Specific types of hormone therapy have been associated with increased breast cancer risk. Chlebowski et al report a 13-year median follow-up of studies evaluating the effect of estrogen plus medroxyprogesterone acetate (E + P) or estrogen alone vs placebo on breast cancer risk. The Women’s Health Initiative enrolled 27 347 women from 1993 through 1998. For E + P users, risk increased during the intervention and decreased afterward, but hazard ratios remained greater than 1. For estrogen users, a reduction in risk during the intervention was not sustained in long-term follow-up. These results underscore a role for progesterone as a driver for breast cancer development. Joshi et al provide an Editorial.
Prophylactic oophorectomy is known to reduce the risk of ovarian cancer in BRCA1 and BRCA2 germline mutation carriers. Metcalfe et al investigated the role of oophorectomy in breast cancer survival for 676 carriers with early-stage breast cancer observed for up to 20 years from diagnosis. Oophorectomy after breast cancer diagnosis was associated with improved breast cancer survival for both BRCA1 and BRCA2 carriers, especially those with estrogen receptor–negative disease. The authors concluded that oophorectomy should become part of the treatment of early-stage breast cancer in these women. Disis provides an Editor’s Note.
Patients with cancer use multiple strategies to optimize health, including exercise, diet, and supplemental products. Daenen et al studied the effect of ingestion of both fish oil supplements and fresh fish on the levels of fatty acid 16:4(n-3), the agent in fish oil associated in mouse models with impairment of chemotherapy activity. In volunteers, moderate ingestion of fish oil supplements and fish such as herring and mackerel increased fatty acid 16:4(n-3) levels to those associated with chemotherapy resistance. The authors conclude that patients receiving chemotherapy should not use fish oil supplements or eat fish.
BRAF and NRAS mutations, frequent in melanoma, are the focus of targeted therapies. Thomas et al report one of the largest studies of the role of BRAF and NRAS mutations in melanoma prognosis in 912 primary cutaneous melanomas (13% NRAS+, 30% BRAF+, 57% wild type) with a median follow-up of 7.6 years. Overall, mutation status made no significant difference in melanoma-specific survival, but BRAF and NRAS mutations were associated with decreased survival in higher risk (>T2b) disease. NRAS-mutated tumors also had significantly fewer tumor-infiltrating lymphocytes, calling into question the mutation’s effect on the immune microenvironment and response to immune-based therapies.
Representatives of the Food and Drug Administration (FDA), industry, oncology practitioners, and patient advocates discuss the role of patient-reported outcomes (PROs) in drug development and regulatory review and make recommendations concerning increasing PROs as part of drug labeling. Basch et al advocate more education on how to collect PROs, development of preferred methods of PRO monitoring suitable for FDA review, increased FDA involvement in encouraging PRO use, and increased training for industry and academic researchers, as well as the FDA, on PRO reporting.
Highlights. JAMA Oncol. 2015;1(3):263. doi:10.1001/jamaoncol.2015.0724