BRCA postive breast cancers and etoposide – pro
BRCA positive cancers overlap with the basal group and have a unique ideology and mutations. Several preclinical studies noted that BRCA positives breast cancer cells respond better to etoposide and cisplatin and the relatively insensitive to drugs such as taxanes. BRCA-defi cient cells have also shown hypersensitivity to etoposide, a topoisomerase II inhibitor. Etoposide binds to topoisomerase II and forms a stable drug-enzyme-DNA complex, thereby inhibiting the final re-ligation step required for replication and eventually resulting in a Dbouble Stranded DNA Break.
Unfortunately, there have not been any clinical studies testing the concept of indvidualizing treatment by BRCA stage and using etoposide can only be defended on the grounds that it is an effective drug for all breast cancer patients. On this ground, it can be defended based on the literature, although most literature is dates, since most of the recent focus has been on newer and potentially more effective drugs.
John L. Nitiss Targeting DNA topoisomerase II in cancer chemotherapy
Nature Reviews Cancer 9, 338-350 (May 2009)
Treszezamsky A, Kachnic L, Feng Z, Zhang J, Tokadjian C, Powell S: BRCA1-
and BRCA2-defi cient cells are sensitive to etoposide-induced DNA
double-strand breaks via topoisomerase II. Cancer Res 2007, 67:7078-7081.
Martín M, Lluch A, Casado A, et al. Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer. J Clin Oncol 1994; 12:986.
Pusztai L, Walters RS, Valero V, et al. Daily oral etoposide in patients with heavily pretreated metastatic breast cancer. Am J Clin Oncol 1998; 21:442.
Saphner T, Weller EA, Tormey DC, et al. 21-day oral etoposide for metastatic breast cancer: a phase II study and review of the literature. Am J Clin Oncol 2000; 23:258.