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Improved systemic therapy goal for triple-negative breast cancer
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Triple-negative breast cancer represents 15% of all breast cancer that carries a relatively poor prognosis. There are about 25,000 to 30,000 cases per year in the United States, but it is responsible for a disproportionate number of deaths, according to Lisa A. Carey, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill.
“When we talk about triple-negative breast cancer, we are mostly talking about the basal-like molecular subtype,” Carey said during her presentation at the 28th Annual Miami Breast Cancer Conference. “Approximately 75% of triple-negative breast cancers are basal-like breast cancer, a subgroup that has unique biology and that is determined by gene expression profiling.”
Although triple-negative breast cancers behave aggressively and typically are associated with early relapse, it is unlikely to occur 8 or more years after diagnosis. Adjuvant chemotherapy is usually effective and is the standard of care for triple-negative breast cancers. In studies of patients with triple-negative breast cancer who received neoadjuvant chemotherapy, patients who had a pathologic complete response had a good prognosis.
“Given the risk of relapse despite modern chemotherapy, a great deal of research interest centers on improved systemic therapy,” Carey said.
One treatment option being studied is the addition of bevacizumab (Avastin, Genentech) to paclitaxel. In a randomized, phase 3 trial in patients with stage IV breast cancer, a subset of patients with triple-negative breast cancer had a PFS of 11.4 months when given paclitaxel plus bevacizumab vs. 6.11 months with paclitaxel alone.
Currently, there are ongoing studies that are examining the role of epidermal growth factor receptor inhibitors, Src kinase inhibitors and mammalian target of rapamycin inhibitors. However, the most exciting agents under investigation, according to Carey, are poly (ADP-ribose) polymerase (PARP) inhibitors. The PARP inhibitor iniparib (BiPar Sciences) significantly improved response rate, PFS and OS when added to gemcitabine (Gemzar, Lilly) and carboplatin in a randomized, phase 2 trial.
Another PARP inhibitor, olaparib (AstraZeneca), has shown promise in patients with triple-negative breast cancer who have BRCA1 or BRCA2 mutations. The overall response rate was 41% in patients who received 400 mg of olaparib twice a day.
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