Abstract :
[en] Although some risk factors for breast cancer might be protective for osteoporosis, several cross-sectional studies
have reported, nevertheless, that patients with breast cancer have a lower bone mass and potentially a higher
incidence of fractures than expected. In any case, it appears that patients with breast cancer are not protected
from osteoporosis, which provides further support for the recommendation that bone health is assessed after a
diagnosis of breast cancer. Most adjuvant therapies will lead to increased bone loss and a higher fracture rate.
Among the adjuvant therapy options for premenopausal patients with breast cancer, endocrine therapy (ovarian
suppression) and chemotherapy can result in cancer treatment-induced bone loss (CTIBL) of up to 10% at the
lumbar spine after one year. Antiresorptive therapies prevent CTIBL in premenopausal women with breast
cancer. Most of the evidence demonstrating the efficacy of bisphosphonates in the prevention of CTIBL is derived
from clinical trials with zoledronic acid. The addition of zoledronic acid 4 mg per six months to adjuvant endocrine
therapy maintained and even increased bone mass during a 3-year treatment period and significantly
improved disease-free survival in a population of young women who underwent menopause due to the adjuvant
treatment. The major contributor to bone loss in the adjuvant treatment of breast cancer in postmenopausal
women is the use of aromatase inhibitors (AIs). Oncology trials have underestimated the fracture risk in the
setting of AI-induced bone loss. In the ABCSG-18 study, the only trial in which fracture incidence was the
primary endpoint, the rate of clinical fractures was close to 10% after 3 years in the placebo group on AIs only.
Bisphosphonates and denosumab at osteoporosis treatment doses can counteract AI-induced bone loss. In the
ABCSG-18 trial, treatment with denosumab 60 mg injection every 6 months reduced the risk of first clinical
fracture relative to placebo by 50%. Current guidelines recommend antiresorptive therapy in patients with a
baseline T score of<−2.0 or with two or more clinical risk factors for fracture. These recent guidelines will
need to be updated, as similar significant protective effects were seen in women with either normal or low bone
mass. Moreover, a formal meta-analysis of individual patient data from more than 18,000 women in 26 randomized
trials of adjuvant zoledronic acid or clodronate treatment for early breast cancer revealed that bisphosphonates
significantly reduced the risk of first distant recurrence in bone and the risk of breast cancer
mortality, at least in postmenopausal women. Even though the increased risk of fracture during adjuvant
treatment for breast cancer in postmenopausal women is notable, an enhanced risk of fracture in long-term
survivors of breast cancer remains under debate. The most recent studies suggest that Caucasian breast cancer
survivors do not have a significantly increased risk of osteoporotic fracture over the long term.
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