Multicenter Trial for Eliminating Breast Cancer Surgery or Radiotherapy in Exceptional Responders to Neoadjuvant Systemic Therapy
2 other identifiers
interventional
120
1 country
8
Brief Summary
This clinical trial studies eliminating surgery and/or radiation therapy in treating breast cancer patients. In HER2 positive and triple negative breast cancers, after systemic therapy, when image-guided biopsy shows no residual cancer, patients then receive standard breast radiotherapy with no surgery. In ER positive/HER2 negative breast cancers, after endocrine therapy and ablative radiotherapy, when image-guided biopsy shows no residual cancer, patients then receive standard endocrine therapy with no surgery. For patients who have HER2 positive and triple negative breast cancers and standard surgery, after systemic therapy, breast radiotherapy is being eliminated when the pathology from surgery shows no residual cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Jan 2017
Longer than P75 for not_applicable
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 24, 2016
CompletedFirst Posted
Study publicly available on registry
October 26, 2016
CompletedStudy Start
First participant enrolled
January 20, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2028
March 9, 2026
March 1, 2026
11 years
October 24, 2016
March 5, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Ipsilateral breast tumor recurrence-free survival (IBT-RFS)
Will monitor IBT-RFS using the method of Thall et al. Will be estimated using the Kaplan-Meier method log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
From confirmation of pathologic complete response (pCR) to the time of ipsilateral breast tumor recurrence or death, whichever occurs first or the time of last contact, assessed for up to 10 years
Overall survival
Will be estimated using the Kaplan-Meier method log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
Up to 10 years
Other Outcomes (6)
Change in biomarkers in blood and plasma
3 months, 3-8 weeks post radiation therapy (if applicable), 6 months, 12 months]
Residual cancer burden (RCB)
Up to 10 years
Incidence of ipsilateral breast and nodal recommendation and performance of biopsy based on breast imaging follow-up
Up to 10 years
- +3 more other outcomes
Study Arms (4)
Cohort A
EXPERIMENTAL* Neoadjuvant chemotherapy therapy * Biopsy: if no disease remaining - stay on the study and receive radiation (skip breast surgery) * H\&P and Imaging every 6 months Treatment (whole breast irradiation, EBRT) Within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo EBRT boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation.
Cohort B
EXPERIMENTAL• Neoadjuvant endocrine therapy for 3 months Cohort B Radiation: Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 5 fractions * Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery) * H\&P and Imaging every 6 months
Cohort C
EXPERIMENTAL* Optional biopsy for nanomechanical biomarker assessment * Neoadjuvant chemotherapy therapy * Surgery (\& optional biopsy nanomechanical biomarker assessment): if no disease remaining - stay on the study and skip radiation * H\&P and Imaging every 6 months
Cohort D
EXPERIMENTAL* Optional biopsy for nanomechanical biomarker assessment * Chart review every year after surgery for 5 years * Eligible patients who have undergone the optional biopsy may later move to Cohort A or C if they meet all eligibility requirements and desire radiation omission.
Interventions
Undergo EBRT
Ancillary studies
Eligibility Criteria
You may qualify if:
- Cohort A1 and A2
- Conditions for patient eligibility: Patients on this portion of the study can receive radiation treatment at any MD Anderson Cancer Center or any outside hospital and may be enrolled prior to, during, or following neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below:
- Pathologically confirmed unicentric invasive breast cancer defined as radiologic clinical stage T1 or T2 (≤ 5 cm), N0 or N1 (≤ 4 abnormal axillary nodes on initial ultrasound), clinical stage M0.
- HER2 positive (IHC 3+ and or FISH amplified) or triple receptor negative (TN, ER/PR\< 10% HER2 negative (IHC 1+ or 2+ FISH non-amplified) receiving any standard routine clinical NST regimen.
- Patient desires breast conserving therapy.
- Age 40 years or older. This age cutoff is justified because breast cancers in women under the age of 40 are known to have a significantly higher risk of IBTR presumably due to underlying biologic differences \[124, 125\].
