HER2 status and response to neoadjuvant anti-HER2 treatment among patients with breast cancer and Li-Fraumeni syndrome.

BACKGROUND

Breast cancer (BC) is the most common cancer among females with Li-Fraumeni syndrome (LFS), but available data on LFS-related BC characteristics are derived from small retrospective cohorts. Prior work has demonstrated a high proportion of HER2-positive BCs, but our understanding of how HER2-positive LFS BCs respond to anti-HER2 treatments is limited.

METHODS

BCs diagnosed in patients with germline TP53 variants between 2002-2022 were assembled from three institutions. Hormone receptor (HR) and HER2 expression were retrieved from pathology records. Pathologic complete response (pCR) was defined as ypT0/is ypN0.

RESULTS

A total of 264 BCs were identified among 232 patients with LFS: 211 (79.9 %) were invasive carcinomas, of which 106 were HER2-positive. Among HER2-positive BCs, most tumors co-expressed HRs (72.6 %) and were more frequent among those diagnosed at younger age (p < 0.001). Mastectomy was the preferred surgical approach among women with nonmetastatic cancers (77.8 %) and most received anti-HER2 targeted therapy (74.7 %). Among 38 patients receiving neoadjuvant therapy with available post-treatment pathology reports, 27 (71.1 %) achieved pCR: 18/26 (69.2 %) among HR-positive and 7/10 (70.0 %) HR-negative. The rate of pCR was 84.6 % among patients treated with an anthracycline-free regimen (all received trastuzumab). Among classifiable HER2-negative BCs (n = 77), 31 (40.3 %) were HER2-low and 46 (59.7 %) HER2-zero.

CONCLUSIONS

Among females with LFS and BC, HER2-positive subtype was associated with younger age at diagnosis and a predominant HR-positivity. Favorable pCR rates were observed among those receiving neoadjuvant HER2-directed therapies, for both HR-positive and negative tumors. These data may inform the counseling and care of patients with LFS.

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest BV reports consultant fees from Lilly (to the institution), Pfizer (to my institution), netcancer, Pierre Fabre, Seagen, Daichii Sankyo (to the institution), Gilead, Novartis (to the institution), MSD (to my institution), AstraZeneca (to the institution), Owkins (to the institution), travel expenses from Lilly, Novartis, Pfizer, Accord Healthcare, Amgen, AstraZeneca, Daichii Sankyo; MIA reports speaker fees from Pfizer, Daichii Sankyo, MSD (to the institution), AZ (to the institution); VG reports personal fees for advisory board membership for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, Pierre Fabre; personal fees as an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Novartis, Roche and Zentiva; personal fees for expert testimony for Eli Lilly; FA reports research grants from AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis and serving as a compensated speaker/advisory board (to the hospital) for AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, relay therapeutics, advisory board compensated to the author for Lilly; JEG reports research collaboration with Ambry Genetics and Invitae (no compensation). The remaining authors have no conflicts of interest to report.