Racial and Ethnic Differences in Multigene Hereditary Cancer Panel Test Results for Women With Breast Cancer.
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ABSTRACT:
SUBMITTER: Yadav S
PROVIDER: S-EPMC8633452 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceDisproportionately aggressive tumor biology among non-Hispanic Black women with early-stage, estrogen receptor (ER)-positive breast cancer contributes to racial disparities in breast cancer mortality. It is unclear whether socioecologic factors underlie racial differences in breast tumor biology.ObjectiveTo examine individual-level (insurance status) and contextual (area-level socioeconomic position and rural or urban residence) factors as possible mediators of racial and ethnic differences in the prevalence of ER-positive breast tumors with aggressive biology, as indicated by a high-risk gene expression profile.Design, setting, and participantsThis retrospective cohort study included women 18 years or older diagnosed with stage I to II, ER-positive breast cancer between January 1, 2007, and December 31, 2015. All data analyses were conducted between December 2022 and April 2023.Main outcomes and measuresThe primary outcome was the likelihood of a high-risk recurrence score (RS) (≥26) on the Oncotype DX 21-gene breast tumor prognostic genomic biomarker.ResultsAmong 69 139 women (mean [SD] age, 57.7 [10.5] years; 6310 Hispanic [9.1%], 274 non-Hispanic American Indian and Alaskan Native [0.4%], 6017 non-Hispanic Asian and Pacific Islander [8.7%], 5380 non-Hispanic Black [7.8%], and 51 158 non-Hispanic White [74.0%]) included in our analysis, non-Hispanic Black (odds ratio [OR], 1.33; 95% CI, 1.23-1.43) and non-Hispanic American Indian and Alaska Native women (OR, 1.38; 95% CI, 1.01-1.86) had greater likelihood of a high-risk RS compared with non-Hispanic White women. There were no significant differences among other racial and ethnic groups. Compared with non-Hispanic White patients, there were greater odds of a high-risk RS for non-Hispanic Black women residing in urban areas (OR, 1.35; 95% CI, 1.24-1.46), but not among rural residents (OR, 1.05; 95% CI, 0.77-1.41). Mediation analysis demonstrated that lack of insurance, county-level disadvantage, and urban vs rural residence partially explained the greater odds of a high-risk RS among non-Hispanic Black women (proportion mediated, 17%; P < .001).Conclusions and relevanceThe findings of this cohort study suggest that the consequences of structural racism extend beyond inequities in health care to drive disparities in breast cancer outcome. Additional research is needed with more comprehensive social and environmental measures to better understand the influence of social determinants on aggressive ER-positive tumor biology among racial and ethnic minoritized women from disadvantaged and historically marginalized communities.
| S-EPMC10993076 | biostudies-literature
Project description:BackgroundIncidence rates of epithelial ovarian cancer (EOC) vary across racial/ethnic groups, yet little is known about the impact of hormone-related EOC risk factors in non-Whites.MethodsAmong 91,625 female Multiethnic Cohort Study participants, 155 incident EOC cases were diagnosed in Whites, 93 in African Americans, 57 in Native Hawaiians, 161 in Japanese Americans, and 141 in Latinas. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between race/ethnicity and EOC risk and between hormone-related factors and EOC risk across racial/ethnic groups.ResultsCompared with Whites, African Americans and Japanese Americans had a lower multivariable-adjusted EOC risk; Native Hawaiians had a suggestive higher risk. Parity and oral contraceptive (OC) use were inversely associated with EOC risk (P int race/ethnicity ≥ 0.43); associations were strongest among Japanese Americans (e.g., ≥4 vs. 0 children; HR = 0.45; CI, 0.26-0.79). Age at natural menopause and postmenopausal hormone (PMH) use were not associated with EOC risk in the overall population, but were positively associated with risk in Latinas (e.g., ≥5 years vs. never PMH use; HR = 2.13; CI, 1.30-3.49).ConclusionsWe observed strong associations with EOC risk for parity and OC use in Japanese Americans and PMH use and age at natural menopause in Latinas. However, differences in EOC risk among racial/ethnic groups were not fully explained by established hormone-related risk factors.ImpactOur study indicates there are racial/ethnic differences in EOC risk and risk factors, and could help improve prevention strategies for non-White women.
| S-EPMC7541726 | biostudies-literature
Project description:BackgroundGermline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC.MethodsMultigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium (TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls.ResultsGermline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants.ConclusionsMultigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.
