Large multicentre cohort shows no significant differences in recurrence rates by surgery type or tumour subtype.
In a prospective cohort study published in JAMA Surgery, researchers report that young women diagnosed with early-stage breast cancer have a low long-term risk of isolated locoregional recurrence (LRR)—regardless of molecular subtype or type of local therapy received.
The analysis, based on the Young Women’s Breast Cancer Study, followed 1,135 women aged 40 or younger for a median of 10.1 years. The cumulative incidence of isolated LRR was just 5.6%, leading the investigators to conclude that “concerns for long-term risk of LRR should not influence surgical decision-making with young women, irrespective of molecular subtype.”
Surgery Type Not a Major Driver of Recurrence
At 10 years, recurrence rates were comparable across surgical approaches: 6.7% after breast-conserving therapy (BCT), 6.5% after mastectomy without radiation, and 2.4% after mastectomy with radiation.
Although mastectomy plus radiation was associated with the lowest risk in multivariable analysis (hazard ratio 0.27; 95% CI, 0.13–0.59), the authors noted that “when examined within molecular subtype, there were no differences seen.” They emphasised that local therapy type should not be a primary driver of surgical choice.
Subtype-Specific Findings
LRR risk remained low across molecular subtypes:
- Luminal A: 4.4%
- Luminal B: 4.7%
- Luminal ERBB2+: 6.1%
- ERBB2+ (HER2-enriched): 2.2%
- Triple negative: 6.5%
They added that “in this contemporary cohort of women diagnosed with breast cancer at age 40 years or younger, risk of isolated LRR was relatively low (5.6%) at a median follow-up of 10.1 years, and significant differences were not seen by tumour subtype.”
“There were no significant differences associated with locoregional treatment type within molecular subtype,” the authors wrote.
Modern Systemic Therapy Makes the Difference
The authors attribute the lower recurrence rates observed to improvements in systemic therapy—particularly the increased use of endocrine and ERBB2-directed treatments. “Patients in our study were more likely to receive neoadjuvant chemotherapy… and more likely to receive ERBB2-directed therapy… largely reflecting the periods of enrolment of the 2 studies,” they wrote, comparing their findings to the earlier POSH cohort.
They also noted, “It is well recognised that optimal systemic therapy significantly reduces the risk for LRR.”
Implications for Clinical Decision-Making
Historically, young age has been associated with higher local recurrence risk, often steering patients toward more aggressive surgical options. But this new analysis challenges that approach.
“The overarching message is reassuring,” the authors suggested, “with modern systemic and local therapy, rates of LRR we observed were comparable with rates observed in contemporary studies inclusive of women of all ages.”
Even among patients with triple-negative breast cancer—the subtype with the highest observed LRR rate (6.5%)—the study found that several late recurrences likely represented new oestrogen receptor–positive primaries. “None of these recurrences were triple negative and likely represented a new primary breast cancer,” the authors wrote.
Need for Continued Long-Term Follow-Up
While results were encouraging, the authors cautioned that long-term monitoring remains important: “Given the lengthy survivorship period for young women with breast cancer and increased numbers of young women being diagnosed, even longer-term follow-up is critical for understanding future LRR risk in these patients.”
They also highlighted the need for better support for endocrine therapy adherence: “Efforts to support adherence to endocrine therapy among young women with hormone-sensitive breast cancer are essential.”
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This large, modern study provides strong evidence that young age alone should not dictate more aggressive surgical treatment. With contemporary systemic therapy and appropriate local management, young women can expect low rates of isolated local recurrence across all molecular subtypes.s
Study Limitations
The study was not without limitations. “Most study participants were White and non-Hispanic, with earlier-stage disease,” the authors acknowledged. They also noted that selection bias may have influenced recurrence outcomes among patients who received mastectomy with radiation, given that these individuals were more likely to have high-risk disease.
Paper: Dominici LS, Zheng Y, King TA, et al. Long-Term Locoregional Outcomes in a Contemporary Cohort of Young Women With Breast Cancer. JAMA Surg. Published online July 23, 2025. doi:10.1001/jamasurg 2025.2324. Access online here.
