Breast Cancer

Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.

The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.

The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.

Recommended Additional Reading:

Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090

Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856

Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001

Swain SM et al; on behalf of the 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

Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.

The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.

The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.

Recommended Additional Reading:

Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090

Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856

Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001

Swain SM et al; on behalf of the 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

Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.

The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.

The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.

Recommended Additional Reading:

Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090

Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856

Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001

Swain SM et al; on behalf of the 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

Premenopausal women with a family history of breast cancer have a greater volume of breast density observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.

“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.

Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.

In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.

In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.

The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.

“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.

The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.

The study was funded by the National Institutes of Health.

Premenopausal women with a family history of breast cancer have a greater volume of breast density observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.

“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.

Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.

In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.

In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.

The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.

“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.

The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.

The study was funded by the National Institutes of Health.

Premenopausal women with a family history of breast cancer have a greater volume of breast density observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.

“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.

Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.

In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.

In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.

The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.

“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.

The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.

The study was funded by the National Institutes of Health.

Key clinical point: A delay in initiation of adjuvant hormone therapy (AHT) beyond 150 days was significantly associated with poor survival in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer (BC) not receiving chemotherapy.

Major finding: Time to AHT (TTH) >150 days vs. ≤150 days was associated with an increased risk for death in the overall population (hazard ratio 1.31; P < .001).

Study details: Findings are from a population-based retrospective study including 144,103 patients with HR-positive/ERBB2-negative early BC who received AHT without chemotherapy, of which 6.4% of patients experienced a delay in AHT initiation (TTH >150 days) and 93.6% initiated AHT on time (TTH ≤150 days).

Disclosures: This study was supported by the Natural Science Foundation of Fujian Province and the Fujian Provincial Health Technology Project. The authors declared no conflicts of interest.

Source: Fu F et al. Association of adjuvant hormone therapy timing with overall survival among patients with hormone receptor–positive human epidermal growth factor receptor-2–negative early breast cancer without chemotherapy. JAMA Netw Open. 2022;5(2):e2145934 (Feb 15). Doi: 10.1001/jamanetworkopen.2021.45934

Key clinical point: A delay in initiation of adjuvant hormone therapy (AHT) beyond 150 days was significantly associated with poor survival in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer (BC) not receiving chemotherapy.

Major finding: Time to AHT (TTH) >150 days vs. ≤150 days was associated with an increased risk for death in the overall population (hazard ratio 1.31; P < .001).

Study details: Findings are from a population-based retrospective study including 144,103 patients with HR-positive/ERBB2-negative early BC who received AHT without chemotherapy, of which 6.4% of patients experienced a delay in AHT initiation (TTH >150 days) and 93.6% initiated AHT on time (TTH ≤150 days).

Disclosures: This study was supported by the Natural Science Foundation of Fujian Province and the Fujian Provincial Health Technology Project. The authors declared no conflicts of interest.

Source: Fu F et al. Association of adjuvant hormone therapy timing with overall survival among patients with hormone receptor–positive human epidermal growth factor receptor-2–negative early breast cancer without chemotherapy. JAMA Netw Open. 2022;5(2):e2145934 (Feb 15). Doi: 10.1001/jamanetworkopen.2021.45934

Key clinical point: A delay in initiation of adjuvant hormone therapy (AHT) beyond 150 days was significantly associated with poor survival in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer (BC) not receiving chemotherapy.

Major finding: Time to AHT (TTH) >150 days vs. ≤150 days was associated with an increased risk for death in the overall population (hazard ratio 1.31; P < .001).

Study details: Findings are from a population-based retrospective study including 144,103 patients with HR-positive/ERBB2-negative early BC who received AHT without chemotherapy, of which 6.4% of patients experienced a delay in AHT initiation (TTH >150 days) and 93.6% initiated AHT on time (TTH ≤150 days).

Disclosures: This study was supported by the Natural Science Foundation of Fujian Province and the Fujian Provincial Health Technology Project. The authors declared no conflicts of interest.

