Traceback: A Proposed Framework to Increase Identification and Genetic Counseling of BRCA1 and BRCA2 Mutation Carriers Through Family-Based Outreach

Abstract

In May 2016, the Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, National Cancer Institute, convened a workshop to discuss a conceptual framework for identifying and genetically testing previously diagnosed but unreferred patients with ovarian cancer and other unrecognized BRCA1 or BRCA2 mutation carriers to improve the detection of families at risk for breast or ovarian cancer. The concept, designated Traceback, was prompted by the recognition that although BRCA1 and BRCA2 mutations are frequent in women with ovarian cancer, many such women have not been tested, especially if their diagnosis predated changes in testing guidelines. The failure to identify mutation carriers among probands represents a lost opportunity to prevent cancer in unsuspecting relatives through risk-reduction intervention in mutation carriers and to provide appropriate reassurances to noncarriers. The Traceback program could provide an important opportunity to reach families from racial, ethnic, and socioeconomic groups who historically have not sought or been offered genetic counseling and testing and thereby contribute to a reduction in health disparities in women with germline BRCA mutations. To achieve an interdisciplinary perspective, the workshop assembled international experts in genetics, medical and gynecologic oncology, clinical psychology, epidemiology, genomics, cost-effectiveness modeling, pathology, bioethics, and patient advocacy to identify factors to consider when undertaking a Traceback program. This report highlights the workshop deliberations with the goal of stimulating research and providing a framework for pilot studies to assess the feasibility and ethical and logistical considerations related to the development of best practices for implementation of Traceback studies.

Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer

“…17,36 Furthermore, a strategy of widespread and more comprehensive testing in patients with cancer may be the most cost-effective approach to identifying genetic predisposition in families. 2,37 Breast cancer is an important early exemplar of the experiences and consequences of more expansive genetic testing in practice. Our findings demonstrate that sequencing more genes offers the potential advantage of more clinically valu-able information and also pinpoints gaps that must be bridged to realize that potential.…”

Estimating the number of potential family members eligible for BRCA1 and BRCA2 mutation testing in a “Traceback” approach

“…Of the 234,467 patients diagnosed with HGOC between 2005 and 2016, approximately 99,409 would be alive in 2017. Contactable patients could be consented to provide a blood sample for genetic testing at a certified laboratory (Samimi et al., ). In the model in which BRCA1/2 genetic testing was projected to increase 2% per year after 2010, a total of 85,571 living patients would not have undergone genetic testing and could potentially be contacted to provide informed consent and undergo counseling and BRCA1/2 mutation testing.…”

“…This number was subtracted by 1 to represent the patient and to estimate the average number of siblings. The life expectancy table in the 2016 CDC Vital Statistic was used to estimate the number of siblings that would be alive in 2017 sample for genetic testing at a certified laboratory (Samimi et al, 2017). In the model in which BRCA1/2 genetic testing was projected to increase 2% per year after 2010, a total of 85,571 living patients would not have undergone genetic testing and could potentially be contacted to provide informed consent and undergo counseling and BRCA1/2 mutation testing.…”

The Role of Genetic Counseling in Gynecological Oncology

“…The Traceback program could offer a valuable opportunity to reach families from different racial, ethnic, and socio-economic groups who historically have not sought or been offered genetic counseling and testing and thereby contribute to a reduction in health disparities in women with germline BRCA mutations. The workshop assembled international experts in genetics, medical and gynecological oncology, clinical psychology, epidemiology, genomics, cost-effectiveness modeling, pathology, bioethics, and patient advocacy to identify factors to consider when undertaking a Traceback program to achieve an interdisciplinary perspective [113][114][115].…”