Emerging Therapies for Triple-Negative Breast Cancer

Anaheim—Although there are a few targeted therapies available to treat patients with triple-negative breast cancer (TNBC), they are not effective. However, researchers are working on new therapies that can be used alone or in combination with chemotherapy. Several experts provided an overview of TNBC and discussed past, current, and future trends associated with the disease during a symposium at the ASHP meeting titled Understanding Triple-Negative Breast Cancer and Emerging Targeted Therapies. Jacquelyn Lauria, RN, MS, APN-C, AOCNP, director of oncology nursing services at the Cancer Institute of New Jersey, New Brunswick, said there were 192,000 breast cancer cases and 40,000 breast cancer–related deaths in the United States in 2009. The severity and pathology depends on several factors, such as age, tumor size, axillary node involvement, lymphovascular invasion, histologic grade, hormone receptor status, and human epidermal growth factor receptor 2 (HER2)/neu amplification. There are 5 subtypes of breast cancer: luminal A, luminal B, basal-like triple negative, HER2 positive, and unclassified. A study that Ms. Lauria discussed found that 84% of patients with luminal A breast cancer survived, with a mean survival of 7.6 years; 87% of patients with luminal B breast cancer survived, with a mean survival of 7.7 years; 75% of patients with basal-like breast cancer survived, with a mean survival of 4.9 years; and 52% of patients with HER2- or estrogen receptor (ER)-negative breast cancer survived, with a mean survival of 6.7 years. Ms. Lauria mentioned approximately 10% to 20% of breast cancer patients have TNBC, which is characterized by earlier relapses, distinct patterns of metastases, and a lack of specific targets for treatment selection. Patients with TNBC are typically younger when diagnosed compared with other cancer patients, and the incidence is higher in African American women. She emphasized that TNBC is not one disease but rather a type of breast cancer. Risk factors for TNBC include a BRCA1 mutation, while other factors are under investigation, such as body mass index, breastfeeding, alcohol use, and elevated waist-to-hip ratio. Ms. Lauria said that neoadjuvant studies have shown that TNBC is sensitive to chemotherapy and has a higher pathologic complete response rate than luminal breast cancers. She also cited studies showing TNBC is associated with poorer outcomes and a higher risk of relapse than other invasive breast cancers. She said the correlation between TNBC and basal-like breast cancer is high, but they are not the same, although people frequently use the terms interchangeably: ≤10% of TNBC cases are not basal-like, while 15% to 40% of basal-like breast cancer cases are not TNBC. Chemotherapy is currently the only effective treatment for TNBC. However, to better understand TNBC, several researchers are studying the BRCA1 pathway that plays an important role in homologous recombination. Currently, studies have indicated that BRCA1 cells are sensitive to DNA damage and develop chromosomal aberrations when exposed to DNAdamaging drugs. Ms. Lauria said that TNBC and BRCA1-deficient tumors share common characteristics. Thus, treatment options available for BRCA1-deficient cancers could possibly work well for TNBC. Next, Chad M. Barnett, PharmD, BCOP, clinical pharmacy specialist at the University of Texas, Houston, spoke about the 2 options available to treat patients with TNBC: chemotherapy and antiangiogenic therapy. Chemotherapy is the standard, although patients with tumors ≤0.5 cm and negative lymph nodes do not require chemotherapy. Endocrine therapy and anti-HER2–directed therapy is not appropriate for patients with TNBC, according to Dr. Barnett. Patients with lymph node–negative early-stage breast cancer typically receive an anthracycline-containing regimen or a nonanthracycline-containing regimen, while patients with lymph node–positive earlystage breast cancer normally have an anthracycline-containing regimen and a concurrent or sequential taxane. To determine the effectiveness of adjuvant taxane regimens, Dr. Barnett cited a pooled analysis of 13 trials involving 22,903 patients. The researchers found that disease-free survival and overall survival were significantly higher in patients taking a taxane. The results were the same whether patients took a sequential or concurrent taxane, whether they took paclitaxel or docetaxel, and whether they were ER-positive or -negative. Dr. Barnett also said that research has shown that neoadjuvant therapy can lead to a pathologic complete response rate and favorable outcomes for early-stage TNBC patients. Chemotherapy options for patients with metastatic breast cancer include anthracyclines, taxanes, antimetabolites, and a combination of agents. In addition, some patients receive targeted therapies such as bevacizumab, an antiangiogenic agent, which Dr. Barnett said can be effective. Christine M. Walko, PharmD, BCOP, clinical pharmacist at the North Carolina Cancer Hospital, Chapel Hill, followed by discussing emerging therapeutic options for TNBC, among them poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, epidermal growth factor receptor (EGFR) targeting agents, and vascular endothelial growth factor (VEGF) targeting agents. Dr. Walko defined PARP inhibitors as intended to resemble nicotinamide adenine dinucleotide and prevent DNA repair. Several phase 1 and 2 trials are studying the effectiveness of PARP inhibitors, such as iniparib, olaparib, veliparib, AG014699, MK482, INO-1001, CEP9272, and BSI-201. EGFR targeting agents include cetuximab, panitumumab, erlotinib, and geftinib. Dr. Walko said cetuximab has low activity in TNBC, but cetuximab combined with cytotoxic therapy could improve the clinical benefit. Researchers must examine the regulation of the EGFR pathway.