Source: Fu F et al. Association of adjuvant hormone therapy timing with overall survival among patients with hormone receptor–positive human epidermal growth factor receptor-2–negative early breast cancer without chemotherapy. JAMA Netw Open. 2022;5(2):e2145934 (Feb 15). Doi: 10.1001/jamanetworkopen.2021.45934

Key clinical point: Pretreatment levels of testosterone and follicle-stimulating hormone (FSH) independently predicted pathological complete response (pCR) in premenopausal and postmenopausal women with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).

Major finding: The likelihood of achieving pCR was higher in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower FSH levels (OR 1.045; P = .005).

Study details: This was a retrospective study of 196 premenopausal and 137 postmenopausal women with invasive BC who received NAC.

Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Lan A et al. Pre-treatment circulating reproductive hormones levels predict pathological and survival outcomes in breast cancer submitted to neoadjuvant chemotherapy. Int J Clin Oncol. 2022 (Mar 3). Doi: 10.1007/s10147-022-02141-9

Key clinical point: Pretreatment levels of testosterone and follicle-stimulating hormone (FSH) independently predicted pathological complete response (pCR) in premenopausal and postmenopausal women with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).

Major finding: The likelihood of achieving pCR was higher in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower FSH levels (OR 1.045; P = .005).

Study details: This was a retrospective study of 196 premenopausal and 137 postmenopausal women with invasive BC who received NAC.

Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Lan A et al. Pre-treatment circulating reproductive hormones levels predict pathological and survival outcomes in breast cancer submitted to neoadjuvant chemotherapy. Int J Clin Oncol. 2022 (Mar 3). Doi: 10.1007/s10147-022-02141-9

Key clinical point: Pretreatment levels of testosterone and follicle-stimulating hormone (FSH) independently predicted pathological complete response (pCR) in premenopausal and postmenopausal women with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).

Major finding: The likelihood of achieving pCR was higher in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower FSH levels (OR 1.045; P = .005).

Study details: This was a retrospective study of 196 premenopausal and 137 postmenopausal women with invasive BC who received NAC.

Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Lan A et al. Pre-treatment circulating reproductive hormones levels predict pathological and survival outcomes in breast cancer submitted to neoadjuvant chemotherapy. Int J Clin Oncol. 2022 (Mar 3). Doi: 10.1007/s10147-022-02141-9

Key clinical point: An anthracycline-containing chemotherapy (AC-T) regimen was not associated with a survival benefit compared with 6 cycles of docetaxel/cyclophosphamide (TC6) in an overall cohort of patients with human epidermal growth factor receptor 2 (HER2)-negative, high-risk, early breast cancer (BC); however, patients with lobular tumor and ≥3 affected lymph nodes may benefit.

Major finding: Although disease-free survival (DFS) was similar between AC-T and TC6 treatment arms in the overall cohort (P = .57), the subgroup of patients with lobular tumor and ≥3 affected lymph nodes showed improved DFS with AC-T vs. TC6 (hazard ratio 3.521; P = .003). The frequency of grade 3/4 adverse events was significantly higher in AC-T vs. TC6 treatment arm (P < .001).

Study details: Findings are from the pooled analysis of two phase 3 studies, SUCCESS-C and PlanB, including 5,924 patients with high-risk HER2-negative invasive early BC who were randomly assigned to receive TC6 or AC-T.

Disclosures: The study did not receive any funding. Some authors declared receiving financial and nonfinancial support from several sources.

Source: Gregorio AD 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 (Feb 22). Doi: 10.1038/s41416-021-01690-6

Key clinical point: An anthracycline-containing chemotherapy (AC-T) regimen was not associated with a survival benefit compared with 6 cycles of docetaxel/cyclophosphamide (TC6) in an overall cohort of patients with human epidermal growth factor receptor 2 (HER2)-negative, high-risk, early breast cancer (BC); however, patients with lobular tumor and ≥3 affected lymph nodes may benefit.

