While advancements in treatment have significantly improved outcomes for patients with breast cancer, those diagnosed at 40 years or younger remain at a heightened risk for locoregional recurrence (LRR). A new analysis presented at the 2026 American Association for Cancer Research AACR Annual Meeting examined a modern cohort of 1058 patients to identify which clinical factors and treatment modalities most significantly impacted the risk of the cancer returning to the original site or nearby lymph nodes.
Top 3 Takeaways
Overall Low Recurrence Rates in Modern Practice
Despite the historical risks associated with young-onset breast cancer, the study reported a 5-year cumulative incidence of LRR at 4.1% after a median follow-up of 3.6 years. This suggested that modern multidisciplinary care is effective, though specific subgroups—particularly those with high tumor stages—remain at higher risk.
Endocrine Therapy Adherence is Crucial for HR+ Disease
For patients with hormone receptor–positive (HR+) disease, the data underscored the protective power of endocrine therapy (ET). Patients who received a lumpectomy with or without radiotherapy, were HR+, and did not receive ET had a significantly higher risk of LRR (sHR, 3.09; 95% CI, 1.17-8.20; P = .023) compared with those who did, which was the reference point, highlighting adherence as a primary modifiable risk factor.
Subdistribution Hazard Ratios for Predicting LRR
To predict LRR among patients with breast cancer, an sHR was used. The investigators highlighted those with stage III disease (sHR, 3.41; 95% CI, 1.07-10.9; P = .04), HR+ disease without ET (sHR, 3.60; 95% CI, 1.42-9.11; P = .007); mastectomy (sHR, 0.22; 95% CI, 0.08-0.59; P = .003); and mastectomy plus radiation therapy (sHR, 0.08; 95% CI, 0.02-0.03; P <.001).
Patient Characteristics and Additional Data
The mean age at primary diagnosis was 35.3 years, 8.8% of patients were germline pathogenic variant carriers, and 51.2% had HR+/HER2– disease. Additionally, 47.1% of patients had stage II disease, 37.4% received lumpectomy plus radiation, and 50.9% were given adjuvant chemotherapy. If the tumor was HR+, ET was given to 80.4% of patients.
At Dana-Farber Cancer Institute, this trial was conducted through a large prospectively maintained database, which included clinicopathologic and treatment information. Patients included women 40 years or younger who underwent surgery from January 2016 to April 2023 and had a minimum of 3 months of follow-up. Follow-up was conducted via medical record review through January 2025.
“When we looked at the factors, individual stage, grade, and tumor size came up as tumor factors that were predictive of LRR. The treatment factors included endocrine therapy, mastectomy vs lumpectomy and radiation therapy, as well as adjuvant chemotherapy. When we looked at these factors together, what arose was the stage of the tumor [and] mastectomy plus radiation,” Kristen Brantley, PhD, instructor in medicine at Dana-Farber Cancer Institute and lead study author, said in an interview with CancerNetwork®. “We combined that as one variable because [patients are] often given mastectomy with or without radiation. The patients with lumpectomy in this cohort all had radiation. The other factor that came out was endocrine therapy. If you were eligible for endocrine therapy, and you had HR+ breast cancer, you tended to do better and not have LRR.”
Reference
Brantley KD, Parker T, Vincuilla J, et al. Risk factors for early locoregional recurrence among young-onset breast cancer patients: findings from a single institutional prospective dataset. Presented at the 2026 American Association for Cancer Research Annual Meeting, San Diego, CA; April 17-22, 2026. Poster 5223.
