Molecular Characterization and Prospective Evaluation of Pathologic Response and Outcomes with Neoadjuvant Therapy in Metaplastic Triple-Negative Breast Cancer
Year: 2022
Type: article
Abstract: PURPOSE: Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies. EXPERIMENTAL DESIGN: To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide-based neoadjuvant therapy. RESULTS: Although not meeting the threshold for statistical significance, patients with MpBCs were less likely to experience a pCR (23% vs. 40%; P = 0.07), had shorter event-free survival (29.4 vs. 32.2 months, P = 0.15), metastasis-free survival (30.3 vs. 32.4 months, P = 0.22); and overall survival (32.6 vs. 34.3 months, P = 0.21). This heterogeneity is mirrored in the molecular profiling. Mutations in PI3KCA (23% vs. 9%, P = 0.07) and its pathway (41% vs. 18%, P = 0.02) were frequently observed and enriched in MpBCs. The gene expression profiles of each histologically defined subtype were distinguishable and characterized by distinctive gene signatures. Among nonmetaplastic (non-Mp) TNBCs, 10% possessed a metaplastic-like gene expression signature and had pCR rates and survival outcomes similar to MpBC. CONCLUSIONS: Further investigations will determine if metaplastic-like tumors should be treated more similarly to MpBC in the clinic. The 23% pCR rate in this study suggests that patients with MpBC should be considered for NAT. To improve this rate, a pathway analysis predicted enrichment of histone deacetylase (HDAC) and RTK/MAPK pathways in MpBC, which may serve as new targetable vulnerabilities.
Source: Clinical Cancer Research
Authors: Clinton Yam, Nour Abuhadra, Ryan Sun, Beatriz E. Adrada, Qing-Qing Ding, Jason B. White, Elizabeth E. Ravenberg, Alyson R. Clayborn, Vicente Valero, Debu Tripathy, Senthilkumar Damodaran, Banu K. Arun, Jennifer K. Litton, Naoto T. Ueno, Rashmi K. Murthy, Bora Lim, Luis Baez, Xiaoxian Li, Aman U. Buzdar, Gabriel N. Hortobagyi, Alistair M. Thompson, Elizabeth A. Mittendorf, Gaiane M. Rauch, Rosalind P. Candelaria, Lei Huo, Stacy L. Moulder, Jeffrey T. Chang
Institutions: The University of Texas MD Anderson Cancer Center, Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, University of Puerto Rico System, Emory University Hospital, Winship Cancer Institute, Brigham and Women's Hospital, Dana-Farber Brigham Cancer Center, The University of Texas Health Science Center at Houston
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Awards: G111615301, G1468253849, A Randomized Clinical Trial Platform with Translational Studies to Overcome Resistance in Triple Negative Breast Cancer, G1805754571, G1901027039, G2518634775, G293715275, Data Science and Informatics Core for Cancer Research, G3899724811, G4276892241, G6736661663, G788993117, G9000034222, G9000318222
OpenAlex ID: W4225422652