Breast Cancer AMA Week: We are here from Facing Our Risk of Cancer Empowered (FORCE) and the National Society of Genetic Counselors to talk about managing breast and ovarian cancer risk and assuring all people have access to cancer risk management. AUA!

Abstract Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are increasingly used to reduce breast and ovarian cancer risk following BRCA1/BRCA2 testing. However, little is known about how genetic counseling influences decisions about these surgeries. Although previous studies have examined intentions prior to counseling, few have examined RRM and RRSO intentions in the critical window between genetic counseling and test result disclosure. Previous research has indicated that intentions at this time point predict subsequent uptake of surgery, suggesting that much decision-making has taken place prior to result disclosure. This period may be a critical time to better understand the drivers of prophylactic surgery intentions. The aim of this study was to examine predictors of RRM and RRSO intentions. We hypothesized that variables from the Health Belief Model would predict intentions, and we also examined the role of affective factors. Participants were 187 women, age 21–75, who received genetic counseling for hereditary breast and ovarian cancer. We utilized multiple logistic regression to identify independent predictors of intentions. 49.2% and 61.3% of participants reported intentions for RRM and RRSO, respectively. Variables associated with RRM intentions include: newly diagnosed with breast cancer (OR = 3.63, 95% CI = 1.20–11.04), perceived breast cancer risk (OR = 1.46, 95% CI = 1.17–1.81), perceived pros (OR = 1.79, 95% CI = 1.38–2.32) and cons of RRM (OR = 0.81, 95% CI = 0.65–0.996), and decision conflict (OR = 0.80, 95% CI = 0.66–0.98). Variables associated with RRSO intentions include: proband status (OR = 0.28, 95% CI = 0.09–0.89), perceived pros (OR = 1.35, 95% CI = 1.11–1.63) and cons of RRSO (OR = 0.72, 95% CI = 0.59–0.89), and ambiguity aversion (OR = 0.79, 95% CI = 0.65–0.95). These data provide support for the role of genetic counseling in fostering informed decisions about risk management, and suggest that the role of uncertainty should be explored further.

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Adapting the coping in deliberation (CODE) framework: A multi-method approach in the context of familial ovarian cancer risk management

Patient Education and Counseling ◽

10.1016/j.pec.2014.07.004 ◽

2014 ◽

Vol 97 (2) ◽

pp. 200-210 ◽

Cited By ~ 3

Author(s):

Jana Witt ◽

Glyn Elwyn ◽

Fiona Wood ◽

Mark T. Rogers ◽

Usha Menon ◽

...

Keyword(s):

Ovarian Cancer ◽

Risk Management ◽

Cancer Risk ◽

Ovarian Cancer Risk ◽

Familial Ovarian Cancer ◽

Multi Method Approach ◽

Method Approach ◽

Cancer Risk Management

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Impact of a decision aid about stratified ovarian cancer risk-management on women’s knowledge and intentions: a randomised online experimental survey study

BMC Public Health ◽

10.1186/s12889-017-4889-0 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 4

Author(s):

Susanne F. Meisel ◽

◽

Maddie Freeman ◽

Jo Waller ◽

Lindsay Fraser ◽

...

Keyword(s):

Ovarian Cancer ◽

Risk Management ◽

Cancer Risk ◽

Decision Aid ◽

Survey Study ◽

Ovarian Cancer Risk ◽

Women's Knowledge ◽

Women’S Knowledge ◽

Cancer Risk Management ◽

Experimental Survey

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Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers

Journal of Clinical Oncology ◽

10.1200/jco.2011.37.8133 ◽

2012 ◽

Vol 30 (12) ◽

pp. 1321-1328 ◽

Cited By ~ 22

Author(s):

Brian S. Finkelman ◽

Wendy S. Rubinstein ◽

Sue Friedman ◽

Tara M. Friebel ◽

Shera Dubitsky ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Risk ◽

Risk Reduction ◽

Ovarian Cancer Risk ◽

Jewish Women ◽

Cancer Risks ◽

Breast And Ovarian Cancer ◽

Mutation Carriers ◽

Significant Difference

Purpose Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.

