Erin Roesch, MD

The addition of pertuzumab to trastuzumab plus chemotherapy has demonstrated improvement in pathologic complete response (pCR) rates compared with trastuzumab plus chemotherapy in early-stage HER2-positive breast cancer.³ The framework of oncology is built on clinical trials through their rigorous design, enrollment, and synthesis of data; however, real-world studies are an integral component of cancer research because they provide a more representative sample of the general population treated in routine clinical practice. Neopearl was a retrospective, observational, real-world study that evaluated the efficacy and safety of trastuzumab plus chemotherapy with or without pertuzumab among 271 patients with stage II-III HER2-positive breast cancer (Fabbri et al). The addition of pertuzumab led to an increase in pCR rate (49% vs 62%; odds ratio 1.74; P = .032) and improvement in 5-year event-free survival (81% vs 93%; hazard ratio 2.22; P = .041), and the benefit on univariate analysis was restricted to patients with positive axillary nodes. Furthermore, there were no significant differences in adverse events, including cardiac, between the two groups. These results serve to strengthen the available data regarding the clinical efficacy and favorable safety profile of dual HER2-targeted therapy combined with neoadjuvant chemotherapy.

Lifestyle factors, including physical activity and diet, are becoming increasingly recognized as important determinants of various cancer-specific outcomes and overall health. Furthermore, because these are modifiable, there is often motivation on behalf of an individual to change behaviors that can affect their outcome. Adherence to the Mediterranean diet (MD) has been associated with reduced risk for breast cancer development and lower mortality among women with breast cancer.^4,5 Data from a prospective multicenter European cohort including 13,270 breast cancer survivors demonstrated that low compared with medium adherence to a MD before a breast cancer diagnosis was associated with a 13% higher risk for all-cause mortality (hazard ratio 1.13; 95% CI 1.01-1.26). A three-unit increase in the adapted relative MD score was associated with an 8% reduced risk for overall mortality (hazard ratio_3-unit 0.92; 95% CI 0.87-0.97); this result was sustained in the postmenopausal population and strengthened in metastatic disease (Castro-Espin et al). The connection between diet and cancer outcomes is complex, and future research evaluating specific dietary interventions and the underlying biologic pathways by which nutrition exerts its effects will be important to inform our counseling for patients with breast cancer in the survivorship setting.

Additional References

1. Whelan TJ, Olivotto IA, Parulekar WR, et al, for the MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-16. doi:10.1056/NEJMoa1415340
2. ClinicalTrials.gov. Regional radiotherapy in biomarker low-risk node positive and T3N0 breast cancer (TAILOR RT). National Library of Medicine. Last updated November 23, 2022. https://www.clinicaltrials.gov/study/NCT03488693
3. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32. doi:10.1016/S1470-2045(11)70336-9
4. Buckland G, Travier N, Cottet V, et al. Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2013;132:2918-27. doi:10.1002/ijc.27958
5. Haslam DE, John EM, Knight JA, et al. Diet quality and all-cause mortality in women with breast cancer from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2023;32:678-686. doi:10.1158/1055-9965.EPI-22-1198

The addition of pertuzumab to trastuzumab plus chemotherapy has demonstrated improvement in pathologic complete response (pCR) rates compared with trastuzumab plus chemotherapy in early-stage HER2-positive breast cancer.³ The framework of oncology is built on clinical trials through their rigorous design, enrollment, and synthesis of data; however, real-world studies are an integral component of cancer research because they provide a more representative sample of the general population treated in routine clinical practice. Neopearl was a retrospective, observational, real-world study that evaluated the efficacy and safety of trastuzumab plus chemotherapy with or without pertuzumab among 271 patients with stage II-III HER2-positive breast cancer (Fabbri et al). The addition of pertuzumab led to an increase in pCR rate (49% vs 62%; odds ratio 1.74; P = .032) and improvement in 5-year event-free survival (81% vs 93%; hazard ratio 2.22; P = .041), and the benefit on univariate analysis was restricted to patients with positive axillary nodes. Furthermore, there were no significant differences in adverse events, including cardiac, between the two groups. These results serve to strengthen the available data regarding the clinical efficacy and favorable safety profile of dual HER2-targeted therapy combined with neoadjuvant chemotherapy.

Lifestyle factors, including physical activity and diet, are becoming increasingly recognized as important determinants of various cancer-specific outcomes and overall health. Furthermore, because these are modifiable, there is often motivation on behalf of an individual to change behaviors that can affect their outcome. Adherence to the Mediterranean diet (MD) has been associated with reduced risk for breast cancer development and lower mortality among women with breast cancer.^4,5 Data from a prospective multicenter European cohort including 13,270 breast cancer survivors demonstrated that low compared with medium adherence to a MD before a breast cancer diagnosis was associated with a 13% higher risk for all-cause mortality (hazard ratio 1.13; 95% CI 1.01-1.26). A three-unit increase in the adapted relative MD score was associated with an 8% reduced risk for overall mortality (hazard ratio_3-unit 0.92; 95% CI 0.87-0.97); this result was sustained in the postmenopausal population and strengthened in metastatic disease (Castro-Espin et al). The connection between diet and cancer outcomes is complex, and future research evaluating specific dietary interventions and the underlying biologic pathways by which nutrition exerts its effects will be important to inform our counseling for patients with breast cancer in the survivorship setting.

