Prognostic factors for survival after neoadjuvant chemotherapy in operable breast cancer: the role of clinical response

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Abstract

The aim of this retrospective study was to assess predictive factors for clinical response to preoperative chemotherapy and prognostic factors for survival. From 1981 to 1992, 936 patients with T2-T3, N0-N1 breast cancer who received 2–6 months (median 4) of preoperative chemotherapy were selected from the Institute Curie database. Preoperative treatment was followed by surgery and/or radiotherapy. Median follow-up was 8.5 years (range 7–211 months). The objective response rate before surgery and/or radiotherapy was 58.3%. In stepwise multivariate analysis (Cox model), favourable prognostic factors for survival were the absence of pathological axillary lymph node involvement (Relative Risk (RR) 1.54; P=0.0004), low histological tumour grade (RR=1.54; P=0.0017), clinical response to preoperative chemotherapy (RR=1.45, P=0.0013), positive progesterone receptor (PR) status (RR=1.56; P=0.0001), smaller tumour size (RR=1.37; P=0.005) and lack of clinical lymph node involvement (RR=1.42; P=0.007). The association of clinical tumour response with survival is independent of the baseline characteristics of the tumour. Clinical response could be used as a surrogate marker for evaluation of the efficacy of neoadjuvant chemotherapy before assessment of the pathological response.

Introduction

Neoadjuvant chemotherapy has become the standard of care for patients with locally advanced breast cancer and has rapidly come to the forefront among potential treatments for patients with earlier-stage operable disease 1, 2. Several clinical trials have compared preoperative and postoperative chemotherapy in operable breast cancer, but no significant advantage in terms of long-term survival has been demonstrated to date 3, 4, 5, 6, 7, 8, 9.The only demonstrated benefit in terms of treatment effects of neoadjuvant chemotherapy in operable breast cancer is the achievement of tumour shrinkage, which allows more conservative treatment in some patients [10]. The response of breast tumours to preoperative chemotherapy might also be predictive of the efficacy of therapy on distant micrometastatic disease and outcome. A possible advantage of primary systemic treatment is to test the in vivo tumour response in order to modify treatment or introduce new drugs postoperatively. However, the response of the primary breast tumour to preoperative chemotherapy could simply be associated with better prognostic factors. The standard predictive and prognostic factors established in primary breast cancer may not carry the same value in breast cancer patients initially treated with chemotherapy rather than surgery. The independent prognostic value of tumour response, distinct from that of other prognostic factors such as tumour size, tumour grade and hormone sensitivity, should be demonstrated.

Since 1981, at the Institut Curie, neoadjuvant chemotherapy has also been used in large operable breast cancers, prior to local regional treatment. The aim of this study was to retrospectively assess the prognostic value of clinical response after preoperative chemotherapy in breast cancers prospectively registered in the database of one institution.

Section snippets

Patients

The present study was a retrospective analysis of the Institut Curie Breast Cancer database. This database was initiated in 1981 to prospectively register data for all patients treated for breast cancer at the Institut Curie [11]. The selection criteria were prior neoadjuvant chemotherapy for operable T2 or T3, N0 or N1 tumours. Patients with metastatic, locally advanced or inflammatory cancer were excluded, as were patients with bilateral tumours, prior cancer and male patients. Between 1981

Results

Pretreatment patient and tumour characteristics are summarised in Table 1. Median age was 47 years. Seventy-five percent of patients were premenopausal. Median tumour size was 4.5 cm (range: 2–12 cm). Sixty-five percent of the patients had clinical lymph node involvement. The pathological and laboratory characteristics of the tumours were as follows: 82% of tumours were grade II or III, 85% of tumours were ductal carcinomas, progesterone receptors (PR) were positive in 54% of patients and

Discussion

As response to preoperative chemotherapy is correlated with survival, response could be used as an intermediate endpoint to determine the value of new chemotherapy regimens or new drugs administered after well-established regimens [17]. Since this intermediate endpoint can be achieved within weeks after starting preoperative chemotherapy, new regimens or new active agents could be evaluated promptly and useful conclusions could be drawn without a 5- to 10-year waiting period, as is currently

Acknowledgements

We would like to acknowledge the Breast Cancer Group of the Institut Curie.

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