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Intervention Review

Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus)

  1. Daniel Hind1,*,
  2. Lynda Wyld2,
  3. Catherine Beverley3,
  4. Malcolm W Reed2

Editorial Group: Cochrane Breast Cancer Group

Published Online: 25 JAN 2006

Assessed as up-to-date: 12 NOV 2007

DOI: 10.1002/14651858.CD004272.pub2


How to Cite

Hind D, Wyld L, Beverley C, Reed MW. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD004272. DOI: 10.1002/14651858.CD004272.pub2.

Author Information

  1. 1

    University of Sheffield, School of Health and Related Research (ScHARR), Sheffield, South Yorkshire, UK

  2. 2

    Sheffield Teaching Hospitals NHS Trust, Academic Surgical Oncology Unit, Sheffield, Sheffield, UK

  3. 3

    Cumbria County Council, Adult Social Care Directorate, Carlisle, UK

*Daniel Hind, School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent Street, Sheffield, South Yorkshire, S1 4DA, UK. D.Hind@sheffield.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 25 JAN 2006

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This is not the most recent version of the article. View current version (16 MAY 2014)

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Several studies have evaluated the clinical effectiveness of endocrine therapy alone in women aged 70 years or over and who are fit for surgery.

Objectives

To identify and review the evidence from randomised trials comparing primary endocrine therapy (endocrine therapy alone) to surgery, with or without adjuvant endocrine therapy, in the management of women aged 70 years or over with operable breast cancer.

Search methods

For this update, the Cochrane Breast Cancer Group Specialised Register was searched 13th November 2007 using the codes for "early breast cancer", "endocrine therapy", "psychosocial" or "surgery".

Selection criteria

Randomised trials comparing primary endocrine therapy with surgery, with or without adjuvant endocrine therapy, in the management of women aged 70 years or over with early breast cancer and who are fit for surgery.

Data collection and analysis

Studies were assessed for eligibility and quality, and data from published trials were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed-effect model was used for meta-analysis. Toxicity and quality-of-life data were extracted, where present. Where outcome data were not available, trialists were contacted and unpublished data requested.

Main results

Seven eligible trials were identified of which six had published time-to-event data and one was published only in abstract form with no usable data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen.

Data, based on an estimated 869 deaths in 1571 women, were unable to show a statistically significant difference in favour of either surgery or primary endocrine therapy in respect of overall survival. However, there was a statistically significant difference in terms of progression-free survival, which favoured surgery with or without endocrine therapy.

The hazard ratios (HR) for overall survival were: 0.98 (95% confidence interval (CI) 0.74 to 1.30, P value 0.9) for surgery alone versus primary endocrine therapy; 0.86 (95% CI 0.73 to 1.00, P value 0.06) for surgery plus endocrine therapy versus primary endocrine therapy. The HRs for progression-free survival were: 0.55 (95% CI 0.39 to 0.77, P value 0.0006) for surgery alone versus primary endocrine therapy; 0.65 (95% CI 0.53 to 0.81, P value 0.0001) for surgery plus endocrine therapy versus primary endocrine therapy (each comparison based on only one trial). Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included paresthesia on the ipsilateral arm and lateral thoracic wall in those who had axillary clearance. One study suggested that those undergoing surgery suffered more psychosocial morbidity at three months postsurgery, although this difference had disappeared by two years.

Authors' conclusions

Primary endocrine therapy should only be offered to women with oestrogen receptor (ER) positive tumours who are unfit for or who refuse surgery. In a cohort of women with significant co-morbid disease and ER-positive tumours it is possible that primary endocrine therapy may be a superior option to surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for an infirm older population with ER-positive tumours.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Surgery versus primary endocrine therapy for elderly women with operable primary breast cancer

While younger women with early-stage breast cancer almost invariably are treated with surgery plus endocrine therapy, (which deprives the cancer of hormones which induce growth of the cancer), women over the age of 70yrs are frequently offered endocrine therapy alone. This is known as primary endocrine therapy.

Primary endocrine therapy using tamoxifen (a drug which blocks oestrogen receptors on the cancer cell, prohibiting its growth) was introduced for older women in the 1980s. Tamoxifen was given without surgery, radiotherapy or chemotherapy on the basis that older patients are more likely to have cancers with oestrogen receptors and will therefore respond well to treatment. In addition they were thought less suitable for major surgery because of other existing health issues. However, a tumour will often only respond to this treatment for between 18 and 24 months and those women who relapse will have to consider additional hormone treatment or opt for surgery or radiotherapy at a greater age. The long-term data suggests that, at 12 years of follow up, more elderly women treated by primary tamoxifen alone will suffer a progression of their cancer than those who had surgery.

