This study evaluated whether the 313-SNP breast cancer polygenic risk score (PRS313) can predict the likelihood of developing ipsilateral or contralateral breast cancer after diagnosis of DCIS or LCIS by analyzing data from patients diagnosed with DCIS (N = 2,169) or LCIS (N = 185) from the Investigate the genetiCs of In situ Carcinoma of the ductaL subtypE (ICICLE) and A study to investigate the Genetics of LobulAr Carcinoma In situ in EuRope (GLACIER) studies, with a median follow-up of 11 years. Outcomes included any further in situ or invasive breast disease (including distant metastasis), ipsilateral breast disease, invasive ipsilateral breast disease, and contralateral breast disease.
This research provides strong evidence that PRS313 can serve as a valuable predictor of future breast cancer events in women with in situ breast cancer, specifically contralateral disease after DCIS and ipsilateral disease after LCIS.
Cox regression analysis revealed a significant association between increasing continuous PRS313 and the risk of contralateral disease following DCIS (HR = 1.30; 95% confidence interval, 1.08-1.56) and a link between PRS313 and ipsilateral disease after LCIS (HR = 2.16; 95% confidence interval, 1.22-3.81).
Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) are preinvasive breast lesions. DCIS is treated more aggressively, as it is more likely to develop into invasive disease than LCIS. Both DCIS and LCIS face an elevated risk of contralateral breast cancer. It is thus important to identify those at high risk of further breast disease in order to personalize treatment.
PRS313 has the potential to guide clinical decisions about surveillance, risk-reduction treatments, and personalized care in those with in situ breast cancers, which could improve outcomes and optimize the use of healthcare resources.
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