As survival rates of patients with breast and prostate cancer increase, the need to address long-term adverse effects of cancer treatment on skeletal health is a priority to long-term survivorship. An individualised approach to assessment and management of all patients receiving endocrine therapy includes a baseline fracture risk assessment and ongoing surveillance. Targeted lifestyle changes and pharmacological therapies can help optimise skeletal health.
- Endocrine therapies for breast and prostate cancer are effective at reducing cancer recurrence but may have adverse skeletal effects that need to be appropriately assessed and managed to optimise benefit.
- Screening, surveillance and management of skeletal health should be tailored to the individual and involve a multidisciplinary team consisting of oncologists, endocrinologists, GPs, physiotherapists and exercise physiologists.
- Adequate dietary calcium, vitamin D and targeted exercise are recommended for all patients receiving endocrine therapy.
- For suitable patients, antiresorptive therapies have been shown to reduce bone mineral density loss, with some evidence of fracture risk reduction.
Breast and prostate cancer are among the most common malignancies in women and men, respectively. Endocrine therapy, an essential part of the armamentarium for the treatment of hormone sensitive breast and prostate cancer, exerts adverse effects on the skeleton and is associated with accelerated bone loss, microstructural decay and increased fracture risk. Fragility fractures are associated with devastating consequences to the individual, such as increased mortality and morbidity, and are also associated with a high socioeconomic burden. As such, preservation of bone health is a key long-term survivorship priority. In this review, we describe how endocrine therapies for breast and prostate cancer affect bone health and outline management strategies to mitigate endocrine therapy-induced bone loss and prevent fragility fractures.
Endocrine therapy for breast cancer
Around 80% of breast cancers are oestrogen-receptor positive and respond to endocrine therapies. Current endocrine therapies inhibit oestradiol-mediated effects on breast cancer progression in one of two ways – they deplete circulating oestradiol by blocking aromatase (aromatase inhibitors, AIs) or they competitively inhibit binding of oestradiol to the oestrogen receptor (ER) in breast tissue (selective oestrogen receptor modulators, SERMs, most commonly tamoxifen). The choice of therapy depends on the woman’s menopausal status, cancer characteristics and contraindications to a particular type of treatment.
AIs have shown superior efficacy to tamoxifen in preventing tumour recurrence and reducing mortality in postmenopausal women, and are generally used as first-line therapy for five years.1 Treatment with AIs is now being extended to 10 years in suitable women with high-risk features, based on clinical trial evidence of a modest reduction in breast cancer recurrence with extended therapy.2 In premenopausal women, tamoxifen is first-line. However, in those who are at higher risk of tumour recurrence, the use of gonadotropin releasing hormone (GnRH) analogues (which suppress ovarian oestradiol production) in combination with tamoxifen improves disease-free survival compared with tamoxifen alone, with further improvements observed with the combination of GnRH analogues and the AI exemestane.3,4 Of importance, AIs cannot be used as monotherapy in premenopausal women because oestradiol depletion reduces negative feedback on the gonadal axis, stimulating further oestradiol production. The use of AIs in this context requires concurrent ovarian function suppression, either with concurrent use of GnRH analogues, bilateral oophorectomy or radiotherapy to both ovaries.