Long-term prognosis of breast cancer patients with 10 or more positive lymph nodes treated with CMF

doi:10.1016/S0959-8049(01)00090-9

European Journal of Cancer

Volume 37, Issue 9, June 2001, Pages 1123-1131

https://doi.org/10.1016/S0959-8049(01)00090-9 Get rights and content

Abstract

The purpose of this investigation was to study the long-term prognosis of breast cancer patients with 10 or more positive lymph nodes after conventional chemotherapy treatment with cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Between 1984 and 1989, 1048 node-positive patients were treated with CMF in two separate trials conducted by the German Breast Cancer Study Group (GBSG). Subgroups either received radiotherapy or tamoxifen in addition. In this study, long-term prognosis in the subgroup of 141 patients with 10 or more positive lymph nodes was investigated. Univariate and multivariate Cox models were used to evaluate the effect of prognostic factors on event-free survival (EFS) and overall survival (OS). Both univariate and multivariate analyses revealed the progesterone receptor (PR) status as the dominating prognostic factor for both EFS and OS, resulting in a strongly increased risk of more than 2-fold for receptor-negative patients. A large number of positive lymph nodes also affected the prognosis for EFS. In univariate analysis, the degree of lymph node involvement (i.e. percentage of positive nodes out of all examined nodes), oestrogen status (ER) status, and tumour grade also showed significant effects. To conclude, the prognosis in the subgroup of patients with 10 or more positive lymph nodes is heterogeneous. Some surprisingly high survival rates have been observed in case series of breast cancer patients treated with high-dose chemotherapy which may be explained by patient selection. From the usual factors investigated in this study, the PR status showed the strongest effect, and, at least this factor should be taken into account in the design and analysis of trials for breast cancer patients with a poor prognosis.

Introduction

Although adjuvant polychemotherapy treatment for breast cancer patients has led to improvements in both event-free survival (EFS) and overall survival (OS) [1], patients with 10 or more positive lymph nodes still have a high rate of recurrence, and EFS rates after five years are below 50% 2, 3, 4. Therefore, the improvement of this poor prognosis by applying new treatment strategies, such as high-dose chemotherapy, is considered as one of the most important topics of current research in breast cancer. Several observational studies have reported EFS and OS rates after treatment with high-dose chemotherapy as being substantially larger than the corresponding rates from a retrospectively chosen control group. However, detailed information about other potential prognostic factors or possible selection criteria for the patients treated with high-dose chemotherapy is often not given [5]. This may be due to the assumption that a further separation of patients with 10 or more positive lymph nodes in subgroups of patients with different prognosis is not possible on account of the strong prognostic effect of the number of positive lymph nodes.

This may explain the limited interest in this issue in the literature. Recently, Schmoor and Schumacher [4] reported a 5-year OS rate in a group of patients with 10 or more positive nodes treated with conventional chemotherapy of approximately 40%. For this poor prognosis group, we therefore wanted to investigate the prognostic value of standard factors for 141 patients with 10 or more positive nodes with a median follow-up of approximately 10 years. These patients represent a subgroup (13%) of 1048 lymph node-positive patients who were all treated with adjuvant conventional chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil; CMF) within two studies of the German Breast Cancer Study Group (GBSG).

Section snippets

Study design

In 1984, the GBSG started two studies (GBSG studies 2 and 3) in patients with primary histologically proven node-positive breast cancer without known distant metastatic spread to compare different adjuvant treatment regimens. Primary local treatment was a modified radical mastectomy (Patey) with en bloc axillary dissection with at least six identifiable lymph nodes in the specimen. Patients were younger than 65 years old and had a Karnofsky index of at least 60. During the recruitment period,

Results

The patient population comprised 141 patients with 10 or more positive axillary lymph nodes, who entered either GBSG trial 2 or 3 between 1984 and 1989. Patient characteristics are displayed in Table 1.

A median number of 13 positive lymph nodes was found (lower quartile=11, upper quartile=17). The median number of lymph nodes examined was 17. Since there was considerable variation in the number of lymph nodes examined (10% quantile=11, lower quartile=14, upper quartile=22, 90% quantile=27), we

Discussion

Here, we presented the long-term prognosis of breast cancer patients with 10 or more positive lymph nodes treated with a standardised, conventional dose CMF chemotherapy within two prospective studies. Existing treatment heterogeneity with respect to additional hormonal treatment or radiotherapy has been accounted for by stratification. There are only a few studies with a sufficient number of patients included and/or a long-term follow-up in this high-risk group 2, 3, 19, 20, 21 although the

Acknowledgements

This study was sponsored by the Bundesministerium für Forschung und Technologie (BMFT) and by the Deutsche Forschungsgemeinschaft (DFG).

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Long-term prognosis of breast cancer patients with 10 or more positive lymph nodes treated with CMF

Abstract

Introduction

Section snippets

Study design

Results

Discussion

Acknowledgements

Control. Clin. Trials

Ann. Oncol.

Int. J. Radiation Oncol. Biol. Phys.

Lancet

Lancet

Polychemotherapy for early breast canceran overview of the randomised trials

Lancet

Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and flourouracil in the treatment of resectable breast cancer with more than three positive axillary nodes

J. Clin. Oncol.

Clinical course of patients with breast cancer with ten or more positive nodes who were treated with doxorubicin-containing adjuvant therapy

Cancer

Methodological arguments for the necessity of randomized trials in high-dose chemotherapy for breast cancer

Breast Cancer Res. Treat.

Much ado about not ... enough datahigh-dose chemotherapy with autologous stem cell rescue for breast cancer

J. Natl. Cancer Inst.

Randomized and non-randomized patients in clinical trialsexperiences with Comprehensive Cohort Studies

Stat. Med.

for the German Breast Cancer Study Group (GBSG)randomized 2×2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients

J. Clin. Oncol.

Comprehensive cohort studyan alternative to randomized consent design in a breast preservation trial

Methods of Information in Medicine

Adjuvant chemotherapy for breast cancer

JAMA

Histological grading and prognosis in breast cancer

Br. J. Cancer

Nonparametric estimation from incomplete observation

J. Am. Stat. Assoc.

Confidence bands for a survival curve from censored data

Biometrika

The Statistical Analysis of Failure Time Data