Postmarketing adverse events of tamoxifen in male and female patients with breast cancer

Postmarketing adverse events of tamoxifen in male and female patients with breast cancer Chengjie Ke and Maohua Chen are joint first authors. Abstract Tamoxifen (TAM), a selective estrogen receptor (ER) modulator, has received approval for use in patients with breast cancer (BC) exhibiting positive ER expression. Given the widespread clinical use of TAM, a comprehensive real-world study of its adverse events (AEs) is warranted. The database for analysis, sourced from the Food and Drug Administration Adverse Event Reporting System (FAERS), covers the period from the first quarter of 2014 to the third quarter of 2023. A disproportionality analysis was conducted to quantify the correlation between TAM and AEs. Subgroup analyses were performed to identify differences between BC AEs in males and females receiving TAM, aiming to assess the risk factors of male BC AEs. Total 4890 reports indicated BC, with 91 and 4190 specifically linked to AEs in male and female patients with BC, respectively. Male-specific AE was libido decreased (reporting odds ratio [ROR]: 43.33), and female-specific AE was uterine disease, including sarcoma uterus (ROR: 519.51), endometrial cancer (ROR: 131.26), uterine polyp (ROR: 40.83), endometriosis (ROR: 11.39), among others. A notably higher risk of AEs in male patients with BC was observed in individuals aged >65 years (χ2 = 20.83, p < .001). Male patients with BC had a relatively higher risk of hospitalization (χ2 = 4.83, p = .03) and a lower risk of deaths (χ2 = 5.32, p = .02). Theses finding may assist healthcare professionals in recognizing the TAM-associated AEs and understanding gender differences, potentially improving safety in clinical applications. Graphical Abstract What's new? While tamoxifen greatly benefits breast cancer prognosis, its use is associated with adverse events (AEs), some of which are serious and result in drug discontinuation. Here, the authors investigated the safety profile of tamoxifen in male and female breast cancer patients using data from the FDA Adverse Event Reporting System. AEs common among both sexes included cardiovascular disease, particularly thromboembolic events and hot flush. Males also tended to experience decreased libido, whereas females exhibited increased rates of uterine disease, including endometrial cancer. The identification of tamoxifen-associated AEs specific to males and females presents novel opportunities for improving breast cancer care. CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest. DATA AVAILABILITY STATEMENT All source code is publicly available on GitHub (https://github.com/18750711181/share-our-source-code). Data sources and handling of the publicly available datasets used in this study are described in the Materials and Methods. The other data that support the findings of this study are available from the corresponding author upon reasonable request.