Dataset Information

Risk-reducing mastectomy decisions among women with mutations in high- and moderate- penetrance breast cancer susceptibility genes.

ABSTRACT:

Background

Women harboring mutations in breast cancer susceptibility genes are at increased lifetime risk of developing breast cancer and are faced with decisions about risk management, including whether to undergo high-risk screening or risk-reducing mastectomy (RRM). National guidelines recommend BRCA1 or BRCA2 mutation carriers consider RRM, but that carriers of moderate penetrance mutations (e.g., ATM or CHEK2) should be managed based on family history. We aimed to investigate determinants of decision for RRM, and hypothesized that mutation status, age, family history, partner status, and breast cancer would impact RRM decision making.

Methods

We performed a retrospective study assessing RRM decisions for 279 women.

Results

Women with BRCA and moderate penetrance gene mutations, a personal history of breast cancer, or a first degree relative with a history of breast cancer were more likely to undergo RRM. Breast cancer status and age showed an interaction effect such that women with breast cancer were less likely to undergo RRM with increasing age.

Conclusion

Although national guidelines do not recommend RRM for moderate penetrance carriers, the rates of RRM for this population approached those for BRCA mutation carriers. Further insights are needed to better support RRM decision-making in this population.

SUBMITTER: Comeaux JG

PROVIDER: S-EPMC9544212 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Risk-reducing mastectomy decisions among women with mutations in high- and moderate- penetrance breast cancer susceptibility genes.

Comeaux Jacob G JG Culver Julie O JO Lee John E JE Dondanville Danielle D McArthur Heather L HL Quinn Emily E Gorman Nicholas N Ricker Charité C Li Ming M Lerman Caryn C

Molecular genetics & genomic medicine 20220825 10

<h4>Background</h4>Women harboring mutations in breast cancer susceptibility genes are at increased lifetime risk of developing breast cancer and are faced with decisions about risk management, including whether to undergo high-risk screening or risk-reducing mastectomy (RRM). National guidelines recommend BRCA1 or BRCA2 mutation carriers consider RRM, but that carriers of moderate penetrance mutations (e.g., ATM or CHEK2) should be managed based on family history. We aimed to investigate determ ...[more]

PMID: 36054727

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Project description:Significant advances have been made to understand the genetic basis of breast cancer. High, moderate and low penetrance variants have been identified with inter-ethnic variability in mutation frequency and spectrum. Genome wide association studies (GWAS) are widely used to identify disease-associated SNPs. Understanding the functional impact of these risk-SNPs will help the translation of GWAS findings into clinical interventions. Here we aim to characterize the genetic patterns of high and moderate penetrance breast cancer susceptibility genes and to assess the functional impact of non-coding SNPs. We analyzed BRCA1/2, PTEN, STK11, TP53, ATM, BRIP1, CHEK2 and PALB2 genotype data obtained from 135 healthy participants genotyped using Affymetrix Genome-Wide Human SNP-Array 6.0. Haplotype analysis was performed using Haploview.V4.2 and PHASE.V2.1. Population structure and genetic differentiation were assessed using principal component analysis (PCA) and fixation index (FST). Functional annotation was performed using In Silico web-based tools including RegulomeDB and VARAdb. Haplotype analysis showed distinct LD patterns with high levels of recombination and haplotype blocks of moderate to small size. Our findings revealed also that the Tunisian population tends to have a mixed origin with European, South Asian and Mexican footprints. Functional annotation allowed the selection of 28 putative regulatory variants. Of special interest were BRCA1_ rs8176318 predicted to alter the binding sites of a tumor suppressor miRNA hsa-miR-149 and PALB2_ rs120963 located in tumorigenesis-associated enhancer and predicted to strongly affect the binding of P53. Significant differences in allele frequencies were observed with populations of African and European ancestries for rs8176318 and rs120963 respectively. Our findings will help to better understand the genetic basis of breast cancer by guiding upcoming genome wide studies in the Tunisian population. Putative functional SNPs may be used to develop an efficient polygenic risk score to predict breast cancer risk leading to better disease prevention and management.

Project description:ImportanceBreast reconstruction has the potential to improve a person's body image and quality of life but has important risks. Variations in who undergoes breast reconstruction have led to questions about the quality of patient decisions.ObjectiveTo assess the quality of patient decisions about breast reconstruction.Design, setting, and participantsA prospective, cross-sectional survey study was conducted from June 27, 2012, to February 28, 2014, at a single, academic, multidisciplinary oncology clinic among women planning to undergo mastectomy for stage I to III invasive ductal or lobular breast cancer, ductal carcinoma in situ, or prophylaxis.ExposuresMastectomy only and mastectomy with reconstruction.Main outcome and measuresKnowledge, as ascertained using the Decision Quality Instrument; preference concordance, based on rating and ranking of key attributes; and decision quality, defined as having knowledge of 50% or more and preference concordance.ResultsDuring the 20-month period, 214 patients were eligible, 182 were approached, and 32 missed. We enrolled 145 patients (79.7% enrollment rate), and received surveys from 131 patients (72.0% participation rate). Five participants became ineligible. The final study population was 126 patients. Among the 126 women in the study (mean [SD] age, 53.2 [12.1] years), the mean (SD) knowledge score was 58.5% (16.2%) and did not differ by treatment group (mastectomy only, 55.2% [15.0%]; mastectomy with reconstruction, 60.5% [16.5%]). A total of 82 of 123 participants (66.7%) had a calculated treatment preference of mastectomy only; 39 of these women (47.6%) underwent mastectomy only. A total of 41 participants (32.5%) had a calculated treatment preference of mastectomy with reconstruction; 36 of these women (87.8%) underwent mastectomy with reconstruction. Overall, 52 of 120 participants (43.3%) made a high-quality decision. In multivariable analysis, white race/ethnicity (odds ratio [OR], 2.72; 95% CI, 1.00-7.38; P = .05), having private insurance (OR, 1.61; 95% CI, 1.35-1.93; P < .001), having a high school education or less (vs some college) (OR, 4.84; 95% CI, 1.22-19.21; P = .02), having a college degree (vs some college) (OR, 1.95; 95% CI, 1.53-2.49; P < .001), and not having a malignant neoplasm (eg, BRCA carriers) (OR, 3.13; 95% CI, 1.25-7.85; P = .01) were independently associated with making a high-quality decision.Conclusions and relevanceA minority of patients undergoing mastectomy in a single academic center made a high-quality decision about reconstruction. Shared decision making is needed to support decisions about breast reconstruction.

Dataset Information

Risk-reducing mastectomy decisions among women with mutations in high- and moderate- penetrance breast cancer susceptibility genes.

Background

Methods

Results

Conclusion

Publications

Risk-reducing mastectomy decisions among women with mutations in high- and moderate- penetrance breast cancer susceptibility genes.

Similar Datasets

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