Cancer Treatment–Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy

Abstract

Opinion statementAbout 70–80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired bone health. Given the high incidence and also the high prevalence of BC, cancer treatment–induced bone loss (CTIBL) represents the most common long-term adverse event experimented by patients with hormone receptor positive tumours. CTIBL is responsible for osteoporosis occurrence and, as a consequence, fragility fractures that may negatively affect quality of life and survival expectancy. As recommended by main international guidelines, BC women on aromatase inhibitors should be carefully assessed for their fracture risk at baseline and periodically reassessed during adjuvant ET in order to early detect significant worsening in terms of bone health. Antiresorptive agents, together with adequate intake of calcium and vitamin D, should be administered in BC patients during all course of ET, especially in those at high risk of osteoporotic fractures, as calculated by tools available for clinicians. Bisphosphonates, such as zoledronate or pamidronate, and anti-RANKL antibody, denosumab, are the two classes of antiresorptive drugs used in clinical practice with similar efficacy in preventing bone loss induced by aromatase inhibitor therapy. The choice between them, in the absence of direct comparison, should be based on patients’ preference and compliance; the different safety profile is mainly related to the route of administration, although both types of drugs are manageable with due care, since most of the adverse events are predictable and preventable. Despite advances in management of CTIBL, several issues such as the optimal time of starting antiresorptive agents and the duration of treatment remain unanswered. Future clinical trials as well as increased awareness of bone health are needed to improve prevention, assessment and treatment of CTIBL in these long-term survivor patients.

Bone health after RRBSO among BRCA1/2 mutation carriers: a population-based study

“…The high prevalence of breast cancer in our study group is another limitation of this study and our analyses stratified on history of breast cancer had low statistical power as many women were tested for BRCA1/2 mutations due to a breast cancer diagnosis. Breast cancer treatments, especially aromatase inhibitors and tamoxifen, are risk factors for bone loss and osteoporotic fractures [ 31 ]. However, a relatively high proportion of BRCA1/2 mutation associated breast cancers are triple negative [ 32 33 ].…”

Perspective Chapter: Management of Bone Health in Breast Cancer Patients

“…In a 2017 published Cochrane analysis, data collected from more than 37,000 patients were also able to demonstrate the benefits of bisphosphonate therapy. This showed a clear survival benefit with addition of bisphosphonates for postmenopausal patients (HR 0.77, 95% CI 0.66-0.90; p = 0.001; 4 studies; 6048 women; high-quality evidence with no evidence of heterogeneity), but not for premenopausal patients (HR 1.03, 95% CI 0.86-1.22; p = 0.78; 2 studies; 3501 women; high-quality evidence with no heterogeneity) [5].…”

“…In advanced breast cancer, 60-80% of patients will develop bone metastasis [5]. Complications are mostly related to skeletal bone and refer mostly to pathological fractures, major surgery, radiotherapy, and spinal cord and nerve compression symptoms.…”

“…Secondly, there is also a clear relationship between osteo-oncologic treatment including densoumab and bisphosphonates and outcome in early breast cancer [4]. Thirdly, in stage IV breast cancer, bone is the most common site of metastasis [5].…”

Efficacy of Antiresorptive Drugs on Bone Mineral Density in Post-Menopausal Women With Early Breast Cancer Receiving Adjuvant Aromatase Inhibitors: A Systematic Review of Randomized Controlled Trials

“…Cancer treatment-induced bone loss (CTIBL) is a frequent side effect of the pharmacotherapy used for treating BC. While chemotherapy might lead to an unspecific increase in bone resorption, hormone therapies (HT) reduce residual serum endogenous estrogen levels, with a consequent decrease in bone mineral density (BMD) and an increase in fragility fracture risk (10)(11)(12)(13)(14)(15)(16)(17). To date, aromatase inhibitors (AI) are considered the gold standard adjuvant therapy for postmenopausal women with hormone receptor (HR)-positive early BC (EBC) (18,19).…”