Major finding: Although disease-free survival (DFS) was similar between AC-T and TC6 treatment arms in the overall cohort (P = .57), the subgroup of patients with lobular tumor and ≥3 affected lymph nodes showed improved DFS with AC-T vs. TC6 (hazard ratio 3.521; P = .003). The frequency of grade 3/4 adverse events was significantly higher in AC-T vs. TC6 treatment arm (P < .001).

Study details: Findings are from the pooled analysis of two phase 3 studies, SUCCESS-C and PlanB, including 5,924 patients with high-risk HER2-negative invasive early BC who were randomly assigned to receive TC6 or AC-T.

Disclosures: The study did not receive any funding. Some authors declared receiving financial and nonfinancial support from several sources.

Source: Gregorio AD 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 (Feb 22). Doi: 10.1038/s41416-021-01690-6

Key clinical point: An anthracycline-containing chemotherapy (AC-T) regimen was not associated with a survival benefit compared with 6 cycles of docetaxel/cyclophosphamide (TC6) in an overall cohort of patients with human epidermal growth factor receptor 2 (HER2)-negative, high-risk, early breast cancer (BC); however, patients with lobular tumor and ≥3 affected lymph nodes may benefit.

Major finding: Although disease-free survival (DFS) was similar between AC-T and TC6 treatment arms in the overall cohort (P = .57), the subgroup of patients with lobular tumor and ≥3 affected lymph nodes showed improved DFS with AC-T vs. TC6 (hazard ratio 3.521; P = .003). The frequency of grade 3/4 adverse events was significantly higher in AC-T vs. TC6 treatment arm (P < .001).

Study details: Findings are from the pooled analysis of two phase 3 studies, SUCCESS-C and PlanB, including 5,924 patients with high-risk HER2-negative invasive early BC who were randomly assigned to receive TC6 or AC-T.

Disclosures: The study did not receive any funding. Some authors declared receiving financial and nonfinancial support from several sources.

Source: Gregorio AD 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 (Feb 22). Doi: 10.1038/s41416-021-01690-6

Key clinical point: Ribociclib plus letrozole was safe and effective in male patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (BC) who did not receive prior endocrine therapy (ET).

Major finding: Male patients vs. overall population experienced fewer treatment-related adverse events (AE), especially neutropenia (all grade 53.8% vs. 74.5%; grade ≥3 41.0% vs. 57.2%). After a median follow-up of 25.4 months, median time to progression was 27.1 months for the overall cohort vs. not reached in males.

Study details: Findings are from an exploratory analysis of the phase 3b CompLEEment-1 trial including 39 males with HR-positive HER2-negative advanced BC who received ribociclib+letrozole but not prior ET for the advanced disease.

Disclosures: The study was supported by Novartis Pharmaceuticals. The authors declared serving as members of speakers’ bureau or receiving honoraria, advisory/consulting fees, expert testimony fees, research grants, or travel and accommodation expenses from several sources, including Novartis. Two authors declared being employees or shareholders of Novartis.

Source: Campone M et al. Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial. Breast Cancer Res Treat. 2022 (Feb 25). Doi: 10.1007/s10549-022-06543-1

Key clinical point: Ribociclib plus letrozole was safe and effective in male patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (BC) who did not receive prior endocrine therapy (ET).

Major finding: Male patients vs. overall population experienced fewer treatment-related adverse events (AE), especially neutropenia (all grade 53.8% vs. 74.5%; grade ≥3 41.0% vs. 57.2%). After a median follow-up of 25.4 months, median time to progression was 27.1 months for the overall cohort vs. not reached in males.

Study details: Findings are from an exploratory analysis of the phase 3b CompLEEment-1 trial including 39 males with HR-positive HER2-negative advanced BC who received ribociclib+letrozole but not prior ET for the advanced disease.

Disclosures: The study was supported by Novartis Pharmaceuticals. The authors declared serving as members of speakers’ bureau or receiving honoraria, advisory/consulting fees, expert testimony fees, research grants, or travel and accommodation expenses from several sources, including Novartis. Two authors declared being employees or shareholders of Novartis.

