Breast cancer prevention trumps cure

Breast cancer is the most prevalent female cancer and is estimated to increase by 50% by 2030 compared to the incidence in 2011. The decision by the National Institute for Health and Care Excellence (NICE), the UK health technology appraiser, to recommend the use of preventive medicines, which are known to decrease the risk of developing breast cancer, is a welcome advance in public health.

These medicines have been rigorously studied, and tens of thousands of women who at high risk of breast cancer have been monitored for decades in clinical trials.

There are three recommended medicines: tamoxifen, raloxifene, and anastrazole. They all prevent oestrogen from stimulating tumour development. However, these medicines are not interchangeable and have different characteristics. Doctors must tailor appropriate medicines for each woman at high risk for breast cancer. Tamoxifen and raloxifene are pioneering selective oestrogen receptor modulators (SERMs) that directly block oestrogen binding to the tumour cell oestrogen receptor (ER), thereby preventing growth of nascent breast tumours[1]
. The third medicine, anastrazole, is an aromatase inhibitor (AI) that prevents the synthesis of oestrogen in the body fat of postmenopausal women. As a result, the tumour cannot develop and grow. Tamoxifen can be used in either pre- or postmenopausal women at high risk, but raloxifene and anastrazole can only be used in postmenopausal women.

Tamoxifen is the first, and perhaps the most successful, targeted medicine in cancer therapeutics[2],[3]
. Tamoxifen had been tested successfully for the treatment and prevention of breast cancer for the past 40 years. Results from worldwide clinical trials have been used to project that millions of women’s lives have been extended or saved by taking five years of adjuvant tamoxifen treatment. Additionally tamoxifen, used as a preventive, not only reduces the incidence of new breast cancers by 50% during therapy, but also continues to be effective in some trials for at least a decade after stopping therapy[4]
.

This remarkable observation means that, following five years of tamoxifen treatment, women will remain protected from breast cancer for the foreseeable future. Early studies with tamoxifen noted a small but significant increase in womb cancer, but only in postmenopausal women; 20 years ago, this meant only three extra womb cancer were detected per 1,000 tamoxifen treated patients per year. Today, this worrying side effect is routinely monitored through gynaecological examination. Indeed, current studies find that cancer of the womb is a rare event.

Raloxifene is approved for the treatment and prevention of osteoporosis in postmenopausal women. The medicine has been used worldwide for the past 20 years. The unique property of the SERM raloxifene is that it increases bone density but prevents breast cancer at the same time[5]
. Raloxifene does not increase womb cancer. The AI anastrazole can only be used in postmenopausal women, but is superior to either tamoxifen or raloxifene in preventing breast cancer. It does not increase incidence of the cancer of the womb. However, the medicine increases osteoporotic fractures and should not be used by women with preexisting osteoporosis.

Cancer kills and healthcare systems are overwhelmed by the relentless cancer increases in our ageing population. We applaud the NICE recommendation to apply the proven therapeutic benefit of chemoprevention, which will avoid tragedy in the family when a solution is available.

Balkees Abderrahman

Postdoctoral fellow

Breast medical oncology

V. Craig Jordan

Dallas/Ft. Worth living legend chair of cancer research

Breast medical oncology

University of Texas MD Anderson Cancer Center

References

[1] Jordan VC, Gapstur S & Morrow M. Selective estrogen receptor modulation and reduction in risk of breast cancer, osteoporosis, and coronary heart disease. J Natl Cancer Inst 2001;93(19):1449–57. doi: 10.1093/jnci/93.19.1449

[2] Jordan VC. Tamoxifen: Catalyst for the change to targeted therapy. Eur J Cancer 2008;44(1):30–38. doi: 10.1016/j.ejca.2007.11.002

[3] Sledge GW, Mamounas EP, Hortobagyi GN et al. Past, present, and future challenges in breast cancer treatment. J Clin Oncol 2014;32(19):1979–86. doi: 10.1200/JCO.2014.55.4139

[4] Cuzick J, Sestak I, Bonoanni B et al. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet 2013;381(9880):1827–34. doi: 10.1016/S0140-6736(13)60140-3

[5] Cummings SR, Eckert S, Krueger KA et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999;281(23):2189–97. doi: 10.1001/jama.281.23.2189

Last updated
Citation
Clinical Pharmacist, CP, January 2017, Vol 9, No 1;9(1):DOI:10.1211/PJ.2016.20202048

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