Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial

Abstract

Background: We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial.

Patients and methods: The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years.

Results: Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06].

Conclusions: Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease.

Clinicaltrialsgov: NCT00004205.

Keywords: breast cancer; cribriform; letrozole; mucinous; tamoxifen; tubular.

© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Patients from the BIG 1-98 trial included and excluded in this study according to treatment group and availability centrally reviewed histology. Other histologies were 651 (15.9%): 406 lobular/ 234 other/11 missing. L, letrozole; T, tamoxifen.

Figure 2.

Kaplan–Meier estimates of disease-free survival (DFS, A), overall survival (OS, B), breast cancer-free interval (BCFI, C), and distant recurrence-free interval (DRFI, D) according to histotype for the 4091 patients in the analytic cohort.

Figure 3.

Kaplan–Meier estimates of disease-free survival (DFS, A), overall survival (OS, B), breast cancer-free interval (BCFI, C), and distant recurrence-free interval (DRFI, D) according to randomly assigned treatment group for the cohort of 183 patients with mucinous, tubular, or cribriform histotypes.

Figure 4.

Proportional hazards model results of disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI) in histology subgroups. Hazard ratios and P values were estimated from the interaction of treatment and histology based on the univariate Cox PH model. There were no events in the tamoxifen arm for tubular or cribriform DRFI, so this comparison is not included in the forest plot.