Polygenic Risk Score Blood Test Predicts Future Breast Cancer

Breast cancer remains the most common cancer among women, accounting for over 15% of all new cancer diagnoses in the United States. While abnormal breast cells such as ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) are not invasive, they can develop into breast cancer over time. However, clinicians currently lack reliable methods to determine which early-stage abnormalities will progress. Now, a new test offers a way to identify women at higher risk of future breast cancer based on their genetic profile.

Researchers from King’s College London (London, UK) conducted a retrospective study evaluating a 313-SNP breast cancer polygenic risk score (PRS313) as a potential predictor for future breast cancer in women previously diagnosed with DCIS or LCIS. The PRS313 test estimates a patient’s cancer risk by analyzing 313 single-nucleotide polymorphisms (SNPs)—gene variants associated with breast cancer. The test, previously validated in healthy populations, was assessed for its ability to predict cancer development in early-stage breast disease cases.

Image: Breast biopsy photomicrograph of ductal carcinoma in situ (DCIS)—The study’s findings could help refine treatment strategies for women with DCIS or LCIS (Photo courtesy of Shutterstock)

The study, published in Cancer Epidemiology, Biomarkers & Prevention, analyzed genetic and clinical data from 2,169 DCIS cases and 185 LCIS cases collected from the UK ICICLE and GLACIER studies. PRS313 scores were divided into quartiles for DCIS patients and correlated with follow-up outcomes. In LCIS cases, associations between increasing PRS313 scores and cancer incidence were assessed to determine predictive accuracy across both disease types.

The findings revealed that DCIS patients in the highest PRS313 quartile were 2.03 times as likely to develop cancer in the opposite (contralateral) breast compared with those in the lowest quartile. While the association with same-breast recurrence was not significant, results for LCIS patients showed that higher PRS313 scores correlated with a 2.16-fold increased risk of cancer in the same (ipsilateral) breast. The predictive effect was even stronger among LCIS patients with a family history of breast cancer, where risk rose more than threefold.

These results suggest that genetic profiling using PRS313 could help refine treatment strategies for women with early-stage breast abnormalities. By identifying individuals at greatest risk of developing invasive disease, physicians could personalize monitoring and preventive therapies—potentially reducing overtreatment for lower-risk patients. Further validation in larger, diverse populations will be essential before clinical adoption.

“The associations found in this study could be useful in helping women decide their treatment options after a diagnosis of DCIS or LCIS. By looking at the full picture, rather than just how cells look under a microscope, we can give women more accurate information about their personal risk of recurrence and help them make informed decisions about their care,” said Jasmine Timbres, clinical information analyst at King’s College London.