Tamoxifen treatment after surgical treatment of pre-cancerous lesions of the breast

Ductal carcinoma in situ (DCIS) is a type of early breast cancer. It has no symptoms but is mostly detected by mammography screening. This type of 'pre' cancer is treated with surgery (e.g. mastectomy or lumpectomy), often in combination with radiotherapy. Some women are also given oral hormone tablets (tamoxifen), but it is unclear whether adding tamoxifen hormone treatment after surgery gives any added benefit. This review examined whether tamoxifen after local excision prevented any further episodes of cancer and whether women taking tamoxifen lived longer compared to those who did not take hormone therapy after local excision.

Our findings are based on two large studies with 3375 participants and should be applicable to most women having treatment for DCIS. Overall tamoxifen did reduce the number of future cancers or DCIS in either breast. However, women taking tamoxifen did not live longer than those who did not take it. A total of 15 women would have to take tamoxifen after treatment of DCIS for one woman to experience a benefit (i.e. no future cancers or DCIS in either breast after taking tamoxifen for five years). There are side effects of tamoxifen treatment such as blood clotting problems (stroke, deep vein thrombosis, pulmonary embolism) and endometrial cancer. However, no risk/benefit conclusions are possible because there was limited information about the side effects in this review. The effects of tamoxifen may have been 'diluted' by the effects of radiotherapy. This review cannot recommend which women might have more benefit from using tamoxifen in terms of age, menopausal status or type of DCIS (oestrogen receptor (ER)-positive versus ER-negative or human epidermal growth factor receptor 2 (HER2)-positive or HER2-negative DCIS).

Authors' conclusions: 

While tamoxifen after local excision for DCIS (with or without adjuvant radiotherapy) reduced the risk of recurrent DCIS (in the ipsi- and contralateral breast), it did not reduce the risk of overall mortality.

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Background: 

Ductal carcinoma in situ (DCIS) is a non-invasive carcinoma of the breast. The incidence of DCIS has increased substantially over the last twenty years, largely as a result of the introduction of population-based mammographic screening. The treatment of DCIS tumours involves surgery with or without radiotherapy to prevent recurrent DCIS and invasive carcinoma. However, there is clinical uncertainty as to whether postoperative hormonal treatment (tamoxifen) after surgery confers benefit in overall survival and incidence of recurrent carcinoma.

Objectives: 

To assess the effects of postoperative tamoxifen in women having local surgical resection of DCIS.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), the Cochrane Breast Cancer Group’s Specialised Register, and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) on 16 August 2011.

Selection criteria: 

Published and unpublished randomised controlled trials (RCTs) and quasi-randomised controlled trials comparing tamoxifen after surgery for DCIS (regardless of oestrogen receptor status), with or without adjuvant radiotherapy.

Data collection and analysis: 

Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the fixed-effect model and the results were expressed as relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs).

Main results: 

We included two RCTs involving 3375 women. Tamoxifen after surgery for DCIS reduced recurrence of both ipsilateral (same side) DCIS (HR 0.75; 95% CI 0.61 to 0.92) and contralateral (opposite side) DCIS (RR 0.50; 95% CI 0.28 to 0.87). There was a trend towards decreased ipsilateral invasive cancer (HR 0.79; 95% CI 0.62 to 1.01) and reduced contralateral invasive cancer (RR 0.57; 95% CI 0.39 to 0.83). The number needed to treat in order for tamoxifen to have a protective effect against all breast events is 15. There was no evidence of a difference detected in all cause mortality (RR 1.11; 95% CI 0.89 to 1.39). Only one study, involving 1799 participants followed-up for 163 months (median) reported on adverse events (i.e. toxicity, mood changes, deep vein thrombosis, pulmonary embolism, endometrial cancer) with no significant difference between tamoxifen and placebo groups, but there was a non-significant trend towards more endometrial cancer in the tamoxifen group.

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