Diagnosing Pathologic Complete Response in the Breast After Neoadjuvant Systemic Treatment of Breast Cancer Patients by Minimal Invasive Biopsy
Joerg Heil, André Pfob, Hans‐Peter Sinn, Geraldine Rauch, Paul Bach, Bettina Thomas, Benedikt Schaefgen, Sherko Küemmel, Toralf Reimer, Markus Hahn, Marc Thill, Jens‐Uwe Blohmer, John Hackmann, Wolfram Malter, Inga Bekes, Kay Friedrichs, Sebastian Wojcinski, Sylvie Joos, Stefan Paepke, Nina Ditsch, Achim Rody, Regina Große, Marion van Mackelenbergh, Mattea Reinisch, Maria Margarete Karsten, Michael Golatta, for the RESPONDER Investigators
Abstract
Objective: We evaluated the ability of minimally invasive, image-guided vacuum-assisted biopsy (VAB) to reliably diagnose a pathologic complete response in the breast (pCR-B). Summary Background Data: Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in up to 80% of women with breast cancer. In such cases, breast surgery, the gold standard for confirming pCR-B, may be considered overtreatment. Methods: This multicenter, prospective trial enrolled 452 women presenting with initial stage 1-3 breast cancer of all biological subtypes. Fifty-four women dropped out; 398 were included in the full analysis. All participants had an imaging-confirmed partial or complete response to NST and underwent study-specific image-guided VAB before guideline-adherent breast surgery. The primary endpoint was the false-negative rate (FNR) of VAB-confirmed pCR-B. Results: Image-guided VAB alone did not detect surgically confirmed residual tumor in 37 of 208 women [FNR, 17.8%; 95% confidence interval (CI), 12.8–23.7%]. Of these 37 women, 12 (32.4%) had residual DCIS only, 20 (54.1%) had minimal residual tumor (<5 mm), and 19 of 25 (76.0%) exhibited invasive cancer cellularity of ≤10%. In 19 of the 37 cases (51.4%), the false-negative result was potentially avoidable. Exploratory analysis showed that performing VAB with the largest needle by volume (7-gauge) resulted in no false-negative results and that combining imaging and image-guided VAB into a single diagnostic test lowered the FNR to 6.2% (95% CI, 3.4%–10.5%). Conclusions: Image-guided VAB missed residual disease more often than expected. Refinements in procedure and patient selection seem possible and necessary before omitting breast surgery.