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Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer.
Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2): hormone receptor positive/ERBB2 negative (70% of patients), ERBB2 positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer–specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive and ERBB2 positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor–positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients with ERBB2-positive tumors receive ERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performed. Increasingly, some systemic therapy is delivered before surgery. Tailoring postoperative treatment based on preoperative treatment response is under investigation. Metastatic breast cancer is treated according to subtype, with goals of prolonging life and palliating symptoms. Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for the other 2 subtypes.
Conclusions and Relevance
Breast cancer consists of 3 major tumor subtypes categorized according to estrogen or progesterone receptor expression and ERBB2 gene amplification. The 3 subtypes have distinct risk profiles and treatment strategies. Optimal therapy for each patient depends on tumor subtype, anatomic cancer stage, and patient preferences.
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Corresponding Author: Eric P. Winer, MD, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215 (email@example.com).
Accepted for Publication: December 10, 2018.
Author Contributions: Drs Waks and Winer had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Both authors.
Acquisition, analysis, or interpretation of data: Waks.
Drafting of the manuscript: Both authors.
Critical revision of the manuscript for important intellectual content: Both authors.
Administrative, technical, or material support: Both authors.
Supervision: Both authors.
Conflict of Interest Disclosures: Dr Winer reported personal fees from Genentech, Roche, Lilly, Tessaro, GlaxoSmithKline, Leap Pharmaceuticals, Carrick Therapeutics, and Jounce Pharmaceuticals and stock options from Verastem outside the submitted work. No other disclosures were reported.
Additional Contributions: We gratefully acknowledge Jennifer Bellon, MD (Dana-Farber Cancer Institute, Boston, Massachusetts), and Tari King, MD (Brigham and Women’s Hospital, Boston, Massachusetts), for their assistance in reviewing portions of this manuscript. They did not receive compensation for their contributions.
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