Therapeutic strategies for metaplastic breast cancer: A clinicopathologic analysis of a single institution cohort.

Abstract

e13128 Background: Metaplastic breast cancer (MpBC) is a rare, aggressive, and histologically diverse subtype, which is associated with worse survival outcomes than other triple-negative breast cancers. Methods: This study is a single-institution retrospective analysis of 30 patients with MpBC, focused on response to therapies in the context of histologic subtype, molecular alterations, and PD-L1 expression. Patients with MpBC who received treatment at our institution consented to share clinical information with a research biorepository. Clinicopathologic and next generation sequencing (NGS) data were obtained from patients’ electronic health records. The primary outcomes are overall survival (OS) and event-free survival (EFS), and the secondary outcomes are responses to neoadjuvant therapy, tumor growth on taxane and/or anthracycline, and responses to systemic therapy in the relapsed/metastatic setting. Results: Among the 30 MpBC patients, the median age at diagnosis was 47.5 years. 86.7% were diagnosed with early-stage disease, 36.7% with squamous cell MpBC, 93.3% with triple-negative disease, and 30% with HER2-low disease. Of the patients diagnosed with early-stage disease, 88.5% received neoadjuvant systemic therapy, 96.2% underwent breast surgery, 92.3% received definitive/adjuvant radiation, and 76.9% received adjuvant systemic therapy. 61.5% of patients with localized disease experienced local and/or distant relapse. Median EFS was 14.0 months (95% CI, 10 to 20 months). Median OS was 26.5 months (95% CI, 20 to 32 months). There was no clearly superior neoadjuvant regimen based on MpBC subtype, but more patients with squamous MpBC experienced tumor growth on taxane-containing therapy compared to those with growth on anthracycline-containing regimens. In the relapsed/metastatic setting, patients with squamous cell MpBC and somatic mutations in the PI3K/Akt/mTOR pathway had prolonged partial responses to combination treatment with an anthracycline, mTOR inhibitor, and VEGF inhibitor. Median treatment duration with sacituzumab govitecan in the 1st or 2nd line metastatic setting was 1.5 months (95% CI, 1 to 4 months) before disease progression. Low tumor mutational burden was seen across all MpBC subtypes (median 2.1, 95% CI 1.6-4.0). 75% of the cases were PD-L1 positive by Immune Cell expression. There was no clear association between PD-L1 expression and response to immunotherapy-containing treatments in the neoadjuvant or relapsed/metastatic setting. Conclusions: Our findings on the presentation of MpBC correlate with other clinicopathologic studies. For squamous MpBC, we noted trends on the utility of anthracycline-containing regimens. Chemoimmunotherapy and antibody-drug conjugates have changed management of triple-negative and HER2-low breast cancer, but more prospective data are needed to determine the optimal therapeutic strategies for MpBC.