BBB Seminar: Helga B. Salvesen
New targets for personalised medicine in endometrial cancer
Helga B. Salvesen
Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen
With a lifetime risk among women of 2-3%, endometrial cancer is the most common pelvic gynaecologic malignancy in industrialised countries. Approximately 75% of cases are diagnosed at an early stage with the tumour being confined to the uterine corpus. Although most patients are cured by surgery alone, about 15-20% with no signs of locally advanced or metastatic disease at primary treatment, experience recurrence showing limited responsiveness to systemic therapy. In light of these recurrences, patients with localised endometrial cancer have 2 major needs: (1) adjuvant therapies that will reduce the recurrence rate, and (2) the ability to target these therapies to the patients where the tumour is most likely to recur. In addition, women with metastatic disease require more effective systemic therapy.
The most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes. Type I, associated with good prognosis, accounts for the majority of cases and is connected with low stage and low grade and endometrioid histology. In contrast, type II is characterised by high stage, high grade and non-endometrioid histology and poor prognosis. However, the prognostic value of this distinction is limited, as up to 20% of type I endometrial cancers recur, while 50% of type II cancers do not. It is a paradox that despite the fact that several clinically validated prognostic markers are available in endometrial cancer, they are not yet systematically applied for treatment stratification. Recent studies have identified new potential targets for novel therapeutics in endometrial carcinomas, such as FGFR2 mutations, mTOR-PTEN changes and alterations in the PI3Kinase- and MYC signalling pathways. The current literature on epidemiology, aetiology, pathology, molecular alterations, staging, treatment and prognostic factors in endometrial cancer will be reviewed. Novel molecular markers will be presented in relation to a clinical case to illustrate how personalised therapy may be implemented for this large patient group in the future.
Host: Aurora Martinez, Department of Biomedicine