Abstract GS5-03: Diagnosing residual disease and pathologic complete response after neoadjuvant chemotherapy in breast cancer patients by image-guided vacuum-assisted breast biopsy: Results of a prospective multicenter trial

Background and objectives: Pathological complete response after neoadjuvant chemotherapy for women with primary breast cancer is achieved in up to 60%. Identification of these women by imaging is imprecise – even clear residual tumors on breast imaging after neoadjuvant chemotherapy frequently show pathologic complete response. Thus, pathologic evaluation of the surgical specimen is the gold standard. However, having women to undergo breast-conserving or even ablative breast surgery to diagnose pathologic complete response could be considered overtreatment. To potentially avoid these surgeries, we first evaluated the accuracy of an image-guided vacuum-assisted biopsy (i.g.VAB) alone to diagnose and rule out residual disease in the breast. Second, we assessed the accuracy of the combination of i.g.VAB with breast imaging results after neoadjuvant chemotherapy. Methods: This multicenter, prospective, diagnostic trial took place at 21 trial sites in Germany (March 2017 to May 2019). 398 women consented, presented with initial clinical tumor stage 1-3 breast cancer of all biological subtypes with partial or complete response by imaging after neoadjuvant chemotherapy and underwent i.g.VAB and guideline-adherent breast surgery. First, we compared i.g.VAB alone - guided either by ultrasound or mammography – with the gold standard evaluation of the surgical specimen to detect pathological residual disease. A pathologically confirmed residual tumor in the surgical specimen but no residual tumor in the i.g.VAB defines a false-negative finding. The study was powered to detect a false-negative rate of the i.g.VAB below 10% (primary efficacy analysis). Second, we combined the results of the i.g.VAB and the breast imaging exams (ultrasound and mammography) after neoadjuvant chemotherapy. A positive test (=residual tumor) was either a residual tumor in the i.g.VAB OR tumor seen on the imaging exam. Thus, a false-negative finding is a pathologically confirmed residual tumor in the surgical specimen but no residual tumor in i.g.VAB AND no residual tumor on the breast imaging exam (secondary explorative analysis). The study was stopped for futility after planned interim analysis. Results: For the whole cohort (n=398) and primary efficacy analysis, i.g.VAB alone failed to detect a residual tumor in 37 of 208 cases with a residual tumor in the surgical specimen (false-negative rate (FNR) = 17.8% (95% CI: 12.8-23.7%)). Only the subgroup in which i.g.VAB used 7 G needles showed a FNR < 10%. The secondary explorative analysis detected residual tumor with a FNR of 6.2% (3.4-10.5%) – 13 out of the 208 cases with a residual tumor in the surgical specimen were false-negative. While this approach increased sensitivity, it decreased specificity but still identified 95 of 190 (50.0%) pathologic tumor-free women. Conclusion The i.g.VAB alone did not reach the anticipated diagnostic accuracy in this study. However, combining the results of i.g.VAB and breast imaging after neoadjuvant chemotherapy detects residual disease in women with breast cancer with a FNR This finding will guide ongoing and future trials aiming for tailoring, de-escalating, and potentially avoiding unnecessary surgery in women without residual disease after neoadjuvant chemotherapy. Trial registration: NCT02948764 Protocol publication: DOI: 10.1186/s12885-018-4760-4 Table 1Primary efficacy analysisSecondary, explorative analysisresidual disease in i.g.VAB specimenno residual disease in i.g. VAB specimenresidual disease in i.g.VAB specimen OR imaging after NACTno residual disease in i.g.VAB specimen AND no tumor on imaging after NACTresidual disease in surgery specimen(n=208)1713719513no residual disease in surgery specimen(n=190)3*1879595FNR (95% CI)17.8% (12.8-23.7)6.2% (3.4-10.5)NPV (95% CI)81.4% (75.3-86.6)88.0% (80.3-93.4)PPV (95% CI)85.9% (80.3-90.4)67.2% (61.5-72.6)*whole tumor was removed by i.g.VAB, thus not false positiveNACT=neoadjuvant chemotherapyi.g.VAB=image-guided vacuum-assisted biopsyFNR=false-negative rateNPV=negative predictive valuePPV=positive predictive value Citation Format: Joerg Heil, André Pfob, Hans-Peter P Sinn, Geraldine Rauch, Paul Bach, Benedikt Schaefgen, Walter Weber, Sherko Kuemmel, Toralf Reimer, Markus Hahn, Marc Thill, Jens-Uwe Blohmer, Michael Golatta, RESPONDER Investigators. Diagnosing residual disease and pathologic complete response after neoadjuvant chemotherapy in breast cancer patients by image-guided vacuum-assisted breast biopsy: Results of a prospective multicenter trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-03.