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Dr. Roesch scans the journals, so you don't have to!

Erin Roesch, MD
The role of adjuvant chemotherapy in addition to endocrine therapy for hormone-receptor positive (HR+) early breast cancer has been studied in prospective trials utilizing genomic assays. The RxPONDER trial included 5,083 women with HR+/HER2-negative breast cancer, 1-3 nodes involved and RS ≤25, and randomized to endocrine therapy alone or chemoendocrine therapy (Kalinsky et al). Premenopausal women were found to have improved 5-year invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) with the addition of chemotherapy; IDFS 89.0% vs 93.9% (HR 0.60, P = 0.002) and DRFS 92.8% vs 96.1% (HR 0.58, P = 0.009) for endocrine group vs chemoendocrine group, respectively. A remaining question is whether the impact of chemotherapy in premenopausal women is related to direct cytotoxic effect or treatment-induced amenorrhea. The benefit of ovarian suppression plus an aromatase inhibitor in premenopausal patients at high recurrence risk was shown in TEXT/SOFT trials, and studies are needed to elucidate whether chemotherapy can be replaced by more effective endocrine therapy in select populations.


Oocyte and embryo cryopreservation are standard fertility preservation techniques, and gonadotropin-releasing hormone agonist (GnRHa) administration during chemotherapy is another strategy to preserve ovarian function. The phase 3 POEMS/S0230 study demonstrated higher pregnancy rates (5-year cumulative incidence 23.1% vs 12.2%, P = 0.03) among premenopausal patients with HR-negative early breast cancer who received GnRHa (goserelin) during chemotherapy vs chemotherapy alone. Furthermore, there was a trend towards improvement in survival outcomes with GnRHa + chemotherapy. Hypothetical concerns have existed regarding the safety of this approach, particularly in HR+ breast cancer. The PROMISE-GIM6 trial randomized 281 patients to receive chemotherapy alone or with GnRHa triptorelin (Lambertini et al) and found no difference in disease-free survival (DFS) or overall survival (OS) between GnRHa vs control groups (12-year DFS 65.7% vs 69.2%, HR 1.16; 12-year OS 81.2% vs 81.3%, HR 1.17). In patients with HR+ disease (80.4%), HR for DFS and OS was 1.02 and 1.12, respectively. The 12-year cumulative incidence of pregnancy was also higher in the GnRHa vs control group (6.5% vs 3.2%). These studies suggest no detrimental effect of GnRHa use during chemotherapy on long-term outcomes, including patients with HR+ disease, and support its role in ovarian protection.

COVID-19 has had various implications on breast cancer care, reflecting institutional policies, resources and patient preferences and potential concerns during the pandemic. A retrospective chart review of patients diagnosed at Mayo Clinic Rochester with a new breast cancer during vs pre-COVID-19, examined trends in diagnosis and treatment approaches during these times (Tonneson et al). Among 573 patients, there was no significant difference in clinical prognostic stage, although a slightly higher percentage of patients who presented with stage II-IV disease during COVID-19 vs pre-COVID-19 (29% vs 26%, P = 0.42). The use of neoadjuvant endocrine therapy (NET) significantly increased during COVID-19, and notably in patients with HR+/HER2- breast cancer (10% pre-COVID-19 vs 23% during COVID-19 (P = 0.001)) with a significant increase in stage I patients (7% vs 22%, P < 0.001). Various societies provided language to support neoadjuvant therapy as a bridge to surgical intervention during COVID-19 in the appropriate clinical scenarios. Extended follow-up of studies examining approaches utilized during the pandemic are desired to further define long-term impact on outcomes.

A pooled analysis of the PALOMA trials demonstrated progression-free survival benefit with palbociclib + endocrine therapy vs endocrine therapy alone in patients ≥65 years, and although myelosuppression was more common in patients ≥75 years, the combination remained well-tolerated. Ismail et al described real-world experience of palbociclib in older patients with advanced HR+ breast cancer. Among 598 patients, palbociclib dose reductions occurred in 33%, and those requiring a dose reduction were older vs those without dose reduction (median age 67 vs 63 years, P = 0.004). Despite higher frequency of dose reductions in older patients, this did not appear to compromise outcomes; time to next treatment was significantly longer (16.9 vs 11.6 months, P = 0.013) than younger patients but OS was similar (20.7 vs 26.7 months, P = 0.051). Although older patients may be at higher risk of toxicities due to co-morbidities or performance status limitations, palbociclib remains a valuable therapeutic option combined with endocrine therapy for advanced HR+/HER2- breast cancer.

References:


Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.

Moore HCF, Unger JM, Phillips K-A, et al. Final analysis of the prevention of early menopause study (POEMS)/SWOG Intergroup S0230. J Natl Cancer Inst. 2019;111(2):210–213.

Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. The COVID-19 pandemic breast cancer consortium. Breast Cancer Res Treat. 2020;181(3):487–97.

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;101:123e33.