Source: Campone M et al. Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial. Breast Cancer Res Treat. 2022 (Feb 25). Doi: 10.1007/s10549-022-06543-1

Key clinical point: Ribociclib plus letrozole was safe and effective in male patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (BC) who did not receive prior endocrine therapy (ET).

Major finding: Male patients vs. overall population experienced fewer treatment-related adverse events (AE), especially neutropenia (all grade 53.8% vs. 74.5%; grade ≥3 41.0% vs. 57.2%). After a median follow-up of 25.4 months, median time to progression was 27.1 months for the overall cohort vs. not reached in males.

Study details: Findings are from an exploratory analysis of the phase 3b CompLEEment-1 trial including 39 males with HR-positive HER2-negative advanced BC who received ribociclib+letrozole but not prior ET for the advanced disease.

Disclosures: The study was supported by Novartis Pharmaceuticals. The authors declared serving as members of speakers’ bureau or receiving honoraria, advisory/consulting fees, expert testimony fees, research grants, or travel and accommodation expenses from several sources, including Novartis. Two authors declared being employees or shareholders of Novartis.

Source: Campone M et al. Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial. Breast Cancer Res Treat. 2022 (Feb 25). Doi: 10.1007/s10549-022-06543-1

Key clinical point: A family history of breast cancer (FHBC) was positively associated with mammographic breast density in premenopausal women, highlighting the role of heredity and the need for initiating early annual screening in women with an FHBC.

Major finding: The volumetric percent density was 25% higher among premenopausal women with vs. without FHBC (odds ratio [OR] 1.25; 95% CI 1.12-1.41) in the discovery cohort, and the odds of having a dense breast was 30% higher in premenopausal women with vs. without FHBC in the validation cohort (OR 1.30; 95% CI 1.17-1.45).

Study details: This study evaluated two retrospective cohorts, a discovery set of 375 premenopausal women and a validation set of 14,040 premenopausal women without any history of cancer, including breast cancer, or breast augmentation/reduction.

Disclosures: This study was supported by US National Institutes of Health (NIH)/National Cancer Institute and the National Institute on Minority Health and Health Disparities of the NIH. The authors declared no conflicts of interest.

Source: Han Y et al. Family history of breast cancer and mammographic breast density in premenopausal women. JAMA Netw Open. 2022;5(2):e2148983 (Feb 17). Doi: 10.1001/jamanetworkopen.2021.48983

Key clinical point: A family history of breast cancer (FHBC) was positively associated with mammographic breast density in premenopausal women, highlighting the role of heredity and the need for initiating early annual screening in women with an FHBC.

Major finding: The volumetric percent density was 25% higher among premenopausal women with vs. without FHBC (odds ratio [OR] 1.25; 95% CI 1.12-1.41) in the discovery cohort, and the odds of having a dense breast was 30% higher in premenopausal women with vs. without FHBC in the validation cohort (OR 1.30; 95% CI 1.17-1.45).

Study details: This study evaluated two retrospective cohorts, a discovery set of 375 premenopausal women and a validation set of 14,040 premenopausal women without any history of cancer, including breast cancer, or breast augmentation/reduction.

Disclosures: This study was supported by US National Institutes of Health (NIH)/National Cancer Institute and the National Institute on Minority Health and Health Disparities of the NIH. The authors declared no conflicts of interest.

Source: Han Y et al. Family history of breast cancer and mammographic breast density in premenopausal women. JAMA Netw Open. 2022;5(2):e2148983 (Feb 17). Doi: 10.1001/jamanetworkopen.2021.48983

Key clinical point: A family history of breast cancer (FHBC) was positively associated with mammographic breast density in premenopausal women, highlighting the role of heredity and the need for initiating early annual screening in women with an FHBC.

Major finding: The volumetric percent density was 25% higher among premenopausal women with vs. without FHBC (odds ratio [OR] 1.25; 95% CI 1.12-1.41) in the discovery cohort, and the odds of having a dense breast was 30% higher in premenopausal women with vs. without FHBC in the validation cohort (OR 1.30; 95% CI 1.17-1.45).

Study details: This study evaluated two retrospective cohorts, a discovery set of 375 premenopausal women and a validation set of 14,040 premenopausal women without any history of cancer, including breast cancer, or breast augmentation/reduction.

Disclosures: This study was supported by US National Institutes of Health (NIH)/National Cancer Institute and the National Institute on Minority Health and Health Disparities of the NIH. The authors declared no conflicts of interest.

Source: Han Y et al. Family history of breast cancer and mammographic breast density in premenopausal women. JAMA Netw Open. 2022;5(2):e2148983 (Feb 17). Doi: 10.1001/jamanetworkopen.2021.48983

Key clinical point: In the real-world setting, adding pertuzumab to trastuzumab+chemotherapy improved overall survival (OS) in a large cohort of patients with metastatic breast cancer (BC).

Major finding: Median OS was higher with pertuzumab+trastuzumab+chemotherapy (40.2 months; 95% CI 35.6-47.8 months) vs. trastuzumab+chemotherapy (25.3 months; 95% CI 22.8-27.6 months), with pertuzumab associated with significantly reduced mortality (hazard ratio 0.66; 95% CI 0.57-0.79). The 1-year cumulative incidence of a direct hospital visit was lower in the pertuzumab+trastuzumab+chemotherapy vs. trastuzumab+chemotherapy group (P < .001).

Study details: Findings are from a population-based retrospective study including 1,158 patients with metastatic BC who received first-line treatment with pertuzumab+trastuzumab+chemotherapy (n = 579) or trastuzumab+chemotherapy (n = 579).

Disclosures: This study was supported by the Canadian Institutes of Health Research. Dr. Liu declared being an employee of ICES, which is funded by the Ontario Ministry of Health and Long-Term Care.

Source: Dai WF et al. Comparative effectiveness and safety of pertuzumab and trastuzumab plus chemotherapy vs trastuzumab plus chemotherapy for treatment of metastatic breast cancer. JAMA Netw Open. 2022;5(2):e2145460 (Feb 28). Doi: 10.1001/jamanetworkopen.2021.45460

Key clinical point: In the real-world setting, adding pertuzumab to trastuzumab+chemotherapy improved overall survival (OS) in a large cohort of patients with metastatic breast cancer (BC).

Major finding: Median OS was higher with pertuzumab+trastuzumab+chemotherapy (40.2 months; 95% CI 35.6-47.8 months) vs. trastuzumab+chemotherapy (25.3 months; 95% CI 22.8-27.6 months), with pertuzumab associated with significantly reduced mortality (hazard ratio 0.66; 95% CI 0.57-0.79). The 1-year cumulative incidence of a direct hospital visit was lower in the pertuzumab+trastuzumab+chemotherapy vs. trastuzumab+chemotherapy group (P < .001).

Study details: Findings are from a population-based retrospective study including 1,158 patients with metastatic BC who received first-line treatment with pertuzumab+trastuzumab+chemotherapy (n = 579) or trastuzumab+chemotherapy (n = 579).

Disclosures: This study was supported by the Canadian Institutes of Health Research. Dr. Liu declared being an employee of ICES, which is funded by the Ontario Ministry of Health and Long-Term Care.

Source: Dai WF et al. Comparative effectiveness and safety of pertuzumab and trastuzumab plus chemotherapy vs trastuzumab plus chemotherapy for treatment of metastatic breast cancer. JAMA Netw Open. 2022;5(2):e2145460 (Feb 28). Doi: 10.1001/jamanetworkopen.2021.45460

Key clinical point: In the real-world setting, adding pertuzumab to trastuzumab+chemotherapy improved overall survival (OS) in a large cohort of patients with metastatic breast cancer (BC).

Major finding: Median OS was higher with pertuzumab+trastuzumab+chemotherapy (40.2 months; 95% CI 35.6-47.8 months) vs. trastuzumab+chemotherapy (25.3 months; 95% CI 22.8-27.6 months), with pertuzumab associated with significantly reduced mortality (hazard ratio 0.66; 95% CI 0.57-0.79). The 1-year cumulative incidence of a direct hospital visit was lower in the pertuzumab+trastuzumab+chemotherapy vs. trastuzumab+chemotherapy group (P < .001).

