HER2-Low Status Does Not Affect Survival Outcomes of Patients with Metastatic Breast Cancer (MBC) Undergoing First-Line Treatment with Endocrine Therapy plus Palbociclib: Results of a Multicenter, Retrospective Cohort Study

Abstract

Background: Approximately 45–50% of breast cancers (BCs) have a HER2 immunohistochemical score of 1+ or 2+ with negative in situ hybridization, defining the “HER2-low BC” subtype. No anti-HER2 agents are currently approved for this subgroup in Europe, where treatment is still determined by HR expression status. In this study, we investigated the prognostic significance of HER2-low status in HR+/HER2- metastatic BC (MBC) patients treated with endocrine therapy (ET) plus palbociclib as first line. Methods: We conducted a retrospective study including 252 consecutive HR+/HER2- MBC patients who received first-line ET plus palbociclib at six Italian Oncology Units between March 2016 and June 2021. The chi-square test was used to assess differences in the distribution of clinical and pathological variables between the HER-0 and HER2-low subgroups. Survival outcomes, progression-free survival (PFS) and overall survival (OS), were calculated by the Kaplan–Meier method, and the log-rank test was performed to estimate the differences between the curves. Results: A total of 165 patients were included in the analysis: 94 (57%) and 71 (43%) patients had HER2-0 and HER2-low disease, respectively. The median age at treatment start was 64 years. No correlation between patients and tumor characteristics and HER2 status was found. Median PFS (mPFS) for the entire study cohort was 20 months (95% CI, 18–25 months), while median OS (mOS) was not reached at the time of analysis. No statistically significant differences, in terms of PFS (p = 0.20) and OS (p = 0.1), were observed between HER2-low and HER2-0 subgroups. Conclusions: In our analysis, HR+ MBC patients with low HER2 expression who received first-line treatment with ET plus Palbociclib reported no statistically different survival outcomes compared to HER2-0 patients. Further prospective studies are needed to confirm the clinical role of HER2 expression level.

Can Patients with HER2-Low Breast Cancer Benefit from Anti-HER2 Therapies? A Review

“…The ORR before surgery was 78.3%, but no patient achieved a pathologic complete response. 97 HER2-low status does not affect survival outcomes of patients with MBC, 98 and CDK4/6 inhibitors may play an important role in the treatment of HER2-low BC when combined with HER2-targeted therapies.…”

Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors

“…Patients with HER2-low disease had significantly worse OS when compared to patients with HER2-0 BC (median OS: 48.7 [42.5-NA] vs 58.3 [55. 7-NA] months, p = 0.029) (Fig. 1b).…”

“…In patients with aBC, recent reports did not find an association between HER2 status and patient prognosis 6 – 9 . However, several of these studies were limited by a low number of patients included 7 , 8 , or by the fact that the prognostic role of HER2 status was evaluated in heterogeneous patient cohorts, i.e., in patients with different tumor biology and receiving different types of systemic therapies 6 , 9 . A recent, large study from the MD Anderson Cancer Center did not find an association between HER2 status and clinical outcomes in 919 HR + /HER2- aBC patients treated with first-line ET plus CDK4/6 inhibitors 15 .…”

“…HER2-low BC has been recently proposed as a distinct biological and clinical BC entity 1 . However, preclinical and clinical evidence supporting this notion is still poor, also due to conflicting results of clinical studies published so far [2][3][4][5][6][7][8][9] , and which may in part derive from the fact that the prognostic significance of HER2 status has been evaluated in heterogeneous clinical contexts, including patients with different tumor stages, or treated with different types of therapies.…”

“…The combination of endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is the standard-of-care, first-line therapy for the vast majority of HR + /HER2-negative aBC patients 11 . However, with the exception of a few small studies [3][4][5][6][7][8][9] , the prognostic impact of HER2 status (i.e., low vs. 0) in HR + /HER2-negative aBC patients treated with ET + CDK4/6i remains unclear. Here, we conducted a multicentric study to investigate the association between HER2 status (low vs. 0) and the PFS or OS of HR + /HER2-aBC patients treated with first-line ET + CDK4/6i.…”