- Female sex.
- If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer.
- Patient must have an initial nodal ultrasound that does not demonstrate more than four suspicious lymph nodes, any suspicious lymph nodes should be biopsied to determine if nodal metastatic disease present.
- Patient understands that the breast lesion size on final breast imaging must be less than or equal to 2 cm prior to the biopsy procedure being performed on study and if the biopsy shows residual carcinoma the patient will be taken off study.
- Cohort B1 and B2
- Conditions for patient eligibility: Patients on this portion of the study will be limited to receive radiation treatment at MD Anderson Cancer Center or other approved locations and must be enrolled prior to any neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below:
- ER and/or PR positive, HER2 negative
- Clinical stage T1N0M0, unicentric non-lobular breast cancer, no lymphovascular space invasion,
- At least 40 years of age.
- +22 more criteria
You may not qualify if:
- Radiologic evidence for a stage T3 or clinical stage T4 breast cancer in Cohort A1/A2/C; radiologic evidence for a stage T2-T3 or clinical stage T4 breast cancer in Cohort B1/B2.
- Clinical or pathologic evidence for distant metastases.
- Prior diagnosis of invasive or ductal carcinoma in situ breast cancer in the ipsilateral breast.
- Clinical evidence of progression of disease \>20% in the breast or new evidence of nodal metastases.
- Patient is known to be pregnant.
- Patient is participating in a NST protocol in which surgical excision of the breast and or lymph nodes are required in Cohort A1/A2/B1/B2.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (8)
MD Anderson Cancer Center - Banner
Gilbert, Arizona, 85234, United States
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Cooper Hospital Univ Med Ctr, MD Anderson at Cooper Voorhees
Voorhees Township, New Jersey, 08103, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (4)
Kuerer HM, Valero V, Smith BD, Krishnamurthy S, Diego EJ, Johnson HM, Lin H, Shen Y, Lucci A, Shaitelman SF, Mitchell MP, Boughey JC, White RL, Hunt KK, Yang WT, Rauch GM; Exceptional Responders Study Group. Selective Elimination of Breast Surgery for Invasive Breast Cancer: A Nonrandomized Clinical Trial. JAMA Oncol. 2025 May 1;11(5):529-534. doi: 10.1001/jamaoncol.2025.0207.
PMID: 40152443DERIVEDJohnson HM, Lin H, Shen Y, Diego EJ, Krishnamurthy S, Yang WT, Smith BD, Valero V, Lucci A, Sun SX, Shaitelman SF, Mitchell MP, Boughey JC, White RL, Rauch GM, Kuerer HM; Exceptional Responders Study Group. Patient-Reported Outcomes of Omission of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial. JAMA Netw Open. 2023 Sep 5;6(9):e2333933. doi: 10.1001/jamanetworkopen.2023.33933.
PMID: 37707811DERIVEDKuerer HM, Smith BD, Krishnamurthy S, Yang WT, Valero V, Shen Y, Lin H, Lucci A, Boughey JC, White RL, Diego EJ, Rauch GM; Exceptional Responders Clinical Trials Group. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2022 Dec;23(12):1517-1524. doi: 10.1016/S1470-2045(22)00613-1. Epub 2022 Oct 25.
PMID: 36306810DERIVEDHariharan N, Rao TS, Rajappa S, Naidu CCK. Precision medicine - A new era in multidisciplinary care. Cancer Treat Res Commun. 2022;32:100577. doi: 10.1016/j.ctarc.2022.100577. Epub 2022 May 17. No abstract available.
PMID: 35617923DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Henry M Kuerer
M.D. Anderson Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 24, 2016
First Posted
October 26, 2016
Study Start
January 20, 2017
Primary Completion (Estimated)
January 31, 2028
Study Completion (Estimated)
January 31, 2028
Last Updated
March 9, 2026
Record last verified: 2026-03