Adjuvant zoledronic acid to treat breast cancer: not for all
Mené sur 1 739 patientes atteintes d'un cancer du sein de stade II ou III, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, d'un traitement adjuvant à base d'acide zolédronique, en fonction d'une amplification du gène MAF dans la tumeur et du statut ménopausique de la patiente
Bisphosphonates have been extensively studied in the adjuvant setting as a host-directed therapy to reduce the risk of breast-cancer relapse. The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) patient-level meta-analysis of adjuvant bisphosphonates, which included 18 776 women with breast cancer, showed a reduction in breast-cancer-associated death among postmenopausal women (hazard ratio [HR] 0·82, 95% CI 0·73–0·93). This outcome was mainly due to the reduction in bone recurrence. Thus, several guidelines have included zoledronic acid and clodronic acid as adjuvant treatments for breast cancer in postmenopausal women.1, 2, 3
Women's age and menopausal status are powerful surrogates for oestrogen concentrations and, thereby, for regulation of bone remodelling. Thus, oestrogen-driven changes in the bone microenvironment might affect the likelihood of women in different age groups developing bone metastases.4 An important and as yet unresolved subject of scientific debate is how ovarian function regulates host-driven responses to cancer cells and mainly host-directed (and bone-selective) treatments, such as zoledronic acid.
Whether premenopausal women with breast cancer should be considered as candidates for adjuvant treatment with bisphosphonates is a relevant question. Adjuvant bisphosphonates have been reserved for use in postmenopausal women, irrespective of the cause of menopause (physiological, surgical, or due to ovarian function suppression [OFS]). Extending these agents to younger women is an attractive strategy because of the inverse association between age at diagnosis and risk of developing bone or visceral distant metastases.5 In this regard, and given concerns about bone health, the growing use of endocrine treatment intensification (eg, OFS plus aromatase inhibitors6) in premenopausal women with high-risk breast cancer, particularly in those younger than 35 years, is expanding the use of bisphosphonates to younger age groups. (...)
The Lancet Oncology , commentaire en libre accès, 2016