Additional References

1. Whelan TJ, Olivotto IA, Parulekar WR, et al, for the MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-16. doi:10.1056/NEJMoa1415340
2. ClinicalTrials.gov. Regional radiotherapy in biomarker low-risk node positive and T3N0 breast cancer (TAILOR RT). National Library of Medicine. Last updated November 23, 2022. https://www.clinicaltrials.gov/study/NCT03488693
3. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32. doi:10.1016/S1470-2045(11)70336-9
4. Buckland G, Travier N, Cottet V, et al. Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2013;132:2918-27. doi:10.1002/ijc.27958
5. Haslam DE, John EM, Knight JA, et al. Diet quality and all-cause mortality in women with breast cancer from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2023;32:678-686. doi:10.1158/1055-9965.EPI-22-1198

The addition of pertuzumab to trastuzumab plus chemotherapy has demonstrated improvement in pathologic complete response (pCR) rates compared with trastuzumab plus chemotherapy in early-stage HER2-positive breast cancer.³ The framework of oncology is built on clinical trials through their rigorous design, enrollment, and synthesis of data; however, real-world studies are an integral component of cancer research because they provide a more representative sample of the general population treated in routine clinical practice. Neopearl was a retrospective, observational, real-world study that evaluated the efficacy and safety of trastuzumab plus chemotherapy with or without pertuzumab among 271 patients with stage II-III HER2-positive breast cancer (Fabbri et al). The addition of pertuzumab led to an increase in pCR rate (49% vs 62%; odds ratio 1.74; P = .032) and improvement in 5-year event-free survival (81% vs 93%; hazard ratio 2.22; P = .041), and the benefit on univariate analysis was restricted to patients with positive axillary nodes. Furthermore, there were no significant differences in adverse events, including cardiac, between the two groups. These results serve to strengthen the available data regarding the clinical efficacy and favorable safety profile of dual HER2-targeted therapy combined with neoadjuvant chemotherapy.

Lifestyle factors, including physical activity and diet, are becoming increasingly recognized as important determinants of various cancer-specific outcomes and overall health. Furthermore, because these are modifiable, there is often motivation on behalf of an individual to change behaviors that can affect their outcome. Adherence to the Mediterranean diet (MD) has been associated with reduced risk for breast cancer development and lower mortality among women with breast cancer.^4,5 Data from a prospective multicenter European cohort including 13,270 breast cancer survivors demonstrated that low compared with medium adherence to a MD before a breast cancer diagnosis was associated with a 13% higher risk for all-cause mortality (hazard ratio 1.13; 95% CI 1.01-1.26). A three-unit increase in the adapted relative MD score was associated with an 8% reduced risk for overall mortality (hazard ratio_3-unit 0.92; 95% CI 0.87-0.97); this result was sustained in the postmenopausal population and strengthened in metastatic disease (Castro-Espin et al). The connection between diet and cancer outcomes is complex, and future research evaluating specific dietary interventions and the underlying biologic pathways by which nutrition exerts its effects will be important to inform our counseling for patients with breast cancer in the survivorship setting.

Additional References

1. Whelan TJ, Olivotto IA, Parulekar WR, et al, for the MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307-16. doi:10.1056/NEJMoa1415340
2. ClinicalTrials.gov. Regional radiotherapy in biomarker low-risk node positive and T3N0 breast cancer (TAILOR RT). National Library of Medicine. Last updated November 23, 2022. https://www.clinicaltrials.gov/study/NCT03488693
3. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32. doi:10.1016/S1470-2045(11)70336-9
4. Buckland G, Travier N, Cottet V, et al. Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2013;132:2918-27. doi:10.1002/ijc.27958
5. Haslam DE, John EM, Knight JA, et al. Diet quality and all-cause mortality in women with breast cancer from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2023;32:678-686. doi:10.1158/1055-9965.EPI-22-1198

The neoadjuvant setting provides a favorable environment to study de-escalation approaches as treatment response (via pathologic complete response [pCR] assessment) can be used as a surrogate marker for outcome. Studies have shown the effect of HER2-enriched subtype and high ERBB2 expression on pCR rates after receipt of a chemotherapy-free, dual HER2-targeted regimen.² The prospective, multicenter, neoadjuvant phase 2 WSG-TP-II trial randomly assigned 207 patients with HR+/HER2+ early breast cancer to 12 weeks of endocrine therapy (ET)–trastuzumab-pertuzumab vs paclitaxel-trastuzumab-pertuzumab. The pCR rate was inferior in the ET arm compared with the paclitaxel arm (23.7% vs 56.4%; odds ratio 0.24; 95% CI 0.12-0.46; P < .001). In addition, an immunohistochemistry ERBB2 score of 3 or higher and ERBB2-enriched subtype were predictors of higher pCR rates in both arms (Gluz et al). This study not only supports a deescalated chemotherapy neoadjuvant strategy of paclitaxel + dual HER2 blockade but also suggests that a portion of patients may potentially be spared chemotherapy with very good results. The role of biomarkers is integral to patient selection for these approaches, and the evaluation of response in real-time will allow for the tailoring of therapy to achieve the best outcome.

Systemic staging for locally advanced breast cancer (LABC) is important for informing prognosis as well as aiding in development of an appropriate treatment plan for patients. The PETABC study included 369 patients with LABC (TNM stage III or IIB [T3N0]) with random assignment to ¹⁸F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of chest/abdomen/pelvis), and was designed to assess the rate of upstaging with each imaging modality and effect on treatment (Dayes et al). In the PET-CT group, 23% (N = 43) of patients were upstaged to stage IV compared with 11% (N = 21) in the conventional-staging group (absolute difference 12.3%; 95% CI 3.9-19.9; P = .002). Fewer patients in the PET-CT group received combined modality treatment vs those patients in the conventional staging group (81% vs 89.2%; P = .03). These results support the consideration of PET-CT as a staging tool for LABC, and this is reflected in various clinical guidelines. Furthermore, the evolving role of other imaging techniques such as ¹⁸F-fluoroestradiol (18F-FES) PET-CT in detection of metastatic lesions related to estrogen receptor–positive breast cancer³ will continue to advance the field of imaging.

