Triple-negative breast cancer (TNBC) is defined as the absence of staining for estrogen receptor, progesterone receptor, and HER2/neu. TNBC is insensitive to some of the most effective therapies available for breast cancer treatment including HER2-directed therapy such as trastuzumab and endocrine therapies such as tamoxifen or the aromatase inhibitors. Combination cytotoxic chemotherapy administered in a dose-dense or metronomic schedule remains the standard therapy for early-stage TNBC. A prospective analysis of 1,118 patients who received neoadjuvant chemotherapy at a single institution, of whom 255 (23%) had TNBC, found that patients with TNBC had higher pathologic complete response (pCR) rates compared with non-TNBC patients (22% vs. 11%; P = 0.034).[Level of evidence: 3iiDiv] Improved pCR rates may be important since in some studies, pCR is associated with improved long-term outcomes.
Platinum agents have recently emerged as drugs of interest for the treatment of TNBC. One trial that treated 28 women with stage II or stage III TNBC with four cycles of neoadjuvant cisplatin resulted in a 22% pCR rate.[Level of evidence: 3iiiDiv] An randomized clinical trial, CALGB-40603 (NCT00861705), evaluated the benefit of carboplatin added to paclitaxel and adriamycin plus cyclophosphamide chemotherapy in the neoadjuvant setting. Another trial, entitled the Triple Negative Trial (NCT00532727), is evaluating carboplatin against docetaxel in the metastatic setting. These trials will help to define the role of platinum agents for the treatment of TNBC. Currently, there is no established role for adding platinum agents to the treatment of early-stage TNBC outside of a clinical trial.
The U.S. Preventive Services Task Force (USPSTF) is recommending sweeping changes in its breast cancer screening guidelines.
The USPSTF, which is a group of independent health experts convened by the Department of Health and Human Services, reviewed and commissioned research to develop computer-simulated models comparing the expected outcomes under different screening scenarios.
Here are the USPSTF's recommendations, based on all that work:
Routine screening of average-risk women should begin...
The poly (ADP-ribose) polymerase (PARP) inhibitors are emerging as promising therapeutics for the treatment of TNBC. PARPs are a family of enzymes involved in multiple cellular processes, including DNA repair. Because TNBC shares multiple clinicopathologic features with BRCA-mutated breast cancers, which harbor dysfunctional DNA repair mechanisms, it is possible that PARP inhibition, in conjunction with the loss of DNA repair via BRCA-dependent mechanisms, would result in synthetic lethality and augmented cell death. PARP inhibitors are currently being evaluated in clinical trials for patients with BRCA mutations and in TNBC.