Preoperative chemotherapy for women with operable breast cancer

 

Abstract

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 methods

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).

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.

 

Plain language summary

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).

 

摘要

背景

可手術切除的女性乳癌患者的術前化學治療

近年來為了讓乳癌手術順利進行，可讓局部腫瘤縮小的術前化學治療已成為局部晚期乳癌的標準治療。自1980年代早期，術前化學治療在早期乳癌治療(或可手術切除乳癌)的角色已成為研究議題。其潛在優勢為：早期引進系統性治療、對化療藥物是否敏感、減少腫瘤的體積與降低手術門檻。但也有人擔憂腫瘤切除術後的局部控制，以及延後對化療有抗藥性的病患接受局部治療。

目標

比較可手術切除的乳癌婦女進行術前化學治療與術後化學治療的療效。

搜尋策略

於2005年8月4日搜尋由Cochrane Breast Cancer Group 編輯維護的specialised register資料庫。

選擇標準

比較可手術切除的乳癌婦女，使用術前化學治療與術後化學治療之間的差異。

資料收集與分析

評估研究的適合性與品質，數據分別由兩位審查者摘錄。危險比(Hazard ratio)則直接從發病時間(timetoevent)取得，或者間接運用Parmar的方法敘述。二元變項以相對危險(Relative risk)表示。而統合分析(Metaanalyses)則以固定效果模式(fixed effect model)進行。

主要結論

我們找到了14篇隨機樣本達5500位婦女的適合研究。追蹤期中位數為18到124個月。有8項研究採合格的隨機分派方式。4620位婦女中預估有1139位死亡，這些數據可供分析,顯示整體存活率相當，其危險比為0.98(95% 信賴區間為0.87至1.09，P值為0.67；無異質性)。術前化學治療不僅增加了乳癌的保存率，也與增加區域復發率相關。然而，只要手術仍屬治療的一部份，即便腫瘤已完全縮小後，此比率仍不會增加。(HR: 1.12; 95% CI: 0.92 至1.37; p值為0.25;無異質性)術前化學治療與一小部份不良影響相關。相較於殘餘腫瘤，病理學完全反應與較佳的存活率比較有相關(HR: 0.48; 95% CI: 0.33 to 0.69; p值 < 10 – 4)。

作者結論

此篇回顧性文獻建議: 為了下階段的手術需求，應安全應用術前化療於治療早期乳癌婦女，以評估其化療敏感度與並促進轉換型研究。

翻譯人

本摘要由中山醫學大學附設醫院郝恩立翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

可手術切除的女性乳癌患者使用術前化學治療已被認為能改善乳癌的存活率。傳統上，這樣的治療被會用在已經歷過一次手術的病人。自1980年代早期，實施術前化療(也就是所知的前置化療)的局部晚期癌症患者有好的療效，於是這種治療開始興起(用於腫瘤大於5公分或者擴散到周邊組織或者淋巴結，亦或兩者皆有)。術前化療的立論基礎為早期導入一系列治療(治療會影響整個生理狀況)，這將讓腫瘤的尺寸減小，因此才能執行許多乳房保留手術。在這篇回顧性文獻中，我們探討在早期乳癌或可接受手術患者不同時間點使用化學治療，兩者間不同的影響性為何。此篇回顧性文獻找到14個隨機對照試驗，研究納入了5500位早期乳癌或可接受手術之乳癌婦女。分析後顯示罹患乳癌婦女在術前或是術後使用化學治療的整體存活率及無病存活率無差異。術前治療可以讓腫瘤在手術前縮小，因而讓乳房保留手術較為可能(RR：0.82 5% CI: 0.76 – 0.89)。然而，這也同時增加局部區域性的復發率(復發在同一個區域 HR: 1.12; 95%: 0.92 – 1.37)。術前化學治療能監測腫瘤反應情況，一旦腫瘤對主要治療出現了耐受性，能夠適當修改治療方案。在不良反應方面，目前的報告中只有一半的研究指出少數接受術前化療的婦女有不良反應。雖然術後的併發症、噁心、嘔吐及掉髮分布情況相同，但心毒性(cardiotoxicity)似乎在接受術前化療的婦女組中較少(RR: 0.74 5% CI: 0.53 – 1.04)。除此之外，接受術前化療的婦女中，嚴重的感染(分析了2799位婦女)發生率也減少(RR: 0.69 5% CI: 0.56 – 0.84)