Osteoporosis management in patients with breast cancer: EMAS position statement

Abstract

Aromatase inhibitors (AIs) are the first-line recommended standard of care for postmenopausal estrogen receptor-positive breast cancer. Because they cause a profound suppression of estrogen levels, concerns regarding their potential to increase the risk of fracture were rapidly raised. There is currently a general consensus that a careful baseline evaluation is needed of the risk of fracture in postmenopausal women about to start treatment with AIs but also in all premenopausal women with early disease. Bisphosphonates have been shown in several phase III trials to prevent the bone loss induced by cancer treatment, although no fracture data are available. Even though they do not have regulatory approval for this indication, their use must be discussed with women at high risk of fracture. Accordingly, several guidelines recommend considering treatment in women with a T-score ≤-2 or those with two or more clinical risk factors. Moreover, recent data suggest that bisphosphonates, especially intravenous zoledronic acid, may have an anticancer effect, in that they reduce bone recurrence as well as extra-skeletal metastasis and breast cancer mortality in postmenopausal women. The anti-RANK ligand antibody denosumab is also emerging as a new adjuvant therapeutic option to prevent AI-induced bone loss. It has been shown to extend the time to first fracture in postmenopausal women treated with AIs. Several issues still need to be addressed regarding the use of these different agents in an adjuvant setting. The purpose of this position statement is to review the literature on antifracture therapy and to discuss the current guidelines for the management of osteoporosis in women with early breast cancer.

Increased Fracture Risk in Women Treated With Aromatase Inhibitors Versus Tamoxifen: Beneficial Effect of Bisphosphonates

“…(7)(8)(9) Several phase III trials and population-based cohort studies have shown the efficacy of BP in preventing the bone loss induced by AIs. (9)(10)(11) A meta-analysis of 26 randomized clinical trials (RCTs), including both intravenous and oral BP administration, reported a small reduction of fracture risk in BP-treated patients with breast cancer. (12) However, these trials analyzed the BP effect in oncological outcomes, not for fractures.…”

Evaluation and management of skeletal disease in cancer care

“…The type of adjuvant therapy used is determined by hormone receptor status and menopausal state (27). For example, treatment of premenopausal women with hormone receptor positive breast cancer is aimed at inhibiting the effect of estrogen on the breast and is usually achieved by estrogen receptor blockage (such as with tamoxifen), or ovarian function suppression with surgical oophorectomy or with the use of GnRH agonist/antagonist therapy (28).…”

“…The superiority of aromatase inhibitors (AIs) over tamoxifen in hormone-receptor positive disease has been established in multiple trials (29, 30). Moreover, the side effects of uterine cancer and thromboembolic events seen with tamoxifen therapy are not observed in AI therapy, which might have led to the increased use of AI therapy in the last decade (27). On the other hand, AI therapy is associated with arthralgia, muscle pain and bone loss, which are not seen in tamoxifen therapy.…”

“…Bisphosphonates have been used in AI-treated patients for almost two decades (27). The earliest studies showed that administration of oral bisphosphonates resulted in significant BMD increase (32–34).…”

“…Bisphosphonates’ role in the adjuvant setting by prevention of breast cancer recurrence and reduction of metastases has been evaluated by multiple studies. It is important to note that endocrine status (i.e, low vs high estrogen setting) may influence the effect of bisphosphonates on disease progression (27). A double-blind randomized trial involving 3,233 women with early stage breast cancer did not show any significant differences in terms of overall survival (OS) and disease-free survival (DFS) between the clodronate and placebo groups (44).…”