Preoperative chemotherapy for women with operable breast cancer

Chemotherapy for patients with early stage breast cancer has been shown to improve survival. Traditionally, this therapy is given once the patient has undergone surgery. Since the early 1980's, interest has risen in administrating chemotherapy before surgery (known as preoperative or neoadjuvant chemotherapy) based on good results achieved in patients with locally advanced disease (cancer which is larger than 5cm and/or has spread to surrounding tissue or lymph nodes, or both). The rationale for preoperative chemotherapy is that an early introduction of systemic treatment (treatment that affects the whole body) will result in a decrease in the size of the tumour, hence making it possible to do more breast-conserving surgery. For this review, we investigated the effect of the difference in timing of chemotherapy treatment for patients with early stage or operable disease.

This review identified 14 randomised controlled trials involving 5,500 women addressing this question. The analyses revealed no difference in overall survival and disease-free survival for women who received either preoperative or postoperative chemotherapy. Preoperative treatment makes more breast-conserving surgery possible because of shrinkage of the tumour before surgical intervention (relative risk, 0.82; 95% confidence interval, 0.76 to 0.89). However, this also results in a increase of loco-regional recurrence (recurrence in the same area) rate (hazard ratio, 1.12; 95% confidence interval, 0.92 to 1.37). Preoperative chemotherapy provides the possibility of monitoring tumour response and making appropriate regimen changes once the tumour appears to be resistant to the primary therapy. Adverse effects, which were reported in only half of the studies, were fewer in women receiving preoperative chemotherapy. Although, postoperative complications, nausea and vomiting, and alopecia were equally distributed, events of cardiotoxicity were less likely (relative risk, 0.74; 95% confidence interval, 0.53 to 1.04) in women receiving preoperative chemotherapy. Also, serious infection (analysed in 2799 women) was less likely to occur in women receiving preoperative chemotherapy (relative risk, 0.69; 95% confidence interval, 0.56 to 0.84).

Authors' conclusions: 

This review suggests safe application of preoperative chemotherapy in the treatment of women with early stage breast cancer in order to down-stage surgical requirement, to evaluate chemosensitivity and to facilitate translational research.

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Background: 

Currently, preoperative chemotherapy is the standard of care in locally advanced breast cancer to achieve local tumour downsizing in order to make surgery possible. Since the early 1980s, the role of preoperative chemotherapy in early stage (or operable) breast cancer has been the subject of study. Potential advantages are early introduction of systemic therapy, determination of chemosensitivity, reduction of tumour volume and downstaging of surgical requirement. Concerns exist about local control after downsized surgery and the delay of local treatment in patients with tumours resistant to chemotherapy.

Objectives: 

To assess the effectiveness of preoperative chemotherapy in women with operable breast cancer when compared to postoperative chemotherapy.

Search strategy: 

The Specialised Register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 4th of August 2005.

Selection criteria: 

Randomised trials comparing preoperative chemotherapy with postoperative in women with operable breast cancer.

Data collection and analysis: 

Studies were assessed for eligibility and quality, and data were extracted by two independent review authors. Hazard ratios were derived for time-to-event outcomes directly or indirectly using the methods described by Parmar. Relative risks were derived for dichotomous outcomes. Meta-analyses were performed using fixed effect model.

Main results: 

We identified 14 eligible studies which randomised a total of 5,500 women. Median follow-up ranged from 18 to 124 months. Eight studies described a satisfactory method of randomisation.

Data, based on 1139 estimated deaths in 4620 women available for analysis, show equivalent overall survival rates with a HR of 0.98 (95% CI, 0.87 to 1.09; p, 0.67; no heterogeneity). Preoperative chemotherapy increases breast conservation rates, yet at the associated cost of increased loco regional recurrence rates. However, this rate was not increased as long as surgery remains part of the treatment even after complete tumour regression (HR, 1.12; 95% CI, 0.92 to 1.37; p, 0.25; no heterogeneity. Preoperative chemotherapy was associated with fewer adverse effects. Pathological complete response is associated with better survival than residual disease (HR, 0.48; 95% CI, 0.33 to 0.69; p, < 10-4).

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