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Dr. Roesch scans the journals, so you don't have to!
Dr. Roesch scans the journals, so you don't have to!

Erin Roesch, MD
The role of adjuvant chemotherapy in addition to endocrine therapy for hormone-receptor positive (HR+) early breast cancer has been studied in prospective trials utilizing genomic assays. The RxPONDER trial included 5,083 women with HR+/HER2-negative breast cancer, 1-3 nodes involved and RS ≤25, and randomized to endocrine therapy alone or chemoendocrine therapy (Kalinsky et al). Premenopausal women were found to have improved 5-year invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) with the addition of chemotherapy; IDFS 89.0% vs 93.9% (HR 0.60, P = 0.002) and DRFS 92.8% vs 96.1% (HR 0.58, P = 0.009) for endocrine group vs chemoendocrine group, respectively. A remaining question is whether the impact of chemotherapy in premenopausal women is related to direct cytotoxic effect or treatment-induced amenorrhea. The benefit of ovarian suppression plus an aromatase inhibitor in premenopausal patients at high recurrence risk was shown in TEXT/SOFT trials, and studies are needed to elucidate whether chemotherapy can be replaced by more effective endocrine therapy in select populations.


Oocyte and embryo cryopreservation are standard fertility preservation techniques, and gonadotropin-releasing hormone agonist (GnRHa) administration during chemotherapy is another strategy to preserve ovarian function. The phase 3 POEMS/S0230 study demonstrated higher pregnancy rates (5-year cumulative incidence 23.1% vs 12.2%, P = 0.03) among premenopausal patients with HR-negative early breast cancer who received GnRHa (goserelin) during chemotherapy vs chemotherapy alone. Furthermore, there was a trend towards improvement in survival outcomes with GnRHa + chemotherapy. Hypothetical concerns have existed regarding the safety of this approach, particularly in HR+ breast cancer. The PROMISE-GIM6 trial randomized 281 patients to receive chemotherapy alone or with GnRHa triptorelin (Lambertini et al) and found no difference in disease-free survival (DFS) or overall survival (OS) between GnRHa vs control groups (12-year DFS 65.7% vs 69.2%, HR 1.16; 12-year OS 81.2% vs 81.3%, HR 1.17). In patients with HR+ disease (80.4%), HR for DFS and OS was 1.02 and 1.12, respectively. The 12-year cumulative incidence of pregnancy was also higher in the GnRHa vs control group (6.5% vs 3.2%). These studies suggest no detrimental effect of GnRHa use during chemotherapy on long-term outcomes, including patients with HR+ disease, and support its role in ovarian protection.

COVID-19 has had various implications on breast cancer care, reflecting institutional policies, resources and patient preferences and potential concerns during the pandemic. A retrospective chart review of patients diagnosed at Mayo Clinic Rochester with a new breast cancer during vs pre-COVID-19, examined trends in diagnosis and treatment approaches during these times (Tonneson et al). Among 573 patients, there was no significant difference in clinical prognostic stage, although a slightly higher percentage of patients who presented with stage II-IV disease during COVID-19 vs pre-COVID-19 (29% vs 26%, P = 0.42). The use of neoadjuvant endocrine therapy (NET) significantly increased during COVID-19, and notably in patients with HR+/HER2- breast cancer (10% pre-COVID-19 vs 23% during COVID-19 (P = 0.001)) with a significant increase in stage I patients (7% vs 22%, P < 0.001). Various societies provided language to support neoadjuvant therapy as a bridge to surgical intervention during COVID-19 in the appropriate clinical scenarios. Extended follow-up of studies examining approaches utilized during the pandemic are desired to further define long-term impact on outcomes.

A pooled analysis of the PALOMA trials demonstrated progression-free survival benefit with palbociclib + endocrine therapy vs endocrine therapy alone in patients ≥65 years, and although myelosuppression was more common in patients ≥75 years, the combination remained well-tolerated. Ismail et al described real-world experience of palbociclib in older patients with advanced HR+ breast cancer. Among 598 patients, palbociclib dose reductions occurred in 33%, and those requiring a dose reduction were older vs those without dose reduction (median age 67 vs 63 years, P = 0.004). Despite higher frequency of dose reductions in older patients, this did not appear to compromise outcomes; time to next treatment was significantly longer (16.9 vs 11.6 months, P = 0.013) than younger patients but OS was similar (20.7 vs 26.7 months, P = 0.051). Although older patients may be at higher risk of toxicities due to co-morbidities or performance status limitations, palbociclib remains a valuable therapeutic option combined with endocrine therapy for advanced HR+/HER2- breast cancer.

References:


Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.

Moore HCF, Unger JM, Phillips K-A, et al. Final analysis of the prevention of early menopause study (POEMS)/SWOG Intergroup S0230. J Natl Cancer Inst. 2019;111(2):210–213.

Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. The COVID-19 pandemic breast cancer consortium. Breast Cancer Res Treat. 2020;181(3):487–97.

