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Table 2 Open issues for bisphosphonate adjuvant treatment in early breast cancer trials

From: Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence

Patient-related issues Biological issues
Histological type (ductal, lobular, etc.) Preclinical models: how closely do animal models of a low-estrogen environment mimic the postmenopausal status in women with breast cancer?
Molecular subtype (luminal, triple negative breast cancers, etc.) Type of bisphosphonate (amino vs non-amino): superiority of one bisphosphonate in selective setting?
Clinical and pathological stage of disease Interaction with hormone therapy and chemotherapy: synergy or not?
Estrogen and progesterone levels Duration of bisphosphonate therapy: how long?
Menopausal status (different menopausal definition in trials)  
Comorbidities  
Personal factors