Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial

Author(s): Prof Savitri Krishnamurthy, MD³ Prof Wei T Yang, MD⁴ Prof Vicente Valero, MD¹ Prof Yu Shen, PhD⁵ Heather Lin, PhD⁵ Prof Anthony Lucci, MD¹ Prof Judy C Boughey, MD⁶ Prof Richard L White, MD⁷ Prof Emilia J Diego, MD⁸ Prof Gaiane M Rauch, MD⁴ on behalf of theExceptional Responders Clinical Trials Group

Source: DOI:https://doi.org/10.1016/S1470-2045(22)00613-1

Dr. Anjan Patel's Thoughts

Interesting non-operative approach for T1-2, N0-1, M0 TNBC or HER2+ breast cancer, 58 patients enrolled in this single-center phase II out of MDA. 62% of patients had CR on biopsy after systemic therapy; if results hold true over a longer follow-up period, this may be of significant impact.

BACKGROUND

Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response.

METHODS

This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1–2N0–1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579.

FINDINGS

Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55–77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2–75·4). At a median follow-up of 26·4 months (IQR 15·2–39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred.

INTERPRETATION

Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed.

Author Affiliations

¹Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ²Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ³Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ⁴Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ⁵Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ⁶Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA ⁷Division of Surgical Oncology, Department of Surgery, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA ⁸Division of Breast Surgery, University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA, USA

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