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Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients

2021; Elsevier BV; Volume: 23; Issue: 1 Linguagem: Inglês

10.1016/s1470-2045(21)00589-1

1474-5488

Christina Yau, Marie Osdoit, Marieke van der Noordaa, Sonal Shad, Jane Wei, Diane De Croze, Anne-Sophie Hamy, Marick Laé, Fabien Reyal, Gabe S. Sonke, Tessa G. Steenbruggen, Maartje van Seijen, Jelle Wesseling, Miguel Martín, María del Monte‐Millán, Sara López‐Tarruella, Judy C. Boughey, Matthew P. Goetz, Tanya L. Hoskin, Rebekah Gould, Vicente Valero, Stephen B. Edge, Jean Abraham, John M.S. Bartlett, Carlos Caldas, Janet Dunn, Helena Earl, Larry Hayward, Louise Hiller, Elena Provenzano, Stephen‐John Sammut, Jeremy Thomas, David Cameron, A Graham, Peter Hall, Lorna Mackintosh, Fang Fan, Andrew K. Godwin, Kelsey Schwensen, Priyanka Sharma, Angela DeMichele, Kimberly Cole, Lajos Pusztai, Mi‐Ok Kim, Laura van ′t Veer, Laura J. Esserman, W. Fraser Symmans, Kathi Adamson, Kathy S. Albain, Adam L. Asare, Smita Asare, Ronald Balassanian, Heather Beckwith, Scott Berry, Donald A. Berry, Judy C. Boughey, Meredith Buxton, Yunn‐Yi Chen, Beiyun Chen, A. Jo Chien, Jane Yuet Ching Hui, Amy S. Clark, Julia L. Clennell, Brian Datnow, Angela DeMichele, Xiuzhen Duan, Kirsten K. Edmiston, Anthony Elias, Erin D. Ellis, Laura Esserman, David Euhus, Oluwole Fadare, Fang Fan, Michael D. Feldman, Andres Forero‐Torres, Barbara Haley, Hyo S. Han, Shuko Harada, Patricia Haugen, Teresa Helsten, Gillian L. Hirst, Nola M. Hylton, Claudine Isaacs, Kathleen Kemmer, Qamar J. Khan, Laila Khazai, Molly Klein, Gregor Krings, Julie E. Lang, Lauren LeBeau, Brian Leyland‐Jones, Minetta C. Liu, Shelly S. Lo, Janice Lu, Anthony M. Magliocco, Jeffrey B. Matthews, Michelle Melisko, Paulette Mhawech‐Fauceglia, Stacy L. Moulder, Rashmi K. Murthy, Rita Nanda, Donald W. Northfelt, Idris Tolgay Ocal, Olufunmilayo I. Olopade, Stefan E. Pambuccian, Melissa Paoloni, John W. Park, Barbara A. Parker, Jane Perlmutter, Garry Peterson, Lajos Pusztai, Mara H. Rendi, Hope S. Rugo, Sunati Sahoo, Sharon B. Sams, Ashish Sanil, Husain Sattar, Richard B. Schwab, Ruby Singhrao, Katherine Steeg, Erica Stringer-Reasor, W. Fraser Symmans, Ossama Tawfik, Debasish Tripathy, Megan L. Troxell, Laura J. van’t Veer, Sara J. Venters, Tuyethoa N. Vinh, Rebecca K. Viscusi, Anne M. Wallace, Shi Wei, Amy Wilson, Christina Yau, Douglas Yee, Jay Zeck,

HER2/EGFR in Cancer Research

BackgroundPrevious studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings.MethodsIn this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I–III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for between-study heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype.FindingsWe analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20–80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0–186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1·55 (95% CI 1·41–1·71) for hormone receptor-positive, HER2-negative patients to 2·16 (1·79–2·61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p<0·0001 for all subtypes). RCB score remained prognostic for event-free survival in multivariable models adjusted for age, grade, T category, and nodal status at baseline: the adjusted HR ranged from 1·52 (1·36–1·69) in the hormone receptor-positive, HER2-negative group to 2·09 (1·73–2·53) in the hormone receptor-negative, HER2-positive group (p<0·0001 for all subtypes).InterpretationRCB score and class were independently prognostic in all subtypes of breast cancer, and generalisable to multiple practice settings. Although variability in hormone receptor subtype definitions and treatment across patients are likely to affect prognostic performance, the association we observed between RCB and a patient's residual risk suggests that prospective evaluation of RCB could be considered to become part of standard pathology reporting after neoadjuvant therapy.FundingNational Cancer Institute at the US National Institutes of Health.