Triple-Negative Breast Cancer

Current Clinical Trials

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.[1] 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).[2][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.[3][Level of evidence: 3iiiDiv] An ongoing randomized clinical trial, CALGB-40603 (NCT00861705), is evaluating 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 poly (ADP-ribose) polymerase (PARP) inhibitors are emerging as promising therapeutics for the treatment of TNBC.[4] 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.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with triple-negative breast cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Mehta RS: Dose-dense and/or metronomic schedules of specific chemotherapies consolidate the chemosensitivity of triple-negative breast cancer: a step toward reversing triple-negative paradox. J Clin Oncol 26 (19): 3286-8; author reply 3288, 2008.  [PUBMED Abstract]
   
   
2. Liedtke C, Mazouni C, Hess KR, et al.: Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26 (8): 1275-81, 2008.  [PUBMED Abstract]
   
   
3. Silver DP, Richardson AL, Eklund AC, et al.: Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol 28 (7): 1145-53, 2010.  [PUBMED Abstract]
   
   
4. Anders CK, Winer EP, Ford JM, et al.: Poly(ADP-Ribose) polymerase inhibition: "targeted" therapy for triple-negative breast cancer. Clin Cancer Res 16 (19): 4702-10, 2010.  [PUBMED Abstract]