Polygenic risk scores (PRS) for breast cancer may help guide screening decisions. However, few studies have examined whether PRS are associated with risk of short-term or poor prognosis breast cancers. The study purpose was to evaluate the association of the 313 SNP breast cancer PRS with 2-year risk of poor prognosis breast cancer.
We evaluated the association of breast cancer PRS with breast cancer overall, ER + and ER- breast cancer, and poor prognosis breast cancer diagnosed within 2 years of a negative mammogram among a cohort of 3657 women using logistic regression adjusted for age, breast density, race/ethnicity, year of screening, and genetic ancestry principal components. Breast cancers were considered poor prognosis if they were metastatic, positive lymph nodes, ER/PR + HER2− and > 2 cm, ER/PR/HER2−, or HER2 + and > 1 cm.
Of the 308 breast cancers, 137 (44%) were poor prognosis. The overall breast cancer PRS was significantly associated with breast cancer diagnosis within 2 years (OR 1.39, 95% CI 1.23–1.57, p < 0.001). The breast cancer PRS was also associated specifically with diagnosis of poor prognosis disease (OR 1.24, 95% CI 1.03–1.49, p = 0.018), but was more strongly associated with good prognosis cancer (OR 1.52 95% CI 1.29–1.80 p = 3.60 × 10–7) The ER + PRS was significantly associated with ER/PR + breast cancer (OR 1.41, 95% CI 1.24–1.61, p < 0.001) and the ER− PRS was significantly associated with ER− breast cancer (OR 1.48, 95% CI 1.08–2.02, p = 0.015).
Breast cancer PRS was independently and significantly associated with diagnosis of both breast cancer overall and poor prognosis breast cancer within 2 years of a negative mammogram, suggesting PRS may help guide decisions about screening intervals and supplemental screening.
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The datasets generated during and/or analyzed during the current study are not publicly available due to patient privacy protections, but de-identified data are available from the corresponding author on reasonable request and with institutional approval.
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This work was supported by the Susan G. Komen Foundation (PI McCarthy CCR17480662).
Conflict of interest
Dr. Lehman reports that her institution, Massachusetts General Hospital, receives research support from GE Healthcare and Hologic, Inc. and that she is a co-founder and serves as a consultant to Clairity, Inc. The other authors report no conflicts of interest.
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McCarthy, A.M., Manning, A.K., Hsu, S. et al. Breast cancer polygenic risk scores are associated with short-term risk of poor prognosis breast cancer. Breast Cancer Res Treat 196, 389–398 (2022). https://doi.org/10.1007/s10549-022-06739-5
- Breast cancer
- Polygenic risk score
- Poor prognosis