Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti‐HER2 agents in the real world setting

Abstract

Additional Supporting Information may be found in the online version of this article.Impact of HR expression on the outcomes of metastatic HER2+ breast cancer treated with novel anti-HER2 agents Int.Cancer Therapy and Prevention other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRsnegative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients. What's new?About half of breast cancers positive for human epidermal growth factor (HER2) also express hormone receptors but the impact of hormone receptor status on the success of HER2-directed treatments is not fully explored. Here the authors retrospectively assessed tumor behavior and treatment outcomes in 738 women with HER2+ metastatic breast cancer treated with new generation anti-HER2 agents. Distinct hormone receptor expression patterns significantly affected the progression free and overall survival, justifying further studies to define optimal treatment regimens and the interplay between hormone receptor and HER2 signaling.

Differences in clinicopathological characteristics, treatment, and survival outcomes between older and younger breast cancer patients

“…Moreover, we found that, when compared to the older patient cohort, younger patients were not only more likely to be HER2-positive, but also more likely to present with triple-positive disease (Table 1 ). Triple positive breast tumors constitute an emerging class of BC, that is increasingly demonstrating distinctive resistance patterns to both anti-HER2 targeting drugs and other endocrine therapies 23 , 24 . To our knowledge, this is the first study to portray a difference in the rate of the triple-positive tumor subtype between young and old BC patients.…”

A scoping review of statistical methods in studies of biomarker-related treatment heterogeneity for breast cancer

“…One study performed interaction analyses and both types of subgroup analyses for time-to-event as well as binary endpoints [ 30 ]. Eight studies showed only results from subgroup analyses: 3 evaluated the treatment effect by biomarker subgroups [ 42 – 44 ], 4 the biomarker effect by treatment subgroups [ 46 – 49 ] and 1 only presented Kaplan-Meier curves for recurrence-free survival for all biomarker-treatment combinations [ 50 ]. Thus, there were 20, 7 and 1 studies that performed subgroup analysis for treatment effect by biomarker subgroup, biomarker effect by treatment subgroup and all biomarker-treatment subgroups, respectively (Table 2 ).…”

A clinical systematic literature review of treatments among patients with advanced and/or metastatic human epidermal growth factor receptor 2 positive breast cancer

“…Bahceci et al included subgroups for patients receiving 1L, 2L and 3L+ is reported in each separate section [ 42 ]. Pizzuti 2020 reported subgroup populations for 1L and 2L [ 48 ]. The RCTs were either phase II (n = 2) or phase III trials (n = 3) and conducted in multinational settings with sample sizes ranging from 210 to 1092 patients ( Table 1 ).…”

“…Seven observational studies on patients with HER2+ a/mBC receiving 2L SOC were included in this SLR [ 42 , 48 , 56–60 ] and were conducted in different countries (Turkey [n = 1], Italy [n = 4], Japan [n = 1] and Spain [n = 1]). Fabi 2017b reported subgroups for patients receiving 2L and 3L+, thus the study is reported in both sections [ 57 ].…”

“…Some studies also included information on prior treatments received ( Table 1 ). Two observational studies did not report patient characteristics for patients receiving 2L treatments [ 42 , 48 ].…”