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Multicenter Study
. 2025 Nov;214(1):69-77.
doi: 10.1007/s10549-025-07795-3. Epub 2025 Aug 2.

Neoadjuvant HER2-targeted regimens with or without anthracyclines for HER2-positive inflammatory breast cancer: a multicenter retrospective study

Toshiaki Iwase  1   2   3 , Nithya Sridhar  1 , Megumi Kai  1   2 , Wenli Dong  4 , Yu Shen  4 , Savitri Krishnamurthy  5   2 , Anthony Lucci  6   2 , H T Carisa Le-Petross  7   2 , Azadeh Nasrazadani  1   2 , Sadia Saleem  1   2 , Rachel M Layman  1   2 , Vincente Valero  1   2 , Debasish Tripathy  1 , Wendy A Woodward  8   2 , Yee Chung Cheng  9 , Faina Nakhlis  10 , Jenifer R Bellon  11 , Filipa Lynce  12 , Naoto T Ueno  13   14   15
Affiliations
Multicenter Study

Neoadjuvant HER2-targeted regimens with or without anthracyclines for HER2-positive inflammatory breast cancer: a multicenter retrospective study

Toshiaki Iwase et al. Breast Cancer Res Treat. 2025 Nov.

Abstract

Purpose: Randomized clinical trials have shown no benefit from adding anthracyclines to neoadjuvant treatment for HER2-positive breast cancer; however, the efficacy in inflammatory breast cancer (IBC) is unknown. Here we compared pathologic response rates for preoperative regimens with or without anthracyclines in HER2-positive primary IBC.

Methods: We retrospectively reviewed patients diagnosed with HER2-positive primary IBC in 2014-2021 who received neoadjuvant therapy and modified radical mastectomy at MD Anderson Cancer Center, IBC Network institutions and Dana-Farber Cancer Institute. The primary outcome was a pathological complete response (pCR) rate. Secondary outcomes included time to local or regional recurrence (TLRR), event-free survival (EFS), and overall survival (OS). Univariate and multivariable analyses were performed with adjustments for clinically relevant covariates.

Results: Of the 101 patients included, 39 received docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and 62 (docetaxel, trastuzumab, pertuzumab, doxorubicin, and cyclophosphamide) received THP-AC regimen. Median follow-up time was 3.02 years. The pCR rates did not differ by regimen type (48.7% TCHP vs. 53.2% THP-AC, p = 0.659). Multivariable logistic regression adjusted for age and estrogen receptor positivity showed no association between pCR or regimen. The multivariable Cox model showed that the patients who received THP-AC had longer TLRR (hazard ratio [HR] 0.279, 95% CI 0.102-0.765, p = 0.0131) and EFS (HR 0.462, 95% CI 0.228-0.936, p = 0.032), with no difference in OS.

Conclusion: These findings indicate that an anthracycline-containing neoadjuvant regimen is not associated with pCR, but may prolong disease control in patients with HER2-positive IBC. Further investigation of the optimal neoadjuvant regimen for such tumors is warranted.

Keywords: Anthracyclines; Inflammatory breast neoplasms; Neoadjuvant therapy; Pertuzumab.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The institutional review boards at The University of Texas MD Anderson Cancer Center and Dana-Farber Cancer Institute approved this study. Consent to participate: Patients’ Consent for study participation was waived owing to the anonymized retrospective nature of the study design. Consent for publication: The MD Anderson IRB waived the consent for publishing due to the nature of the anonymized retrospective study design.

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