Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a subtype of breast cancer in which tumor cells lack expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 protein — the three receptors most commonly used to guide targeted treatment. Approximately 15% of all breast cancers are TNBC. It grows and spreads faster than hormone-receptor-positive subtypes, tends to occur at younger ages, and has historically had fewer targeted treatment options. Recent advances have significantly changed outcomes: immunotherapy with pembrolizumab (Keytruda) added to chemotherapy is now standard for early-stage and PD-L1-positive metastatic TNBC following the KEYNOTE-522 trial results. Antibody-drug conjugates including sacituzumab govitecan (Trodelvy) have improved survival in metastatic disease. Olaparib and talazoparib are options for BRCA-mutated metastatic TNBC.

• New breast lump or thickening in breast or underarm
• Change in breast size, shape, or appearance
• Nipple discharge (other than breastmilk)
• Redness, dimpling, or pitting of breast skin (peau d'orange)
• Inverted or newly retracted nipple
• Lump or swelling in the axillary (armpit) lymph nodes

The American Cancer Society recommends annual mammography beginning at age 40. The USPSTF 2024 updated its recommendation to annual mammography starting at age 40 (previously 50), partly in recognition of earlier-onset disease in Black women. Black women should discuss earlier initiation with their provider given higher TNBC risk and younger average onset. BRCA genetic testing is appropriate for individuals with a family history of breast or ovarian cancer, Ashkenazi Jewish ancestry, any male breast cancer in the family, or a first-degree relative diagnosed with breast cancer before age 50. TNBC diagnosis before age 60 itself is an indication for genetic counseling and testing per NCCN guidelines.

Treatment is guided by stage and biomarker profile. Neoadjuvant chemotherapy (before surgery) is preferred for most early-stage TNBC to assess tumor response and guide adjuvant decisions. Pembrolizumab (Keytruda) is FDA-approved in combination with chemotherapy for high-risk early-stage TNBC (KEYNOTE-522) and for PD-L1-positive metastatic TNBC. Surgery (lumpectomy or mastectomy) follows neoadjuvant therapy. Patients with residual disease after neoadjuvant chemotherapy receive adjuvant capecitabine or olaparib (if BRCA-mutated). Sacituzumab govitecan (Trodelvy) is the preferred antibody-drug conjugate for metastatic TNBC. Olaparib and talazoparib are PARP inhibitors approved for BRCA-mutated metastatic TNBC. Enrollment in clinical trials is strongly encouraged — TNBC-focused trials are active at major academic centers.