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Personalized radiation therapy for low-risk early breast cancer

A Randomised Phase III Trial of Adjuvant Radiation Therapy Versus Observation Following Breast Conserving Surgery and Endocrine Therapy in Patients With Molecularly Characterised Luminal A Early Breast Cancer

NA · Breast Cancer Trials, Australia and New Zealand · NCT02889874

This study is testing if some women with low-risk early breast cancer can skip radiation therapy after surgery to see if it helps them avoid unnecessary treatment and side effects.

Quick facts

PhaseNA
Study typeInterventional
Enrollment1167 (estimated)
Ages50 Years and up
SexFemale
SponsorBreast Cancer Trials, Australia and New Zealand (other)
Drugs / interventionschemotherapy, radiation
Locations68 sites (Rosario, Santa Fe and 67 other locations)
Trial IDNCT02889874 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness of omitting radiation therapy after breast conserving surgery in women with stage I luminal A breast cancer, as determined by the Prosigna (PAM50) Assay. It aims to identify patients who are unlikely to benefit from radiation therapy, thereby reducing unnecessary treatment and associated side effects. The study is randomized and focuses on tailoring treatment based on individual recurrence risks rather than conventional clinical-pathologic characteristics. By utilizing multigene assays, the trial seeks to personalize radiation therapy decisions for early breast cancer patients.

Who should consider this trial

Good fit: Ideal candidates are female patients aged 50 and older with stage I luminal A breast cancer who have undergone breast conserving surgery with negative margins.

Not a fit: Patients with more aggressive breast cancer subtypes or those requiring radiation therapy for effective treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce overtreatment and improve the quality of life for patients with low-risk early breast cancer.

How similar studies have performed: Other studies have shown promise in personalizing treatment for breast cancer using multigene assays, indicating a potential for success in this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria: for registration in the study:

1. Female patients aged ≥ 50 years of any menopausal status.
2. Primary tumour characteristics as assessed by conventional histopathology:

   * Unifocal histologically confirmed invasive breast carcinoma
   * Maximum microscopic size ≤2 cm
   * Grade 1 or 2 histology
   * ER and PR positive in ≥10% of tumour cells in either the biopsy or breast conserving surgical specimen
   * HER2 negative on IHC (score 0 or 1+) or in situ hybridisation (ERBB2-amplification Ratio ERBB2/centromeres \<2.0 or mean gene copy number \<6). Equivocal IHC score (2+) must be assessed by ISH.
3. Primary tumour must be resected by breast conserving surgery with microscopically negative margins for invasive carcinoma and any associated ductal carcinoma in situ (no cancer cells adjacent to any inked edge/surface of specimen) or re-excision showing no residual disease.
4. Histologically confirmed negative nodal status determined by sentinel node biopsy or axillary dissection. Patients with pN0 (i+) disease are eligible for study participation (malignant cells ≤0.2 mm in regional lymph node(s) detected by hematoxylin-eosin (H\&E) stain or IHC, including isolated tumour cells).
5. No evidence of distant metastasis.
6. Eligible for and willing to have adjuvant endocrine therapy.
7. ECOG performance status 0-2.
8. Availability of FFPE tumour block for Prosigna (PAM50) Assay.

For randomization to the study, patients must fulfill all of the following criteria:

1. Primary tumour characteristics as assessed by Prosigna (PAM50) Assay:

* Luminal A intrinsic subtype
* ROR score ≤60

Exclusion Criteria:

Any one of the following is regarded as a criterion for exclusion from the study:

1. Primary tumour characteristics:

   * Presence of multifocal or multicentric invasive carcinoma or ductal carcinoma in situ;
   * Evidence of clinical or pathologic T4 disease (extension to the chest wall, oedema or ulceration of skin, satellite skin nodules, inflammatory carcinoma);
   * The invasive component of the primary tumour is present as micro-invasion only;
   * Grade 3 histology;
   * Presence of lymphovascular invasion
2. Contra-indication or unwillingness to have adjuvant endocrine therapy.
3. Planned to receive adjuvant chemotherapy or biologic therapy after breast cancer surgery, i.e. any systemic therapy other than endocrine therapy is not permitted. Any therapy unrelated to cancer is permitted at the discretion of investigators.
4. Treated with neoadjuvant endocrine therapy, chemotherapy or biologic therapy prior to breast cancer surgery.
5. Prior breast or thoracic RT for any condition.
6. Pre-operative breast imaging evidence of disease aside from the primary carcinoma resected by breast conserving surgery.
7. Concurrent invasive breast carcinoma or ductal carcinoma in situ (synchronous or metachronous).
8. Prior diagnosis of invasive breast carcinoma or ductal carcinoma in situ in either breast irrespective of disease free interval.
9. A diagnosis of non-breast malignancy \<5 years prior to randomisation with the following exceptions:

   * Patients who are diagnosed with carcinoma in situ of cervix, endometrium or colon; melanoma in situ; and basal or squamous cell carcinoma of the skin at any time prior to randomisation are not excluded from study participation.
   * Patients who are diagnosed with other non-breast malignancy ≥5 years prior to randomisation and without evidence of disease recurrence are not excluded from study participation.
10. Significant comorbidity precluding definitive RT for breast cancer (e.g. cardiovascular or pulmonary disease, scleroderma, systemic lupus erythematosus).
11. Life expectancy \<10 years.
12. Documented mutation of BRCA1, BRCA2 or TP53, or at high genetic risk of breast cancer.
13. Pregnant or lactating patients.
14. Inability to be registered to the study ≤8 weeks after the last surgical procedure for breast cancer.
15. Inability to commence RT (if randomised to receive RT) no later than 12 weeks from the last surgical procedure for breast cancer.
16. Inability to provide written informed consent.
17. Psychiatric, addictive, or any disorder that precludes compliance with protocol requirements.

Where this trial is running

Rosario, Santa Fe and 67 other locations

+18 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Early Stage Breast Carcinoma, Radiation therapy, omission, non-inferiority, breast cancer

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.