Estrogen deprivation effects of endocrine therapy in breast cancer patients: Incidence, management and outcome

: Endocrine therapy is one of the standard adjuvant treatments to reduce the risk of recurrence and mortality in patients with hormone receptor positive early breast cancer. Despite its proven efficacy, ET side effects, which persist over time even if low grade, may deteriorate quality of life. During follow-up visits, emphasis is generally placed on the risk of disease recurrence, while the topic of ET side effects is commonly neglected and discussed only briefly. This could lead to poor adherence to therapy and early treatment discontinuation, resulting in worse survival outcomes. The aim of this review is to provide an overview of the available evidence on the incidence and reporting of ET-related side effects (including vasomotor symptoms, musculoskeletal disorders and genitourinary syndrome of menopause, as well as fatigue, psychological and ocular disorders, dysmetabolic effects and loss of bone density) and of the pharmacological and non-pharmacological strategies available to mitigate symptom burden

The evolving therapeutic landscape of trastuzumab-drug conjugates: Future perspectives beyond HER2-positive breast cancer

: A novel class of drugs, antibody-drug conjugates (ADCs), are now rapidly emerging as highly effective treatments for solid tumours. ADCs conjugate conventional chemotherapeutics with highly selective targeted monoclonal antibodies. Anti-HER2 therapies selectively target cancer cells expressing human epidermal growth factor receptor 2 (HER2), among them trastuzumab has been the first HER2-targeting monoclonal antibody to achieve successful results that made it the backbone of anti-HER2 therapies. Trastuzumab drug conjugates (T-DCs), use trastuzumab as a selective antibody to lead cytotoxic drugs inside cancer cells. Trastuzumab-emtansine (T-DM1) and trastuzumab-deruxtecan (T-Dxd) are the two approved T-DCs. T-Dxd along with other five T-DCs represents "second generation ADCs" that has been firstly tested in HER2 positive breast cancer (BC) and then in HER2-low BC and other cancers showing promising results thanks to extraordinary and innovative pharmacokinetic and pharmacodynamic characteristics. The evidence generated so far are establishing them as a completely new class of agents effective in solid cancer treatments but also warrants physicians against unconventional toxicity profiles. The role of T-DCs in HER2-positive BC has been largely reviewed, while in this review, we provided for the first time in literature an overview of trastuzumab drug conjugates (T-DCs) approved and/or in clinical development with a specific focus on their efficacy and safety profile in HER2-low BC and other solid tumours different from BC. We started by analysing T-DCs biological characteristics that underly the differences in T-DCs pharmacodynamics and safety profile, then presented the main evidence on the activity and efficacy of these emerging T-DCs in HER2-low BC and other HER2 overexpressing and/or mutated solid tumours and lastly, we provided an overview of the complex and still evolving scenario in which these compounds should be allocated. A specific focus on possible combination strategies with other drugs such as immunotherapy, chemotherapy and target therapy, to increase T-DCs activity and eventually overcome future upcoming resistance mechanisms, are here also critically reviewed