Prospective Evaluation of Universal BRCA Testing for Women With Triple-Negative Breast Cancer.

BACKGROUND: Limited published literature exists on women with triple-negative breast cancer (TNBC) diagnosed over the age of 60 years with breast cancer gene (BRCA) pathogenic variants. Our study determined whether the rate of BRCA pathogenic variants in a prospective cohort of TNBC patients outside the definition of current clinical genetic testing (GT) guidelines warrants a change in recommendations. METHODS: A prospective study of 395 women with TNBC underwent genetic counseling and 380 (96.2%) underwent clinical BRCA GT regardless of age of diagnosis beginning January 2014 to October 2015 at The University of Texas MD Anderson Cancer Center, Houston. TNBC patients older than 60 years who did not meet clinical GT guidelines had comprehensive sequencing and large rearrangement GT as part of the research protocol. RESULTS: Fifty-one of 380 (13.4%) women with TNBC who underwent clinical BRCA GT were BRCA positive. Of the 86 patients diagnosed at age over 60 years and underwent GT, only two (2.3%) were positive for BRCA. These two patients would have met clinical testing criteria due to family or ancestral history. CONCLUSIONS: Our study does not support universal BRCA testing for TNBC patients diagnosed older than 60 years as their only risk factor for a BRCA pathogenic variant. Both of the positive BRCA patients older than 60 years identified would have met current National Comprehensive Cancer Network criteria for testing. Therefore, our study demonstrates that the National Comprehensive Cancer Network guidelines provide sufficient criteria for identifying BRCA pathogenic variants in women with TNBC at 60 years or younger.

Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian.

BACKGROUND: Previous studies have reported additional cancers associated with BRCA mutations; however, the type, magnitude of risk, and sex differences remain to be clarified. The purpose of this study was to evaluate the incidence of cancers other than breast and ovarian cancer in known mutation carriers. METHODS: An institutional review board-approved study identified 1072 patients who had genetic counseling at the authors' institution and tested positive for a deleterious BRCA mutation. The expected number of cancer cases was calculated from the number of individuals in the study sample multiplied by the cancer incidence rates for the general population. The expected and observed numbers of cases were calculated in 5-year intervals to accommodate different age-related incidence rates. Standardized incidence ratios (SIRs) for each cancer type were calculated. RESULTS: Among the 1072 mutation carriers, 1177 cancers of 30 different cancer types were identified. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian cancer; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P < .001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P = .002). CONCLUSIONS: The results of this study uphold the current recommendations for hereditary breast and ovarian cancer screening of cancers other than breast and ovarian cancer by the National Comprehensive Cancer Network. Larger cohorts and collaborations are needed to further verify these findings.

Outcomes of children exposed in utero to chemotherapy for breast cancer.

INTRODUCTION: The incidence of breast cancer diagnosed during pregnancy is expected to increase as more women delay childbearing in the United States. Treatment of cancer in pregnant women requires prudent judgment to balance the benefit to the cancer patient and the risks to the fetus. Prospective data on the outcomes of children exposed to chemotherapy in utero are limited for the breast cancer population. METHODS: Between 1992 and 2010, 81 pregnant patients with breast cancer were treated in a single-arm, institutional review board-approved study with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in the adjuvant or neoadjuvant setting. Labor and delivery records were reviewed for each patient and neonate. In addition, the parents or guardians were surveyed regarding the health outcomes of the children exposed to chemotherapy in utero. RESULTS: In total, 78% of the women (or next of kin) answered a follow-up survey. At a median age of 7 years, most of the children exposed to chemotherapy in utero were growing normally without any significant exposure-related toxicity or health problems. Three children were born with congenital abnormalities: one each with Down syndrome, ureteral reflux or clubfoot. The rate of congenital abnormalities in the cohort was similar to the national average of 3%. CONCLUSIONS: During the second and third trimesters, pregnant women with breast cancer can be treated with FAC safely without concerns for serious complications or short-term health concerns for their offspring who are exposed to chemotherapy in utero. Continued long-term follow-up of the children in this cohort is required. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00510367. Other Study ID numbers: ID01-193, NCI-2012-01578. Registration date: 31 July 2007.