Breast tumor-bed biopsy for pathological complete response prediction: The NRG-BR005 nonrandomized clinical trial

Authors

Mark Basik, Jewish General Hospital, Montréal, Québec, Canada.
Reena S. Cecchini, NRG Oncology Statistics and Data Management Center, and University of Pittsburgh School of Public Health, Department of Biostatistics and Health Data Science, Pittsburgh, Pennsylvania.
Jennifer F. De Los Santos, Washington University School of Medicine, Saint Louis, Missouri.
Heidi R. Umphrey, NEA Baptist Memorial Hospital, Jonesboro, Arkansas.
Thomas B. Julian, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania.
Eleftherios P. Mamounas, Orlando Health UF Cancer Center, Orlando, Florida.
Julia R. White, Ohio State University Comprehensive Cancer Center, Columbus.
Peter C. Lucas, University of Pittsburgh School of Medicine, and UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.
Christa R. Balanoff, University of Kansas Medical Center and Cancer Center, Kansas City, Kansas.
Antoinette R. Tan, Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, North Carolina.
Joseph J. Weber, Advocate Health - MidwestFollow
David A. Edmonson, Brown University/Women & Infants Hospital, Providence, Rhode Island.
Ursa A. Brown-Glaberman, University of New Mexico Comprehensive Cancer Center, Albuquerque.
Emilia J. Diego, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Mediget Teshome, University of Texas MD Anderson Cancer Center LAPS, Houston.
Cindy B. Matsen, University of Utah - Huntsman Cancer Institute LAPS, Salt Lake City.
Samantha A. Seaward, Kaiser Permanente Oncology Clinical Trials, Vallejo, California.
Irene L. Wapnir, Stanford Cancer Institute Palo Alto, Stanford, California.
Jamie L. Wagner, University of Kansas Medical Center and Cancer Center, Kansas City, Kansas.
Judy A. Tjoe, Advocate Health - MidwestFollow
Alastair M. Thompson, Baylor College of Medicine, Houston, Texas.
Norman Wolmark, NSABP Foundation Inc, University of Pittsburgh School of Medicine, and UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.

Recommended Citation

Basik M, Cecchini RS, De Los Santos JF, et al. Breast Tumor-Bed Biopsy for Pathological Complete Response Prediction: The NRG-BR005 Nonrandomized Clinical Trial. JAMA Surg. Published online May 7, 2025. doi:10.1001/jamasurg.2025.1072

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 .

Type

Article

PubMed ID

40332918