Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy
- PMID: 39571402
- DOI: 10.1016/j.ctrv.2024.102852
Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy
Abstract
Neoadjuvant chemoimmunotherapy (NACIT) has been shown to improve pathologic complete response (pCR) rates and survival outcomes in stage II-III triple-negative breast cancer (TNBC). Promising pCR rate improvements have also been documented for selected patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). However, one size does not fit all and predicting which patients will benefit from NACIT remains challenging. Accurate predictions would be useful to minimize immune-related toxicity, which can be severe, irreversible, and potentially impact fertility and quality of life, and to identify patients in need of alternative treatments. This review aims to capitalize on the existing translational and clinical evidence on predictors of treatment response in patients with early-stage BC treated with neoadjuvant chemotherapy (NACT) and NACIT. It summarizes evidence suggesting that NACT/NACIT effectiveness may correlate with pre-treatment tumor characteristics, including mutational profiles, ER expression and signaling, immune cell presence and spatial organization, specific gene signatures, and the levels of proliferating versus quiescent cancer cells. However, the predominantly qualitative and descriptive nature of many studies highlights the challenges in integrating various potential response determinants into a validated, comprehensive, and multimodal predictive model. The potential of novel multi-modal approaches, such as those based on artificial intelligence, to overcome current challenges remains unclear, as these tools are not free from bias and shortcut learning. Despite these limitations, the rapid evolution of these technologies, coupled with further efforts in basic and translational research, holds promise for improving treatment outcome predictions in early HER2- BC.
Keywords: Breast cancer; Estrogen receptor; Immunotherapy; Microenvironment; Neoadjuvant; Neoadjuvant chemoimmunotherapy; Neoadjuvant chemotherapy; Prediction.
Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of competing interest CCo reports travel/accommodations (to scientific meeting) from Veracyte, past support by the IEO-Monzino Foundation (2023), and is supported by Fondazione Gianni Bonadonna (FGB) and Associazione Italiana per la Ricerca contro il Cancro (AIRC) (2024-2026). All the competing interests were outside the submitted work. BBK, BK, TR, FC, LP and SKK have no potential conflicts of interest to disclose. GB reports fees for advisory boards, travel grants, consultancy: Seagen, Eli Lilly, Novartis, Pfizer, Roche, AstraZeneca, MSD, Daiichi Sankyio, Eisai, Gilead, Exact Science, Stemline, Agendia. All the competing interests were outside the submitted work. CCr reports personal fees for consulting, advisory role and speakers’ bureau from Lilly, Roche, Novartis, MSD, Seagen, Gilead and Pfizer. All the competing interests were outside the submitted work. GC reports the following honoraria for speaker's engagement: Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, NanoString, Samsung, Celltrion, BMS, MSD; Honoraria for providing consultancy: Roche, Seattle Genetics, NanoString; Honoraria for participating in Advisory Board: Roche, Lilly, Pfizer, Foundation Medicine, Samsung, Celltrion, Mylan; Honoraria for writing engagement: Novartis, BMS; Honoraria for participation in Ellipsis Scientific Affairs Group; Institutional research funding for conducting phase I and II clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dome, Janssen-Cilag, Philogen, Bayer, Medivation, Medimmune. All the competing interests were outside the submitted work. ACG-C reports research funding (to the Institution) from AstraZeneca, Daiichi-Sankyo, Merck, Gilead Sciences, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica International AB, and Foundation Medicine; and travel/accommodations (to scientific meeting) from Roche/Genentech. AGW institutional research support from Reveal Genomics, Genentech, Macrogenics, and Merck and personal fees from AstraZeneca outside the submitted work. EAM reports service on scientific advisory boards for Astra Zeneca, Exact Sciences, Roche/Genentech, and Merck; steering committee service for BMS, Lilly, and Roche/Genentech; and institutional research support from Roche/Genentech, Gilead, as well as research funding from Susan Komen for the Cure and participation as a member of the American Society of Clinical Oncology board of directors outside the submitted work. SMT reports a consulting or advisory role for Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi-Sankyo, Gilead, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Sumitovant Biopharma, Umoja Biopharma, Artios Pharma, Menarini/Stemline, Aadi Biopharma, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, Systimmune, eFFECTOR, and Hengrui USA; reports institutional research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, NanoString Technologies, Seattle Genetics, and OncoPep, and receives travel support from Eli Lilly, Sanofi, Gilead, and Pfizer. All the competing interests were outside the submitted work.
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