Introduction and current guidance
Breast cancer is the most common cancer in women in England and Wales, and also occurs rarely in men. Most breast cancers are diagnosed at an early stage, when all detected deposits of the disease are in the breast or nearby lymph nodes and can be removed surgically. Early breast cancer is subdivided into 2 major categories, in situ disease and invasive cancer. Although most women with early breast cancer now survive, some have undetected deposits of cancer cells remaining after surgery in or near the breast, or at distant sites (for example, in bone). These can start to proliferate, sometimes many years later, resulting in a recurrence of the original breast cancer. Therefore, adjuvant treatments may be given in addition to surgery for early breast cancer to try to kill any remaining cancer cells (NICE guideline on early and locally advanced breast cancer: diagnosis and treatment and EBCTCG: Early Breast Cancer Trialists' Collaborative Group).
The NICE guideline on early and locally advanced breast cancer covers diagnosis and surgical and pharmacological treatment of women and men with early and locally advanced breast cancer (currently being updated). An interactive flowchart brings together everything NICE has published on this subject.
In women treated for breast cancer, aromatase inhibitors and chemotherapy-induced premature menopause are associated with osteoporosis, which increases the risk of bone fractures. Therefore, NICE guidance on early breast cancer recommends that people with early invasive breast cancer should have a baseline dual energy X-ray absorptiometry (DEXA) scan to assess bone mineral density if they:
are starting adjuvant aromatase inhibitor treatment
are starting ovarian ablation or suppression therapy
have treatment-induced menopause.
Bisphosphonates should be offered to women identified by the algorithms in Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK expert group (see appendix 2 of NICE's full guideline).
The NICE guideline on advanced breast cancer recommends that bisphosphonates should also be considered for people newly diagnosed with bone metastases to prevent skeletal adverse events and reduce pain.
Bisphosphonates may also have a role in the prevention of metastatic disease. It has been hypothesised that, in bone with high turnover, excess osteoclast activity could be associated with excess production of growth factors, which could in turn affect the survival of tumour micrometastases. Using bisphosphonates to reduce osteoclast activity might reduce expression of these factors, thereby preventing the establishment of micrometastatic disease. However, RCTs examining this possible effect have found mixed results (Brufsky and Mathew 2015).This evidence summary considers the best available evidence for using bisphosphonates off-label as adjuvant treatments for early breast cancer, to prevent recurrence and improve survival, rather than for their licensed indications, such as treating or preventing osteoporosis or skeletal events, or managing bone pain.