Hormone Therapy and Ovarian Cancer

Gynaecological Clinic, Rigshospitalet, Copenhagen University, 2100 Copenhagen, Denmark.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 08/2009; 302(3):298-305. DOI: 10.1001/jama.2009.1052
Source: PubMed

ABSTRACT Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration.
To assess risk of ovarian cancer in perimenopausal and postmenopausal women receiving different hormone therapies.
Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates.
A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy.
Ovarian cancer.
In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian cancers, of which 2681 were epithelial cancers, were detected. Compared with women who never took hormone therapy, current users of hormones had incidence rate ratios for all ovarian cancers of 1.38 (95% confidence interval [CI], 1.26-1.51) and 1.44 (95% CI, 1.30-1.58) for epithelial ovarian cancer. The risk declined with years since last use: 0 to 2 years, 1.22 (95% CI, 1.02-1.46); more than 2 to 4 years, 0.98 (95% CI, 0.75-1.28); more than 4 to 6 years, 0.72 (95% CI, 0.50-1.05), and more than 6 years, 0.63 (95% CI, 0.41-0.96). For current users the risk of ovarian cancer did not differ significantly with different hormone therapies or duration of use. The incidence rates in current and never users of hormones were 0.52 and 0.40 per 1000 years, respectively, ie, an absolute risk increase of 0.12 (95% CI, 0.01-0.17) per 1000 years. This approximates 1 extra ovarian cancer for roughly 8300 women taking hormone therapy each year.
Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.

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Available from: Ellen Løkkegaard, Sep 29, 2015
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    • "The Million Women Study (MWS) and the Danish Sex Hormones Register Study (DaHoRS) provided more than half of cases [4] [5]. The MWS was based on self reporting questionnaires and was not designed to analyze ovarian cancer as a primary outcome. "
    Maturitas 05/2015; 81(1). DOI:10.1016/j.maturitas.2015.02.011 · 2.94 Impact Factor
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    • "Risk factors including nulliparity, early age of menarche, late age of menopause, hormone replacement, obesity, and protective factors including oral contraceptive use, indicate an association with increased lifetime ovulations and/or greater lifetime exposure to estrogen. A higher risk of ovarian cancer has been reported with cyclical use of hormone replacement therapy rather than continuous use or any use of estrogen or progestin after menopause (79) for both BRCA mutation carriers and non-carriers (72). "
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    ABSTRACT: Women who have an inherited mutation in the BRCA1 or BRCA2 genes have a substantial increased lifetime risk of developing epithelial ovarian cancer (EOC), and epidemiological factors related to parity, ovulation, and hormone regulation have a dramatic effect on the risk in both BRCA mutation carriers and non-carriers. The most common and most aggressive histotype of EOC, high-grade serous carcinoma (HGSC), is also the histotype associated with germline BRCA mutations. In recent years, evidence has emerged indicating that the likely tissue of origin of HGSC is the fallopian tube. We have reviewed, what is known about the fallopian tube in BRCA mutation carriers at both the transcriptional and translational aspect of their biology. We propose that changes of the transcriptome in BRCA heterozygotes reflect an altered response to the ovulatory stresses from the microenvironment, which may include the post-ovulation inflammatory response and altered reproductive hormone physiology.
    Frontiers in Oncology 01/2014; 4:5. DOI:10.3389/fonc.2014.00005
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    • "In contrast, estrogen has been considered as a risk factor for epithelial ovarian cancer. The proliferation of ovarian tissue with estrogenic stimulation and estrogen/hormone replacement therapy (HRT) may possibly increase the risk of ovarian cancer [37,38]. Approximately 61% to 79% of ovarian cancers express the ER [35]. "
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    ABSTRACT: Objective p73 and p63 are two structural and functional homologs of p53, and their biological functions in cancer progression have attracted attention due to the presence of variants generated by genetic polymorphisms. Recently, three single nucleotide polymorphisms (SNPs) in the p63 and p73 genes have been associated with female reproduction. In the present study, we aimed to evaluate the relationship between these SNPs and ovarian cancer susceptibility and clinical pathology. Methods We genotyped the p63 (rs873330 [Genbank, refSNP ID] T > C [T: original base, C: mutant base]) and p73 (rs4648551 G > A and rs6695978 G > A) SNPs in ovarian cancers and healthy controls and analyzed the distributions of genotype frequencies to evaluate the association of the genotypes with the risk of ovarian cancer and the clinicopathological characteristics. Logistic regression models were applied in statistical analyses. Results Our research revealed that p73 rs6695978 G > A was significantly associated with ovarian cancer patients. Women with the A allele were at increased risk of ovarian cancer compared to carriers of the G allele (OR = 1.55; 95% CI:1.07–2.19; P = 0.003). Meanwhile, the at-risk A allele was positively related with the occurrence of mucinous ovarian cancer (OR = 3.48; 95% CI:1.15-6.83; P = 0.001), low degree of differentiation (OR = 1.87; 95% CI:1.03-3.47; P = 0.003), lymph node metastasis (OR = 1.69; 95% CI: 1.14-2.75; P = 0.010) and estrogen receptor positive (OR = 2.72; 95% CI: 1.38-4.81; P = 0.002). However, we were unable to find any associations of the polymorphisms in another two SNPs (rs4648551 G > A, rs873330 T > C) with ovarian cancer risk and clinicopathological parameters. Conclusions The p73 rs6695978 G > A polymorphism will serve as a modifier of ovarian cancer susceptibility and prognosis. Further investigations with large sample sizes and of the mechanistic relevance of p73 polymorphism will be warranted
    Journal of Experimental & Clinical Cancer Research 10/2012; 31(1):89. DOI:10.1186/1756-9966-31-89 · 4.43 Impact Factor
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