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

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

Highlights

• •Ovarian tumor development through hormonal pathways may differ from breast cancer.
• •Postmenopausal women were more likely to develop PR(–) ovarian tumors.
• •Women with a tubal ligation tended to develop ERα(–) ovarian tumors.

Objective

We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status.

                                Conclusions

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 ERα and PR pathways may differ.

Methods

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) were frequency matched on age. Cases were considered receptor positive if ≥1% of tumor cells stained positive. Associations by ERα and PR status were assessed using polytomous logistic regression. p-Value for heterogeneity was calculated using a likelihood ratio test.

Results

45% of ovarian tumors were PR(+), 78% were ERα(+) and 45% were ERα(+)/PR(+), while 22% were ERα(–)/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 5 years: 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 ERα(–) versus ERα(+) tumors (p-het = 0.002 and 0.05, respectively). No differential associations were observed for oral contraceptive or hormone therapy use.

Conclusions

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 ERα and PR pathways may differ.