This review was undertaken to assess the evidence for the clinical effectiveness of surgery (with or without endocrine therapy) compared with primary endocrine therapy in the treatment of operable breast cancer in women aged 70 years and over. Based on seven trials and an estimated 869 deaths in 1571 women, the results of this review showed no benefit in respect to survival for either surgery or primary endocrine therapy. However, women who had surgery were less likely to relapse than women on primary endocrine therapy.

The authors conclude that surgery controls breast cancer better than tamoxifen alone in older women but does not extend survival. Both interventions were associated with adverse events. Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included tingling or numbness on the arm on the side of the surgery and psychosocial problems. On this basis, primary endocrine therapy should only be offered to women with oestrogen receptor (ER) positive tumours who are unfit for, or who refuse surgery. Further trials are needed to evaluate the clinical effectiveness of other agents such as aromatase inhibitors for use as primary endocrine therapy for an infirm older population with ER-positive tumours.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

在患有可行手術原發性乳癌之年紀較大婦女(超過70歲)其使用手術與單獨內分泌療效之比較

許多研究已針對單獨作內分泌治療的臨床療效在符合手術條件且年紀大於七十歲的婦女做過探討。

目標

由臨床隨機研究中的研究證據辨認與回顧單獨內分泌療法,與內分泌輔佐治療的手術及單純手術治療,在70歲及過了手術年齡之婦女的效果比較。

搜尋策略

於2003年8月21日用 “早期的乳癌” “內分泌治療” “社會心理” 或 “手術” 等關鍵字在 Cochrane r乳腺癌小組專業搜索器中搜尋。 關於註冊與使用關鍵字搜索的流程細節可參考考科藍圖書館的考科藍乳癌小組。

選擇標準

比較主要內分泌療法(單獨內分泌療法)與手術在患有可行手術的原發性乳癌且年紀大於七十歲的婦女有或沒有佐藥內分泌療法的隨機試驗。

資料收集與分析

為了估計研究的合適性和質量,由二個獨立審閱者從出版試驗的數據來擷取。 用危險比率來看時間對事件的結果,若可能的話,固定作用模組使用來作整合分析。呈現擷取毒性和生活品質數據。 如果結果的數據不可利用的, 接洽測試者,並且請求未出版的數據。

主要結論

在7個合格試驗中,已經確定了其中6個公佈了存活數據(timetoevent data),其中一個研究只公佈摘要格式,並且無有效數據。有三個研究,隨機分派的方式之隱匿性品質是充分的,但其他的研究方法不明。每一個研究之內分泌療法都使用他莫息芬(tamoxifen),資料中1571位婦女估計有869人死亡,但以整體存活(overall survival)來說無法顯現出以手術治療與單獨內分泌療法之間的統計顯著性。然而,使用單純手術治療或是手術伴隨內分泌治療之無病存活率(progressionfree survival)在統計上是顯著的。其整體存活之hazard ratios(HR): 單純使用手術治療與單獨內分泌治療之HR為0.98(95% 信賴區間(CI)為0.74 – 1.30, P value為0.9);以手術伴隨內分泌治療與單獨內分泌治療之HR為0.86(95% CI: 0.73 – 1.00, P value 0.06)。其無病存活之HRs為:單純使用手術治療與單獨內分泌治療之HR為0.55(95% CI: 0.39 – 0.77, P value0.0006);以手術伴隨內分泌治療與單獨內分泌治療(每單獨一個試驗相比)之HR為0.65(95% CI: 0.53 – 0.81, P value0.0001)。他莫昔芬相關的不利影響包括潮熱,皮疹,陰道分泌物,消化不良,乳房疼痛,困倦,頭痛,眩暈,瘙癢,脫髮,膀胱炎,急性血栓性靜脈炎,噁心和消化不良。手術相關的不利影響包括:在腋窩清除術(axillary clearance)部位之同側上臂與同側胸壁外側,會有皮膚感覺異常(paresthesia)發生。一項研究認為,儘管在術後2年內異常感會消失,但歷經手術者在術後三個月內會有心理疾病的發生。

作者結論

單獨內分泌治療只應給那些不適合或拒絕手術且有雌激素受體(ER)陽性腫瘤的婦女。對於有重大及併發症的疾病和ER陽性腫瘤的婦女而言選擇主要內分泌治療比手術更適當。臨床試驗必需評估以芳香羥作為主要療法的體弱老年人且有ER陽性腫瘤臨床療效。

翻譯人

本摘要由中山醫學大學附設醫院陳坤鍾翻譯。

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

總結

而患有早期乳癌之較年輕婦女除了手術之外,幾乎無例外地也接受內分泌治療,而70歲以上的婦女仍常接受單獨內分泌治療(primary endocrine therapy)。此回顧性研究證實,對於大於適合開刀年齡的婦女局部控制乳癌,單獨內分泌治療療效不如手術治療(伴隨內分泌治療或是單獨手術治療),然而手術也無法顯著的提高整體存活率。