Abstract P6-08-20: Cancer risk management and family sharing of genetic test results among women with inherited breast cancer genes

Abstract Background A diagnosis of suspected Lynch syndrome (SLS) is given when a tumour displays characteristics consistent with Lynch syndrome (LS), but no germline pathogenic variant is identified. This inconclusive diagnosis results in uncertainty around appropriate cancer risk management. This qualitative study explored how patients with CRC interpret and respond to an SLS diagnosis. Methods Semi-structured telephone interviews were conducted with 15 patients with CRC who received an SLS diagnosis, recruited from cancer genetics services across Australia. Interviews were transcribed verbatim and analysed using thematic analysis. Participant responses were compared with appointment summary letters from cancer genetics services. Results Participants’ interpretations of genetic test results were found to vary widely. While this variation often aligned with variation in interpretations by cancer genetics services, participants also had difficulties with the complexity and recall of genetic test results. Participants had a range of psychological responses to the uncertainty that their results presented, from relief to disappointment and doubt. Cancer risk perceptions also varied widely, with participants’ interpretations of their genetic test results just one of several influencing factors. Despite this variability, almost all participants adhered to cancer risk management advice, although different participants received different advice. All participants also communicated any cancer risk management advice to first-degree relatives, motivated by protecting them, but information communicated was not always consistent with advice received. Conclusions Our study findings highlight the variability in patients’ interpretations of their diagnosis, cancer risk management and family communication when a diagnosis of SLS is received, and provide novel insights into how healthcare professionals can better support patients with SLS.

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Cancer risk management and family communication of genetic test results among women with inherited breast cancer genes.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1532 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1532-1532

Author(s):

Tuya Pal ◽

Anne Weidner ◽

Ann Tezak ◽

Kate Clouse ◽

Deborah Cragun

Keyword(s):

Breast Cancer ◽

Family Communication ◽

Genetic Test ◽

Bilateral Mastectomy ◽

Test Results ◽

Genetic Test Results ◽

Family Testing ◽

Inherited Breast Cancer ◽

History Of ◽

Risk Reducing

1532 Background: Identification of inherited breast cancer may guide care, with benefits amplified through family testing. Methods: Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about cancer risk management, family communication of genetic test results, and family testing. Comparisons were made across genes. Results: The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and 61% had a prior breast cancer diagnosis. For women with P/LP variants in BRCA1/2, PALB2, and ATM/CHEK2, bilateral mastectomy rates were 79%, 61%, and 52%, respectively; and risk-reducing oophorectomy rates were 89%, 30%, and 37%, respectively. All women with PALB2 and ATM/CHEK2 P/LP variants with a bilateral mastectomy had a personal or family history of breast cancer; however, only 27% of those with a risk-reducing oophorectomy had a family history of ovarian cancer. Family communication of genetic test results and family testing rates were higher for those with P/LP variants in BRCA1/2 compared to others. Conclusions: Bilateral mastectomy and risk-reducing oophorectomy were relatively common among women with PALB2 and ATM/CHEK2 P/LP variants in our study, suggesting overtreatment through risk-reducing surgery. Furthermore, strategies to improve family communication of genetic test results and family testing are needed to amplify testing benefits.

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BRCA testing concordance with national guidelines for patients with breast cancer in community cancer programs.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1526 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1526-1526

Author(s):

Leigh Boehmer ◽

Latha Shivakumar ◽

Christine B. Weldon ◽

Julia Rachel Trosman ◽

Stephanie A. Cohen ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Genetic Test ◽

