Triple-negative breast cancer (TNBC) is a rare, heterogeneous phenotype of breast cancer whose clinical features include high invasiveness, high metastatic potential, proneness to relapse, and poor prognosis. TNBC accounts for approximately 15-20% of all breast cancer cases diagnosed in the US. It is more common in women under 40 years old than other types of breast cancer. The average age of a TNBC diagnosis is 54, compared to 60 for other breast cancers. Black women are nearly twice as likely to be diagnosed with TNBC than white women.
While the exact cause of TNBC is not known, many cases may be linked to a mutation in a BRCA gene. BRCA 1 and BRCA 2 are genes that help prevent cancer by repairing DNA and keeping cells from growing too fast. When a BRCA gene is damaged or changed, it can lead to the uncontrolled growth of tumors, including breast cancer tumors. While BRCA gene mutations are rare—only 0.25% of the population carries a BRCA gene mutation—about 10-15% of women with TNBC test positive for a BRCA1 mutation, indicating that this mutation may be linked to TNBC in some cases.
TNBC is different from other types of breast cancer because its tumor cells do not contain the three most common receptors known to fuel breast cancer growth: the breast cancer cells test negative for estrogen receptors (ER-), progesterone receptors (PR-), and hormone epidermal growth factor receptor 2 (HER2-). Because TNBC tumors lack ER, PR, and HER2 expression, they are not sensitive to endocrine therapy or HER2 treatment, and standardized TNBC treatment regimens are still lacking. To date, traditional treatments like surgery, chemotherapy and radiation therapy must be used. New therapeutics such as immunotherapy, targeted agents, and antibody-drug conjugates (ADCs) in first-line and subsequent-line settings are now available.
New research findings with an experimental vaccine could offer fresh hope to women diagnosed with TNBC. (1) The clinical trial involved 18 patients with localized TNBC. All had undergone chemotherapy, followed by surgery to remove their breast tumors which were then analyzed to find the unique genetic mutations in their cancer cells. The research team then crafted a personalized cancer vaccine for each patient, based on those mutations. Each patient received three doses of the vaccine, which taught their immune systems to recognize the key mutations in their specific breast tumors and attack the cancer cells. Results showed that 14 out of the 18 TNBC patients developed an immune response to the vaccine. 16 of the 18 patients remained cancer-free three years after receiving the vaccine, which taught their immune systems to kill off any remaining cancer cells. By comparison, only half of patients who received surgery alone remained cancer-free after three years, according to historical data. “These results were better than we expected,” said senior researcher Dr. William Gillanders, a professor of surgery at Washington University School of Medicine in St. Louis.
“We are excited about the promise of these neo-antigen vaccines,” Gillanders added. Larger clinical trials will be needed to prove the vaccine’s effectiveness.
