Breast Cancer Susceptibility Gene Sequence Variations and Development of Contralateral Breast Cancer
2024

Breast Cancer Gene Variants and Contralateral Breast Cancer Risk

Sample size: 1290 publication 10 minutes Evidence: moderate

Author Information

Author(s): Reiner Anne S. MPH, Watt Gordon P. PhD, Malone Kathleen E. PhD, Lynch Charles F. MD PhD, John Esther M. PhD, Knight Julia A. PhD, Woods Meghan MPH, Liang Xiaolin MS, Tischkowitz Marc MD PhD, Conti David V. PhD, Robson Mark E. MD, Mellemkjær Lene PhD, Teraoka Sharon N. PhD, Concannon Patrick PhD, Bernstein Jonine L. PhD

Primary Institution: Memorial Sloan Kettering Cancer Center

Hypothesis

Are moderate- to high-risk breast cancer susceptibility variants associated with development of estrogen receptor (ER)-positive and ER-negative contralateral breast cancer (CBC) subtypes?

Conclusion

Deleterious variants in breast cancer susceptibility genes are associated with different rates of ER-specific contralateral breast cancer subtypes.

Supporting Evidence

  • The rate of ER-positive CBC was 5 to 6 times higher in women with deleterious variants in BRCA2, ATM, and CHEK2.
  • The rate of ER-negative CBC was 26 times higher in women with deleterious BRCA1 variants.
  • First primary breast cancer ER status did not modify associations between deleterious variants and ER-specific CBC development.

Takeaway

Women with certain gene changes are more likely to develop breast cancer in the other breast, depending on the type of cancer they had first.

Methodology

This case-control study included women diagnosed with breast cancer and examined the association of gene variants with contralateral breast cancer.

Potential Biases

Potential bias due to non-standardized HR status determination and limited genotyping of other variants.

Limitations

The study had a relatively small number of carriers with deleterious variants and wide confidence intervals due to the small sample size.

Participant Demographics

Women younger than 55 years at first invasive breast cancer diagnosis.

Statistical Information

P-Value

p<0.001

Confidence Interval

95% CI, 1.11-21.08; 95% CI, 2.61-13.26; 95% CI, 8.01-85.44

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1001/jamanetworkopen.2024.52158

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication