HER2-Low Breast Cancer: Clinical Characteristics, Prognosis, and Evolution from Diagnosis to Residual Disease

Abstract

Paper 1 Abstract Introduction: We have previously found that HER2 expression is dynamic, and can change from the primary tumor to matched recurrences. With this work, we aimed to assess the dynamics of HER2 during neo- adjuvant treatment (NAT). Methods: We reviewed HER2 expression in pre- and post-treatment samples from consecutive patients with early- stage breast cancer that received NAT and underwent surgery at Dana-Farber Brigham Cancer Center between 01/2016–08/2022. The primary outcome was evolution of HER2 expression from pre- to post-NAT specimens in patients with residual disease. Results: Among 1613 patients receiving NAT, 1080 had residual disease at surgery. A total of 319 patients (29.5%) experienced a change in HER2 expression (HER2 0 vs. HER2-low vs. HER2-positive) from the pre- treatment sample to residual disease, with roughly equal distribution between decreased (50.5%) and increased HER2 expression (49.5%). Similar rates of change in HER2 expression were observed with anthracycline-based (31.8%) or taxane/platinum-based regimens (32.4%). Patients with HER2–0 or HER2-low tumors at diagnosis were likelier to experience a change in HER2 expression post-NAT compared to HER2- positive (32.3% vs. 21.3%, p 0.001). Changes in HER2 expression post-NAT were prognostic among pa- tients with HER2-positive tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 71.6% vs. 89.6%, p = 0.006) but not among those with HER2-negative tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 79.3% vs. 81.1%, p = 0.31). Conclusions: Nearly 30% of patients with early-stage breast cancer showed a change in HER2 expression after NAT. Changes in HER2 expression post-NAT were only prognostic in the setting of HER2-positive tumors becoming HER2-negative at surgery.

Paper 2 Abstract Introduction: There are no known studies comparing the prognosis of HER2-low versus HER2-0 in male breast cancer (MaBC). With this study, we aim to assess the prognosis and distribution of HER2-low versus HER2-0 status in men. Methods: We received and analyzed clinicopathologic data of 73 MaBC patients that received treatment at Dana Farber Cancer Institute (DFCI) from January 2007 to February 2024. 64 of the 73 patients were included in the full cohort analysis. Unadjusted and adjusted Cox models were performed to assess the association of HER2-low and HER2-0 subtypes, with the primary outcome of disease-free survival (DFS). DFS was defined as the period from surgery to disease recurrence or death from any cause, whichever occurred first. Death and recurrences were obtained from a manual chart review of the DFCI Epic database. Spearman’s correlation between DFS and oncotype dx score were done for the entire population and HER2-low status subtype. A stepwise forward and backward selection logistic regression model were performed for oncotype dx score (to assess the risk of recurrence of breast cancer), our secondary outcome of interest. Results: Among the 64 patients that underwent surgery, 58 were included in the primary cohort analysis with 49 patients of HER2-low status, with 4 deaths and 5 recurrences in this group and 9 patients with the HER2-0 subtypes, with 2 deaths and no recurrences. The unadjusted hazard ratio (HR) for DFS was 0.39 (95% CI = 0.07 – 2.05) with a p-value of 0.30. A multivariable adjustment was done, with age and clinical stage adjusted for, and the HR was 0.46 (95% CI = 0.08 – 2.60) and a p-value of 0.70. The prevalence of HER2-low was found to be about 77%. There was no correlation found between DFS and oncotype dx score. Conclusion: From this study, about 77% of men were found to have HER2-low disease which was different from what have been reported in other studies, and there were no factors that were significantly associated with prognosis (DFS) between HER2-low and HER2-0 in males.