Phd in MOLECULAR MEDICINE

Thesis title: Aromatase inhibitor consequences in breast cancer treatment: a “new” form of carpal tunnel syndrome?

Introduction: Female breast cancer was the leading cause of malignant tumor in 2020; about two-thirds of cases are hormone receptor positive: in these patients, aromatase inhibitors are a mainstay of treatment but associated musculoskeletal symptoms can negatively affect the compliance. Aromatase inhibitor induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with non-compliance rate up to 67% and possible increase in cancer mortality. The aim of the study is to investigate estrogen receptor expression in its tissues, to better define etiopathogenesis and to derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. Materials and methods: At the Jewish Hospital of Rome, between 2021 and 2023, we recruited 24 patients: 12 cases of aromatase inhibitor induced carpal tunnel syndrome (study group) and 12 of postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated with clinic visit, questionnaire, instrumental exams, serum hormone dosages and treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. Histological analysis was performed with particular attention to any pathological findings; for immunohistochemical experiments, sections were treated with anti-ERα and anti-ERβ antibodies. Results: Histological and immunohistochemical features in the study and control group are similar, demonstrating aromatase inhibitor induced carpal tunnel syndrome tissues as a target of direct estrogen action and correlating estrogen deprivation to disease etiogenesis. Surgery is effective in patient treatment. Conclusions: Aromatase inhibitor induced carpal tunnel syndrome is a disease form of new definition; it represents one of the main causes of aromatase inhibitor discontinuation, due to the negative impact on patient quality of life. Identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance: an early diagnosis and prompt management can improve patient compliance and, overall, breast cancer treatment results.