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The association between reproductive and hormonal factors and ovarian cancer by estrogen-? and progesterone receptor status.

ABSTRACT: We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-? (ER?) and progesterone receptor (PR) status.Tissue microarrays were used to assess ER? and PR expression among 197 Nurses' Health Study (NHS), 42 NHSII and 76 New England Case-Control Study (NECC) ovarian cancer cases. NHS/NHSII cases were matched to up to 4 controls (n=954) on diagnosis date and birth year. NECC controls (n=725) were frequency matched on age. Cases were considered receptor positive if ?1% of tumor cells stained positive. Associations by ER? and PR status were assessed using polytomous logistic regression. p-Value for heterogeneity was calculated using a likelihood ratio test.45% of ovarian tumors were PR(+), 78% were ER?(+) and 45% were ER?(+)/PR(+), while 22% were ER?(-)/PR(-). Postmenopausal status was associated with an increased risk of PR(-) tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity=0.01) and age at natural menopause was inversely associated with PR(-) tumors (OR, per 5years: 0.77; 95%CI: 0.61-0.96; p-het=0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het=0.0009). Number of children and tubal ligation were more strongly associated with ER?(-) versus ER?(+) tumors (p-het=0.002 and 0.05, respectively). No differential associations were observed for oral contraceptive or hormone therapy use.Postmenopausal women have an increased risk of developing PR(-) ovarian tumors compared to premenopausal women. The associations observed for ovarian cancer differ from those seen for breast cancer suggesting that the biology for tumor development through ER? and PR pathways may differ.

SUBMITTER: Shafrir AL

PROVIDER: S-EPMC5116396 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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The association between reproductive and hormonal factors and ovarian cancer by estrogen-α and progesterone receptor status.

Shafrir Amy L AL Rice Megan S MS Gupta Mamta M Terry Kathryn L KL Rosner Bernard A BA Tamimi Rulla M RM Hecht Jonathan L JL Tworoger Shelley S SS

Gynecologic oncology 20161005 3

<h4>Objective</h4>We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status.<h4>Methods</h4>Tissue microarrays were used to assess ERα and PR expression among 197 Nurses' Health Study (NHS), 42 NHSII and 76 New England Case-Control Study (NECC) ovarian cancer cases. NHS/NHSII cases were matched to up to 4 controls (n=954) on diagnosis date and birth year. NECC controls (n=725 ...[more]

PMID: 27720231

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Project description:ObjectivesTo investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer.DesignProspective, nationwide cohort study.SettingDenmark, 1995-2014.ParticipantsAll women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1?879?227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (?1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives.Main outcome measuresPoisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated.ResultsDuring 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13?344?531 person years. Never users had 771 ovarian cancers during 8?150?250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ?1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100?000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21%-that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population.ConclusionsUse of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age-an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.

Dataset Information

The association between reproductive and hormonal factors and ovarian cancer by estrogen-? and progesterone receptor status.

Publications

The association between reproductive and hormonal factors and ovarian cancer by estrogen-α and progesterone receptor status.

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