Home > DARE Reviews > Tamoxifen for the management of breast...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review

F Kunath, B Keck, G Antes, B Wullich, and JJ Meerpohl.

Review published: 2012.

CRD summary

The authors concluded that available evidence suggested tamoxifen had good efficacy for the prevention and treatment of breast events induced by non-steroidal antiandrogens. These conclusions appear to reflect the evidence presented, but limitations of the evidence base means that the reliability of these conclusions is undecided.

Authors' objectives

To compare the benefits and harms of tamoxifen with other treatment options for the prophylaxis or treatment of breast events induced by non-steroidal antiandrogens in prostate cancer patients.

Searching

MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to April, 2012, with no language restrictions. Search terms were reported in an appendix. The reference lists of all identified papers were manually searched to locate further studies. Three clinical trial registers and abstracts from three conferences (reported in paper) were also searched to April, 2012, for trials that were completed or ongoing.

Study selection

Parallel group, randomised controlled trials (RCTs) which compared tamoxifen with any other therapy in preventive and therapeutic settings for the management of breast events in prostate cancer patients were eligible for inclusion. Breast events had to have been induced by non-steroidal antiandrogens. Outcomes of interest included gynaecomastia, breast pain, the incidence of adverse events and discontinuation due to adverse events. Patients with neoplasms other than prostate cancer or with breast events induced by other diseases (such as alcoholism) were excluded.

All included trials were multi-centre and were conducted in Europe or North America. Intervention arms received tamoxifen only; control arms received anastrozole (1mg/day), placebo, no additional therapy, or radiotherapy. Most trials administered 20mg of tamoxifen daily and compared it to multiple control arms. Patients were all treated with bicalutamide (150mg/day) as the androgen-suppression therapy. All trials assessed breast pain with direct patient questioning; gynaecomastia was assessed in various ways.

Two reviewers examined the full texts of studies to assess their eligibility for inclusion; any discrepancies were resolved by double-checking the full texts, discussion, and consultation with a third reviewer when necessary.

Assessment of study quality

Two reviewers assessed the risk of bias for each trial according to random sequence generation, allocation concealment, blinding of participants, personnel and the outcome assessment, incomplete outcome data, selective reporting and other possible bias.

Data extraction

Two reviewers extracted data on outcomes to calculate risk ratios (RR) and 95% confidence intervals (CI).

Methods of synthesis

Risk ratios and their 95% confidence intervals were pooled using the fixed-effect Mantel-Haenszel method. Statistical heterogeneity was assessed using Χ² and Ι². A random-effects model was also applied as a sensitivity analysis if the initial Ι² value exceeded 50%.

Results of the review

Four RCTs were included in the review and meta-analysis (466 patients). Random sequence generation seemed adequate across all of the trials; allocation concealment and double blinding of participants, personnel and outcome assessment were each reported by three trials. No evidence for missing data was found; all trials were assessed as having a low risk of bias for selective reporting, although study protocols were not always available. Other potential sources of bias were reported.

Compared with untreated control groups, a statistically significant lower risk of gynaecomastia was found with tamoxifen at three months (RR 0.06, 95% CI 0.01 to 0.43; one trial), six months (RR 0.10, 95% CI 0.05 to 0.22; two trials) and nine to 12 months (RR 0.17, 95% CI 0.09 to 0.31; two trials). No substantial statistical heterogeneity was shown (Ι² values all 0%). Similar results were shown for risk of breast pain at three months (RR 0.09, 95% CI 0.03 to 0.24, two trials; Ι²=74%), six months (RR 0.06, 95% CI 0.02 to 0.17; two trials; Ι²=27%) and nine to 12 months (RR 0.13, 95% CI 0.06 to 0.27; two trials; Ι²=0%). A random-effects sensitivity analysis demonstrated a similarly lower risk of breast pain at three months with tamoxifen versus controls (RR 0.10, 95% CI 0.01 to 0.90).

After a median of 12 months, tamoxifen (20mg daily) showed a statistically significant benefit over anastrozole (1mg/day) for the prevention of gynecomastia (RR 0.22, 95% CI 0.08 to 0.58; one trial) and breast pain (RR 0.25, 95% CI 0.10 to 0.64; two trials; Ι²=0%). Similar results for prevention of gynecomastia (RR 0.24, 95% CI 0.09 to 0.65; one trial) and breast pain (RR 0.20, 95% CI 0.06 to 0.65) were shown when tamoxifen (10mg daily) was compared with radiotherapy at six months.

Statistically significant differences favouring tamoxifen to control groups were found for the treatment of breast events at three months (one trial) and improvement of symptoms related to gynaecomastia, breast pain or both at nine months (one trial). Radiotherapy in one trial (a single fraction of 12Gy) significantly increased the risk of nipple erythema and skin irritation, when compared with tamoxifen, but the events were resolved after a median of four weeks. No other significant differences related to adverse events were found (four trials); further detail was reported in the paper.

Authors' conclusions

Available evidence suggested that tamoxifen had good efficacy for the prevention and treatment of breast events induced by non-steroidal antiandrogens.

CRD commentary

The review question was clear and inclusion criteria were clearly defined. Relevant data sources were searched for both published and unpublished literature and no language restrictions were applied, which reduced the likelihood of language bias. It appeared that attempts were made to minimise the risk of reviewer error and bias throughout the review process.

Quality assessment was performed according to suitable quality domains. All trials were assessed as having a low risk of bias for selective reporting even though none of the study protocols were available. Study details were presented. Some clinical diversity existed between the trials, particularly in relation to patients' treatment backgrounds, criteria for diagnosis of gynaecomastia, and grading for severity of breast pain. As a result, the meta-analytic methods employed may not have been appropriate even though statistical heterogeneity was generally low. The small sample sizes of the four included trials and reporting of some outcomes by only one trial also highlight that the evidence base available was limited.

The limitations of the evidence base mean that the reliability of these conclusions is undecided.

Implications of the review for practice and research

Practice: The authors stated that the review provided evidence-based guidance to clinicians on this clinically relevant topic.

Research: The authors stated that the impact of tamoxifen on long-term adverse events, disease progression and survival remained unclear. High-quality RCTs with longer follow-up terms were required to investigate the benefits and harms of tamoxifen at daily doses of 10mg and 20mg, in comparison to radiotherapy.

Funding

The Deutsch Gesellschaft fur Urologie (German Society of Urology).

Bibliographic details

Kunath F, Keck B, Antes G, Wullich B, Meerpohl JJ. Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review. BMC Medicine 2012; 10:96. [PMC free article: PMC3464149] [PubMed: 22925442]

Indexing Status

Subject indexing assigned by CRD

MeSH

Tamoxifen; Androgen Antagonists; Prostatic Neoplasms; Breast Neoplasms; Humans

AccessionNumber

12012048006

Database entry date

13/02/2013

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22925442

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...