| S-EPMC6093350 | biostudies-literature
Project description:The epidemiologic information regarding international differences in bone mineral density (BMD) in women is currently insufficient. We compared BMD in older women across five racial/ethnic groups in four countries. The femoral neck, total hip, and lumbar spine BMD were measured in women (aged 65-74 years) from the Study of Osteoporotic Fractures (SOF) (5,035 Caucasian women and 256 African American women in the US), the Tobago Women's Health Study (116 Afro-Caribbean women), the Ms Os Hong Kong Study (794 Hong Kong Chinese women) and the Namwon Study (1,377 South Korean women). BMD was corrected according to the cross-site calibration results for all scanners. When compared with US Caucasian women, the age adjusted mean BMD measurements at the hip sites were 21-31 % higher among Tobago Afro-Caribbean women and 13-23 % higher among African American women. The total hip and spine BMD values were 4-5 % lower among Hong Kong Chinese women and 4-7 % lower among South Korean women compared to US Caucasians. The femoral neck BMD was similar in Hong Kong Chinese women, but higher among South Korean women compared to US Caucasians. Current/past estrogen use was a significant contributing factor to the difference in BMD between US versus non-US women. Differences in body weight partially explained the difference in BMD between Asian versus non-Asian women. These findings show substantial racial/ethnic differences in BMD even within African or Asian origin individuals, and highlight the contributing role of body weight and estrogen use to the geographic and racial/ethnic variation in BMD.
| S-EPMC4109723 | biostudies-literature
Project description:Gastric cancer (GC) has long been a 'Cinderella' among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7%). Seven out of fifty (14%) patients who underwent SGT for unknown mutations were carriers of a PV in CDH1 (n = 3), BRCA2 (n = 2), BRCA1 (n = 1), and MSH2 (n = 1), while one patient (2%) carried two variants of unknown significance (VUSs). CDH1 and MSH2 emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying five PVs (13.5%), including three (3/5:60%) in an HR gene (BRCA2, ATM, RAD51D) and at least one VUS in 13 patients (35.1%). Comparing PV carriers and non-carriers, we observed a statistically significant difference in PVs between patients with and without family history of GC (p-value: 0.045) or Lynch-related tumors (p-value: 0.036). Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspecific phenotypes, although it led to challenging results.
| S-EPMC10218517 | biostudies-literature
Project description:Half of the high-risk colorectal cancer families that fulfill the clinical criteria for Lynch syndrome lack germline mutations in the mismatch repair (MMR) genes and remain unexplained. Genetic testing for hereditary cancers is rapidly evolving due to the introduction of multigene panels, which may identify more mutations than the old screening methods. The aim of this study is the use of a Next Generation Sequencing panel in order to find the genes involved in the cancer predisposition of these families. For this study, 98 patients from these unexplained families were tested with a multigene panel targeting 94 genes involved in cancer predisposition. The mutations found were validated by Sanger sequencing and the segregation was studied when possible. We identified 19 likely pathogenic variants in 18 patients. Out of these, 8 were found in MMR genes (5 in MLH1, 1 in MSH6 and 2 in PMS2). In addition, 11 mutations were detected in other genes, including high penetrance genes (APC, SMAD4 and TP53) and moderate penetrance genes (BRIP1, CHEK2, MUTYH, HNF1A and XPC). Mutations c.1194G>A in SMAD4, c.714_720dup in PMS2, c.2050T>G in MLH1 and c.1635_1636del in MSH6 were novel. In conclusion, the detection of new pathogenic mutations in high and moderate penetrance genes could contribute to the explanation of the heritability of colorectal cancer, changing the individual clinical management. Multigene panel testing is a more effective method to identify germline variants in cancer patients compared to single-gene approaches and should be therefore included in clinical laboratories.
