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Prevalence of Germline Pathogenic and Likely Pathogenic Variants in Patients With Second Breast Cancers.


ABSTRACT:

Background

Few studies have examined gene-specific associations with contralateral and/or second breast cancer (SBC).

Methods

The frequency of pathogenic and likely pathogenic (P/LP) variants in clinically actionable genes (BRCA1, BRCA2, PTEN, TP53, CHEK2, CDH1, ATM, PALB2, NBN, and NF1) was compared between women with a primary breast cancer (PBC) and SBC who underwent multigene panel testing at a single diagnostic testing laboratory. Race- and ethnicity-specific logistic regression burden tests adjusted for age at diagnosis of first breast cancer, histology, presence of first- or second-degree relatives with breast cancer, and prior testing for BRCA1/2 genes were used to test for associations with SBC. All statistical tests were 2-sided.

Results

The study was comprised of 75 550 women with PBC and 7728 with SBC. Median time between breast cancers for SBC was 11 (interquartile range?=?6-17) years. Restricting to women tested for all actionable genes (n?=?60 310), there were 4231 (7.8%) carriers of P/LP variants in actionable genes among the controls (PBC) compared with 652 (11.1%) women with SBC (P< .001). Among Caucasians, exclusive of Ashkenazi Jewish women, those carrying a P/LP variant in a clinically actionable gene were 1.44 (95% confidence interval [CI] = 1.30 to 1.60) times as likely to have SBC than noncarriers, after accounting for potential confounders. Among African American and Hispanic women, a P/LP variant in a clinically actionable gene was 1.88 (95% CI = 1.36 to 2.56) and 1.66 (9% CI = 1.02 to 2.58) times as likely to be associated with SBC, respectively (P < .001 and P = .03).

Conclusion

Women with P/LP variants in breast cancer predisposition genes are more likely to have SBC than noncarriers. Prospective studies are needed confirm these findings.

SUBMITTER: Yao K KA 

PROVIDER: S-EPMC7771422 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Prevalence of Germline Pathogenic and Likely Pathogenic Variants in Patients With Second Breast Cancers.

Yao K Katharine A KA   Clifford Jacob J   Li Shuwei S   LaDuca Holly H   Hulick Peter P   Gutierrez Stephanie S   Black Mary Helen MH  

JNCI cancer spectrum 20201026 6


<h4>Background</h4>Few studies have examined gene-specific associations with contralateral and/or second breast cancer (SBC).<h4>Methods</h4>The frequency of pathogenic and likely pathogenic (P/LP) variants in clinically actionable genes (<i>BRCA1</i>, <i>BRCA2</i>, <i>PTEN</i>, <i>TP53</i>, <i>CHEK2</i>, <i>CDH1</i>, <i>ATM</i>, <i>PALB2</i>, <i>NBN</i>, and <i>NF1</i>) was compared between women with a primary breast cancer (PBC) and SBC who underwent multigene panel testing at a single diagno  ...[more]

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