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Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

ABSTRACT: Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials.

SUBMITTER: Bossuyt V

PROVIDER: S-EPMC4804123 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

Bossuyt V V Provenzano E E Symmans W F WF Boughey J C JC Coles C C Curigliano G G Dixon J M JM Esserman L J LJ Fastner G G Kuehn T T Peintinger F F von Minckwitz G G White J J Yang W W Badve S S Denkert C C MacGrogan G G Penault-Llorca F F Viale G G Cameron D D

Annals of oncology : official journal of the European Society for Medical Oncology 20150527 7

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical met ...[more]

PMID: 26019189

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Project description:ImportanceImage-guided breast biopsy of a residual imaging abnormality or tumor bed after neoadjuvant chemotherapy (NACT) is increasingly used to assess residual cancer, facilitate risk-adaptive surgery, and potentially identify exceptional responders in whom local therapy may be de-escalated.ObjectiveTo further assess the accuracy of post-NACT image-guided biopsy to predict residual cancer in the breast.Design, setting, and participantsThis diagnostic study analyzed multicenter patient-level data of patients with breast cancer who were treated with NACT and underwent image-guided biopsy before surgery at Royal Marsden Hospital in London, UK; Seoul National University Hospital in Seoul, South Korea; and MD Anderson Cancer Center in Houston, Texas. Data were analyzed from June to July 2019.Main outcomes and measuresDiagnostic accuracy of post-NACT image-guided biopsy. Final surgical pathology was used as reference standard.ResultsData from 166 women were analyzed. The median (range) age was 49 (25-76) years. The median (range) tumor size on pretreatment and posttreatment imaging was 33.5 (12-100) mm and 10 (0-100) mm, respectively. The overall pathologic complete response rate was 51.2% (n = 85) (16.1% [5 of 31] for hormone receptor-positive/ERBB2 (formerly HER2)-negative; 44.7% [21 of 47] for hormone receptor-positive/ERBB2-positive; 69% [20 of 29] for hormone receptor-negative/ERBB2-positive; and 66.1% [39 of 59] for triple negative). The majority (143 [86.1%]) underwent image-guided vacuum-assisted biopsy (VAB), and 23 had core-cut biopsy. The median (range) needle gauge was 10 (7-14), and the median (range) number of samples was 6 (2-18). When image-guided biopsy (VAB and core-cut biopsy) was representative (159 [95.8%]), the false-negative rate across the whole cohort was 18.7% (95% CI, 10.6%-29.3%). Subgroup analysis of patients with a complete/partial clinical response and residual imaging abnormality of 2 cm or smaller with at least 6 VABs taken (76 [45.8%]) demonstrated a false-negative rate of 3.2% (95% CI, 0.1%-16.7%), a negative predictive value of 97.4% (95% CI, 86.5%-99.9%), and an overall accuracy of 89.5% (95% CI, 80.3%-95.3%).Conclusions and relevanceThis large multicenter pooled data analysis suggests that a standardized protocol using image-guided VAB of a tumor bed measuring 2 cm or smaller with 6 or more representative samples allows reliable prediction of residual disease. These results could inform the design of de-escalation trials in NACT exceptional responders testing the safety of eliminating surgery.

Project description:ObjectiveTo evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and Scopus to 1 December 2020.Eligibility criteria for study selectionRandomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors.Data extraction and synthesisTrial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival.MethodsA weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R2) was used to quantify the association. The secondary objective was to explore heterogeneity of results in preplanned subgroups analysis, stratifying trials according treatment type in the experimental arm, definition used for pathological complete response (breast and lymph nodes v breast only), and biological features of the disease (HER2 positive or triple negative breast cancer). The surrogate threshold effect was also evaluated, indicating the minimum value of the relative risk for pathological complete response necessary to confidently predict a non-null effect on hazard ratio for disease-free survival or overall survival.Results54 randomised clinical trials comprising a total of 32 611 patients were included in the analysis. A weak association was observed between the log(relative risk) for pathological complete response and log(hazard ratio) for both disease-free survival (R2=0.14, 95% confidence interval 0.00 to 0.29) and overall survival (R2 =0.08, 0.00 to 0.22). Similar results were found across all subgroups evaluated, independently of the definition used for pathological complete response, treatment type in the experimental arm, and biological features of the disease. The surrogate threshold effect was 5.19 for disease-free survival but was not estimable for overall survival. Consistent results were confirmed in three sensitivity analyses: excluding small trials (<200 patients enrolled), excluding trials with short median follow-up (<24 months), and replacing the relative risk for pathological complete response with the absolute difference of pathological complete response rates between treatment arms.ConclusionA lack of surrogacy of pathological complete response was identified at trial level for both disease-free survival and overall survival. The findings suggest that pathological complete response should not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.

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Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

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Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

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