Recent advances in endocrine therapy of breast cancer

Abstract

Regression of advanced breast cancer as a result of endocrine therapy was first described over 100 years ago.1 Interest in this form of treatment increased when treatment with the antioestrogen tamoxifen after surgery for breast cancer was shown to improve patients' survival. Treatment also reduced the incidence of new cancers in the contralateral breast, which has led to a number of trials of tamoxifen as a preventive measure in women at high risk. 4 New, potentially more active endocrine agents are now being introduced into clinical practice. In this review we outline the mechanism of action of these treatments and summarise recent results of clinical trials assessing their efficacy in comparison with older drugs; we also speculate about future trends in endocrine therapy and summarise clinical trials in progress. MethodsThis article is based, in part, on our own collaborative experimental work and close association with pharmaceutical companies developing new endocrine agents. Additional reviews and original articles were obtained from searches of oncological journals. Recent data were obtained from presentations at the May meeting of the American Society for Clinical Oncology. Mechanism of action of newer endocrine therapiesBreast cancer cells that are endocrine dependent need oestrogen to proliferate.5 Most endocrine therapies either block the binding of oestrogen to its receptor in the nucleus of responsive cells or reduce serum and tumour concentrations of oestradiol. In postmenopausal women androgens (mainly from the adrenal glands) are converted into oestrogens by the enzyme aromatase, which is present in a range of tissues and is found in 60-70% of breast carcinomas. The trend for endocrine therapies over the past 100 years has been towards simpler and more widely applicable treatments. Originally pharmacological doses of oestrogens were used to block the proliferative effect of oestrogen, but now this is achieved with tamoxifen.2 Oestrogen concentrations were reduced by surgery (oophorectomy, adrenalectomy, and hypophysectomy), but now analogues of luteinising hormone releasing hormone, which effectively ablate ovarian steroidogenesis, may be used in premenopausal women; aromatase inhibitors are used in postmenopausal women.

Trends in 1-year survival of people admitted to hospital in Ontario, 1994–2009

“…These mechanisms could also explain improved survival in patients admitted to hospital. Improved survival may reflect advances in medical care since the early 1990s, such as interventions for acute coronary syndromes, 20 aggressive use of statin and antiplatelet therapy in chronic coronary artery disease, 20 the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers and β-blockers for congestive heart failure, 2 0 implantable cardioverter defibrillators for sudden cardiac death, 20 aromatase inhibitors and other hormone treatments for breast cancer, 21 and effective antiretroviral therapy for AIDS. 22 This trend may also reflect increased uptake of evidence-based treatments.…”

Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study

“…Hormone dependence is a fundamental hallmark of the majority of breast cancers, and tumour growth can be inhibited either by deprivation of circulating oestrogens or by antagonising the effect of these hormones on their receptors [1]. The selective oestrogen receptor (ER) modulator tamoxifen has long been the most commonly used adjuvant therapy for patients with advanced hormone-sensitive breast cancer [2].…”

Effect of anastrozole and tamoxifen on lipid metabolism in Japanese postmenopausal women with early breast cancer

“…Many breast cancers depend on estrogen for their continued growth, and depriving tumors of this stimulus is an established method of treating the disease [1,2]. Separate treatment strategies are available for reducing the effects of estrogens on breast cancer.…”