Elsevier

European Journal of Cancer

Volume 39, Issue 3, February 2003, Pages 309-316
European Journal of Cancer

Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10851 comparing tamoxifen alone with modified radical mastectomy

https://doi.org/10.1016/S0959-8049(02)00673-1Get rights and content

Abstract

For treatment of early breast cancer in older women, little evidence is available from randomised trials. We conducted a randomised trial comparing modified radical mastectomy (MRM) with tamoxifen (TAM) as the sole initial therapy in 164 patients aged ⩾70 years with operable breast cancer. 82 were treated by MRM and 82 with TAM. Survival curves were estimated using the Kaplan–Meier method: multivariate analyses were performed using the Cox's proportional hazards model. Endpoints included survival, time to first relapse or progression, loco-regional progression, time to distant progression and progression-free survival. After a median follow-up of approximately 10 years, there was a significantly decreased time to progression in the TAM only group (logrank P<0.0001) and significantly shorter time to local progression within the TAM group (logrank P<0.0001). Overall survival of the two groups was similar. The results indicate that tamoxifen alone leads to an unacceptably high rate of local progression or relapse.

Introduction

Management of breast cancer is becoming an increasing problem since age is the major risk factor for breast cancer [1]. For the guidance of the oncologist, there is little evidence from randomised trials and many patients do not see an oncologist because of misconceptions that breast cancer in older women is a more indolent disease compared with younger patients, despite evidence to the contrary 2, 3. Many older women suffer under-treatment and the reasons for this are often arbitrary and bear little or no relation to the presence of co-morbidity 4, 5.

As a result of concerns about competing deaths from co-morbidity in older patients, women aged ⩾70 years were excluded from all the trials of breast conservation therapy so that there are no trial-based results comparing mastectomy with standard breast conservation therapy in older women. In an effort to reduce the extent of surgery in older women with breast cancer, several clinicians treated patients with tamoxifen alone in non-randomised studies 6, 7, 8.

In 1984, the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Cooperative Group designed two prospective randomised trials, designated 10850 and 10851, for older women with operable breast cancer. At that time, there were no reported results from randomised trials. It was agreed that a modified radical mastectomy had to be regarded as standard treatment and also was decided that adjuvant tamoxifen should not be given since the only results which were available on tamoxifen in older patients were derived from the Danish Breast Cancer Cooperative Group which had not found any benefit by that time [9]. In terms of the experimental treatment, some surgeons wished to excise the cancer and then give tamoxifen in a pseudo-adjuvant role. Others were hoping to avoid hospitalisation in older patients and wanted to use tamoxifen to control or destroy the tumour. Because of the incompatibility of these aims, it was decided to run two trials in parallel, with contributing centres entering patients into only one of the studies. In EORTC 10851, patients were randomised to either modified radical mastectomy (MRM) or tamoxifen (TAM) 20 mg daily. The first analysis of this trial is reported in this paper.

Section snippets

Patients and methods

Eligible patients were women aged ⩾70 years with operable breast cancer (T1 T2 T3a, N0 N1a N1b, M0), who were suitable for either form of treatment. There had to be only one primary tumour and no evidence of Paget's disease of the nipple. Staging investigations including full blood count, biochemical screen, chest X-ray, bilateral mammograms and bone scan were performed to confirm that there was no evidence of tumour spread. None had had prior breast cancer treatment nor previous or concomitant

Results

The study started in October 1985 and closed in November 1991, during which time 177 patients were entered from 14 institutions. The major contributors were University Hospital Gasthuisberg, K.U. Leuven (72), Daniel Den Hoed RRTI, Rotterdam (30), Antoni van Leeuwenhoekhuis/The Netherlands Cancer Institute Amsterdam (23), Medical Academy Lodz (19), Sophia Ziekenhuis, Zwolle (10, Institute of Oncology, Warsaw (9) and Twee Steden Ziekenhuis, Tilburg (6). There were 88 (49.7%) patients randomised

Discussion

This was the first prospective randomised trial of treatment for operable breast cancer in which tamoxifen alone was compared with modified radical mastectomy. The statistical consideration and the design of this study both suffer from the lack of precision that would be required nowadays and the results of the study have to be regarded within this limitation. Thus far, with a median follow-up of 11.2 years, overall survival is similar for the two forms of treatment and we found no significant

Acknowledgements

This publication was supported by grants number 5U10CA11488-15 through 2U10CA11488-31 from the National Cancer Institute (Bethesda, Maryland, USA). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. We thank Dr. Richard Sylvester for Statistical advice, Dr. Liliana Baila as Medical Advisor and Francoise Mignolet and Monica Devos for their conscientious Data Management.

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