We have investigated gene amplification of fibroblast growth factor receptor-4 (FGFR4) gene in 30 primary breast tumor samples and 15 gynecological tumor samples. Ten percent of the breast tumors showed 2- to 4-fold amplification. Amplification was found more frequently in estrogen- and progesterone-receptor-positive tumors and in tumors with high lymph-node involvement. Breast tumor samples were also analyzed for the amplification of fgfr3 and erbB2 genes and the chromosome 11q13 located genes hst1/int2/bcl1/sea. erbB2 gene was amplified 2- to 13-fold in 13% of the cases, but no amplification of int2/hst1/bcl1/sea amplicon was found. Gynecological tumors were also analyzed for the amplification of fgfr4 and fgfr3 genes and for int2 and hst1 oncogenes. Eleven of the 15 gynecological tumors were ovarian neoplasms including 2 benign tumors; the remainder comprised 1 ovarian metastasis of breast cancer; 1 endometrial cancer; 1 uterine leiomyosarcoma and 1 carcinosarcoma of the fallopian tube. In gynecological tumors, fgfr4 gene was found to be amplified in 2 ovarian tumors. Amplification of hst1 was found in 1 benign ovarian tumor. Thus, the fgfr4 gene may be involved in breast and ovarian tumorigenesis.

This study evaluates the effect of different modes of estradiol-progestagen therapy (EPT) regimens on the postmenopausal endometrial cancer risk in Finland. Women diagnosed with endometrial cancer in 1995-2007 at the age of 50-80 years were identified from the Finnish Cancer Registry (N 5 7,261). For each case, three age-matched controls were retrieved from the Finnish Population Register. The use of EPT since 1994 was ascertained from the national Medical Reimbursement Register. Odds ratios (ORs) for different EPT regimens were calculated with conditional logistic regression analysis, adjusted for parity and ages at the deliveries. For use of <5 years, the OR for sequential EPT was 0.67 (95% confidence interval 0.52-0.86), for continuous EPT 0.45 (0.27-0.73), and for estradiol plus levonorgestrel-releasing intrauterine device system (LNG-IUS) 0.39 (0.17-0.88). A decreased risk persisted for the use of continuous EPT and estradiol plus LNG-IUS of up to 10 years. The use of long-cycle EPT showed a tendency toward an elevated risk both for exposure of <5 years (1.40; 0.82-2.38) and for estimated use of >5 years (1.63; 1.12-2.38). For an estimated exposure of >10 years, the risk for endometrial cancer was elevated for both users of long-cycle EPT (2.95; 2.40-3.62) and sequential EPT (1.38; 1.15-1.66). Norethisterone acetate and medroxyprogesterone acetate as parts of EPT did not differ in their endometrial cancer risk. The use of tibolone showed no endometrial risk. The use of sequential and long-cycle EPT is associated with an increased risk of endometrial cancer, whereas the use of continuous EPT or estradiol plus LNG-IUS shows a decreased risk.

II.