Breast Cancer Susceptibility Gene Sequence Variations and Development of Contralateral Breast Cancer
Anne S Reiner1, Gordon P Watt1, Kathleen E Malone2
1Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
JAMA Network Open
|January 9, 2025
Summary
Deleterious germline variants in breast cancer genes are linked to specific estrogen receptor (ER)-positive and ER-negative contralateral breast cancer (CBC) development. The ER status of the first primary breast cancer did not alter these associations.
Area of Science:
- Oncology
- Genetics
- Epidemiology
Background:
- Heterogeneity in estrogen receptor (ER)-specific breast cancer development is influenced by germline variants in moderate- to high-penetrance susceptibility genes.
- The association between these germline variants and ER-specific contralateral breast cancer (CBC) is not well understood.
Purpose of the Study:
- To investigate the association between deleterious germline variants in breast cancer susceptibility genes and the development of ER-specific CBC.
- To determine if the ER status of the first primary breast cancer modifies these associations.
Main Methods:
- A population-based case-control study (WECARE Study) included 1290 women diagnosed with breast cancer.
- Participants were matched on several factors, including age and race, and countermatched on radiation treatment.
- Deleterious germline variants in ATM, BRCA1, BRCA2, and CHEK2 1100delC were analyzed.
Main Results:
- Deleterious ATM variants were associated with a 4-fold higher rate of ER-positive CBC (RR, 4.84).
- Deleterious BRCA2 and CHEK2 1100delC variants showed 5- to 6-fold higher rates of ER-positive CBC (RR, 5.88 and 6.06, respectively).
- Deleterious BRCA1 variants were linked to a 26-fold higher rate of ER-negative CBC (RR, 26.16).
- The ER status of the first primary breast cancer did not modify these associations.
Conclusions:
- Deleterious germline variants in breast cancer susceptibility genes are differentially associated with ER-specific CBC development.
- Germline genetic profiles may help predict outcomes for ER-specific CBC subtypes.
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