BMC Cancer 2002, 2 http://www.biomedcentral.com/1471-2407/2/26 Table 3: SIR values(95% CI) in relation to tumour type and different time intervals of follow up since diagnosis of gynecomastia. Also number of individuals and personyears for each interval are shown. The lead time between gynecomastia and tumour diagnosis was for esophageal cancer 8 years (6–10 years), skin cancer 6 years (3–25 years) and testicular carcinoma 10 years (3–18) years. Table 4: Age at gynecomastia diagnosis and risk of tumours in relation to follow up time. SIR values(95% CI). Tumour type all sites testicle esophagus ca 0.00(0.00–46.43) skin cancer (melanoma excl.) number personyears Tumour type follow up testicle esophagus cancer skin cancer (melanoma excl.) number personyears 0–2 years 0.15(0.00–0.85) 0.00(0.00–116.2) 2.57(0.07–14.35) 0.00(0.00–12.33) 443 870 Age at diagnosis <50 years 0–49 years 6.71(1.38–19.60) 0.00(0.00–337.54) 0.00(0.00–36.76) 246 4869 lar cancer was predominantly seen in unilateral cases (table 5). Discussion The present study, being the so far only published pro- spective investigation in the literature with a maximum follow up time of 30 years, demonstrates a significantly increased risk for testicular and squamous skin cancer in men with a prior histopathological diagnosis of gyneco- mastia. Also a non-significantly increased risk for esopha- geal cancer was noted while no cases of male breast cancer was seen. Overall the male patients with gynecomastia did not show an incidence of malignancy different to that in the general population. Gynecomastia develops in a setting of imbalance between androgens and estrogens where there is a relative estrogen excess [2–4]. Gynecomastia is more common at pubertal ages and in oldermen [1]. This was also evident in our ma- terial (table 1). It has previously been shown in case series that testicular cancer may sometimes prior to diagnosis in- duce gynecomastia due to pathologic HCG secretion [5– 7]. In this prospective series two patients developed testic- ular seminomas and one patient a testicular teratoma fol- Time interval since diagnosis of gynecomastia >2–10 years 1.19(0.81–1.68) 6.60(0.17–36.76) 6.31(0.76–22.79) 2.23(0.72–5.20) 426 3076 =10 years 1.07(0.75–1.49) 6.02(0.73–21.73) 3.82 (0.79–11.17) 5.30(2.29–10.43) 337 4428 overall 1.03 (0.80–1.30) 5.82 (1.20–17.00) 3.21(1.71–5.48) 445 8375 =50–99 years 0.00(0.00–119.54) 0.00(0.00–27.61) 7.87(1.62–22.99) 124 1135 >50 years =50–99 years 0.00(0.00–107.07) 4.75(1.00–13.90) 2.84(1.36–5.23) 197 2292 lowing the diagnosis of gynecomastia years earlier. Chemotherapy may injure gonadal and hormonal func- tions and are associated with development of gynecomas- tia [14–16]. Some drugs, mimicking or having estrogenic or antiandrogenic effects, may also be associated with de- velopment of gynecomastia [2–4]. This explains the rather large group of cases with gynecomastia with a prior diag- nosis of prostate carcinoma where estrogens have been used as a treatment. Interestingly in our study there was no sign of a protective effect for prostate carcinoma due to the relative estrogen excess. A rare malignancy, male breast cancer, has in epidemio- logical studies been associated with prior history of gyne- comastia [8–12]. In our investigation no prospective cases of male breast cancer was seen, while two men after they had developed male breast cancer later developed gyneco- mastia that was not drug induced in the contralateral breast. Also one of the cases had gynecomastia surround- ing the breast tumour at diagnosis. In 44 of the 445 cases bilateral extirpation of the breast tissue was done and in the remaining cases a unilateral excision was done. This surgical removal of breast tissue in men potentially prone to develop breast carcinomas due to the gynecomastia, Page 4 of 6 (page number not for citation purposes)