >70 months, a >2-year PFS benefit was observed in the pertuzumab+trastuzumab+AI vs trastuzumab+AI treatment group (20.6 vs 15.8 months; stratified hazard ratio 0.67; P = .006). No new safety signals were identified.
Study details: Findings are from the phase 2 PERTAIN study including 258 postmenopausal patients with previously untreated HER2+/HR+ metastatic or locally advanced BC who were randomly assigned to receive pertuzumab+trastuzumab+AI or trastuzumab+AI.
Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. Some authors declared serving as advisors or on speaker’s bureau for or receiving research grants, travel, or accommodation expenses from several sources. Four authors declared being employees of or owning stocks in F. Hoffmann-La Roche.
Source: Arpino G et al. Pertuzumab, trastuzumab, and an aromatase inhibitor for HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer: PERTAIN final analysis. Clin Cancer Res. 2023 (Jan 30). Doi: 10.1158/1078-0432.CCR-22-1092
Key clinical point: According to the PERTAIN trial’s final analysis, the progression-free survival (PFS) benefit associated with the addition of pertuzumab to trastuzumab+aromatase inhibitor (AI) persisted even after >6 years of follow-up in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC).
Major finding: After a median follow-up of >70 months, a >2-year PFS benefit was observed in the pertuzumab+trastuzumab+AI vs trastuzumab+AI treatment group (20.6 vs 15.8 months; stratified hazard ratio 0.67; P = .006). No new safety signals were identified.
Study details: Findings are from the phase 2 PERTAIN study including 258 postmenopausal patients with previously untreated HER2+/HR+ metastatic or locally advanced BC who were randomly assigned to receive pertuzumab+trastuzumab+AI or trastuzumab+AI.
Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. Some authors declared serving as advisors or on speaker’s bureau for or receiving research grants, travel, or accommodation expenses from several sources. Four authors declared being employees of or owning stocks in F. Hoffmann-La Roche.
Source: Arpino G et al. Pertuzumab, trastuzumab, and an aromatase inhibitor for HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer: PERTAIN final analysis. Clin Cancer Res. 2023 (Jan 30). Doi: 10.1158/1078-0432.CCR-22-1092
Key clinical point: According to the PERTAIN trial’s final analysis, the progression-free survival (PFS) benefit associated with the addition of pertuzumab to trastuzumab+aromatase inhibitor (AI) persisted even after >6 years of follow-up in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC).
Major finding: After a median follow-up of >70 months, a >2-year PFS benefit was observed in the pertuzumab+trastuzumab+AI vs trastuzumab+AI treatment group (20.6 vs 15.8 months; stratified hazard ratio 0.67; P = .006). No new safety signals were identified.
Study details: Findings are from the phase 2 PERTAIN study including 258 postmenopausal patients with previously untreated HER2+/HR+ metastatic or locally advanced BC who were randomly assigned to receive pertuzumab+trastuzumab+AI or trastuzumab+AI.
Disclosures: This study was supported by F. Hoffmann-La Roche Ltd. Some authors declared serving as advisors or on speaker’s bureau for or receiving research grants, travel, or accommodation expenses from several sources. Four authors declared being employees of or owning stocks in F. Hoffmann-La Roche.
Source: Arpino G et al. Pertuzumab, trastuzumab, and an aromatase inhibitor for HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer: PERTAIN final analysis. Clin Cancer Res. 2023 (Jan 30). Doi: 10.1158/1078-0432.CCR-22-1092
Anti-HER2 therapy may be omitted in patients with HER2+ ILC
Key clinical point: Survival outcomes in human epidermal growth factor receptor 2-positive (HER2+) invasive lobular carcinoma (ILC), a rare and poorly characterized subtype of breast cancer (BC), were similar to those in HER2+ invasive ductal carcinoma (IDC) or HER2-negative (HER2−) ILC and did not improve with anti-HER2 treatment.
Major finding: Compared with patients with HER2+ ILC, patients with HER2+ IDC and HER2− ILC had similar overall survival (OS; P = .6 and P = .29, respectively) and disease-free survival (DFS; P = .69 and P = .18, respectively) outcomes. Anti-HER2 therapy did not improve OS or DFS in patients with HER2+/HER2−ILC (both P = .2), although it improved survival outcomes in patients with HER2+ IDC (P < .001).
Study details: Findings are from a population-based study including 833 patients with HER2+ IDC, 62 patients with HER2+ ILC, and 685 patients with HER2− ILC.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Kada Mohammed S et al. HER2-positive invasive lobular carcinoma: A rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study. Breast Cancer. 2023 (Jan 30). Doi: 10.1007/s12282-022-01432-3
Key clinical point: Survival outcomes in human epidermal growth factor receptor 2-positive (HER2+) invasive lobular carcinoma (ILC), a rare and poorly characterized subtype of breast cancer (BC), were similar to those in HER2+ invasive ductal carcinoma (IDC) or HER2-negative (HER2−) ILC and did not improve with anti-HER2 treatment.
Major finding: Compared with patients with HER2+ ILC, patients with HER2+ IDC and HER2− ILC had similar overall survival (OS; P = .6 and P = .29, respectively) and disease-free survival (DFS; P = .69 and P = .18, respectively) outcomes. Anti-HER2 therapy did not improve OS or DFS in patients with HER2+/HER2−ILC (both P = .2), although it improved survival outcomes in patients with HER2+ IDC (P < .001).
Study details: Findings are from a population-based study including 833 patients with HER2+ IDC, 62 patients with HER2+ ILC, and 685 patients with HER2− ILC.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Kada Mohammed S et al. HER2-positive invasive lobular carcinoma: A rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study. Breast Cancer. 2023 (Jan 30). Doi: 10.1007/s12282-022-01432-3
Key clinical point: Survival outcomes in human epidermal growth factor receptor 2-positive (HER2+) invasive lobular carcinoma (ILC), a rare and poorly characterized subtype of breast cancer (BC), were similar to those in HER2+ invasive ductal carcinoma (IDC) or HER2-negative (HER2−) ILC and did not improve with anti-HER2 treatment.
Major finding: Compared with patients with HER2+ ILC, patients with HER2+ IDC and HER2− ILC had similar overall survival (OS; P = .6 and P = .29, respectively) and disease-free survival (DFS; P = .69 and P = .18, respectively) outcomes. Anti-HER2 therapy did not improve OS or DFS in patients with HER2+/HER2−ILC (both P = .2), although it improved survival outcomes in patients with HER2+ IDC (P < .001).
Study details: Findings are from a population-based study including 833 patients with HER2+ IDC, 62 patients with HER2+ ILC, and 685 patients with HER2− ILC.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Kada Mohammed S et al. HER2-positive invasive lobular carcinoma: A rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study. Breast Cancer. 2023 (Jan 30). Doi: 10.1007/s12282-022-01432-3