Additional References

1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22:489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum in: Lancet Oncol. 2021;22(5):e184. doi: 10.1016/S1470-2045(21)00194-7
2. Prat A, Pascual T, De Angelis C, et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. J Natl Cancer Inst. 2020;112:46-54. doi: 10.1093/jnci/djz042
3. Ulaner GA, Jhaveri K, Chandarlapaty S, et al. Head-to-head evaluation of ¹⁸F-FES and ¹⁸F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med. 2021;62:326-331. doi: 10.2967/jnumed.120.247882

The neoadjuvant setting provides a favorable environment to study de-escalation approaches as treatment response (via pathologic complete response [pCR] assessment) can be used as a surrogate marker for outcome. Studies have shown the effect of HER2-enriched subtype and high ERBB2 expression on pCR rates after receipt of a chemotherapy-free, dual HER2-targeted regimen.² The prospective, multicenter, neoadjuvant phase 2 WSG-TP-II trial randomly assigned 207 patients with HR+/HER2+ early breast cancer to 12 weeks of endocrine therapy (ET)–trastuzumab-pertuzumab vs paclitaxel-trastuzumab-pertuzumab. The pCR rate was inferior in the ET arm compared with the paclitaxel arm (23.7% vs 56.4%; odds ratio 0.24; 95% CI 0.12-0.46; P < .001). In addition, an immunohistochemistry ERBB2 score of 3 or higher and ERBB2-enriched subtype were predictors of higher pCR rates in both arms (Gluz et al). This study not only supports a deescalated chemotherapy neoadjuvant strategy of paclitaxel + dual HER2 blockade but also suggests that a portion of patients may potentially be spared chemotherapy with very good results. The role of biomarkers is integral to patient selection for these approaches, and the evaluation of response in real-time will allow for the tailoring of therapy to achieve the best outcome.

Systemic staging for locally advanced breast cancer (LABC) is important for informing prognosis as well as aiding in development of an appropriate treatment plan for patients. The PETABC study included 369 patients with LABC (TNM stage III or IIB [T3N0]) with random assignment to ¹⁸F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of chest/abdomen/pelvis), and was designed to assess the rate of upstaging with each imaging modality and effect on treatment (Dayes et al). In the PET-CT group, 23% (N = 43) of patients were upstaged to stage IV compared with 11% (N = 21) in the conventional-staging group (absolute difference 12.3%; 95% CI 3.9-19.9; P = .002). Fewer patients in the PET-CT group received combined modality treatment vs those patients in the conventional staging group (81% vs 89.2%; P = .03). These results support the consideration of PET-CT as a staging tool for LABC, and this is reflected in various clinical guidelines. Furthermore, the evolving role of other imaging techniques such as ¹⁸F-fluoroestradiol (18F-FES) PET-CT in detection of metastatic lesions related to estrogen receptor–positive breast cancer³ will continue to advance the field of imaging.

Additional References

1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22:489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum in: Lancet Oncol. 2021;22(5):e184. doi: 10.1016/S1470-2045(21)00194-7
2. Prat A, Pascual T, De Angelis C, et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. J Natl Cancer Inst. 2020;112:46-54. doi: 10.1093/jnci/djz042
3. Ulaner GA, Jhaveri K, Chandarlapaty S, et al. Head-to-head evaluation of ¹⁸F-FES and ¹⁸F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med. 2021;62:326-331. doi: 10.2967/jnumed.120.247882

The neoadjuvant setting provides a favorable environment to study de-escalation approaches as treatment response (via pathologic complete response [pCR] assessment) can be used as a surrogate marker for outcome. Studies have shown the effect of HER2-enriched subtype and high ERBB2 expression on pCR rates after receipt of a chemotherapy-free, dual HER2-targeted regimen.² The prospective, multicenter, neoadjuvant phase 2 WSG-TP-II trial randomly assigned 207 patients with HR+/HER2+ early breast cancer to 12 weeks of endocrine therapy (ET)–trastuzumab-pertuzumab vs paclitaxel-trastuzumab-pertuzumab. The pCR rate was inferior in the ET arm compared with the paclitaxel arm (23.7% vs 56.4%; odds ratio 0.24; 95% CI 0.12-0.46; P < .001). In addition, an immunohistochemistry ERBB2 score of 3 or higher and ERBB2-enriched subtype were predictors of higher pCR rates in both arms (Gluz et al). This study not only supports a deescalated chemotherapy neoadjuvant strategy of paclitaxel + dual HER2 blockade but also suggests that a portion of patients may potentially be spared chemotherapy with very good results. The role of biomarkers is integral to patient selection for these approaches, and the evaluation of response in real-time will allow for the tailoring of therapy to achieve the best outcome.

