THE RELATIONSHIP OF ENDOCRINE DISRUPTORS WITH PITUITARY, GONADAL, THYROID HORMONES AND SOME RECEPTORS IN NIGERIAN WOMEN WITH BREAST CANCER

Abstract

Endocrine Disruptors (EDs) such as lead, cadmium, arsenic, polychlorinated biphenyls (PCBs) and bisphenol-A (BPA) are associated with increased risk of Breast Cancer (BCa). Human epithelial receptor, oestrogen, progesterone and their receptors, gonadotrophins and thyroid hormones are also implicated in the aetiology of BCa but remains controversial. Although, several studies have been conducted on BCa, the relationship of EDs with the hormones and receptors has not been fully explored. This study was designed to examine the relationship of these endocrine disruptors with pituitary, gonadal, thyroid hormones and selected receptors in Nigerian women with breast cancer. One hundred and seventy non-pregnant women aged 48.3±1.3 years were purposively selected from the Surgical Oncology Clinic, University College Hospital, Ibadan. The study comprised of 85 Histologically-Confirmed Breast Cancer pre-therapy (HCBCa) which were sub-divided into premenopausal-HCBCa and postmenopausal-HCBCa. These were matched with 85 Apparently Healthy Women without BCa (AHWB) comprising of premenopausal-AHWB and postmenopausal-AHWB according to age and menstrual phase. Anthropometry and Blood Pressure (BP) were determined with standard methods. Blood was obtained from participants and centrifuged to obtain serum. Serum lead, cadmium and arsenic were determined using atomic absorption spectrophotometry. Bisphenol-A and PCBs were determined using HPLC and gas chromatography, respectively. Oestradiol, progesterone, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Thyroid Stimulating Hormone (TSH), Free Thyroxine (FT4) and Free Triiodothyronine (FT3) levels were determined using ELISA. Expression of Oestrogen Receptor (ER), Progesterone Receptor (PR) and Human Epithelial Receptor 2 (HER2) were determined using immunohistochemistry. Data were analysed using descriptive statistics, Student’s t-test and multiple regression at α0.05. Waist Circumference (WC), Hip Circumference (HC), weight, height, Waist-Hip-Ratio (WHR), Waist-Height-Ratio (WHtR) were significantly higher in HCBCa compared with AHWB (89.9±1.1 vs 82.6±1.2 cm; 101.8±1.1 vs 98.5±1.0 cm; 69.2±1.4 vs 62.1±1.1 kg; 1.63±0.0 vs 1.58±0.0 m; 0.9±0.0 vs 0.8±0.0; 55.3±0.7 vs 52.4±0.7, respectively). The HCBCa had significantly higher levels of lead, cadmium, arsenic, PCBs and bisphenol-A compared with AHWB (5.5±0.2 vs 1.8±0.0 µg/dL; 0.04±0.0 vs 0.01±0.0 µg/dL; 0.30±0.0 vs 0.04±0.0 µg/dL; 0.8±0.5 vs 0.3±0.0 µg/dL; 0.8±0.7 vs 0.4±0.0 mg/dL, respectively). The FT4 was significantly higher in HCBCa than AHWB (17.8±0.4 vs 14.7±0.3 pmol/L). There was no difference in LH, FSH and TSH in HCBCa compared with AHWB. Progesterone and oestradiol were higher in postmenopausal-HCBCa compared with postmenopausal-AHWB. (2.09±0.35 vs 1.04±0.10 nmol/L;156.48±12.42 vs 90.42±3.59 pmol/L, respectively) Regression analysis showed that in HCBCa, oestradiol and WC jointly predicted lead and cadmium (β>0.348, β>5.830, respectively). Diastolic-BP predicted cadmium (β=0.299), WHR and HC predicted arsenic (β>2.732) while FT3, WHtR and height positively predicted BPA (β>0.404). Contrarily, these relationships were absent in AHWB. Fifty-five tumour samples (69.6%) exhibited ER˗, PR˗ and HER2˗ expressions (triple negative) while 2 (2.5%) demonstrated ER+, PR+ and HER2+ expressions. Fifty-two tumour samples (100%) in premenopausal-HCBCa exhibited ER˗/PR˗ co-expressions while 46 (88.5%) exhibited HER2˗ expression. However, 18 (66.7%), 18 (66.7%) and 17 (63.0%) postmenopausal-HCBCa exhibited ER˗, PR˗ and HER2˗ tumour expressions, respectively. Endocrine disruptors could have contributed to adiposity and be associated with negative receptor expression, which may induce cell proliferation and probably cause derangement in thyroid metabolism. Keywords: Adiposity, Women with breast cancer, Endocrine disruptors, Hormone receptors. Word count: 499