Triple-negative breast cancer is a subtype of breast cancer where cancer cells do not contain estrogen receptors or progesterone receptors, and HER2 receptors are also absent or present at low levels. Triple-negative breast cancer accounts for roughly 15% of all breast cancer cases and can be somewhat more aggressive than hormone-positive or HER2-positive breast cancer.
Who is most at risk for triple-negative breast cancer?
While triple-negative breast cancer can affect anyone, it is more common in younger women and Black women. Triple-negative breast cancer may also be associated with having an inherited mutation in the BRCA1 or BRCA2 gene.
How is triple-negative breast cancer diagnosed?
The status of breast cancer cells is typically determined through a biopsy. The breast tissue sample is sent to a pathologist to determine the presence and levels of hormone receptors and HER2 receptors. If hormone receptors are not present and HER2 receptors are not present or low, then the cancer is triple-negative.
In some cases of triple-negative breast cancer, cancer cells express some degree of HER2 though at a level too low to be considered HER2-positive; these tumors are called HER2-low. About 40% of triple-negative breast cancers are HER2-low.
Additional tests identify biomarkers that help guide treatment:
- PD-L1: An immunohistochemistry test determines if a tumor is PD-L1-positive and could respond to treatment with immunotherapy. About 35%-40% of patients with metastatic TNBC are PD-L1 positive.
- Tumor genetic testing: Next-generation sequencing of tumor cells identifies the number and type of mutations in cancer cells, which can guide treatment selection or point to clinical trial options.
- Germline genetic testing: Germline sequencing can determine if inherited mutations, such as in the BRCA1 or BRCA2 gene, are present.
How is triple-negative breast cancer treated?
Because triple-negative cancer cells lack estrogen and progesterone receptors, and do not contain sufficient levels of the HER2 protein, hormonal therapy, and HER2-targeted treatments such as trastuzumab are not effective.
Several therapies for patients with triple-negative breast cancer have been approved as standard therapies in recent years. The options vary depending on the stage of the cancer and biomarker test results.
Approved therapies include:
- Combination immunotherapy plus chemotherapy. The immunotherapy drug pembrolizumab in combination with chemotherapy has improved outcomes for patients with triple-negative breast cancer in clinical trials.
- This combination therapy is approved as preoperative treatment for patients with early-stage (stage II or III) triple-negative breast cancer, and as a first-line option for patients with metastatic (stage IV) triple-negative breast cancer whose tumor is PD-L1-positive.
- Immunotherapy with pembrolizumab may also be used in patients with breast cancers that have rare features that can be identified using next-generation tumor sequencing, such as having a high number of mutations or microsatellite instability.
- PARP inhibitors: PARP inhibitors are targeted drugs that prevent cancer cells from repairing themselves and encourage cancer cell death.
- The PARP inhibitors olaparib or talazoparib are approved as treatment for patients with metastatic triple-negative breast cancer who have an inherited BRCA1 or BRCA2 mutation.
- Olaparib is also approved as therapy given after completion of local therapy (e.g., surgery, radiation) and chemotherapy (called adjuvant therapy) in patients with high-risk early-stage triple-negative breast cancer who carry an inherited BRCA1 or BRCA2 mutation.
- Antibody-drug conjugates: Antibody-drug conjugates (ADCs) are a promising new direction for triple-negative breast cancer treatment. They are designed to deliver high doses of chemotherapy selectively into cancer cells via specific targets.
- Two ADCs have been FDA-approved for the treatment of metastatic triple-negative breast cancer (after at least one prior chemotherapy for metastatic disease):
- Sacituzumab govitecan targets a protein called TROP2, which is often overexpressed in triple-negative breast cancer.
- Trastuzumab deruxtecan targets HER2 and is approved for HER2-low cancers.
How can I participate in triple-negative breast cancer research?
Several ongoing clinical trials at the Susan F. Smith Center for Women’s Cancers at Dana-Farber are studying new options for patients with triple-negative breast cancer. Studies include investigations of:
- Novel targeted therapies alone and in combination with other treatments.
- Antibody-drug conjugates in early-stage cancers, as first-line therapy for metastatic disease, and in combination with other therapies.
- Novel immunotherapy combinations and approaches, including vaccines.
In addition, Dana-Farber has developed a triple-negative breast cancer registry, which is a biorepository or collection of samples and data from patients with newly diagnosed triple-negative breast cancer. The registry contains data from over 200 patients who are receiving care from member facilities across the Dana-Farber Cancer Care Collaborative.
The registry creates a comprehensive platform that researchers can use to look for important new biomarkers and answer outstanding questions. Samples include tumor tissue, blood, and stool samples, clinical data, and survey data. The registry enables researchers to discover potentially important biomarkers and to explore new avenues of research, such as the role of the microbiome in the disease. Many studies using the registry are underway.
Other breast cancer subtypes:
- What Is Hormone Therapy?
- How Does Alcohol Cause Cancer?
- Voices Podcast – Episode #1: Breast Cancer ‘SoulMates’
- What Is Lobular Breast Cancer?
Learn more about triple-negative breast cancer research and treatment at the Susan F. Smith Center for Women’s Cancers at Dana-Farber.
About the Medical Reviewer
Dr. Garrido-Castro is a medical oncologist specialized in breast cancer at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School. Since joining the Breast Oncology Center at Dana-Farber in 2016, Dr. Garrido-Castro has established an active clinical practice and research efforts focused on the development of novel therapies to improve outcomes in patients with breast cancer. Dr. Garrido-Castro is Co-Director of the Triple-Negative Breast Cancer (TNBC) Working Group at Dana-Farber and leads clinical trials studying immunotherapy and targeted therapy approaches for patients with breast cancer.