Tailoring Adjuvant Therapy for Younger Patients with Low-Risk Breast Cancer

Lior Braunstein

When considering adjuvant therapy preferences for younger patients ages 50 to 69 with early-stage, low genomic risk breast cancer, is it reasonable to omit radiotherapy (RT) or endocrine therapy (ET) after lumpectomy?

A large retrospective cohort study at MSK found that locoregional recurrence (LRR) rates were significantly lower for those who completed at least one form of adjuvant therapy after lumpectomy. Further, patients who received RT had the lowest 72-month LRR rate, regardless of ET duration. The findings were published September 17, 2025, in JAMA Network Open. (1)

“Our findings suggest that younger patients with early-stage, low genomic risk breast cancer may be able to consider foregoing either radiotherapy or endocrine therapy with modestly increased risk – but should not skip both,” said MSK radiation oncologist Lior Braunstein, MD, the senior author of the paper.”

De-escalating Adjuvant Therapy After Lumpectomy

Lumpectomy followed by adjuvant RT provides excellent disease control and survival outcomes and has been the standard breast-conserving therapy for early-stage breast cancer for decades. (2) (3) (4) (5) However, the landmark studies that established this treatment strategy were conducted before the advent of disease subtyping and molecular profiling.

More recent observations have revealed subgroups with a very low risk of LRR who may not benefit from RT. The PRIME II and CALGB 9343 trials both demonstrated that older patients (65 and 70 years or more, respectively) with hormone receptor-positive breast cancer can forgo RT without compromising survival outcomes despite the marginally higher LRR risk.  (6) (7) (8)

Ongoing studies incorporating molecular and genomic biomarkers aim to identify low-risk groups in other age groups. (9) (10)Recent studies, such as the LUMINA  (11), IDEA (12) , and PRECISION (13) trials, have found that the Ki67 and genomic recurrence scores can identify younger low-risk patients who may only benefit modestly from RT. 

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The Oncotype Dx Recurrence Score

The ODX RS is a robust tool for systemic therapy decision-making, given its ability to predict the risk of distant recurrence and chemotherapy benefit.  (14) (15) (16) Most recently, emerging data suggest that ODX RS correlates with LRR and may be instructive for determining local therapy.  (17) (18) (19) (20) (21)

International randomized trials evaluating ODX RS and other molecular assays for RT decision-making are currently underway, including the DEBRA trial (NCT04852887) at more than 800 locations, including MSK, and the EXPERT trial (NCT02889874) at more than 65 study sites in Australia, New Zealand, Europe, and Taiwan. 

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Study Design

The present retrospective study included data from 2,249 patients between the ages of 50 and 69 with T1N0, hormone receptor-positive, ERBB2-negative breast cancer and an ODX RS of 18 or lower. Patients were treated at MSK between January 2007 and January 2023 with lumpectomy and ET, with or without adjuvant RT.  (1)

ET adherence was defined as receiving therapy for five or more years. A total of 2,075 patients (92%) received RT after lumpectomy. 

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Study Findings

The 72-month cumulative LRR rates were as follows: (1)

  • 1.1% with RT versus 8.0% without RT
  • 5.5% for patients adherent to ET alone
  • 11% for patients who did not receive any adjuvant therapy (no RT and were ET nonadherent)

Additional findings: (1)

  • Patients who received ET for five or more years had a significantly higher disease-free survival (DFS) than those who received less than five years (hazard ratio 0.53; p = 0.004).
  • There was no association between overall survival and receiving RT.
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Advancing Breast Cancer Research at MSK

MSK treats more than 4,500 patients with breast cancer annually. The multidisciplinary Breast Cancer Team at MSK comprises more than 80 breast cancer specialists, including radiation oncologists, surgeons, medical oncologists, reconstruction surgeons, and advanced practice providers.

MSK breast cancer experts are dedicated to discovering new ways to improve patient outcomes through both retrospective and prospective clinical research. Learn more about breast cancer clinical trials at MSK. 

 

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