Systemic staging for locally advanced breast cancer (LABC) is important for informing prognosis as well as aiding in development of an appropriate treatment plan for patients. The PETABC study included 369 patients with LABC (TNM stage III or IIB [T3N0]) with random assignment to ¹⁸F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of chest/abdomen/pelvis), and was designed to assess the rate of upstaging with each imaging modality and effect on treatment (Dayes et al). In the PET-CT group, 23% (N = 43) of patients were upstaged to stage IV compared with 11% (N = 21) in the conventional-staging group (absolute difference 12.3%; 95% CI 3.9-19.9; P = .002). Fewer patients in the PET-CT group received combined modality treatment vs those patients in the conventional staging group (81% vs 89.2%; P = .03). These results support the consideration of PET-CT as a staging tool for LABC, and this is reflected in various clinical guidelines. Furthermore, the evolving role of other imaging techniques such as ¹⁸F-fluoroestradiol (18F-FES) PET-CT in detection of metastatic lesions related to estrogen receptor–positive breast cancer³ will continue to advance the field of imaging.

Additional References

1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22:489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum in: Lancet Oncol. 2021;22(5):e184. doi: 10.1016/S1470-2045(21)00194-7
2. Prat A, Pascual T, De Angelis C, et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. J Natl Cancer Inst. 2020;112:46-54. doi: 10.1093/jnci/djz042
3. Ulaner GA, Jhaveri K, Chandarlapaty S, et al. Head-to-head evaluation of ¹⁸F-FES and ¹⁸F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med. 2021;62:326-331. doi: 10.2967/jnumed.120.247882

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. 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.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. 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.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

The advantages of neoadjuvant therapy (NAT), including the downstaging of the primary tumor/nodal burden and assessment of the tumor biology via response to chemotherapy, can have prognostic and therapeutic implications in the adjuvant setting. Additionally, trials in the neoadjuvant space allow rapid assessment of new agents that can help patients gain access to these therapies in an expedited fashion. Three-year outcomes from the neoadjuvant I-SPY2 trial have shown that achievement of pathologic complete response (pCR) after NAT is associated with an approximately 80% reduction in recurrence rate, regardless of molecular subtype or treatment regimen (including various novel therapy combinations).³ An analysis of individual data from 3710 patients with human epidermal growth factor receptor 2 (HER2)–positive early BC from 11 neoadjuvant trials evaluated additional prognostic factors to better characterize pCR (van Mackelenbergh et al). A total of 1497 patients (40%) had pCR, and these patients had improved event-free survival (hazard ratio 0.39; P < .001) and overall survival (hazard ratio 0.32 P < .001) compared to those with residual disease after NAT. Among patients who had pCR, tumor size at presentation (cT1-2 vs cT3-4) and nodal status (cN0 vs cN+) were independent prognostic factors for event-free survival (hazard ratio 0.67 [P = .007] and 0.72 [P = .039], respectively). These data support the role of pCR as an indicator of outcome post-NAT and, furthermore, identify additional features beyond pCR that can affect recurrence risk. It is valuable to take these other factors into account when considering patients for adjuvant therapies, even in the context of pCR.

Advances in detection modalities and treatments have led to improved survival after BC diagnosis, and as a result, more women in the survivorship setting are experiencing side effects that affect quality of life. The prevalence of sexual dysfunction is variable, perhaps owing to how this variable is defined and reported, and includes symptoms of low libido, dyspareunia, vaginal dryness, and anorgasmia.⁴Chang and colleagues performed a population-based study evaluating sexual dysfunction among a cohort of 19,709 BC survivors ≥ 18 years of age from the Utah Cancer Registry and 93,389 cancer-free women matched by age and birth state from the general population. BC survivors had a higher risk for sexual dysfunction (hazard ratio 1.60; 95% CI 1.51-1.70) compared with the general population, and this effect was more prominent within 1-5 years after diagnosis (hazard ratio 2.05; 95% CI 1.89-2.22) and in those < 50 years of age (hazard ratio 3.05; 95% CI 2.65-3.51). Furthermore, BC survivors who received chemotherapy and ET had an increased risk for sexual dysfunction (hazard ratio 1.16 and 1.46, respectively). These findings underscore the importance of recognition and communication regarding survivorship issues, such as sexual health, which can affect medication adherence, quality of life, and outcomes for patients.

Additional References

1. 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.200535
2. Anderson RA, Lambertini M, Hall PS, et al. Survival after breast cancer in women with a subsequent live birth: Influence of age at diagnosis and interval to subsequent pregnancy. Eur J Cancer. 2022;173:113-12 doi: 10.1016/j.ejca.20206.048
3. I-SPY2 Trial Consortium. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6:1355-1362. doi: 10.1001/jamaoncol.2020.2535
4. Panjari M, Bell RJ, Davis SR. Sexual function after breast cancer. J Sex Med. 2011;8:294-302. doi: 10.1111/j.1743-6109.2010.0203x

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

However, a combined analysis of two other trials (PlanB and SUCCESS C) did not show a benefit with the addition of anthracycline for most patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer.²Roy and colleagues performed a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including 1106 women ≥ 66 years of age with node-positive TNBC, of whom 69.3% received adjuvant chemotherapy (N = 767). The use of chemotherapy led to a statistically significant improvement in survival outcomes (3-year cancer-specific survival [CSS] 81.8% vs 71.4%; overall survival 70.7% vs 51.3%). Although the anthracycline/taxane–based therapy did not improve CSS in the overall population vs taxane-based (hazard ratio [HR] 0.94; P = .79), among patients aged ≥ 76 years with four or more positive nodes, there was improvement in CSS with anthracycline/taxane therapy (HR 0.09; P = .02). These data further support the benefits of adjuvant chemotherapy in older patients when indicated; stimulate consideration of nonanthracycline combinations, particularly now with the use of immunotherapy for early TNBC; and highlight the need for inclusion of older individuals in clinical trials.

