BACKGROUND: Breast cancer (BC) disparities may widen with genomic advances. The authors compared non‐Hispanic white (NHW), black, and Hispanic BC survivors for 1) cancer risk‐management practices among BRCA carriers and 2) provider discussion and receipt of genetic testing.METHODS: A population‐based sample of NHW, black, and Hispanic women who had been diagnosed with invasive BC at age 50 years or younger from 2009 to 2012 were recruited through the state cancer registry. Multiple logistic regression was used to compare cancer risk‐management practices in BRCA carriers and associations of demographic and clinical variables with provider discussion and receipt of testing.RESULTS: Of 1622 participants, 159 of 440 (36.1%) black women, 579 of 897 (64.5%) NHW women, 58 of 117 (49.6%) Spanish‐speaking Hispanic women, and 116 of 168 (69%) English‐speaking Hispanic women underwent BRCA testing, of whom 90 had a pathogenic BRCA mutation identified. Among BRCA carriers, the rates of risk‐reducing mastectomy and risk‐reducing salpingo‐oophorectomy were significantly lower among black women compared with Hispanic and NHW women after controlling for clinical and demographic variables (P = .025 and P = .008, respectively). Compared with NHW women, discussion of genetic testing with a provider was 16 times less likely among black women (P < .0001) and nearly 2 times less likely among Spanish‐speaking Hispanic women (P = .04) after controlling for clinical and sociodemographic factors.CONCLUSIONS: The current results suggest that the rates of risk‐reducing salpingo‐oophorectomy are lower among black BRCA carriers compared with their Hispanic and NHW counterparts, which is concerning because benefits from genetic testing arise from cancer risk‐management practice options. Furthermore, lower BRCA testing rates among blacks may partially be because of a lower likelihood of provider discussion. Future studies are needed to improve cancer risk identification and management practices across all populations to prevent the widening of disparities. Cancer 2017;123:2497–05. © 2017 American Cancer Society.

Purpose: A meta-analytic approach was used to estimate the frequency of: (a) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and (b) various histologic subtypes of mismatch repair (MMR)-deficient epithelial ovarian cancers. Methods: A systematic search of the Medline electronic database was conducted to identify articles published between January 1, 1966, and December 31, 2007, that examined MMR deficiency in ovarian cancers. Data were extracted on the study population, sample size, MSI-H frequency, and histology of MMR-deficient ovarian tumors. Results: The pooled proportion of MSI-H ovarian cancers was 0.12 [95% confidence interval (CI), 0.08-0.17] from 18 studies with 977 cases. The proportion of histologic subtypes in the pooled analysis from 15 studies with 159 cases was serous at 0.32 (95% CI, 0.20-0.44), mucinous at 0.19 (95% CI, 0.12-0.27), endometrioid at 0.29 (95% CI, 0.22-0.36), clear cell at 0.18 (95% CI, 0.09-0.28), and mixed at 0.24 (95% CI, 0.07-0.47). There was significant heterogeneity between studies. Conclusions: The frequency of the MSI-H phenotype in unselected ovarian cancers approximates 12%. MMR-deficient ovarian cancers also seem to be characterized by an overrepresentation of nonserous histologic subtypes. Knowledge of histologic subtype may aid clinicians in identifying the relatively large proportion of ovarian cancers due to MMR defects; such knowledge has potential implications for medical management.

BACKGROUND: Black women are disproportionately affected with triple‐negative breast cancer and have relatively poor survival. To the authors' knowledge, it is not known to what extent differences in the clinical presentation of breast cancer between non‐Hispanic white women and black women can be accounted for by the presence of mutations in the BRCA1 and BRCA2 genes. The authors sought to evaluate the frequency of BRCA pathogenic variants in a population‐based sample of young black women with breast cancer.METHODS: Black women diagnosed with invasive breast cancer at age ≤50 years from 2009 to 2012 were recruited to the study through the Florida Cancer Registry. Participants underwent genetic counseling, completed a study questionnaire, and consented to release of their medical records. Saliva specimens were collected for BRCA sequencing and large rearrangement testing through multiplex ligation‐dependent probe amplification.RESULTS: A DNA sample was evaluated for 396 women, 49 of whom (12.4%) had a mutation in BRCA1 or BRCA2. Eight recurrent mutations accounted for 49% of all pathogenic variants.CONCLUSIONS: To the authors' knowledge, the prevalence of BRCA mutations among the Florida‐based sample of young black women with breast cancer in the current study exceeds that previously reported for non‐Hispanic white women. It is appropriate to recommend BRCA testing in all young black women with invasive breast cancer. Cancer 2015;121:4173–4180. © 2015 American Cancer Society.

Ovarian cancer ranks fifth in both cancer incidence and mortality among women in the United States. Defects in the mismatch‐repair (MMR) pathway that arise through genetic and/or epigenetic mechanisms may be important etiologically in a reasonable proportion of ovarian cancers. Genetic mechanisms of MMR dysfunction include germline and somatic mutations in the MMR proteins. Germline mutations cause hereditary nonpolyposis colorectal cancer (HNPCC), which is the third most common cause of inherited ovarian cancer after BRCA1 and BRCA2 mutations. An epigenetic mechanism known to cause inactivation of the MMR system is promoter hypermethylation of 1 of the MMR genes, mutL homolog 1 (MLH1). Various laboratory methods, in addition to clinical and histopathologic criteria, can be used to identify MMR‐deficient ovarian cancers. Such methods include microsatellite instability analysis, immunohistochemistry, MLH1 promoter hypermethylation testing, and germline mutation analysis. In this review, the authors describe the existing literature regarding the molecular, clinical, and histologic characteristics of MMR‐deficient ovarian cancers along with the possible effect on survival and treatment response. By further defining the profile of MMR‐deficient ovarian cancers and their associated etiologic mechanisms, there may be a greater potential to distinguish between those of hereditary and sporadic etiology. The ability to make such distinctions may be of diagnostic, prognostic, and therapeutic utility. Cancer 2008. © 2008 American Cancer Society.

Next‐generation sequencing enables testing for multiple genes simultaneously (‘panel‐based testing’) as opposed to sequential testing for one inherited condition at a time (‘syndrome‐based testing’). This study presents results from patients who underwent hereditary colorectal cancer (CRC) panel‐based testing (‘ColoNext^™’). De‐identified data from a clinical testing laboratory were used to calculate (1) frequencies for patient demographic, clinical, and family history variables and (2) rates of pathogenic mutations and variants of uncertain significance (VUS). The proportion of individuals with a pathogenic mutation who met national syndrome‐based testing criteria was also determined. Of 586 patients, a pathogenic mutation was identified in 10.4%, while 20.1% had at least one VUS. After removing eight patients with CHEK2 mutations and 11 MUTYH heterozygotes, the percentage of patients with ‘actionable’ mutations that would clearly alter cancer screening recommendations per national guidelines decreased to 7.2%. Of 42 patients with an ‘actionable’ result, 30 (71%) clearly met established syndrome‐based testing guidelines. This descriptive study is among the first to report on a large clinical series of patients undergoing panel‐based testing for inherited CRC. Results are discussed in the context of benefits and concerns that have been raised about panel‐based testing implementation.