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Epidemiology, risk factors and the clinical approach to ER/PR negative, HER2-negative (Triple-negative) breast cancer

Carey K Anders, MD
Lisa A Carey, MD
Section Editor
Daniel F Hayes, MD
Deputy Editor
Sadhna R Vora, MD


Triple-negative breast cancer is a term that has historically been applied to cancers that are low in expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative breast cancer tends to behave more aggressively than other types of breast cancer. Unlike other breast cancer subtypes (ie, ER-positive, HER2-positive subtypes), there are no approved targeted treatments available, other than the administration of chemotherapy. For purposes of this review, we will consider "triple-negative" to mean cancers that have ≤1 percent expression of ER and PR as determined by immunohistochemistry (IHC), and that are either 0-1+ by IHC, or 2+ and fluorescence in situ hybridization (FISH)-negative (not amplified), according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines [1-3]. Although the basic principles of diagnosis and management of triple-negative breast cancer are similar to those of breast cancer in general, many aspects, including risk factors, molecular and pathologic characteristics, natural history, and chemotherapy sensitivity, are unique to triple-negative breast cancer and will be reviewed here.

A more extensive discussion on surgical management, neoadjuvant chemotherapy, adjuvant chemotherapy of nonmetastatic breast cancer, and the treatment of metastatic breast cancer is covered separately.

(See "Overview of the treatment of newly diagnosed, non-metastatic breast cancer".)

(See "Systemic treatment for metastatic breast cancer: General principles".)


Triple-negative breast cancer accounts for approximately 20 percent of breast cancers diagnosed worldwide, which amounts to almost 200,000 cases each year [4]. Triple-negative breast cancer is more commonly diagnosed in women younger than 40 years compared with hormone-positive breast cancer. In one study, there was a twofold higher attributable risk of triple-negative breast cancer in women under 40 years compared with women over 50 years (odds ratio [OR] 2.13, 95% CI 1.34-3.39) [5]. In addition, triple-negative breast cancer appears to be more common among black women compared with white women (OR 2.41, 95% CI 1.81-3.21) [5].

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Literature review current through: Nov 2017. | This topic last updated: Jun 06, 2017.
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