Treatment strategies to improve efficacy and minimize toxicity are highly desired for patients with early breast cancer (EBC). As an example, for small, node-negative, HER2-positive tumors, adjuvant systemic therapy with 12 weeks of paclitaxel/trastuzumab followed by continuation of trastuzumab to complete 1 full year has demonstrated excellent survival outcomes at over 10 years of follow-up.³ In the WSG-ADAPT-TP phase 2 trial, 375 patients with hormone receptor–positive , HER2-positive EBC were randomized to receive neoadjuvant T-DM1 (trastuzumab emtansine) with or without endocrine therapy or trastuzumab plus endocrine therapy. Similar 5-year invasive disease-free and overall survival rates were seen between the three arms. Patients who achieved a pathologic complete response (pCR) vs non-pCR had improved 5-year invasive disease-free survival (iDFS) rates (92.7% vs 82.7%; unadjusted HR 0.40). Furthermore, among the 117 patients who achieved pCR, the omission of adjuvant chemotherapy did not compromise survival outcomes (5-year iDFS 93% vs 92.1% for those who had vs those who did not have chemotherapy, respectively; unadjusted HR 1.15) (Harbeck et al). De-escalation approaches should ideally focus on the identification of biomarkers of response and resistance, as well as tools that can help predict patient outcomes and allow modification of therapy in real time. An example of this latter concept is the use of ¹⁸F-FDG-PET to identify patients with HER2-positive EBC who were likely to benefit from a chemotherapy-free dual HER2 blockade (trastuzumab/pertuzumab) treatment approach.⁴

Gynecologic surgery has been shown to reduce the risk for breast cancer,⁵ although the specific type of surgery and the impact of hormone replacement therapy add complexity to understanding the risks and outcomes for women. A prospective cohort, the Sister Study, included 50,701 women without a prior diagnosis of breast cancer but with a biological sister who had breast cancer; of these, 13.8% reported having hysterectomy only and 18.1% reported having bilateral oophorectomy with or without hysterectomy. Bilateral oophorectomy was inversely associated with breast cancer incidence (HR 0.91; 95% CI 0.83-1.00), with comparable results for women receiving estrogen only or combination estrogen plus progestin hormone replacement therapy. Contrary to these findings, having a hysterectomy only showed a positive association with breast cancer incidence (HR 1.12; 95% CI 1.02-1.23), with the strongest association among women who used combination estrogen and progestin therapy (HR 1.25; 95% CI 1.01-1.55) (Lovett et al). The impact of other gynecologic surgeries (such as salpingectomy)⁶ and the timing of the initiation of hormone replacement therapy, as well as the duration, should be investigated in future research.

Additional References

1. Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647e55. doi: 10.1200/JCO.2016.71.4147

2. de Gregorio A, Janni W, Friedl TW, et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022;126:1715-1724. doi: 10.1038/s41416-021-01690-6

3. Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: Final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24:273-285. doi: 10.1016/S1470-2045(23)00051-7

4. Pérez-García JM, Gebhart G, Ruiz Borrego M, et al; on behalf of PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): A multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021;22:858-871. doi: 10.1016/S1470-2045(21)00122-4

5. Chow S, Raine-Bennett T, Samant ND, Postlethwaite DA, Holzapfel M. Breast cancer risk after hysterectomy with and without salpingo-oophorectomy for benign indications. Am J Obstet Gynecol. 2020;223:900.e1-900.e7. doi: 10.1016/j.ajog.2020.06.040

6. ACOG Committee Opinion No. 774: Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet Gynecol. 2019;133:e279-e284. doi: 10.1097/AOG.0000000000003164

However, a combined analysis of two other trials (PlanB and SUCCESS C) did not show a benefit with the addition of anthracycline for most patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer.²Roy and colleagues performed a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including 1106 women ≥ 66 years of age with node-positive TNBC, of whom 69.3% received adjuvant chemotherapy (N = 767). The use of chemotherapy led to a statistically significant improvement in survival outcomes (3-year cancer-specific survival [CSS] 81.8% vs 71.4%; overall survival 70.7% vs 51.3%). Although the anthracycline/taxane–based therapy did not improve CSS in the overall population vs taxane-based (hazard ratio [HR] 0.94; P = .79), among patients aged ≥ 76 years with four or more positive nodes, there was improvement in CSS with anthracycline/taxane therapy (HR 0.09; P = .02). These data further support the benefits of adjuvant chemotherapy in older patients when indicated; stimulate consideration of nonanthracycline combinations, particularly now with the use of immunotherapy for early TNBC; and highlight the need for inclusion of older individuals in clinical trials.

Treatment strategies to improve efficacy and minimize toxicity are highly desired for patients with early breast cancer (EBC). As an example, for small, node-negative, HER2-positive tumors, adjuvant systemic therapy with 12 weeks of paclitaxel/trastuzumab followed by continuation of trastuzumab to complete 1 full year has demonstrated excellent survival outcomes at over 10 years of follow-up.³ In the WSG-ADAPT-TP phase 2 trial, 375 patients with hormone receptor–positive , HER2-positive EBC were randomized to receive neoadjuvant T-DM1 (trastuzumab emtansine) with or without endocrine therapy or trastuzumab plus endocrine therapy. Similar 5-year invasive disease-free and overall survival rates were seen between the three arms. Patients who achieved a pathologic complete response (pCR) vs non-pCR had improved 5-year invasive disease-free survival (iDFS) rates (92.7% vs 82.7%; unadjusted HR 0.40). Furthermore, among the 117 patients who achieved pCR, the omission of adjuvant chemotherapy did not compromise survival outcomes (5-year iDFS 93% vs 92.1% for those who had vs those who did not have chemotherapy, respectively; unadjusted HR 1.15) (Harbeck et al). De-escalation approaches should ideally focus on the identification of biomarkers of response and resistance, as well as tools that can help predict patient outcomes and allow modification of therapy in real time. An example of this latter concept is the use of ¹⁸F-FDG-PET to identify patients with HER2-positive EBC who were likely to benefit from a chemotherapy-free dual HER2 blockade (trastuzumab/pertuzumab) treatment approach.⁴