Breast Conserving Surgery ◽

Test Results ◽

Cancer Genes ◽

National Guidelines ◽

Genetic Test Results ◽

The Impact

1526 Background: Current National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment state that testing for highly penetrant breast/ovarian cancer genes is clinically indicated for women with early onset (≤ 45 years) or metastatic HER-2 negative breast cancer. A recent Association of Community Cancer Centers (ACCC) survey (N = 95) showed that > 80% of respondents reported ≤ 50% testing rate of patients with breast cancer who met guidelines. Given this disconnect, ACCC partnered with 15 community cancer programs to assess practice gaps and support interventions to improve access to genetic counseling (GC)/testing. Methods: Pre-intervention data from 9/15 partner programs for women diagnosed with stages 0-III breast cancer between 01/01/2017 and 06/30/2019 was collected. De-identified variables included: family history documentation, GC appointment/test results, and timing of results relative to treatment decisions. Results: There were 2691 women with stages 0-III breast cancer. Forty-eight percent (1284/2691) had a documented high-risk family history, 57% (729/1284) of whom had a GC appointment. This was a significantly higher rate of GC compared to the 23% (181/778) of women with no family history and 6% (35/629) of women with no documentation of family history (p < 0.0001). Patients ≤ 45 years old attended a GC appointment 72% (199/278) of the time and 49% (135/278) had genetic test results, with 84% (113/135) receiving results before surgery. For women with test results available before surgery, 37% (119/322) had breast conserving surgery, compared to 60% (144/240) with test results disclosed post-operatively (p < 0.0001). Conclusions: Genetic testing is underutilized in a community cohort of women with breast cancer. Further analysis is needed to understand the impact genetic test results have on surgical decisions. Opportunities exist to improve current rates of appropriate GC/testing. ACCC will share results of quality improvement projects to illuminate which strategies hold promise in reducing the hereditary breast cancer GC/testing practice gap.

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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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IMProving care After inherited Cancer Testing (IMPACT) study: protocol of a randomized trial evaluating the efficacy of two interventions designed to improve cancer risk management and family communication of genetic test results

BMC Cancer ◽

10.1186/s12885-021-08822-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Deborah Cragun ◽

Jason Beckstead ◽

Meagan Farmer ◽

Gillian Hooker ◽

Marleah Dean ◽

...

Keyword(s):

Risk Management ◽

Genetic Testing ◽

Family Communication ◽

Genetic Test ◽

Test Results ◽

Impact Study ◽

Inherited Cancer ◽

Genetic Test Results ◽

Cancer Risk Management

Abstract Background Implementing genetic testing for inherited cancer predisposition into routine clinical care offers a tremendous opportunity for cancer prevention and early detection. However, genetic testing itself does not improve outcomes; rather, outcomes depend on implemented follow-up care. The IMPACT study is a hybrid type I randomized effectiveness-implementation trial to simultaneously evaluate the effectiveness of two interventions for individuals with inherited cancer predisposition focused on: 1) increasing family communication (FC) of genetic test results; and 2) improving engagement with guideline-based cancer risk management (CRM). Methods This prospective study will recruit a racially, geographically, and socioeconomically diverse population of individuals with a documented pathogenic/likely pathogenic (P/LP) variant in an inherited cancer gene. Eligible participants will be asked to complete an initial trial survey and randomly assigned to one of three arms: A) GeneSHARE, a website designed to increase FC of genetic test results; B) My Gene Counsel’s Living Lab Report, a digital tool designed to improve understanding of genetic test results and next steps, including CRM guidelines; or C) a control arm in which participants continue receiving standard care. Follow-up surveys will be conducted at 1, 3, and 12 months following randomization. These surveys include single-item measures, scales, and indices related to: 1) FC and CRM behaviors and behavioral factors following the COM-B theoretical framework (i.e., capability, opportunity, and motivation); 2) implementation outcomes (i.e., acceptability, appropriateness, exposure, and reach); and 3) other contextual factors (i.e., sociodemographic and clinical factors, and uncertainty, distress, and positive aspects of genetic test results). The primary outcomes are an increase in FC of genetic test results (Arm A) and improved engagement with guideline-based CRM without overtreatment or undertreatment (Arm B) by the 12-month follow-up survey. Discussion Our interventions are designed to shift the paradigm by which individuals with P/LP variants in inherited cancer genes are provided with information to enhance FC of genetic test results and engagement with guideline-based CRM. The information gathered through evaluating the effectiveness and implementation of these real-world approaches is needed to modify and scale up adaptive, stepped interventions that have the potential to maximize FC and CRM. Trial registration This study is registered at Clinicaltrials.gov (NCT04763915, date registered: February 21, 2021). Protocol version September 17th, 2021 Amendment Number 04.

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