A polygenic risk score (PRS) may help identify women who are at a greater risk of developing a future breast cancer after treatment for in situ breast disease, a retrospective study suggests.

The blood-based test, called PRS313, gauges 313 gene variants (single nucleotide polymorphisms) associated with breast cancer susceptibility. It has already been shown to reliably predict breast cancer risk in the general population.

Now a team at King’s College London, London, England, reports that PRS313 may also predict the risk for future in situ or invasive disease after ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS). They published their findings in Cancer Epidemiology, Biomarkers & Prevention.

The score — if validated prospectively — could be practice changing, according to Salvatore Nardello, DO, surgical breast oncologist at Tufts Medical Center in Boston.

Nardello, who was not involved in the study, noted that histopathology alone often cannot predict which in situ lesions will become invasive.

Incorporating PRS313, he said, could potentially help clinicians better tailor treatment, surveillance, and risk-reduction strategies — helping to lessen the risks for both over- and undertreatment.

To assess the risk score, Jasmine Timbres and colleagues used data from two UK breast cancer studies: ICICLE (focused on DCIS) and GLACIER (focused on LCIS). They looked at the association between PRS313 scores and outcomes (further in situ disease or invasive disease) for 2169 women with DCIS and 185 with LCIS, followed for a median of 11 years.

Nearly all patients with DCIS underwent a lumpectomy or mastectomy, with or without radiotherapy. Most patients with LCIS had surgery, with 78% undergoing lumpectomy, but few received radiotherapy.

Overall, the 10-year risk for further breast disease was 16.3% and 17.5% in the DCIS and LCIS groups, respectively; the corresponding risks for invasive ipsilateral disease were 4% and 5%.

The analysis found that PRS313 scores helped predict the risk for future in situ or invasive disease, but the results varied between DCIS and LCIS.

For DCIS, patients within the highest risk score quartile had a two times greater risk for contralateral breast disease than patients in the lowest quartile. No association was found between the risk score and ipsilateral breast disease — likely because DCIS treatment substantially cuts the risk for recurrence in the same breast, the researchers noted.

However, among patients with LCIS, there was a clear association between the continuous PRS313 score and ipsilateral breast disease: Increasing scores corresponded to a more than twofold increase in the risk for ipsilateral in situ or invasive disease. There was no statistically significant association between the risk score and contralateral breast disease.

Digging deeper, the investigators found that a family history of breast cancer played a key role in results for patients with LCIS. Those with increasing PRS313 scores plus a family history had more than triple the odds of developing either any ipsilateral disease or invasive disease.

Meanwhile, the risk for ipsilateral disease was increased by more than fourfold if patients with LCIS with higher scores had not received mastectomy or radiotherapy.

In a press release, Timbres said that although LCIS is typically managed less aggressively, these findings suggest that PRS313 and family history could help guide those treatment decisions.

Nardello agreed. “In the context of LCIS,” he said, “a high PRS, especially in the presence of family history, might shift management to favor high-risk screening and chemoprevention.”

On the flip side, Nardello added, patients with a low PRS “could potentially be spared more intensive treatment or follow-up, which aligns with ongoing de-escalation strategies in early breast cancer management.”

For patients with DCIS, he said, a high PRS313 score might spur clinicians to “more proactively” recommend endocrine therapy, for example. Timbre’s team noted that ongoing trials are evaluating the safety of active surveillance (without surgery) for women considered to have low-risk DCIS. The PRS, they suggest, could potentially help refine the patient group most suited to active surveillance.

The risk score shows promise for patient care, agreed Nancy Chan, MD, director of breast cancer clinical research at NYU Langone Health in New York City.

Besides helping to guide treatment decisions, Chan noted, a high PRS313 score might encourage some patients to incorporate more lifestyle measures that could further reduce their risk for future breast cancer.

Nardello stressed that prospective data on the score’s utility are still needed — particularly for LCIS, where this study had a limited sample size.

In addition, the researchers pointed out, PRS313 was designed to predict invasive disease specifically and therefore may be missing “important but as-yet-unknown” gene variants associated with in situ disease.

The study had no commercial funding. One coauthor disclosed having financial ties with AstraZeneca, Pfizer, and several other pharmaceutical companies.

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.