Phase 2 Study to Evaluate the Effect of Bevacizumab in Metastatic Triple Negative Breast Cancer

Breast cancer is the most common non cutaneous cancer in U.S. women, with an estimated 63,960 cases of in situ disease and 266,120 cases of invasive disease in 2018. (American Cancer Society: Cancer Facts and Figures 2018). On the basis of ER, PR, and HER2/neu results, breast cancer is classified as one of the following types:

Hormone receptor positive , HER2/neu positive and Triple negative (ER, PR, and HER2/neu negative).

ER, PR, and HER2 status are important in determining prognosis and in predicting response to endocrine and HER2-directed therapy.(Harris JR, Morrow M, Lippman ME, et al . 1996) Metatstaic Triple-negative breast cancer (TNBC) is a diagnosis of exclusion, defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) .

TNBC tends to occur in younger, often premenopausal patients, African Americans, and in association with hereditary syndromes, most commonly germline BRCA1 mutations. It constitutes up to 15% of all breast cancers but accounts for > 25% of breast cancer-related deaths as it has an inherent predisposition for rapid dissemination and visceral metastases with limited improvements in overall survival and inferior clinical outcomes . It is characterized by higher incidence of brain metastases and rapid progression from the onset of metastasis to death. Having aggressive biology more than other breast types due to high risk of early relapse between the first and third years after diagnosis , metastases are rarely preceded by local recurrence and most deaths occur in the first 5 years ( Livasy CA et al . 2006 ) Due to the palliative intent of treatment as in MBC and Optimal chemotherapy regimens have yet to be established in treatment of metastatic TNBC; however, there have been advances in the systemic treatment of triple-negative breast cancer in the neoadjuvant, adjuvant, and metastatic settings. ( J.M. Lebert , R. Lester , E. Powell et el current oncology journal 2018 ) it is critical that an individualized approach is taken that incorporates patient, disease, and treatment-related factors, including an individual oncologist treatment preference.(Geels P, et al 2000 ).

There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course.