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Clinical Trial
. 2025 Jul 1;160(7):723-731.
doi: 10.1001/jamasurg.2025.1072.

Breast Tumor-Bed Biopsy for Pathological Complete Response Prediction: The NRG-BR005 Nonrandomized Clinical Trial

Mark Basik  1 , Reena S Cecchini  2 , Jennifer F De Los Santos  3 , Heidi R Umphrey  4 , Thomas B Julian  5 , Eleftherios P Mamounas  6   7 , Julia R White  8   9 , Peter C Lucas  10   11 , Christa R Balanoff  12 , Antoinette R Tan  13 , Joseph J Weber  14 , David A Edmonson  15 , Ursa A Brown-Glaberman  16 , Emilia J Diego  17 , Mediget Teshome  18   19 , Cindy B Matsen  20 , Samantha A Seaward  21 , Irene L Wapnir  22 , Jamie L Wagner  12 , Judy A Tjoe  23   24 , Alastair M Thompson  25 , Norman Wolmark  26
Affiliations
Clinical Trial

Breast Tumor-Bed Biopsy for Pathological Complete Response Prediction: The NRG-BR005 Nonrandomized Clinical Trial

Mark Basik et al. JAMA Surg. .

Erratum in

  • Error in Limitations.
    [No authors listed] [No authors listed] JAMA Surg. 2025 Jul 1;160(7):826. doi: 10.1001/jamasurg.2025.1980. JAMA Surg. 2025. PMID: 40465236 Free PMC article. No abstract available.

Abstract

Importance: Use of modern neoadjuvant chemotherapy (NAC) regimens has markedly increased rates of pathologic complete response (pCR) in breast cancer, raising the question of whether surgical removal of the primary tumor is required for patients with pCR. For surgery to be omitted, one must be able to accurately predict pCR before surgery.

Objective: To investigate if adding post-NAC core needle biopsy of the tumor bed to trimodality imaging in patients who have clinical complete response (cCR) will predict pCR (resolution of both invasive disease and ductal carcinoma in situ) in 90% or more cases.

Design, setting, and participants: This was a phase 2, prospective, nonrandomized clinical trial. Patients were enrolled from August 2017 to June 2019. This is the final analysis, which was completed in December 2023. The setting included academic and community hospital center members of NRG (ie, the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group) in the US and Canada. Patients with operable (T1-T3, stage I-III) invasive ductal carcinoma who completed NAC and achieved cCR and radiological complete response (rCR) or near rCR by mammography (mass ≤1 cm and no malignant microcalcifications), ultrasound (mass ≤2 cm), and magnetic resonance imaging (no mass with rapid rise or washout kinetics).

Interventions: Patients underwent marker-directed stereotactic multiple-core needle biopsy of the tumor bed with marker placement before breast-conservation surgery.

Main outcomes and measures: End points were negative predictive value (NPV) and sensitivity of the biopsy.

Results: A total of 105 patients were enrolled with 101 evaluable (mean [SD] age, 52.8 [10.5] years); 77 patients (76.2%) were younger than 60 years, and all breast cancer subtypes were represented with 32 (31.7%) triple-negative breast cancer, 21 (20.8%) hormone receptor-positive/epidermal growth factor receptor 2 (ERBB2; formerly HER2)-negative (ERBB2-) breast cancer, and 46 (45.5%) ERBB2-positive (ERBB2+) breast cancer. In 101 evaluable patients, 36 had residual disease at surgery (pCR = 64%). With imaging criteria, NPV of the biopsy was 78.3% (95% CI, 67.9%-86.6%), and the sensitivity of the biopsy was 50% (95% CI, 32.9%-67.1%). In an exploratory subset analysis, the NPV in patients with ERBB2+ breast cancer was 90% (95% CI, 76.3%-97.2%). On retrospective central review, 62 of 101 enrolled patients met imaging eligibility criteria. In this exploratory post hoc analysis, NPV in these patients was 86.8% (95% CI, 74.7%-94.5%).

Conclusions and relevance: These findings do not support breast conservation treatment without surgery based on the study criteria for cCR and rCR/near rCR by trimodality imaging and negative tumor-bed biopsy. Strict adherence to imaging criteria may be required to achieve acceptable predictive values.

Trial registration: ClinicalTrials.gov Identifier: NCT03188393.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Basik reported receiving speaker fees/honoraria from AstraZeneca and Merck and research funding from Pfizer and LabCorp to institution, all outside the submitted work. Dr Mamounas reported receiving consultant/speaker fees from Merck, Novartis, AstraZeneca, Exact Sciences, GE Healthcare, Biotheranostics, Provapharm, and Delphi Diagnostics outside the submitted work. Dr Lucas reported having an equity interest in Amgen outside the submitted work. Dr Brown-Glaberman reported receiving consulting/speaker fees from Gilead and Novartis outside the submitted work. Dr Teshome reported receiving travel accommodations to attend a conference from Endomagnetics LTD outside the submitted work. Dr Seaward reported receiving grants from NCORP (National Cancer Institute [NCI] Community Oncology Research Program) during the conduct of the study. Dr Wolmark reported grants from the National Institutes of Health/NCI and the Breast Cancer Research Foundation (BCRF), with all grants paid to institution during the conduct of the study, and travel fees from ASA Medallion and Genentech outside the submitted work. No other disclosures were reported.

Comment on

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