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;101:123e33.

Erin Roesch, MD
The role of adjuvant chemotherapy in addition to endocrine therapy for hormone-receptor positive (HR+) early breast cancer has been studied in prospective trials utilizing genomic assays. The RxPONDER trial included 5,083 women with HR+/HER2-negative breast cancer, 1-3 nodes involved and RS ≤25, and randomized to endocrine therapy alone or chemoendocrine therapy (Kalinsky et al). Premenopausal women were found to have improved 5-year invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) with the addition of chemotherapy; IDFS 89.0% vs 93.9% (HR 0.60, P = 0.002) and DRFS 92.8% vs 96.1% (HR 0.58, P = 0.009) for endocrine group vs chemoendocrine group, respectively. A remaining question is whether the impact of chemotherapy in premenopausal women is related to direct cytotoxic effect or treatment-induced amenorrhea. The benefit of ovarian suppression plus an aromatase inhibitor in premenopausal patients at high recurrence risk was shown in TEXT/SOFT trials, and studies are needed to elucidate whether chemotherapy can be replaced by more effective endocrine therapy in select populations.


Oocyte and embryo cryopreservation are standard fertility preservation techniques, and gonadotropin-releasing hormone agonist (GnRHa) administration during chemotherapy is another strategy to preserve ovarian function. The phase 3 POEMS/S0230 study demonstrated higher pregnancy rates (5-year cumulative incidence 23.1% vs 12.2%, P = 0.03) among premenopausal patients with HR-negative early breast cancer who received GnRHa (goserelin) during chemotherapy vs chemotherapy alone. Furthermore, there was a trend towards improvement in survival outcomes with GnRHa + chemotherapy. Hypothetical concerns have existed regarding the safety of this approach, particularly in HR+ breast cancer. The PROMISE-GIM6 trial randomized 281 patients to receive chemotherapy alone or with GnRHa triptorelin (Lambertini et al) and found no difference in disease-free survival (DFS) or overall survival (OS) between GnRHa vs control groups (12-year DFS 65.7% vs 69.2%, HR 1.16; 12-year OS 81.2% vs 81.3%, HR 1.17). In patients with HR+ disease (80.4%), HR for DFS and OS was 1.02 and 1.12, respectively. The 12-year cumulative incidence of pregnancy was also higher in the GnRHa vs control group (6.5% vs 3.2%). These studies suggest no detrimental effect of GnRHa use during chemotherapy on long-term outcomes, including patients with HR+ disease, and support its role in ovarian protection.

COVID-19 has had various implications on breast cancer care, reflecting institutional policies, resources and patient preferences and potential concerns during the pandemic. A retrospective chart review of patients diagnosed at Mayo Clinic Rochester with a new breast cancer during vs pre-COVID-19, examined trends in diagnosis and treatment approaches during these times (Tonneson et al). Among 573 patients, there was no significant difference in clinical prognostic stage, although a slightly higher percentage of patients who presented with stage II-IV disease during COVID-19 vs pre-COVID-19 (29% vs 26%, P = 0.42). The use of neoadjuvant endocrine therapy (NET) significantly increased during COVID-19, and notably in patients with HR+/HER2- breast cancer (10% pre-COVID-19 vs 23% during COVID-19 (P = 0.001)) with a significant increase in stage I patients (7% vs 22%, P < 0.001). Various societies provided language to support neoadjuvant therapy as a bridge to surgical intervention during COVID-19 in the appropriate clinical scenarios. Extended follow-up of studies examining approaches utilized during the pandemic are desired to further define long-term impact on outcomes.

A pooled analysis of the PALOMA trials demonstrated progression-free survival benefit with palbociclib + endocrine therapy vs endocrine therapy alone in patients ≥65 years, and although myelosuppression was more common in patients ≥75 years, the combination remained well-tolerated. Ismail et al described real-world experience of palbociclib in older patients with advanced HR+ breast cancer. Among 598 patients, palbociclib dose reductions occurred in 33%, and those requiring a dose reduction were older vs those without dose reduction (median age 67 vs 63 years, P = 0.004). Despite higher frequency of dose reductions in older patients, this did not appear to compromise outcomes; time to next treatment was significantly longer (16.9 vs 11.6 months, P = 0.013) than younger patients but OS was similar (20.7 vs 26.7 months, P = 0.051). Although older patients may be at higher risk of toxicities due to co-morbidities or performance status limitations, palbociclib remains a valuable therapeutic option combined with endocrine therapy for advanced HR+/HER2- breast cancer.

References:


Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.

Moore HCF, Unger JM, Phillips K-A, et al. Final analysis of the prevention of early menopause study (POEMS)/SWOG Intergroup S0230. J Natl Cancer Inst. 2019;111(2):210–213.

Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. The COVID-19 pandemic breast cancer consortium. Breast Cancer Res Treat. 2020;181(3):487–97.

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;101:123e33.

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