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. 2025 Oct 2;11(1):110.
doi: 10.1038/s41523-025-00816-w.

Predictors of response to neoadjuvant chemo-immunotherapy in metaplastic triple-negative breast cancer

Nour Abuhadra  1 , Fresia Pareja  2 , Charlie White  3 , Yuan Chen  3 , Hannah Wen  2 , Esra Dikoglu  2 , Jinae Park  4 , Stephanie Downs-Canner  5 , Larry Norton  4 , George Plitas  5 , Atif Khan  6 , Sarat Chandarlapaty  4 , Pedram Razavi  4 , Mark Robson  4 , Monica Morrow  5 , Giacomo Montagna  5
Affiliations

Predictors of response to neoadjuvant chemo-immunotherapy in metaplastic triple-negative breast cancer

Nour Abuhadra et al. NPJ Breast Cancer. .

Abstract

Metaplastic breast cancer (MpBC) treated with standard chemotherapy has low rates of complete pathological response (pCR)(2-23%). In this study, we evaluate the response to neoadjuvant chemo-immunotherapy (NACI) in early-stage MpBC. Thirty-two stage I-III MpBC patients treated with NACI (KEYNOTE-522 regimen) were prospectively enrolled in an institutional rare tumor program. All MpBC were triple negative; most were of chondromyxoid/matrix-producing (12/32, 38%). The majority had stage II (78%) tumors, 12/32 (37.5%) patients completed NACI, 11/32 (34%) progressed during NACI, and in the remaining 9, NACI was discontinued due to side effects. The pCR rate in the entire cohort was 22% (7/32) and it was statistically higher (5/8, 62%) among patients with high ( ≥ 60%) stromal tumor-infiltrating lymphocytes (sTILs) as compared to patients with < 60% sTILs (1/11, 9%). Most patients received adjuvant systemic therapy (capecitabine 16/32, pembrolizumab 20/32). At a median follow-up of 13 months, there were a total of 2 local recurrences, 10 distant recurrences, and 7 deaths. We demonstrated a modest pCR rate in MpBC with the addition of pembrolizumab (22%). Nonetheless, amongst patients with high sTILs, high pCR rates-comparable to those in the KEYNOTE-522 trial-were observed. These findings suggest that sTILs can be used to triage MpBC patients for NACI.

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Conflict of interest statement

Competing interests: Nour Abuhadra, abuhadn@mskcc.org: Professional Services and Activities for Boxer Capital, LLC, Medscape, MJH Life Sciences, and OncLive. Fresia Pareja, parejaf@mskcc.org: Membership on the Scientific Advisory Board of MultiplexDx; Consultancy Fees and Membership on the Advisory Board of AstraZeneca; Funding from National Institutes of Health grant No. NIH/NCI P50 CA24779 01 and from a grant from the Starr Cancer Consortium. Stephanie Downs-Canner, downscas@mskcc.org: Funding from National Institutes of Health grant No. NIH/NCI 1 K08 CA259533-01A1. Larry Norton, nortonl@mskcc.org: Founding Editor-in-Chief and Advisory Editor, npj Breast Cancer. Atif Khan, khana7@mskcc.org: Research grants from Merck, Clovis Oncology, and Varian; Patents: Patent awarded for oncology use for the drug riluzole; Stock/Stock Options: Novavax and Xtrava Inc. Sarat Chandarlapaty, chandars@mskcc.org: Editor-in-Chief, npj Breast Cancer; Professional Services and Activities for AstraZeneca, Blueprint Medicines, Casdin Capital, LLC, Daiichi Sankyo, Encore Medical Education. Genesis Therapeutics, Novartis, Prelude Therapeutics, SAGA Diagnostics, and Springer Nature Limited; Uncompensated Professional Services and Activities for Eli Lilly and Company; Equity in Totus Medicines Inc. Pedram Razavi, razavip@mskcc.org: Consultant/Ad Board/Advisor for: Novartis, AstraZeneca, Pfizer, Lilly, Tempus, Prelude Therapeutics, NeoGenomics, Regor Pharmaceuticals, Natera, SAGA Diagnostics, Guardant Health, Myriad, and Foresight Diagnostics; Grant/Research Support: Institutional/grant funding from Grail, Novartis, AstraZeneca, Biothernostics, Tempus, Sophia Genetics, Biovica, Guardant Health, Personalis, Myriad, Foresight Diagnostics, and SAGA Diagnostics. Mark Robson, robsonm@mskcc.org: Professional Services and Activities for Change Healthcare Inc., Clinical Care Options, Genome Quebec, myMedEd, Inc., and WebMD; Uncompensated Professional Services and Activities for Artios Pharma Limited, AstraZeneca, Foundation Medicine, and Pfizer, Inc.All other authors declare no financial or non-financial competing interests.

Figures

Fig. 1
Fig. 1. Overview of clinical course.
(© 2024 Memorial Sloan-Kettering Cancer Center, Memorial Hospital for Cancer and Allied Diseases, and Sloan-Kettering Institute for Cancer Research, each in New York, NY. All rights reserved. Published with permission.) pCR pathologic complete response, RD residual disease, PD progressive disease, DR distant recurrence, LR local recurrence, AC/Pembro doxorubicin and cyclophosphamide, and pembrolizumab, Carbo/Taxol/Pembro carboplatin/ paclitaxel/pembrolizumab.
Fig. 2
Fig. 2. Rate of downstaging to breast-conserving surgery.
NACI neoadjuvant chemo-immunotherapy, BCS breast-conserving surgery.
Fig. 3
Fig. 3. Pathologic complete response by stage at presentation.
(© 2024 Memorial Sloan-Kettering Cancer Center, Memorial Hospital for Cancer and Allied Diseases, and Sloan-Kettering Institute for Cancer Research, each in New York, NY. All rights reserved. Published with permission.) pCR, pathologic complete response, RCB, residual cancer burden.
Fig. 4
Fig. 4. Event-free survival and overall survival Kaplan-Meier curves stratified by type of response to neoadjuvant chemo-immunotherapy.
A Event-free survival in entire cohort; B event-free survival by response; C overall survival in entire cohort; D overall survival by response; and E cumulative incidence of recurrence by response. CI confidence interval, pCR pathologic complete response, RD residual disease.
Fig. 5
Fig. 5. Management of stage I-III metaplastic triple negative breast cancers.
sTILs stromal tumor-infiltrating lymphocytes, MMG mammogram, US ultrasound, PET positron emission tomography, NACI neoadjuvant chemo-immunotherapy, pCR pathologic complete response.
See this image and copyright information in PMC

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