# Breast cancer risk level and prediction of tumor aggressiveness in the Athena Breast Health Network

## TL;DR

This study found that high breast cancer risk scores are linked to non-advanced tumors, which are often hormone receptor-positive, suggesting the risk model could help identify candidates for hormone therapy.

## Contribution

The study links BCSC risk scores to tumor aggressiveness, showing they are associated with non-advanced rather than advanced breast cancer.

## Key findings

- High BCSC risk scores were associated with non-advanced invasive breast cancer (OR = 2.25).
- High BCSC risk scores were not significantly associated with advanced breast cancer (OR = 1.20).
- Non-advanced cancers were more likely to be hormone receptor-positive, suggesting BCSC could help identify endocrine therapy candidates.

## Abstract

Determine the association between the Breast Cancer Surveillance Consortium v2 model (BCSC) risk score and advanced and non-advanced invasive breast cancer (IBC).

We estimated BCSC 5-year invasive breast cancer risk for 11,915 participants in a prospective screening cohort with median follow-up of 6.9 years prior to breast cancer diagnosis. Individuals in the top 25% by age of BCSC risk standard were considered high-risk, those in the bottom 75% low-risk.

We obtained cancer outcomes, including American Joint Committee on Cancer (AJCC) prognostic pathologic stage, from the San Francisco Mammography Registry and an institutional cancer registry. We examined the associations of BCSC risk scores with advanced (≥ AJCC prognostic stage II) and non-advanced (AJCC prognostic stage I) IBC using Fisher’s exact test and logistic regression.

Of 11,915 participants, 4,005 (34%) were high-risk. There were 254 incident IBC cases, of which 40 (16%) were advanced and 214 (84%) were non-advanced. The median 5-year BCSC risk score for women with and without IBC was 1.83% and 1.45%, respectively (p < 0.001). High BCSC risk among women diagnosed with breast cancer was associated with non-advanced cancer (OR = 2.25, 95% CI = 1.71–2.95, p < 0.0001), but not with advanced cancer (OR = 1.20, 95% CI = 0.63–2.29, p = 0.57) compared to women not diagnosed with breast cancer.

High BCSC risk scores were associated with high rates of non-advanced IBC. As non-advanced cancers are more likely to be hormone receptor-positive, BCSC may optimally identify candidates for endocrine risk reduction.

The online version contains supplementary material available at 10.1007/s10549-025-07894-1.