Abstract PO5-01-03: Neoadjuvant HER2-targeted regimens with or without anthracyclines for HER2-positive inflammatory breast cancer (IBC): a multicenter retrospective study
Authors: Iwase Toshiaki , Nithya Sridhar , Kai Megumi , Willey Jie , Dong Wenli , Shen Yu , Krishnamurthy Savitri , Lucci Anthony , Le-Petross H. T. Carisa , Nasrazadani Azadeh , Saleem Sadia , Layman Rachel , Valero Vicente , Tripathy Debu , Woodward Wendy , Cheng Yee Chung , Nakhlis Faina , Bellon Jennifer , Lynce Filipa , Ueno Naoto 
Published: May 2024

Background Previous randomized clinical trials have shown no significant benefit with the addition of anthracyclines to neoadjuvant treatment for HER2-positive breast cancer. However, these studies did not focus on inflammatory breast cancer (IBC), or a small minority of patients on these trials. The study aims to compare pathologic complete response rates with and without anthracyclines in HER2-positive IBC. Methods We reviewed patients diagnosed with Stage III HER2-positive IBC who underwent neoadjuvant therapy and modified radical mastectomy at MD Anderson Cancer Center and Dana-Farber Cancer Institute between 2014 and 2021. Patients received either docetaxel/trastuzumab/pertuzumab-doxorubicin/cyclophosphamide (THP-AC) or docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP). The primary outcome was pathologic complete response (pCR) rate, defined as ypTisT0/N0. Secondary outcomes included 2-year event-free survival (EFS) and overall survival (OS). Univariate and multivariable analyses were performed with adjustments for clinically relevant covariates. Results Ninety-nine patients were included in the analysis. Thirty-nine patients received TCHP and 60 received THP-AC. The median follow-up time was 3.02 years. Three patients had disease progression during neoadjuvant therapy. pCR rates did not differ between the two regimens (48.7% TCHP vs. 51.7% THP-AC; p = 0.774). Patient’s baseline characteristics did not significantly affect the pCR rate, except for age. A multivariable logistic regression model adjusted for age and estrogen receptor (ER) status did not show a significant association between pCR and regimen (odds ratio 1.232, 95% CI 0.537–2.829 for THP-AC vs. TCHP, p = 0.623). The 2-year EFS rates for TCHP and THP-AC were 57% and 74%, respectively. In univariate analysis, patients who received THP-AC had better EFS than patients who received TCHP (hazard ratio [HR] 0.423, 95% CI 0.214–0.835, p = 0.013). The EFS benefit of THP-AC remained statistically significant after adjusting for age and type of adjuvant therapy in the final reduced multivariable Cox model (HR 0.441, 95% CI 0.220–0.882, p = 0.021). Univariate analysis did not show a significant association between EFS and other baseline covariates (body mass index, race, N and M category, nuclear grade, ER status, and HER2-targeted therapy). OS did not differ between the THP-AC and TCHP groups (HR 0.419, 95% CI 0.122–1.440, p = 0.167). Conclusions The present analysis revealed that a non–anthracycline-containing regimen in HER2-positive IBC patients had no significant difference in pCR rates but was associated with lower 2-year EFS when compared to an anthracycline-containing regimen. However, OS was similar. Limitations of the study include a small sample size, lack of temporal analysis, and retrospective design with its possible selection bias. Further investigation of the optimal neoadjuvant regimen for patients with HER2-positive IBC is warranted.

Citation Format: Toshiaki Iwase, Sridhar Nithya, Megumi Kai, Jie Willey, Wenli Dong, Yu Shen, Savitri Krishnamurthy, Anthony Lucci, H. T. Carisa Le-Petross, Azadeh Nasrazadani, Sadia Saleem, Rachel Layman, Vicente Valero, Debu Tripathy, Wendy Woodward, Yee Chung Cheng, Faina Nakhlis, Jennifer Bellon, Filipa Lynce, Naoto Ueno. Neoadjuvant HER2-targeted regimens with or without anthracyclines for HER2-positive inflammatory breast cancer (IBC): a multicenter retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-03.