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. 2022 Jul 11;8(1):80.
doi: 10.1038/s41523-022-00448-4.

Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer

Rachel Yoder  1 , Bruce F Kimler  2 , Joshua M Staley  1 , Kelsey Schwensen  3 , Yen Y Wang  1 , Karissa Finke  4 , Anne O'Dea  3 , Lauren Nye  3 , Manana Elia  5 , Gregory Crane  6 , Richard McKittrick  6 , Robert Pluenneke  7 , Sheshadri Madhusudhana  8 , Larry Beck  9 , Anuj Shrestha  10 , Larry Corum  11 , Mark Marsico  12 , Shane R Stecklein  2 , Andrew K Godwin  1   13 , Qamar J Khan  3 , Priyanka Sharma  14
Affiliations

Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer

Rachel Yoder et al. NPJ Breast Cancer. .

Abstract

Triple-negative breast cancer (TNBC) is classically defined by estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry expression <1% and absence of HER2 amplification/overexpression. HER2-negative breast cancer with low ER/PR expression (1-10%) has a gene expression profile similar to TNBC; however, real-world treatment patterns, chemotherapy response, endocrine therapy benefit, and survival outcomes for the Low-ER group are not well known. 516 patients with stage I-III HER2-negative breast cancer and ER/PR expression ≤10% who were enrolled in a multisite prospective registry between 2011 and 2019 were categorized on the basis of ER/PR expression. TNBC (ER and PR < 1%) and Low-ER (ER and/or PR 1-10%) groups comprised 87.4% (n = 451) and 12.6% (n = 65) of patients, respectively. Demographic, clinical, and treatment characteristics, including prevalence of germline BRCA1/2 mutation, racial and ethnic distribution, and chemotherapy use were not different between TNBC and Low-ER groups. No difference was observed in recurrence-free survival (RFS) and overall survival (OS) between TNBC and Low-ER groups (3-year RFS 82.5% versus 82.4%, respectively, p = 0.728; 3-year OS 88.0% versus 83.4%, respectively, p = 0.632). Among 358 patients receiving neoadjuvant chemotherapy, rates of pathologic complete response were similar for TNBC and Low-ER groups (49.2% vs 51.3%, respectively, p = 0.808). The HER2-negative Low-ER group is often excluded from TNBC clinical trials assessing novel treatments (immunotherapy and antibody-drug conjugates), thus limiting efficacy data for newer effective therapies in this group. Given that HER2-negative Low-ER disease displays clinical characteristics and outcomes similar to TNBC, inclusion of this group in TNBC clinical trials is encouraged.

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Conflict of interest statement

The authors declare no competing non-financial interests but the following competing financial interests: Mark Marsico reports salary, employment by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and ownership interest in Merck & Co., Inc., Kenilworth, NJ, USA; Priyanka Sharma reports consulting fees and contract research to the institution from Merck & Co., Kenilworth, NJ, USA Inc. All remaining authors report no potentially competing financial interests.

Figures

Fig. 1
Fig. 1. Survival by ER/PR expression group.
a Recurrence-free survival. b Overall survival.
Fig. 2
Fig. 2. Survival by pathologic response and ER/PR expression group.
a Recurrence-free survival. b Overall survival. RD residual disease.
See this image and copyright information in PMC

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