“Researchers conducted an analysis that included nearly 10,000 women with the BRCA1 or BRCA2 genetic mutations to estimate the age-specific risk of breast or ovarian cancer for women with these mutations, according to a study published by JAMA.
“The optimal clinical management of women with BRCA1 and BRCA2 mutations depends on accurate age specific cancer risk estimates. These can be used to estimate the absolute risk reduction from preventive strategies and to inform decisions about the age at which to begin cancer screening. Antonis C. Antoniou, Ph.D., of the University of Cambridge, England, and colleagues included 6,036 BRCA1 and 3,820 BRCA2 female carriers (5,046 unaffected and 4,810 with breast or ovarian cancer or both at study entry) in the analysis.”
“Clinical data on the role of platinum salts in the treatment of triple-negative breast cancer (TNBC) — particularly germline (g) BRCA1-related TNBC — are encouraging in the neoadjuvant setting, where the pathologic complete response rate is improved with the addition of a platinum to anthracycline and taxane-based chemotherapy.
“Data have emerged to show the utility of incorporating platinums into the metastatic setting in TNBC as well, with the strongest evidence for use in patients who are BRCA1/2 mutation carriers or who express a BRCA-like genomic instability signature.”
“TNFSF11, also known as RANKL, shows potential as a genetic pathway in the prevention of breast cancer for women carrying BRCA1 mutations. Early study findings, published in Nature Medicine, show that a drug currently used in the treatment of osteoporosis, denosumab (Xgeva)—an inhibitor of RANKL—could also be used for the prevention and delay of tumor growth for BRCA1-mutation carriers.
“ ‘These findings imply an integral role for the RANK pathway in tumor initiation in BRCA1-mutation carriers and lend support to clinical studies for the “repurposing” of denosumab as a novel preventative therapy strategy in these and possibly other “high-risk” women,’ wrote study authors.”
Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.
“A new clinic in San Francisco is opening with an unusual mission: to provide care for people affected by mutations in two particular genes linked to a high risk of cancer. The move highlights the ways growing knowledge about the genetics of the disease is reshaping care for patients.
“The clinic, at University of California, San Francisco, will treat patients with abnormalities in the genes known as BRCA1 and BRCA2. The mutations are widely recognized as inheritable causes of breast and ovarian cancers.”
“The vast majority of young women with breast cancer are being tested for mutations in the cancer-susceptibility genes BRCA1 and BRCA2, a new study led by Dana-Farber Cancer Institute investigators suggests, and many of them are using the results of those tests to guide their treatment.
“The study, published in the Journal of the American Medical Association Oncology, provides encouraging evidence that patients are largely following National Comprehensive Cancer Network guidelines that women diagnosed with breast cancer at age 50 or younger undergo genetic testing. At the same time, however, the researchers found that many patients who don’t carry BRCA1 or 2 mutations are choosing to have both breasts removed, even though their risk of cancer in the unaffected breast is no higher than average.”
“Olaparib (Lynparza) has received an FDA breakthrough therapy designation as a treatment for patients with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer (mCRPC) in those who have received a prior taxane-based chemotherapy and at least either hormonal agent enzalutamide (Xtandi) or abiraterone acetate (Zytiga).
“The designation, which will accelerate the development and review of the first-in-class oral PARP inhibitor, is based on data from the phase II TOPARP-A trial that demonstrated that olaparib monotherapy had an overall response rate (ORR) of nearly 90% in a biomarker-defined subgroup of patients who had DNA-repair defects.“
“BRCA1/2 mutation carriers have increased risk of contralateral breast cancer (CBC), with age at first diagnosis a significant predictor of CBC risk, according to a study published online Dec. 23 in the Journal of Clinical Oncology.
“Alexandra J. van den Broek, from the Netherlands Cancer Institute in Amsterdam, and colleagues examined overall and age-specific estimates of CBC risk for young patients with breast cancer with or without BRCA1/2 mutations. Data were included for 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003; participants were tested for the most prevalent BRCA1/2 mutations.”
“Multigene testing of women who tested negative for BRCA1 and BRCA2 found some of them harbored other harmful genetic mutations—most commonly, moderate-risk breast and ovarian cancer genes, as well as Lynch syndrome genes (which increase the risk of ovarian cancer)—according to an article by Desmond et al in JAMA Oncology.
“Multigene panel genetic tests are increasingly recommended for patients evaluated for a predisposition to hereditary breast/ovarian cancer. However, the rapid introduction of these tests has raised concerns, because many of the tested genes are low- to moderate-risk genes for which consensus management guidelines have not been introduced or were introduced only very recently, according to the study background.
“Leif W. Ellisen, MD, PhD, of Massachusetts General Hospital Cancer Center, and coauthors wanted to determine how often multigene panel testing would identify mutations that warranted some clinical action among women appropriately tested but lacking BRCA1 and BRCA2 mutations.”
“Breast cancer survivors with a family history of the disease, including those who carry BRCA1 and BRCA2 gene mutations, gained more weight over the course of four years than cancer-free women—especially if they were treated with chemotherapy, according to a prospective study by Johns Hopkins Kimmel Cancer Center researchers.
“Data from earlier studies suggest that breast cancer survivors who gain weight may have a higher risk of having their cancer return, the researchers say, noting that gains of 11 pounds or more are also associated with a higher risk of developing cardiovascular disease.
“For the study, the researchers reviewed a baseline questionnaire and a follow-up one completed four years later by 303 breast cancer survivors and 307 cancer-free women enrolled in an ongoing and long-term study at the Kimmel Cancer Center of women with a family history of breast or ovarian cancer. Study participants completed a baseline and at least one follow-up questionnaire between 2005 and 2013, and one-quarter of the subjects were premenopausal.”