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Multi-center prospective analysis of risk-reducing salpingo-oophorectomy to prevent BRCA-associated breast and ovarian cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1003 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1003-1003 ◽

Cited By ~ 5

Author(s):

N. D. Kauff ◽

S. M. Domchek ◽

T. M. Friebel ◽

J. B. Lee ◽

R. Roth ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Risk ◽

Genetic Test ◽

Ovarian Cancer Risk ◽

Test Results ◽

Breast And Ovarian Cancer ◽

Genetic Test Results ◽

Risk Reducing

1003 Background: Our groups previously reported on the efficacy of risk-reducing salpingo-oophorectomy (RRSO) for the prevention of BRCA-associated breast and ovarian cancer. (Kauff ND, et al. NEJM 2002; Rebbeck TR, et al. NEJM 2002) Limitations of those reports included relatively short prospective follow-up and lack of power to analyze the protection of RRSO when participants were stratified by BRCA1 vs. BRCA2. To address these limitations, we have pooled our updated datasets to provide robust estimates of the efficacy of RRSO. Methods: 886 women ≥ 30 years of age, with a deleterious mutation in BRCA1 or BRCA2 and ovaries in-situ at time of genetic test results, were enrolled on prospective follow-up studies at one of eleven centers from 11/1/1994 - 12/1/2004. Women chose to participate in either ovarian surveillance or undergo RRSO. Follow-up information was collected by questionnaire and medical record review. Follow-up time was counted from time of RRSO or from time of genetic test results for women who did not undergo RRSO. After excluding cancers diagnosed within the first 6 months of follow-up, the effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results: 559 (63%) participants underwent RRSO a median of 5 months after genetic test results. 12 occult ovarian or fallopian tube cancers were diagnosed at time of RRSO. During a mean 40 months follow-up, RRSO was associated with a 52% reduction in breast cancer risk and a 91% reduction in ovarian cancer risk (see Table ). When the cohort was stratified by mutation status, RRSO was associated with a reduced risk of BRCA1-associated ovarian cancer and BRCA2-associated breast cancer. Conclusions: The results confirm that RRSO is highly protective against BRCA-associated breast and ovarian cancer. These results also generate the hypothesis that the protection conferred by RRSO against specific cancers may differ between carriers of BRCA1 and BRCA2 mutations. [Table: see text] No significant financial relationships to disclose.

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Do breast cancer treatment and imaging providers follow hereditary breast and ovarian cancer risk screening guidelines?

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.e17626 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. e17626-e17626

Author(s):

Christine B. Weldon ◽

Julia Rachel Trosman ◽

Melissa A Simon ◽

Danielle Dupuy ◽

Betty Roggenkamp ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Risk ◽

Cancer Treatment ◽

Breast Cancer Treatment ◽

Ovarian Cancer Risk ◽

Breast And Ovarian Cancer ◽

Risk Screening ◽

Screening Guidelines

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CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival

Cancers ◽

10.3390/cancers14020353 ◽

2022 ◽

Vol 14 (2) ◽

pp. 353

Author(s):

Jordi Minguillón ◽

María José Ramírez ◽

Llorenç Rovirosa ◽

Pilar Bustamante-Madrid ◽

Cristina Camps-Fajol ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Dna Damage ◽

Dna Repair ◽

Homologous Recombination ◽

Cancer Risk ◽

Brca2 Mutation ◽

Ovarian Cancer Risk ◽

Breast And Ovarian Cancer ◽

Increased Risk

BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes.

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Laboratory Determination of Hereditary Susceptibility to Breast and Ovarian Cancer

Archives of Pathology & Laboratory Medicine ◽

10.5858/1999-123-1023-ldohst ◽

1999 ◽

Vol 123 (11) ◽

pp. 1023-1026

Author(s):

Tom S. Frank

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Prophylactic Surgery ◽

Ovarian Cancer Risk ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Management Options ◽

Increased Risk ◽

Hereditary Susceptibility ◽

Risk Of Cancer

Abstract Inherited mutations in the genes BRCA1 and BRCA2 are associated with a significantly increased risk of breast cancer, particularly before the age of 50 years, as well as an increased risk of ovarian cancer. Patients with early-onset breast cancer or ovarian cancer at any age with a family history of either disease are at higher risk of carrying a mutation in BRCA1 or BRCA2. Laboratory analysis of these genes can determine whether a patient has inherited an increased risk of breast and ovarian cancer. In the absence of a mutation that has been previously identified in a family member, most tests for hereditary breast-ovarian cancer risk analyze the entire coding sequences of BRCA1 and BRCA2. The gene sequencing process itself can be automated, but the data must be interpreted by an individual with training in molecular diagnostics. Management options generally available to individuals with hereditary susceptibility to breast and ovarian cancer include heightened surveillance, prophylactic surgery, and chemoprevention. The use of genetic techniques to identify women with increased risk of cancer demonstrates the application of recent advances in the understanding of the genetic basis of malignancy to laboratory medicine and clinical care.

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