Study details: Findings are from a population-based retrospective study including 1,158 patients with metastatic BC who received first-line treatment with pertuzumab+trastuzumab+chemotherapy (n = 579) or trastuzumab+chemotherapy (n = 579).

Disclosures: This study was supported by the Canadian Institutes of Health Research. Dr. Liu declared being an employee of ICES, which is funded by the Ontario Ministry of Health and Long-Term Care.

Source: Dai WF et al. Comparative effectiveness and safety of pertuzumab and trastuzumab plus chemotherapy vs trastuzumab plus chemotherapy for treatment of metastatic breast cancer. JAMA Netw Open. 2022;5(2):e2145460 (Feb 28). Doi: 10.1001/jamanetworkopen.2021.45460

Key clinical point: HD201, a trastuzumab biosimilar, and reference trastuzumab display equivalence in terms of efficacy (along with a similar safety profile) in patients with human epidermal growth factor receptor 2 (ERBB2)-positive early breast cancer (BC) treated in the neoadjuvant setting.

Major finding: At the time of surgery, the rate of total pathological complete response with HD201 vs. referent trastuzumab was 45% vs. 48.7%, respectively, with the difference between the groups within the predefined equivalence margin (−3.8%; 95% CI −12.8% to 5.4%). Treatment-emergent adverse events of special interest for trastuzumab were reported by 88% and 84.5% of patients receiving HD201 and trastuzumab, respectively.

Study details: Findings are from the phase 3 TROIKA study including 502 women with ERBB2-positive early BC who were randomly assigned to receive HD201 or trastuzumab in a neoadjuvant setting along with chemotherapy.

Disclosures: This study was funded by Prestige BioPharma Ltd. Some of the authors declared serving as unpaid advisors or receiving personal fees and grants from several sources, including Prestige BioPharma Ltd. Three authors declared being employees of DICE Ltd.

Source: Pivot X et al. Efficacy of HD201 vs referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting: A multicenter phase 3 randomized clinical trial. JAMA Oncol. 2022 (Mar 3). Doi: 10.1001/jamaoncol.2021.8171

Key clinical point: HD201, a trastuzumab biosimilar, and reference trastuzumab display equivalence in terms of efficacy (along with a similar safety profile) in patients with human epidermal growth factor receptor 2 (ERBB2)-positive early breast cancer (BC) treated in the neoadjuvant setting.

Major finding: At the time of surgery, the rate of total pathological complete response with HD201 vs. referent trastuzumab was 45% vs. 48.7%, respectively, with the difference between the groups within the predefined equivalence margin (−3.8%; 95% CI −12.8% to 5.4%). Treatment-emergent adverse events of special interest for trastuzumab were reported by 88% and 84.5% of patients receiving HD201 and trastuzumab, respectively.

Study details: Findings are from the phase 3 TROIKA study including 502 women with ERBB2-positive early BC who were randomly assigned to receive HD201 or trastuzumab in a neoadjuvant setting along with chemotherapy.

Disclosures: This study was funded by Prestige BioPharma Ltd. Some of the authors declared serving as unpaid advisors or receiving personal fees and grants from several sources, including Prestige BioPharma Ltd. Three authors declared being employees of DICE Ltd.

Source: Pivot X et al. Efficacy of HD201 vs referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting: A multicenter phase 3 randomized clinical trial. JAMA Oncol. 2022 (Mar 3). Doi: 10.1001/jamaoncol.2021.8171

Key clinical point: HD201, a trastuzumab biosimilar, and reference trastuzumab display equivalence in terms of efficacy (along with a similar safety profile) in patients with human epidermal growth factor receptor 2 (ERBB2)-positive early breast cancer (BC) treated in the neoadjuvant setting.