Gynecologic surgery has been shown to reduce the risk for breast cancer,⁵ although the specific type of surgery and the impact of hormone replacement therapy add complexity to understanding the risks and outcomes for women. A prospective cohort, the Sister Study, included 50,701 women without a prior diagnosis of breast cancer but with a biological sister who had breast cancer; of these, 13.8% reported having hysterectomy only and 18.1% reported having bilateral oophorectomy with or without hysterectomy. Bilateral oophorectomy was inversely associated with breast cancer incidence (HR 0.91; 95% CI 0.83-1.00), with comparable results for women receiving estrogen only or combination estrogen plus progestin hormone replacement therapy. Contrary to these findings, having a hysterectomy only showed a positive association with breast cancer incidence (HR 1.12; 95% CI 1.02-1.23), with the strongest association among women who used combination estrogen and progestin therapy (HR 1.25; 95% CI 1.01-1.55) (Lovett et al). The impact of other gynecologic surgeries (such as salpingectomy)⁶ and the timing of the initiation of hormone replacement therapy, as well as the duration, should be investigated in future research.

Additional References

1. Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647e55. doi: 10.1200/JCO.2016.71.4147

2. de Gregorio A, Janni W, Friedl TW, et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022;126:1715-1724. doi: 10.1038/s41416-021-01690-6

3. Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: Final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24:273-285. doi: 10.1016/S1470-2045(23)00051-7

4. Pérez-García JM, Gebhart G, Ruiz Borrego M, et al; on behalf of PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): A multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021;22:858-871. doi: 10.1016/S1470-2045(21)00122-4

5. Chow S, Raine-Bennett T, Samant ND, Postlethwaite DA, Holzapfel M. Breast cancer risk after hysterectomy with and without salpingo-oophorectomy for benign indications. Am J Obstet Gynecol. 2020;223:900.e1-900.e7. doi: 10.1016/j.ajog.2020.06.040

6. ACOG Committee Opinion No. 774: Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet Gynecol. 2019;133:e279-e284. doi: 10.1097/AOG.0000000000003164

However, a combined analysis of two other trials (PlanB and SUCCESS C) did not show a benefit with the addition of anthracycline for most patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer.²Roy and colleagues performed a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including 1106 women ≥ 66 years of age with node-positive TNBC, of whom 69.3% received adjuvant chemotherapy (N = 767). The use of chemotherapy led to a statistically significant improvement in survival outcomes (3-year cancer-specific survival [CSS] 81.8% vs 71.4%; overall survival 70.7% vs 51.3%). Although the anthracycline/taxane–based therapy did not improve CSS in the overall population vs taxane-based (hazard ratio [HR] 0.94; P = .79), among patients aged ≥ 76 years with four or more positive nodes, there was improvement in CSS with anthracycline/taxane therapy (HR 0.09; P = .02). These data further support the benefits of adjuvant chemotherapy in older patients when indicated; stimulate consideration of nonanthracycline combinations, particularly now with the use of immunotherapy for early TNBC; and highlight the need for inclusion of older individuals in clinical trials.

Treatment strategies to improve efficacy and minimize toxicity are highly desired for patients with early breast cancer (EBC). As an example, for small, node-negative, HER2-positive tumors, adjuvant systemic therapy with 12 weeks of paclitaxel/trastuzumab followed by continuation of trastuzumab to complete 1 full year has demonstrated excellent survival outcomes at over 10 years of follow-up.³ In the WSG-ADAPT-TP phase 2 trial, 375 patients with hormone receptor–positive , HER2-positive EBC were randomized to receive neoadjuvant T-DM1 (trastuzumab emtansine) with or without endocrine therapy or trastuzumab plus endocrine therapy. Similar 5-year invasive disease-free and overall survival rates were seen between the three arms. Patients who achieved a pathologic complete response (pCR) vs non-pCR had improved 5-year invasive disease-free survival (iDFS) rates (92.7% vs 82.7%; unadjusted HR 0.40). Furthermore, among the 117 patients who achieved pCR, the omission of adjuvant chemotherapy did not compromise survival outcomes (5-year iDFS 93% vs 92.1% for those who had vs those who did not have chemotherapy, respectively; unadjusted HR 1.15) (Harbeck et al). De-escalation approaches should ideally focus on the identification of biomarkers of response and resistance, as well as tools that can help predict patient outcomes and allow modification of therapy in real time. An example of this latter concept is the use of ¹⁸F-FDG-PET to identify patients with HER2-positive EBC who were likely to benefit from a chemotherapy-free dual HER2 blockade (trastuzumab/pertuzumab) treatment approach.⁴

Gynecologic surgery has been shown to reduce the risk for breast cancer,⁵ although the specific type of surgery and the impact of hormone replacement therapy add complexity to understanding the risks and outcomes for women. A prospective cohort, the Sister Study, included 50,701 women without a prior diagnosis of breast cancer but with a biological sister who had breast cancer; of these, 13.8% reported having hysterectomy only and 18.1% reported having bilateral oophorectomy with or without hysterectomy. Bilateral oophorectomy was inversely associated with breast cancer incidence (HR 0.91; 95% CI 0.83-1.00), with comparable results for women receiving estrogen only or combination estrogen plus progestin hormone replacement therapy. Contrary to these findings, having a hysterectomy only showed a positive association with breast cancer incidence (HR 1.12; 95% CI 1.02-1.23), with the strongest association among women who used combination estrogen and progestin therapy (HR 1.25; 95% CI 1.01-1.55) (Lovett et al). The impact of other gynecologic surgeries (such as salpingectomy)⁶ and the timing of the initiation of hormone replacement therapy, as well as the duration, should be investigated in future research.

