The role of estro-progestinic pills in female patients with melanoma

Introduction: several studies showed contradictory results on the association between oral contraceptive use, high levels of estrogens and the development of melanoma (MM). Some authors postulated that high levels of estrogens might cause an increased risk of malignant MM, however these data are controversial. Material/methods: we reviewed clinical data of our female patients with a diagnosis of MM, in order to better identify MM clinic-pathological features, evaluating a possible impact of a positive history of estro-progestinic pill (EP) on MM. We studied also the time to melanoma (TTM), that means the time between the begin of the EP pill assumption and the time of onset of MM. Disease-free survival (DFS) was calculated from diagnosis of primary tumor to date of the first recurrence, while overall survival (OS) was calculated from diagnosis of the primary tumor to date of death and/or last follow-up. The Kaplan–Meier product was used to estimate survival curves. In all statistical methods a p value < 0.05 was considered as significant. Results: the data for 2.088 melanoma patients were retrieved, among them, 1.036 were women (49.6%) with a mean age of 54 years. Specifically, 4 patients showed an age ˂ 19 years, 65 patients between 19-29 years, 393 between 30 and 50 years and the remaining 559 patients ≥ 51 years. A positive familiar history of MM was present in 67 patients (6.5%), while a double MM was diagnosed in 88 patients (8.5%). Median Breslow thickness was 0.4 mm. Median DFS was 64 months, while general median OS was 70 months. One-hundred and three (n=103) patients referred a positive history for EP treatment during the diagnosis of MM. Among them, 40 patients performed ethinylestradiol+gestodene, 35 patients ethinylestradiol+acetate cyproterone and 28 patients ethinylestradiol+drospirenone. Median age of female patients that developed a MM during an EP treatment was 49 years. Median TTM was equal to 120 months after the first assumption of the EP pill; while, general median time of assumption of the EP agent was 96 months. Sixty-seven (n=67) patients performed the therapy for contraceptive purposes, 5 for acne, 23 for polycystic ovaries, 4 for uterine fibromas, 3 for irregular period. Only 1 patient had a positive history of in vivo fertilization and embryo transfer (IVF). Three patients showed a double MM. Median DFS and OS were respectively 62 and 70 months. A positive familial history for MM was present in 4 patients (3.8%), while 6 patients had a positive history for also other malignancies: 2 thyroid cancers, 1 breast cancer, 1 colon cancer, 1 breast cancer and 1 basal cell carcinoma. Patients with a MM ≥ 1.01 mm showed a TTM of 206 months versus 170 months of MM with a Breslow thickness ≤ 1.00 mm (p =0.04). Besides, patients with ulceration showed TTM of 249 versus 160 months of patients without ulceration.(p=0.03) Finally, the presence of mitoses ≥1/mm2, the peripheral site and the absence of an infiltrate were all related to a longer TTM. Conclusions: according to our data, EP does not increase a risk of MM. MM with risk factors (as thicker Breslow, ulceration and presence of mitoses ≥1/mm2) showed a longer TTM compared to the other ones, justifying the fact the assumption of EP does not influence the onset of MM, although a possible effect of “cumulative dose” of the EP may be implicated in the onset of ticker tumors and with other risk factors. Finally, there were no significant differences in both DFS and OS in patients with a positive history for an EP with the general population