Background and Objectives: Improvements in neoadjuvant systemic therapy (NST) for breast cancer patients have led to increasing rates of pathologic complete response (pCR). In patients with an excellent response, imaging alone is not reliable enough to differentiate between patients with residual disease, who should be surgically treated or patients with pCR where surgery could be considered overtreatment. Several trials currently investigate the accuracy of minimal invasive biopsies to assess presence of pCR of the breast. We initiated the MICRA trial (Minimal Invasive Complete Response Assessment NTR6120) combining MRI and minimal invasive biopsies of the breast. Methods: Breast cancer patients treated with NST resulting in a radiologic complete (rCR) or partial response (rPR, > 30 % decrease and < 2 cm residual diameter) on MRI are eligible. Post-NST, eight ultrasound-guided 14G core biopsies of the pre-NST marked tumor area are obtained. Pathology results of biopsies and surgical specimens are compared. The primary endpoint is the false-negative rate (FNR) of the biopsy procedure i.e. the proportion of patients with non-pCR in the surgical specimen but with pCR in the biopsies. Here we report results of the interim analysis. Results: 219 patients were enrolled in the trial. Biopsies were successfully obtained and analyzed in 167 patients. Main age was 49 yrs (range 24-74). Tumor subtype was 26% hormone receptor positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-), 14% HR-/HER2+, 36% triple negative and 24% HR+HER2+. 135 patients had a rCR and 32 patients a rPR on MRI. There were 89 patients (53%) with pCR in the surgical specimen, all correctly identified by post-NST biopsies (false-positive rate 0%). Post-NST biopsies however missed residual disease in 29/78 patients (FNR 37%). FNR was higher in patients with rCR (FNR 45%; 26/55 patients with residual disease missed on biopsies) than in patients with rPR (FNR 13 %; 3/23 patients with residual disease missed with biopsies). The conditional power estimating the probability of the FNR being ≤ 8% at final analysis was < 1%. MICRA patients total n=167Specimen negSpecimen posBiopsy neg8929118FNR= 29/7837%Biopsy pos049498978167 Conclusions: Ultrasound-guided core biopsies of the breast in patients with excellent response on MRI after NST are not accurate enough to safely select patients with pCR for omission of surgery. Citation Format: Marie-Jeanne T.F.D. Vrancken Peeters, A van Loevezijn, M EM van der Noordaa, F H van Duijnhoven, C E Loo, E van Werkhoven, K K van de Vijver, T Wiersma, H AO Winter-Warnars, G S Sonke, C. Blanken, B. Zonnevels. Towards omitting breast surgery in patients with a pathologic complete response after neoadjuvant systemic treatment: interim analysis of the MICRA trial (Minimally Invasive Complete Response Assessment) [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 GS5-06.
Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with breast cancer is associated with improved survival. Further assessment of the extent of residual disease, using the pathological anatomic American Joint Committee on Cancer staging method (ypStage) or the Residual Cancer Burden (RCB) method, have been shown to add prognostic information for patients with residual disease. Neo-Bioscore, an alternate system to classify response to NAC, includes clinical stage at diagnosis and biology and defines eight prognostic groups. The goal of this study was to compared three scoring systems (anatomic ypStage (7th ed), RCB Class and Neo-Bioscore) and assess whether RCB Class and Neo-Bioscore provide additional prognostic value in the context above anatomic ypStage, the most commonly used method for post-neoadjuvant residual disease assessment. Methods: Data from 5161 patients treated with NAC was pooled from 12 sites. Patients without clinical and pathological staging were excluded, as were patients with HER2+ breast cancer who did not receive neoadjuvant HER2-targeted therapy, leaving 3730 for analysis. PCR was defined as no residual invasive tumor in breast and nodes, i.e. RCB-0 or ypT0/Tis and ypN0. Patients with discordant pCR status by RCB Class vs ypStage (n=9) were excluded. Associations between each scoring system and event-free survival (EFS) were evaluated using the log rank test. EFS at 5 years was estimated using the Kaplan Meier method. Associations between Neo-Bioscore and EFS were assessed in the pCR group. For patients with residual disease, we assessed RCB and Neo-Bioscore within each ypStage. Analysis was performed overall and within subtype. Subgroups with <5 patients were excluded from the survival analyses. Results: ypAJCC staging, RCB class and Neo-Bioscore were all associated with EFS in the overall population and within each subtype (log rank p<0.0001). Of note, 13 patients with a Neo-Bioscore of 7 all recurred or died within 19 months of follow-up. Overall, 34% (1264/3721) of patients achieved a pCR. Their Neo-Bioscore ranges from 0-5, where 3% (37/1264) has a Neo-Bioscore of 5 despite achieving pCR. The Neo-Bioscore was not associated with EFS in case of a pCR, with EFS estimates at 5 years of 95%, 94%, 92%, 93%, 90% and 92% for Neo-Bioscores 0-5 respectively. As HR and HER2 status are components of the score, the range of Neo-Bioscore in the pCR group differs by subtype. However, similar to the overall analysis, the Neo-Bioscore was not prognostic within subtypes in case of pCR. Overall, among the patients who did not achieve pCR, both RCB class and Neo-Bioscore were associated with EFS within ypStages I, II and III. However, the ypStage within which RCB and Neo-Bioscore are prognostic is different for each subtype. RCB class was prognostic in ypStage I in both HR+ subtypes: patients with ypStage-I/RCB-I had significantly improved survival compared to patients with ypStage-I/RCB-II (5-year EFS: 100% vs 83% in HR+HER2- and 95% vs 77% in HR+HER2+). In contrast, for patients with triple negative breast cancer, RCB class was prognostic within ypStage II and III. Analysis by clinical stage and the components of the three systems that contribute most to prognosis will be presented. Conclusions: The degree of response to NAC adds important information to pCR versus residual disease. The Neo-Bioscore was not prognostic among patients with pCR, suggesting that clinical stage (including subtype and grade) adds little information in the setting of a pCR. In contrast, both RCB and Neo-Bioscore provide additional prognostic information to the conventional ypAJCC staging among non-pCR patients, suggesting that clinical stage, tumor biology as well as extent of residual disease all contribute to prognosis in the setting of residual disease after NAC. Citation Format: Marieke EM van der Noordaa, Christina Yau, Sonal Shad, Marie Osdoit, Tessa G Steenbruggen, Diane de Croze, Anne-Sophie Hamy, Marick Lae, Fabien Reyal, Maria Del Monte-Millán, Miguel Martin, Sara Lopez Tarruella, I-SPY 2 TRIAL Consortium, Judy C Boughey, Matthew Goetz, Tanya Hoskin, Rebecca Gould, Vincent Valero, Gabe Sonke, Maartje van Seijen, Jelle Wesseling, John Bartlett, Stephan Edge, Mi-Ok Kim, Jean Abraham, Carlos Caldas, Helena Earl, Elena Provenzano, Stephen-John Sammut, David Cameron, Ashley Graham, Peter Hall, Lorna MacKintosh, Fang Fan, Andrew K Godwin, Kelsey Schwensen, Priyanka Sharma, Angela DeMichele, Janet Dunn, Louise Hiller, Larry Hayward, Jeremy Thomas, Kimberley Cole, Lajos Pusztai, Laura van 't Veer, Fraser Symmans, Laura Esserman. Assessing prognosis after neoadjuvant therapy: A comparison between anatomic ypAJCC staging, residual cancer burden class and neo-bioscore [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-07.
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