Aromatase inhibitors are recommended as alternative options to tamoxifen for treating early breast cancer that is oestrogen receptor positive in postmenopausal women, says draft guidance for the NHS published this week.
The National Institute for Health and Clinical Excellence (NICE) advises on the use of treatments by the NHS in England and Wales. It recommended that the choice of treatment for oestrogen receptor positive breast cancer should be made after discussion between the patient and their doctor about the risks and benefits of the options available.
The options are primary adjuvant treatment with an aromatase inhibitor; switching from tamoxifen to an aromatase inhibitor; or use of an aromatase inhibitor after completion of five years of treatment with tamoxifen. This discussion should include whether the patient has received tamoxifen as part of their treatment so far, the side effects of the individual drugs, and, in particular, the assessed risk of recurrence.
Aromatase inhibitors block the conversion of androgens to oestrogens in peripheral tissues in postmenopausal women. This reduces circulating concentrations of oestrogen, depriving breast cancer cells that are oestrogen receptor positive of the hormone that drives the proliferation of tumours. They therefore act by a different mechanism to tamoxifen, the current standard hormonal treatment for early breast cancer, which inhibits the binding of oestrogen to its receptor in the nucleus of responsive cells.
Michael Baum, emeritus professor of surgery at University College London, said, “By embracing these innovative treatments and recommending their use immediately after surgery, NICE has confirmed that aromatase inhibitors are becoming the ‘gold standard’ treatment and allowed all eligible women access to more effective and better tolerated medicines. Importantly, this guidance may help the NHS to further improve breast cancer mortality rates in the UK—which have been steadily falling over the years.”
The NICE appraisal committee reviewed seven randomised clinical trials with three aromatase inhibitors—anastrozole, exemestane, and letrozole. It found consistent evidence that aromatase inhibitors improve clinical outcomes when used as primary adjuvant treatment (used instead of tamoxifen immediately after surgery), in unplanned switching (changing from tamoxifen to an aromatase inhibitor at any time) and as extended adjuvant treatment (used after five years of tamoxifen).
But the appraisal found no evidence from any individual study that aromatase inhibitors improved overall survival compared with tamoxifen. The draft guidance noted the different side effects of aromatase inhibitors compared with tamoxifen, with higher rates of bone fracture with aromatase inhibitors and greater risk of endometrial cancer and other gynaecological conditions with tamoxifen.
The appraisal is available for comment until 13 June 2006, after which the final guidance will be developed.
In a further development in breast cancer treatment, the European Commission approved trastuzumab (Herceptin) to be licensed for the treatment of patients with early HER2 positive breast cancer, after surgery and standard chemotherapy.
NICE’s consultation document, Breast Cancer (Early): Hormonal Treatments , is available at www.nice.org.uk/page.aspx?o=318564.