291P - Prognostic implications of HER2 gain in patients with HR+/HER2- breast cancer (BC) and TNBC after neoadjuvant chemotherapy (NAC)

Background

Residual disease (RD) after NAC is a well-established risk factor for recurrence in patients (pts) with triple-negative breast cancer (TNBC) or high-risk hormone receptor-positive (HR+)/ HER2-negative (-) BC. Biologic and prognostic significance of HER2 gain on RD after NAC are unknown. We sought to determine invasive disease-free survival (IDFS) in patients with HER2 gain in a cohort of consecutive patients with HER2(-) BC treated with NAC.

Methods

We identified pts with HER2(-) BC treated with NAC followed by surgery at our institution between 8/2019 and 12/2021. Pathologic complete response [pCR] (ypT0/is ypN0) rates and HER2 status pre- and post-NAC were assessed, the latter by 2018 ASCO/CAP guidelines. HER2-low was defined as IHC 1+ or IHC 2+, FISH non-amplified. IDFS was analyzed using the Kaplan-Meier method and differences assessed by log-rank test. Chi-square, Fisher’s exact, Wilcoxon rank sum test, and logistic regression were used to evalute baseline features associated with HER2 gain. Any p-value less than 0.05 was deemed to be statistically significant.

Results

We included 528 HER2(-) pts [274 (52%) HR+/HER2- and 252 (48%) TNBC]. Overall, pCR was achieved in 40% of TNBC and 9% of HR+/HER2(-). The median follow-up was 17.5 months (14.5-21.3). Among 401 pts with RD, the rate of HER2 gain was 5% (20/401) (Table). HER2-low and HR+ status assessed on initial biopsy were independently associated with HER2 gain on the surgery sample with OR=3.05 (95%CI:1.07-10.9) and OR=4.09 (95%CI: 1.02-27.5), respectively, while high grade was not (OR=0.68; 0.24-1.78). After surgery, all but two pts with HER2 gain received anti-HER2 therapy. The 2-year IDFS rate was 100% in pts with HER2 gain and 85% (95%CI: 81-90%) in pts with HER2(-) RD (p=0.07).

Conclusions

HER2 gain after NAC was a rare event, more commonly occurring in pts with HR+/HER2(-) BC compared to TNBC, likely related to HER2 heterogeneity. Optimal adjuvant regimen remains to be established. Table: 291P

Details of patients with HER2 gain

F: FISH test; CN: copy number; V: vinorelbine; T: paclitaxel.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Modi: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Genentech, AstraZeneda, Seagen, Macrogenics; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Daiichi Sankyo; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Genentech, AstraZeneca, Seagen. A. Seidman: Financial Interests, Personal, Other: Fairmont Founds Management, Hackensack Univerisity , MJH Associates, Novartis, Parexel International , myMEDEd, Spectrum Pharmaceuticals , Ortley BIO LCC, Stemline, Affinia Therapeutics, Cancer Expert Now, Merck, Envision Communications; Financial Interests, Personal and Institutional, Other: AstraZeneca, Eli Lilly, Genentech, Gilead, Pfizer. H. Wen: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Speaker’s Bureau: Roche. M. Robson: Financial Interests, Personal, Other, Review guideline pathways: Change Healthcare; Financial Interests, Personal, Invited Speaker, Speaker at CME events (NOT speaker's bureau): Physician's Education Resource, MJH Holdings; Financial Interests, Personal, Advisory Board, Speaker at CME events (NOT speaker's bureau): MyMedEd; Financial Interests, Personal, Invited Speaker, Speaker at CME events (not Speakers' bureau): Clinical care Options; Financial Interests, Institutional, Local PI, Funding for research study (ICEBERG, dating to 2007): AstraZeneca; Financial Interests, Personal, Steering Committee Member, Steering Committee Member for CAPITELLO-290, uncompensated: AstraZeneca; Financial Interests, Institutional, Other, Co-PI for Merck IIT of neoadjuvant olaparib/pembrolizumab in BRCA carriers, no personal compensation: Merck; Financial Interests, Personal, Steering Committee Member, Steering Committee member for KEYLNK-009, no compensation: Merck; Financial Interests, Institutional, Local PI, Local PI of KEYLNK009: Merck; Financial Interests, Institutional, Other, Local co-PI of clinical trial of ZEN03694 and talazoparib in TNBC, no personal compensation: Pfizer; Non-Financial Interests, Advisory Role: Zenith Pharmaceuticals, Tempus Labs; Non-Financial Interests, Personal, Other, Editorial services for writing of reports for ABRAZO clinical trial: Pfizer; Non-Financial Interests, Personal, Other, Editorial services for medical writing of reports resulting from OlympiAD trial: AstraZeneca; Non-Financial Interests, Member: ASCO. C. Dang: Financial Interests, Personal and Institutional, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Gilead, Novartis, Pfizer, SeaGen. All other authors have declared no conflicts of interest.