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Prognostic Significance of Tumor Subtypes in Women With Breast Cancer According to Stage

A Population-based Study

Leone, José P. MD*; Leone, Julieta MD; Zwenger, Ariel O. MD, PhD†,‡; Vallejo, Carlos T. MD; Leone, Bernardo A. MD

American Journal of Clinical Oncology: July 2019 - Volume 42 - Issue 7 - p 588–595
doi: 10.1097/COC.0000000000000563
Original Articles: Breast

Objectives: The contribution of tumor subtypes (TS) in each stage of breast cancer with the use of contemporary therapies is unclear. The aim of this study was to analyze differences in overall survival (OS) by TS according to stage compared with other factors.

Materials and Methods: We evaluated women with breast cancer diagnosed between 2010 and 2013 with known estrogen receptor and progesterone receptor (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status reported to the SEER program. Patient characteristics were compared between TS. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Breast cancer–specific survival was a secondary endpoint.

Results: We included 166,054 patients. TS distribution was: 72.5% HR-positive/HER2-negative, 10.8% HR-positive/HER2-positive, 4.8% HR-negative/HER2-positive, and 12% triple-negative (TN). Patients with HR-positive/HER2-negative tumors were older, had a lower grade and presented with the earlier stage (all P<0.0001). OS was significantly different according to TS in each stage (Pinteraction<0.0001). HR-positive/HER2-negative had the best OS in stage I (3-year OS, 97.2%). In contrast, HR-positive/HER2-positive had the best 3-year OS in stage II (94.5%), stage III (87.8%), and stage IV (54.8%). There was a 40.1% difference in OS at 3 years in stage IV between TN and HR-positive/HER2-positive. Multivariate analysis adjusted for age, race, grade, histology, and marital status confirmed these results.

Conclusions: Although HR-positive/HER2-negative tumors had better clinicopathologic features, the HR-positive/HER2-positive group had the best OS in most stages. OS was significantly different by TS in each of the 4 stages and these results remained significant in the multivariate model.

*Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Grupo Oncológico Cooperativo del Sur (GOCS)

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Neuquen, Argentina

Presented in part at the 2017 Annual Meeting of the American Society of Clinical Oncology: abstract 1070.

J.P.L. reports that the institution (The University of Iowa) received research funding from Merck. The remaining authors declare no conflicts of interest.

Reprints: José P. Leone, MD, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215. E-mail:

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