Tamoxifen

Tamoxifen is an oestrogen receptor antagonist which is used in the treatment of breast cancer (1,2,3,4)

• a partial oestrogen agonist (has antagonistic actions in breast cancers, but has agonist actions on endometrium, lipids, and bone)
• as effective at 20 mg/day as at higher doses
• effective in all age groups, and in premenopausal and postmenopausal women
• beneficial effects greater when given for five years rather than two - however no evidence shows that tamoxifen is of additional benefit if taken for more than five years, and it may be detrimental
  • tamoxifen taken for 5 years following surgical treatment is a standard part of the treatment regime for postmenopausal women with hormone-receptor-positive breast cancer. If used in this context then tamoxifen (4)
    • increases the proportion of women who survive for at least 10 years from about 50% to 60% among those with lymph-node involvement
    • increases the proportion of women who survive for at least 10 years without lymph-node involvement from about 73% to 79%
    • almost halves the risk of development of cancer in the contralateral breast
• may less effective against human epidermal growth factor receptor 2 (HER2) positive tumours
• more effective when given after chemotherapy (when this is also indicated) rather than concurrently

The International Breast Cancer Intervention Study (5), which investigated the use of tamoxifen in the unlicensed indication of breast cancer prevention, revealed that women treated with tamoxifen had an approximately 2.3x increased risk of venous thromboembolism (VTE) than those treated with placebo. Approximately 40% of the VTE cases occurred within 3 months of surgery or following immobility. This led to the Chairman of the study, in March 2002, recommending that women should no longer be treated with tamoxifen for the PREVENTION of breast cancer (i.e. prevention of occurrence rather than management of diagnosed disease).

Use of tamoxifen 5mg per day in prevention of recurrence of breast cancer:

Iinvestigated the use of tamoxifen at a dose of 5mg per day in the prevention of breast cancer recurrence (6,7)

• randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation
  • randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ
• primary end point was the incidence of invasive breast cancer or DCIS
• number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years
  • benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02).
• study authors concluded that:
  • tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events
  • no between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period

Tamoxifen is also used in the treatment of anovulatory infertility.

The summary of product characteristics should be consulted before prescribing this drug.

Reference:

1. BMJ. 2006 Jan 28;332(7535):223-4.
2. BMJ 2006;332:34-37
3. BMJ 2006;332:101-103
4. Drug and Therapeutics Bulletin (2003), 41 (8), 57-59.
5. Current Problems in Pharmacovigilance (2002), 28, 10.
6. DeCensi A et al. Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia. J Clin Oncol. 2019 Jul 1;37(19):1629-1637. doi: 10.1200/JCO.18.01779.
7. Lazzeroni M et al.Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study Journal of Clinical Oncology March 14th 2023.