Endometrium cancer

It seems reasonable that pure antiestrogens might be used as a good alternative to tamoxifen in the treatment of breast cancer, due to their beneficial effects, without increasing the risk of endometrium cancer (Simard et al. 1997). 

The administration of hormone therapy is based on the knowledge from hormone-dependent carcinogenesis and on the hormone sensitivity and dependency of classic tumors (breast, prostate, endometrium cancer) after in vitro and in vivo studies in experimental models [1]. Significant therapeutic experience has been further gained from certain analogs of peptide-hormones that are also reported below ... 

Dorman BH, Genta VM, Mass MJ, et al. 1981. Benzo[a]pyrene binding to DNA in organ cultures of human endometrium. Cancer Res 41 2718-2722. 

Fukuchi T, Sakamoto M, Tsuda H, et al. Beta-catenin mutation in carcinoma of the uterine endometrium. Cancer Res. 1998 58 3526-3528. 

NB There is also conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium) Oral contraceptives, sequential (Suppl. 7 1987)... 

OTRs are mainly expressed in myoepithelial cells of the galactiferus channels and the myometrium. The OTRs in vascular endothelial cells, renal epithelial cells (macula densa, proximal tubule) and cardiomyocytes induce the production of NO (vasodilation), natriuresis and release of ANP, respectively. The endometrium, ovary, amnion, testis, epididymis, prostate and thymus also express the OTR supporting a paracrine role of this peptide. Osteoblasts, osteoclasts, pancreatic islets cells, adipocytes, and several types of cancer cells also express OTRs. More over, expression of the OTR... 

Uterine Fibroids Adenomyosis Endometrial polyps Gynecologic cancers Alteration of endometrium, changes in uterine contractility Alteration of endometrium, changes in uterine contractility Alteration of endometrium Various dysplastic alterations of endometrium, uterus, cervix... 

Tamoxifen is discussed in Chap. 61, Breast Cancer raloxifene is discussed in Chap. 3, Osteoporosis. Raloxifene decreases bone loss in recently menopausal women without affecting the endometrium and has estrogen-like actions on lipid metabolism. It may exacerbate vasomotor symptoms, and it increases the risk of venous thromboembolism and stroke. 

The rate of invasive ER-positive breast cancer, a secondary objective in the MORE trial, showed an 84% reduction after 4 years of followup (Cauley et al. 2001) moreover, during the subsequent 4 years of followup in the so-called CORE trial (Continuous Outcomes Relevant to Evista), invasive ER-positive breast cancer, the primary objective of the study, was reduced by 66%. Over the 8 years of both trials, the incidences of invasive breast cancer and ER-positive invasive breast cancer were reduced by 66% and 76%, respectively, in the raloxifene group compared with the placebo group (Martino et al. 2004). These effects have not been associated with harmful effects on the endometrium (Cohen et al. 2000) or the pelvic floor (Goldstein et al. 2001). 

Addo S, Yates RA, Laight A (2002) A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers. Br J Cancer 87 1354-1359... 

There are evidences showing that lower daily doses of tamoxifen, between 1 and 5 mg, can obtain antiproliferative effects on in situ or small invasive cancers similar to those observed with the usual dose of 20 mg (Decensi et al. 2003). If that proves to be true with respect to the protective effect in primary prevention, it would probably allow skipping the negative effects on endometrium and coagulation, both dose related. 

Descriptive as well as case-control and cohort studies have shown that tamoxifen may cause alterations, including cancer, in human endometrium. The findings have been observed in studies using ultrasound technology or histology data. 

Studies carried out with transvaginal ultrasound (TVU) in postmenopausal women with breast cancer have shown that the endometrium is thickened more frequently in women receiving tamoxifen than in those not treated with the drug. For example, in a transversal study Cohen et al. observed that 94.6% of women treated with tamoxifen and nonsymptomatic from a gynecological point of view had an endometrial thickness > 5 mm, an observation that was present in only 40% of women who did not receive this treatment (Cohen et al. 1994). 

A randomized placebo-controlled trial found that 39% of the tamoxifen-treated women had an endometrial abnormality, a percentage that was reduced to 10% of women on placebo (p < 0.0001) (Kedar et al. 1994), though no cases of endometrial cancer were diagnosed in this study. The histological abnormalities found in the tamoxifen group were atypical hyperplasia (16%), proliferative endometrium (13%), polyps (8%), or presence of mitosis (2%). The authors concluded that the predicative value of an endometrium thickness... 

Clinical evidence indicates that the use of tamoxifen increases survival up to 10 years in women with breast cancer. Tamoxifen also seems to diminish the incidence of breast cancer in healthy women with a high risk of suffering from the tumor. Its use as a therapy in breast cancer should be accompanied by careful periodic vigilance of the endometrium. In healthy women, a careful evaluation of the risk/benefit for each and every woman should be imposed. 

Bese T, Kosebay D, Demirkiran F, Arvas M, Bese N, Mandel N (1996) Ultrasonographic appearence of endometrium in postmenopausal breast cancer patients receiving tamoxifen. Eur J Obstet Gynecol Reprod Biol 67 157-162... 

Isaksson E, Cline JM, Skoog L, Soderqvist G, Wilking N, von Schoultz E, von Schoultz B (1999) p53 expression in breast and endometrium during estrogen and tamoxifen treatment of surgically postmenopausal cynomolgus macaques. Breast Cancer Res Treat 53(l) 61-67... 

This is an unusual drug in that it contains a metal atom, platinum (Pt) in this case. Cisplatin reacts with DNA to cross-link bases, disrupting normal DNA structure and function. This agent has found broad use in cancer chemotherapy, including efficacy in tumors of the testis, ovary, bladder, head and neck, thyroid, cervix, and endometrium. It is also active against neuroblastoma and osteogenic sarcoma. 

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