Relationships between pathological factors and long-term outcomes in patients enrolled in two prospective randomized controlled trials comparing the efficacy of oral tegafur\u2013uracil with CMF (N\xb7SAS-BC\xa001 trial and CUBC trial)

Shinji Ohno,Masafumi Kurosumi,Nobuaki Sato,Hideo Inaji,Futoshi Akiyama,Akihiko Shimomura,Shintaro Takao,Toru Watanabe,Hitoshi Tsuda,Yasuo Ohashi,Norikazu Masuda,Shigehira Saji,Shozo Ohsumi,Yutaka Tokuda

doi:10.1007/s10549-020-06018-1

Abstract

PurposeTo evaluate the efficacies of cyclophosphamide, methotrexate, and fluorouracil (CMF) and tegafur–uracil (UFT) as adjuvant therapy in patients with resected stage I–IIIA breast cancer by immunohistochemistry (IHC)-based subtype and to determine the relationships between clinicopathological factors and long-term outcomes.MethodsA pooled analysis of the randomized controlled N·SAS-BC 01 and CUBC studies was conducted. Expression of hormone receptors (HRs; estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and Ki67were assessed by IHC. Tumor-infiltrating lymphocytes (TILs) and nuclear/histological grades were determined by hematoxylin and eosin staining. Relapse-free survival (RFS) and overall survival (OS) were estimated by Kaplan–Meier analysis and hazard ratios were determined by Cox model adjusted for baseline tumor size and nodal status.ResultsA total of 689 patients (342 CMF and 347 UFT) were included in the analyses with a median follow-up of 11.1 years. There was no significant difference in RFS or OS between the two cohorts (RFS: 0.96 [95% confidence interval: 0.71–1.30], log-rank test p = 0.80; OS: 0.93 [0.64–1.35], p = 0.70). There was no difference in RFS or OS between the two cohorts for HR+/HER2− and HR+/HER2+ subtypes. RFS was significantly longer in patients treated with UFT compared with CMF in patients with HR−/HER2+ subtype (0.30 [0.10–0.88], p = 0.03). A high TILs level was associated with a better OS compared with low TILs level (p = 0.02).ConclusionsThis long-term follow-up study showed that RFS and OS were similar in patients with luminal-type breast cancer treated with CMF and UFT.

Highlights

CMF + TAM in Adjuvant Therapy for Breast Cancer ER Estrogen receptor fluorescence in situ hybridization (FISH) Fluorescence in situ hybridization human epidermal growth factor receptor 2 (HER2) Human epidermal growth factor receptor 2 hormone receptors (HRs) Hormone receptor N·SAS-BC National Surgical Adjuvant Study for Breast Cancer overall survival (OS) Overall survival PgR Progesterone receptor RFS Relapse-free survival TAM Tamoxifen tumor-infiltrating lymphocytes (TILs) Tumor-infiltrating lymphocytes UFT Tegafur–uracil
In this cross-sectional, observational, pooled study, we evaluated the efficacies of adjuvant CMF and UFT according to immunohistochemistry (IHC)-based intrinsic subtypes and the relationships between the clinicopathological factors and updated long-term follow-up prognostic outcomes in patients with resected stage I–IIIA breast cancer enrolled in the randomized N·SAS-BC 01 and CUBC studies to identify a subset of patients responsive to UFT and CMF
The patients treated with CMF and UFT were well balanced in terms of age, tumor size, nodal stage, tumor subtype, Ki67, and TILs expression, and nuclear and histological grades (Table 1)

Summary

Introduction

CMF + TAM in Adjuvant Therapy for Breast Cancer ER Estrogen receptor FISH Fluorescence in situ hybridization HER2 Human epidermal growth factor receptor 2 HR Hormone receptor N·SAS-BC National Surgical Adjuvant Study for Breast Cancer OS Overall survival PgR Progesterone receptor RFS Relapse-free survival TAM Tamoxifen TILs Tumor-infiltrating lymphocytes UFT Tegafur–uracil. We examined the expression of ER, PgR, HER2, Ki67, and tumor-infiltrating lymphocytes (TILs), as well as nuclear and histological grades, in tumor specimens from patients enrolled in these two studies using the currently available measurement methods. In this cross-sectional, observational, pooled study, we evaluated the efficacies of adjuvant CMF and UFT according to immunohistochemistry (IHC)-based intrinsic subtypes and the relationships between the clinicopathological factors and updated long-term follow-up prognostic outcomes in patients with resected stage I–IIIA breast cancer enrolled in the randomized N·SAS-BC 01 and CUBC studies to identify a subset of patients responsive to UFT and CMF

Methods

Results

Conclusion