Abstract PO3-03-11: Receptor discordance after neoadjuvant chemotherapy with pembrolizumab in early-stage triple-negative breast cancer
Authors: LeVee Alexis , Wong Megan , Flores Sarah , Ruel Nora , McArthur Heather , Waisman James , Mortimer Joanne 
Published: May 2024

Background: Discordance in hormone receptor (HR) and/or HER2 status between matched primary tumors and residual specimens following neoadjuvant therapy is a known phenomenon. In the neoadjuvant setting, systemic treatment is primarily informed by the HR and HER2 status from the diagnostic biopsy. Current guidelines recommend additional adjuvant capecitabine and/or pembrolizumab and/or olaparib for patients with triple-negative breast cancer (TNBC) after neoadjuvant systemic therapy if residual disease is present at the time of surgery. Discordance in biomarker status between the initial diagnosis and residual cancer may impact postoperative systemic therapy recommendations. This study aims to investigate the discordance rate in HR and HER2 status after neoadjuvant chemotherapy (NAC) plus pembrolizumab in early-stage TNBC. Furthermore, given the emerging data in support of novel antibody-drug conjugates (ADCs) for HER2-low breast cancer, the prevalence of HER2-low disease following standard-of-care neoadjuvant therapy may have critical clinical importance.

Methods: We performed a single-institution, retrospective study of early-stage TNBC patients diagnosed between February 1st, 2020 and December 1st, 2022 who were treated with neoadjuvant chemotherapy and pembrolizumab. Patients who had not undergone definitive surgery were excluded. Demographic information, clinical and pathologic characteristics, and treatment data were collected from an institutional database. Pathologic complete response (pCR) was defined as ypT0/Tis and ypN0. HR and HER2 status before and after neoadjuvant therapy were collected. This study was approved by an Institutional Review Board.

Results: Among the 94 patients included the median age was 55 years (IQR 47.0-61.8). The majority of patients had invasive ductal carcinomas (90.4%), were clinical T2 stage (68.1%), and node negative (55.3%). On the core tumor biopsy, estrogen receptor (ER) was &lt; 1% in 90 (95.7%) patients and 1-10% in 4 (4.3%) of patients. Progesterone receptor (PR) was &lt; 1% in 91 (96.8%) of patients and 1-10% in 3 (3.2%) of patients. HER2 was 0 by IHC in 49 (52.1%) patients, 1+ in 30 (31.9%) patients, 2+ in 11 (11.7%) patients, and not performed in 4 (4.3%) patients. A pCR (ypT0/Tis ypN0) was achieved in 60 (63.8%) of the 94 patients. In the 34 patients with residual disease, 29 patients had ER status evaluated at the time of surgery. Of these patients, 4 had tumors with ER &lt; 1% at baseline but &gt;5% at surgery. 28 patients with residual disease had PR evaluated at the time of surgery. Of these patients, all had tumors with PR &lt; 1% at the time of surgery. 28 patients had residual tumors with HER2 status evaluated at the time of surgery (table). Of these patients, 18 (64.3%) tumor specimens were HER2-ultra-low, 9 (32.1%) were HER2-low-positive, and 1 (3.6%) was HER2-positive.

Conclusion: Receptor discordance from the time of initial biopsy to residual disease can occur in patients with early-stage TNBC treated with NAC with pembro. As additional systemic therapy is indicated in patients who do not achieve pCR, accurate tumor marker status is critical. This study highlights the potential impact of reassessment of HR and HER2 status on the surgical tumor specimen. Clinical trials that tailor adjuvant therapy recommendations based on residual biomarker analyses may further improve outcomes for women with high risk TNBC.

Table. Discordance in HER2 Status Between Primary Tumor and Residual Specimen

Citation Format: Alexis LeVee, Megan Wong, Sarah Flores, Nora Ruel, Heather McArthur, James Waisman, Joanne Mortimer. Receptor discordance after neoadjuvant chemotherapy with pembrolizumab in early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-11.