Relationships between pathological factors and long-term outcomes in patients enrolled in two prospective randomized controlled trials comparing the efficacy of oral tegafur-uracil with CMF (N·SAS-BC 01 trial and CUBC trial).

Abstract

PURPOSE:

To 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.

METHODS:

A 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.

RESULTS:

A 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).

CONCLUSIONS:

This long-term follow-up study showed that RFS and OS were similar in patients with luminal-type breast cancer treated with CMF and UFT.

• Authors: Shinji Ohno, Shigehira Saji, Norikazu Masuda, Hitoshi Tsuda, Futoshi Akiyama, Masafumi Kurosumi, Akihiko Shimomura, Nobuaki Sato, Shintaro Takao, Shozo Ohsumi, Yutaka Tokuda, Hideo Inaji, Toru Watanabe, Yasuo Ohashi
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 186 Issue 1 Pg. 135-147 (Feb 2021) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 33259001 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• Tegafur
• Cyclophosphamide
• Fluorouracil
• Methotrexate

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy)
• Chemotherapy, Adjuvant
• Cyclophosphamide (therapeutic use)
• Disease-Free Survival
• Female
• Fluorouracil (therapeutic use)
• Follow-Up Studies
• Humans
• Methotrexate (therapeutic use)
• Neoplasm Recurrence, Local
• Prospective Studies
• Randomized Controlled Trials as Topic
• Tegafur