Major finding: At the time of surgery, the rate of total pathological complete response with HD201 vs. referent trastuzumab was 45% vs. 48.7%, respectively, with the difference between the groups within the predefined equivalence margin (−3.8%; 95% CI −12.8% to 5.4%). Treatment-emergent adverse events of special interest for trastuzumab were reported by 88% and 84.5% of patients receiving HD201 and trastuzumab, respectively.

Study details: Findings are from the phase 3 TROIKA study including 502 women with ERBB2-positive early BC who were randomly assigned to receive HD201 or trastuzumab in a neoadjuvant setting along with chemotherapy.

Disclosures: This study was funded by Prestige BioPharma Ltd. Some of the authors declared serving as unpaid advisors or receiving personal fees and grants from several sources, including Prestige BioPharma Ltd. Three authors declared being employees of DICE Ltd.

Source: Pivot X et al. Efficacy of HD201 vs referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting: A multicenter phase 3 randomized clinical trial. JAMA Oncol. 2022 (Mar 3). Doi: 10.1001/jamaoncol.2021.8171

Key clinical point: Patients with metastatic breast cancer (BC) with a lobular subtype may have worse outcomes compared with those with a ductal subtype.

Major finding: Invasive lobular carcinoma (ILC) vs. invasive ductal carcinoma (IDC) subtype was significantly associated with worse survival (hazard ratio [HR] 1.31; P < .0001) and progression-free survival (HR 1.15; P < .0001).

Study details: Findings are from a retrospective analysis of 13,111 patients with metastatic BC with ILC (13.8%) or IDC (86.2%) subtype from the UNICANCER Epidemiological Strategy and Medico Economics (ESME)-metastatic BC cohort.

Disclosures: ESME is supported by Roche, Pfizer, and other pharmaceutical companies. The authors declared no conflicts of interest.

Source: Dalenc F et al. Impact of lobular versus ductal histology on overall survival in metastatic breast cancer: a French retrospective multicentre cohort study. Eur J Cancer. 2022;164:70-79 (Feb 14). Doi: 10.1016/j.ejca.2021.12.031

Key clinical point: Patients with metastatic breast cancer (BC) with a lobular subtype may have worse outcomes compared with those with a ductal subtype.

Major finding: Invasive lobular carcinoma (ILC) vs. invasive ductal carcinoma (IDC) subtype was significantly associated with worse survival (hazard ratio [HR] 1.31; P < .0001) and progression-free survival (HR 1.15; P < .0001).

Study details: Findings are from a retrospective analysis of 13,111 patients with metastatic BC with ILC (13.8%) or IDC (86.2%) subtype from the UNICANCER Epidemiological Strategy and Medico Economics (ESME)-metastatic BC cohort.

Disclosures: ESME is supported by Roche, Pfizer, and other pharmaceutical companies. The authors declared no conflicts of interest.

Source: Dalenc F et al. Impact of lobular versus ductal histology on overall survival in metastatic breast cancer: a French retrospective multicentre cohort study. Eur J Cancer. 2022;164:70-79 (Feb 14). Doi: 10.1016/j.ejca.2021.12.031

Key clinical point: Patients with metastatic breast cancer (BC) with a lobular subtype may have worse outcomes compared with those with a ductal subtype.

Major finding: Invasive lobular carcinoma (ILC) vs. invasive ductal carcinoma (IDC) subtype was significantly associated with worse survival (hazard ratio [HR] 1.31; P < .0001) and progression-free survival (HR 1.15; P < .0001).

Study details: Findings are from a retrospective analysis of 13,111 patients with metastatic BC with ILC (13.8%) or IDC (86.2%) subtype from the UNICANCER Epidemiological Strategy and Medico Economics (ESME)-metastatic BC cohort.

Disclosures: ESME is supported by Roche, Pfizer, and other pharmaceutical companies. The authors declared no conflicts of interest.

Source: Dalenc F et al. Impact of lobular versus ductal histology on overall survival in metastatic breast cancer: a French retrospective multicentre cohort study. Eur J Cancer. 2022;164:70-79 (Feb 14). Doi: 10.1016/j.ejca.2021.12.031