Additional References

1. Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647e55. doi: 10.1200/JCO.2016.71.4147

2. de Gregorio A, Janni W, Friedl TW, et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022;126:1715-1724. doi: 10.1038/s41416-021-01690-6

3. Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: Final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24:273-285. doi: 10.1016/S1470-2045(23)00051-7

4. Pérez-García JM, Gebhart G, Ruiz Borrego M, et al; on behalf of PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): A multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021;22:858-871. doi: 10.1016/S1470-2045(21)00122-4

5. Chow S, Raine-Bennett T, Samant ND, Postlethwaite DA, Holzapfel M. Breast cancer risk after hysterectomy with and without salpingo-oophorectomy for benign indications. Am J Obstet Gynecol. 2020;223:900.e1-900.e7. doi: 10.1016/j.ajog.2020.06.040

6. ACOG Committee Opinion No. 774: Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet Gynecol. 2019;133:e279-e284. doi: 10.1097/AOG.0000000000003164

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

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

The risk for disease recurrence, and specifically distant relapse, for women with high-risk early breast cancer highlights the need for novel therapies in this population.^2,3 The phase 3 randomized monarchE trial investigated the role of the CDK4/6 inhibitor abemaciclib combined with endocrine therapy vs standard endocrine therapy alone in 5637 patients with high-risk (≥ 4 positive axillary nodes or 1-3 positive nodes and either grade 3 tumor, tumor size ≥ 5 cm or Ki-67 ≥ 20%) hormone receptor–positive/HER2-negative early breast cancer. At a median follow-up of 42 months, the median invasive disease-free survival (iDFS) benefit was sustained with abemaciclib + endocrine therapy vs endocrine therapy alone (HR 0.664; nominal P < .0001); the absolute 4-year iDFS benefit was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group). Furthermore, this effect appeared to deepen over time, as the previous absolute iDFS differences were 2.8% (2 years) and 4.8% (3 years). Abemaciclib was associated with a higher rate of grade 3 or higher adverse events (49.9% vs 16.9%), the most common being neutropenia, leukopenia, and diarrhea (Johnston et al). Although adjuvant palbociclib trials (PALLAS⁴ and PENELOPE-B⁵) did not meet their primary endpoint, longer follow-up of monarchE and results from NATALEE with ribociclib are anxiously awaited to further define the role of CDK4/6 inhibitors in this space.

Aromatase inhibitors (AI) are an integral component of treatment for hormone receptor–positive breast cancer for many women. However, joint pain and stiffness associated with these agents can affect compliance. Various management strategies, including trials of alternative AI or endocrine therapies and pharmacologic (duloxetine) and non-pharmacologic (acupuncture,⁶ exercise) modalities, have been investigated. A randomized trial including 226 women with early-stage breast cancer receiving AI therapy with baseline joint pain (Brief Pain Inventory Worst Pain [BPI-WP] item score of ≥ 3) evaluated whether true acupuncture (TA) provided a sustained reduction in pain symptoms compared with sham acupuncture (SA) or waiting-list control (WC). Acupuncture protocols consisted of 6 weeks of intervention (2 sessions per week) followed by 1 session per week for another 6 weeks. At 52 weeks, mean BPI-WP scores were 1.08 points lower in the TA group compared with the SA group (P = .01) and were 0.99 points lower in the TA group compared with the WC group (P = .03) (Hershman et al). These data support consideration of acupuncture as a mechanism to help maintain patients on aromatase inhibitors, particularly for patients who wish to avoid or have not received benefit from pharmacologic therapy.

Additional References

1. Puglisi F, Gerratana L, Lambertini M, et al. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2021;7:82. Doi: 10.1038/s41523-021-00286-w
2. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021;57:5-17. Doi: 10.1016/j.breast.2021.02.009
3. Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol.2022;18:2667-2682. Doi: 10.2217/fon-2022-0310
4. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): Interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. Doi: Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-The Penelope-B trial. J Clin Oncol. 2021;39(14):1518-1530. Doi: Liu X, Lu J, Wang G, et al. Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. Doi: 10.1177/1534735420980811

The risk for disease recurrence, and specifically distant relapse, for women with high-risk early breast cancer highlights the need for novel therapies in this population.^2,3 The phase 3 randomized monarchE trial investigated the role of the CDK4/6 inhibitor abemaciclib combined with endocrine therapy vs standard endocrine therapy alone in 5637 patients with high-risk (≥ 4 positive axillary nodes or 1-3 positive nodes and either grade 3 tumor, tumor size ≥ 5 cm or Ki-67 ≥ 20%) hormone receptor–positive/HER2-negative early breast cancer. At a median follow-up of 42 months, the median invasive disease-free survival (iDFS) benefit was sustained with abemaciclib + endocrine therapy vs endocrine therapy alone (HR 0.664; nominal P < .0001); the absolute 4-year iDFS benefit was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group). Furthermore, this effect appeared to deepen over time, as the previous absolute iDFS differences were 2.8% (2 years) and 4.8% (3 years). Abemaciclib was associated with a higher rate of grade 3 or higher adverse events (49.9% vs 16.9%), the most common being neutropenia, leukopenia, and diarrhea (Johnston et al). Although adjuvant palbociclib trials (PALLAS⁴ and PENELOPE-B⁵) did not meet their primary endpoint, longer follow-up of monarchE and results from NATALEE with ribociclib are anxiously awaited to further define the role of CDK4/6 inhibitors in this space.