| S-EPMC6157886 | biostudies-literature
Project description:ImportanceTo our knowledge, there is no consensus regarding differences in treatment and mortality between non-Hispanic African American and non-Hispanic White women with triple-negative breast cancer (TNBC). Little is known about whether racial disparities vary by sociodemographic, clinical, and neighborhood factors.ObjectiveTo examine the differences in clinical treatment and outcomes between African American and White women in a nationally representative cohort of patients with TNBC and further examine the contributions of sociodemographic, clinical, and neighborhood factors to TNBC outcome disparities.Design, setting, and participantsThis population-based, retrospective cohort study included 23 123 women who received a diagnosis of nonmetastatic TNBC between January 1, 2010, and December 31, 2015, followed up through December 31, 2016, and identified from the Surveillance, Epidemiology, and End Results data set. The study was conducted from July 2019 to November 2020. The analyses were performed from July 2019 to June 2020.ExposuresRace and ethnicity, including non-Hispanic African American and non-Hispanic White race.Main outcomes and measuresUsing logistic regression analysis and competing risk regression analysis, we estimated odds ratios (ORs) of receipt of treatment and hazard ratios (HRs) of breast cancer mortality in African American patients compared with White patients.ResultsOf 23 213 participants, 5881 (25.3%) were African American women and 17 332 (74.7%) were White women. Compared with White patients, African American patients had lower odds of receiving surgery (OR, 0.69; 95% CI, 0.60-0.79) and chemotherapy (OR, 0.89; 95% CI, 0.81-0.99) after adjustment for sociodemographic, clinicopathologic, and county-level factors. During a 43-month follow-up, 3276 patients (14.2%) died of breast cancer. The HR of breast cancer mortality was 1.28 (95% CI, 1.18-1.38) for African American individuals after adjustment for sociodemographic and county-level factors. Further adjustment for clinicopathological and treatment factors reduced the HR to 1.16 (95% CI, 1.06-1.25). This association was observed in patients living in socioeconomically less deprived counties (HR, 1.26; 95% CI, 1.14-1.39), urban patients (HR, 1.21; 95% CI, 1.11-1.32), patients having stage II (HR, 1.19; 95% CI, 1.02-1.39) or III (HR, 1.15; 95% CI, 1.01-1.31) tumors that were treated with chemotherapy, and patients younger than 65 years (HR, 1.24; 95% CI, 1.12-1.37).Conclusions and relevanceIn this retrospective cohort study, African American women with nonmetastatic TNBC had a significantly higher risk of breast cancer mortality compared with their White counterparts, which was partially explained by their disparities in receipt of surgery and chemotherapy.
| S-EPMC8120441 | biostudies-literature
Project description:The use of multigene panel testing for patients with a predisposition to breast/ovarian cancer is increasing as the identification of variants is useful for diagnosis and disease management. We identified pathogenic and likely pathogenic (P/LP) variants of high-and moderate-risk genes using a 23-gene germline cancer panel in 518 patients with hereditary breast and ovarian cancers (HBOC). The frequency of P/LP variants was 12.4% (64/518) for high- and moderate-penetrant genes, namely, BRCA2 (5.6%), BRCA1 (3.3%), CHEK2 (1.2%), MUTYH (0.8%), PALB2 (0.8%), MLH1 (0.4%), ATM (0.4%), BRIP1 (0.4%), TP53 (0.2%), and PMS2 (0.2%). Five patients possessed two P/LP variants in BRCA1/2 and other genes. We also compared the results from in silico splicing predictive tools and exon splicing patterns from patient samples by analyzing RT-PCR product sequences in six P/LP intronic variants and two intronic variants of unknown significance (VUS). Altered transcriptional fragments were detected for P/LP intronic variants in BRCA1, BRIP1, CHEK2, PARB2, and PMS2. Notably, we identified an in-frame deletion of the BRCA1 C-terminal (BRCT) domain by exon skipping in BRCA1 c.5152+6T>C-as known VUS-indicating a risk for HBOC. Thus, exon splicing analysis can improve the identification of veiled intronic variants that would aid decision making and determination of hereditary cancer risk.
| S-EPMC7540976 | biostudies-literature
Project description:Background. Expansion of routine genetic testing for hereditary breast and ovarian cancer from conventional BRCA testing to a multigene test could improve diagnostic yield and increase the opportunity for cancer prevention in both identified carriers and their relatives. We use an economic decision model to assess whether the current knowledge on non-BRCA mutation prevalence, cancer risk, and patient preferences justifies switching to a multigene panel for testing of early-onset breast cancer patients. Methods. We evaluated routine testing by BRCA testing, a 7-gene panel, and a 14-gene panel using individual-level simulations of annual health state transitions over a lifetime perspective. Breast and ovarian cancer incidence is reduced and posttreatment survival is improved when high-risk mutations are detected and risk-reducing treatment offered. Most model inputs were synthesized from published literature. Intermediate health outcomes included breast and ovarian cancer incidence rates, along with organ-specific cancer mortality. Cost-effectiveness outcomes were health sector costs and quality-adjusted life years. Results. Intermediate health outcomes improved by testing with multigene panels. At a cost-effectiveness threshold of $77,000, a 7-gene panel test with five non-BRCA genes was the optimal strategy with an incremental cost-effectiveness ratio of $53,310 per quality-adjusted life year compared to BRCA-only testing. Limitations. Unable to stratify carriers to specific mutations within genes, we can only make predictions on the gene level, with combined risk estimates for known variants. As mutation prevalence is the absolute upper bound of returns to more expansive testing, the rarity of modelled mutations makes analysis outcomes sensitive to model implementation. Conclusions. A 7-gene panel to diagnose hereditary breast and ovarian cancer in early-onset breast cancer patients can be a cost-effective alternative to current BRCA-only testing in Norway.
| S-EPMC6360477 | biostudies-literature
Project description:Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women.We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry.Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38-0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36-0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07-0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09-0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57-1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56-3.8, p = 0.45) women.African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.
| S-EPMC3663918 | biostudies-literature