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. 2017 Jun;163(2):383-390.
doi: 10.1007/s10549-017-4181-0. Epub 2017 Mar 9.

Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients

Beth Crawford  1 , Sophie B Adams  1   2 , Taylor Sittler  1   3 , Jeroen van den Akker  3 , Salina Chan  1 , Ofri Leitner  4 , Lauren Ryan  1   3 , Elad Gil  3 , Laura van 't Veer  5
Affiliations

Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients

Beth Crawford et al. Breast Cancer Res Treat. 2017 Jun.

Abstract

Purpose: Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing.

Methods: We tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma.

Results: Across the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene.

Conclusions: Among women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing.

Keywords: BRCA1; BRCA2; Breast cancer; Hereditary cancer; Ovarian cancer; Panel testing.

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Conflict of interest statement

Conflicts of interest

Beth Crawford, Salina Chan, and Laura van’t Veer have no conflicts of interest to disclose. Taylor Sittler, Jeroen Van den Akker, Lauren Ryan, and Elad Gil are full-time employees at Color Genomics and own Color Genomics stock. Sophie B. Adams, and Ofri Leitner were paid consultants at Color Genomics during this study. No authors have received any other financial compensation for professional services from another organization related to this research.

Informed consent

All patients in this study were previously enrolled in the long-term Cancer Risk Program Cohort study at UCSF, including informed consent for genetic testing.

Research involving animal and human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board at UCSF and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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