Aromatase inhibitors (AI) are an integral component of treatment for hormone receptor–positive breast cancer for many women. However, joint pain and stiffness associated with these agents can affect compliance. Various management strategies, including trials of alternative AI or endocrine therapies and pharmacologic (duloxetine) and non-pharmacologic (acupuncture,⁶ exercise) modalities, have been investigated. A randomized trial including 226 women with early-stage breast cancer receiving AI therapy with baseline joint pain (Brief Pain Inventory Worst Pain [BPI-WP] item score of ≥ 3) evaluated whether true acupuncture (TA) provided a sustained reduction in pain symptoms compared with sham acupuncture (SA) or waiting-list control (WC). Acupuncture protocols consisted of 6 weeks of intervention (2 sessions per week) followed by 1 session per week for another 6 weeks. At 52 weeks, mean BPI-WP scores were 1.08 points lower in the TA group compared with the SA group (P = .01) and were 0.99 points lower in the TA group compared with the WC group (P = .03) (Hershman et al). These data support consideration of acupuncture as a mechanism to help maintain patients on aromatase inhibitors, particularly for patients who wish to avoid or have not received benefit from pharmacologic therapy.

Additional References

1. Puglisi F, Gerratana L, Lambertini M, et al. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2021;7:82. Doi: 10.1038/s41523-021-00286-w
2. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021;57:5-17. Doi: 10.1016/j.breast.2021.02.009
3. Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol.2022;18:2667-2682. Doi: 10.2217/fon-2022-0310
4. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): Interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. Doi: Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-The Penelope-B trial. J Clin Oncol. 2021;39(14):1518-1530. Doi: Liu X, Lu J, Wang G, et al. Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. Doi: 10.1177/1534735420980811

The risk for disease recurrence, and specifically distant relapse, for women with high-risk early breast cancer highlights the need for novel therapies in this population.^2,3 The phase 3 randomized monarchE trial investigated the role of the CDK4/6 inhibitor abemaciclib combined with endocrine therapy vs standard endocrine therapy alone in 5637 patients with high-risk (≥ 4 positive axillary nodes or 1-3 positive nodes and either grade 3 tumor, tumor size ≥ 5 cm or Ki-67 ≥ 20%) hormone receptor–positive/HER2-negative early breast cancer. At a median follow-up of 42 months, the median invasive disease-free survival (iDFS) benefit was sustained with abemaciclib + endocrine therapy vs endocrine therapy alone (HR 0.664; nominal P < .0001); the absolute 4-year iDFS benefit was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group). Furthermore, this effect appeared to deepen over time, as the previous absolute iDFS differences were 2.8% (2 years) and 4.8% (3 years). Abemaciclib was associated with a higher rate of grade 3 or higher adverse events (49.9% vs 16.9%), the most common being neutropenia, leukopenia, and diarrhea (Johnston et al). Although adjuvant palbociclib trials (PALLAS⁴ and PENELOPE-B⁵) did not meet their primary endpoint, longer follow-up of monarchE and results from NATALEE with ribociclib are anxiously awaited to further define the role of CDK4/6 inhibitors in this space.

Aromatase inhibitors (AI) are an integral component of treatment for hormone receptor–positive breast cancer for many women. However, joint pain and stiffness associated with these agents can affect compliance. Various management strategies, including trials of alternative AI or endocrine therapies and pharmacologic (duloxetine) and non-pharmacologic (acupuncture,⁶ exercise) modalities, have been investigated. A randomized trial including 226 women with early-stage breast cancer receiving AI therapy with baseline joint pain (Brief Pain Inventory Worst Pain [BPI-WP] item score of ≥ 3) evaluated whether true acupuncture (TA) provided a sustained reduction in pain symptoms compared with sham acupuncture (SA) or waiting-list control (WC). Acupuncture protocols consisted of 6 weeks of intervention (2 sessions per week) followed by 1 session per week for another 6 weeks. At 52 weeks, mean BPI-WP scores were 1.08 points lower in the TA group compared with the SA group (P = .01) and were 0.99 points lower in the TA group compared with the WC group (P = .03) (Hershman et al). These data support consideration of acupuncture as a mechanism to help maintain patients on aromatase inhibitors, particularly for patients who wish to avoid or have not received benefit from pharmacologic therapy.

Additional References

1. Puglisi F, Gerratana L, Lambertini M, et al. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 2021;7:82. Doi: 10.1038/s41523-021-00286-w
2. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021;57:5-17. Doi: 10.1016/j.breast.2021.02.009
3. Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol.2022;18:2667-2682. Doi: 10.2217/fon-2022-0310
4. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): Interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. Doi: Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-The Penelope-B trial. J Clin Oncol. 2021;39(14):1518-1530. Doi: Liu X, Lu J, Wang G, et al. Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: A systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. Doi: 10.1177/1534735420980811

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. 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
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. 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
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. 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
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388