Indian Journal of Surgery | 2021
Breast disorders due to imatinib mesylate: Rare but significant
Abstract
Dear Editor-in-chief, Imatinib mesylate is a tyrosine kinase inhibitor which inhibits the c-kit and platelet-derived growth factor receptor (PDGFR) tyrosine kinases. It is considered as one of the breakthrough discovery in the field of targeted therapy [1]. It is used commonly to treat a variety of neoplastic conditions like chronic myeloid leukemia and other blood malignancies, g a s t r o i n t e s t i n a l s t r om a l t umo r (G I ST ) , a n d dermatofibrosarcoma protuberans. The role of imatinib mesylate was also proved in melanoma, anaplastic carcinoma, Kaposi’s sarcoma, chordoma, etc. [1]. By inhibiting the tyrosine kinase, it inhibits the growth of the cells and promotes apoptosis. It is available as an oral drug with a usual strength of 400 mg. It is a well-tolerated drug with minimal side effects and is generally used for long periods ranging in years. There are many case reports of breast complaints in patients taking imatinib mesylate for long periods. Bilateral gynecomastia is the most common breast complaint. The authors have come across one such manifestation in a patient on imatinib mesylate adjuvant therapy for high risk jejunal GIST. The patient has presented with bilateral breast enlargement. On examination, the bilateral breasts were enlarged and there was a 3 × 3-cm firm swelling in the right breast lateral to the nipple (Fig. 1). Core needle biopsy was suggestive of fibroadenoma. In a study by Liu H et al., out of 57 patients on imatinib mesylate six patients had bilateral gynecomastia with a palpable small firm swelling beneath the nipple areolar complex [2]. Gambacorti-Passerini et al. compared pre and post imatinib mesylate treatment testosterone levels and found that patients with gynecomastia had a decrease in the serum free testosterone levels [3]. This was hypothesized due to the blockade of c-kit and PDGFR tyrosine kinases which are expressed in the testis and play a role in steroid hormone synthesis [4]. The role of PDGFR in the normal function of germ cells and Leydig cells has also been demonstrated in animal models [5]. In spite of decrease in the free testosterone concentration, impotence was rarely reported in patients on imatinib mesylate. Fibroadenomas may be a concern for the patient as they may cause pain and discomfort. In the older age group, core needle biopsy is required to rule out breast malignancy. Imatinib mesylate was also proposed to cause secondary tumors in the breast by snooping in the Ephrin receptor pathway [6, 7]. However, strong evidence in this regard is lacking. Gynecomastia due to imatinibmesylate responds to tamoxifen therapy. Both imatinib mesylate and tamoxifen are metabolized by the same enzyme CYP3A4 [8]. So, the possibility of drug interaction should be watched for. To conclude, the beneficial effects of imatinib mesylate far outweigh its side effects. Gynecomastia is manageable with reassurance and tamoxifen therapy. Breast swellings during the course of the therapy should be evaluated thoroughly to rule out the rare possibility of breast carcinoma. Regards