ObjectiveTo investigate the incidence and characteristics of breast cancer in transgender people in the Netherlands compared with the general Dutch population.DesignRetrospective, nationwide cohort study.SettingSpecialised tertiary gender clinic in Amsterdam, the Netherlands.Participants2260 adult trans women (male sex assigned at birth, female gender identity) and 1229 adult trans men (female sex assigned at birth, male gender identity) who received gender affirming hormone treatment.Main outcome measuresIncidence and characteristics (eg, histology, hormone receptor status) of breast cancer in transgender people.ResultsThe total person time in this cohort was 33 991 years for trans women and 14 883 years for trans men. In the 2260 trans women in the cohort, 15 cases of invasive breast cancer were identified (median duration of hormone treatment 18 years, range 7-37 years). This was 46-fold higher than in cisgender men (standardised incidence ratio 46.7, 95% confidence interval 27.2 to 75.4) but lower than in cisgender women (0.3, 0.2 to 0.4). Most tumours were of ductal origin and oestrogen and progesterone receptor positive, and 8.3% were human epidermal growth factor 2 (HER2) positive. In 1229 trans men, four cases of invasive breast cancer were identified (median duration of hormone treatment 15 years, range 2-17 years). This was lower than expected compared with cisgender women (standardised incidence ratio 0.2, 95% confidence interval 0.1 to 0.5).ConclusionsThis study showed an increased risk of breast cancer in trans women compared with cisgender men, and a lower risk in trans men compared with cisgender women. In trans women, the risk of breast cancer increased during a relatively short duration of hormone treatment and the characteristics of the breast cancer resembled a more female pattern. These results suggest that breast cancer screening guidelines for cisgender people are sufficient for transgender people using hormone treatment.

Cross-sex hormone treatment of transsexual people may be associated with the induction and growth stimulation of hormone-related malignancies. We report here five cases of breast cancer, three in female-to-male (FtoM) transsexual subjects and two in male-to-female (MtoF) transsexual subjects. In the general population the incidence of breast cancer increases with age and with duration of exposure to sex hormones. This pattern was not recognised in these five transsexual subjects. Tumours occurred at a relatively young age (respectively, 48, 41, 41, 52 and 46 years old) and mostly after a relatively short span of time of cross-sex hormone treatment (9, 9-10 but in one after 30 years). Occurrence of breast cancer was rare. As has been reported earlier, breast tumours may occur in residual mammary tissue after breast ablation in FtoM transsexual people. For adequate treatment and decisions on further cross-sex hormone treatment it is important to have information on the staging and histology of the breast tumour (type, grade and receptor status), with an upcoming role for the androgen receptor status, especially in FtoM transsexual subjects with breast cancer who receive testosterone administration. This information should be taken into account when considering further cross-sex hormone treatment.

Oncokompas including a BC module is considered feasible, but needs further optimization to increase user satisfaction. This study shows the value of tailoring eHealth applications for cancer survivors to their specific tumor type. Oncokompas including the BC module seems to improve patient activation among BC survivors.

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin-pathway (PI3K/AKT/mTOR-pathway) plays a role in the regulation of cell proliferation, cell survival, angiogenesis and resistance to anti-tumor treatments. In many tumor types the PI3K/AKT/mTOR-pathway is found activated through several different underlying mechanisms. Since this pathway is believed to largely drive the malignant behavior of several of these tumors, mTOR-inhibition is considered an attractive means to apply as anti-tumor treatment. Currently, four mTOR-inhibitors are explored for clinical use: rapamycin, temsirolimus (CCI-779), everolimus (RAD001) and deforolimus (AP23573). As monotherapy, mTOR-inhibitors yield interesting anti-tumor activity against various tumor types at the expense of relatively mild toxicities. This recently resulted in the registration of two mTOR-inhibitors for patients with metastatic renal cell carcinoma (RCC) while randomized studies in other tumors are currently in progress. Furthermore, mTOR-inhibitors are well-suited drugs to combine with other anti-tumor drugs as in preclinical models mTOR-inhibition overcomes chemoresistance. Consequently, mTOR-inhibitor-containing multidrug regimens are subject to clinical studies. As holds true for all anti-tumor therapies, identification of patients who are likely to respond to mTOR-inhibitor-containing therapies is of utmost importance to avoid over- or undertreatment. Preliminary results suggest that several factors reflecting activation of mTOR in tumors may be used for this purpose. This review addresses the mechanism of action and current clinical experience with mTOR-inhibitors as well as their role in overcoming resistance to conventional therapies. Additionally, potential predictors of outcome to mTOR-inhibition are discussed.

BackgroundThe aim of this study was to estimate the total economic and health related burden of breast cancer in the Netherlands.MethodsData on incidence, prevalence, mortality and survival were extracted from the Dutch National Cancer Registry and were used to calculate the economic and health related burden of breast cancer for overall, DCIS (stage 0), early- (stage I), locally advanced- (stage II-III) and metastatic- (stage IV) breast cancer by age groups and by year (if applicable).ResultsThe overall incidence of breast cancer increased from 103.4 up to 153.2 per 100,000 women between 1990 and 2014. The increase was driven by DCIS and early breast cancer as the incidence of locally advanced and metastatic breast cancer remained stable. Between 1990 and 2014, ten-year overall survival rates increased from 87% to 93% for early breast cancer, 41% to 62% for locally advanced- and from 6% to 9% for metastatic disease. Annually, breast cancer in the Netherlands is responsible for approximately 3100 deaths, 26,000 life years lost, 65,000 Disability Adjusted Life Years (DALYs) and an economic burden of €1.27 billion.ConclusionsThis study provides a comprehensive assessment of the burden of breast cancer and subsequent trends over time in the Netherlands.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4158-3) contains supplementary material, which is available to authorized users.