This weekly update brings you the latest in breast cancer guidelines and research from the past week. We summarize guidelines and highlight key points to help patients, caregivers, and health care professionals stay current with this dynamic, evolving field. Note that both U.S. and international guidelines and research are included, so that we are inclusive of both domestic and international audiences.

The week’s top guidelines and research:

1. Long-term effect of neoadjuvant denosumab treatment in high-risk early breast cancer (GeparX)
GeparX is a randomized, open-label, phase II study comparing neoadjuvant treatment with or without denosumab and two different nab-paclitaxel (nPac) schedules. Invasive disease-free survival (iDFS), distant disease-free survival (DDFS), overall survival (OS), and locoregional recurrence-free interval (LRRFI) were considered as time-to-event endpoints. Denosumab as part of neoadjuvant therapy, although not improving the pathological complete response (pCR) rate, significantly reduced the risk of distant relapses. Other long-term outcome parameters did not differ between the treatment arms. Triple-negative breast cancer (TNBC) patients, especially when not achieving pCR, seem to benefit from weekly nPac. Long-term GeparX results showed no improvement in pCR, DFS, or OS with perioperative denosumab.

Key message:
Denosumab does increase pathological response rates in high-risk early breast cancer, however it could have an impact in reducing distant recurrence, in line with prior data regarding use of anti-resorptive agents for high risk patients.

Reference: ESMO Open, 2025 — Read here

2. Endocrine-based strategies after CDK4/6 inhibitors in biomarker-selected HR+ advanced breast cancer: A systematic review and network meta-analysis
Key takeaways:

• In estrogen receptor 1 (ESR1)-mutated tumors, oral selective ER degraders (SERDs) outperform fulvestrant and work even better when combined with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) or mammalian target of Rapamycin (mTOR) inhibitors.
• PI3K/AKT/mTORi + fulvestrant provides the strongest activity with early overall survival (OS) benefit.
• Biomarker-directed sequencing improves progression-free survival (PFS) outcomes.

Key message:
Optimal post-CDK4/6i management requires precision-guided endocrine combinations, with biomarker driven decisions.

Reference: Cancer Treatment Reviews, 2025 — Read here

3. Breast cancer risk during oral contraceptive use in women with high polygenic risk
Oral contraceptive (OC) use is widespread globally. Despite their significant benefits, concerns persist about a potential rise in breast cancer risk linked to their use. Both OC use and a high polygenic risk score (PRS) increase the risk of breast cancer. According to this study, there is a trend toward a decreased relative risk associated with OC use among those with higher genetic predisposition. Therefore, there is no evidence to suggest that women with a high genetic risk for breast cancer are more adversely affected by OC use.

Key message:
Oral contraceptive-associated breast cancer risk is modest and does not increase in women with high genetic risk.

Reference: Breast Cancer Research, 2025 — Read here