Abstract

Abstract Introduction: The increased risk of breast cancer is the most controversial and most feared adverse effect of combined oral contraceptives (COC) by women. The mechanisms by which COC would act on the breast parenchyma leading to its increased incidence, are not yet well known. Objectives: To calculate and compare α estrogen receptor (ERα) and progesterone receptor (PR) expression in the mammary epithelium in the first, second, third and fourth weeks of patients who do not use COC (natural cycle) and those who use one cycle of COC composed of 30 µg ethinyl estradiol (EE) and 150 µg levonorgestrel (LNG). Casuistic and Methods: A retrospective study with paraffin blocks of 118 women from February 2001 to February 2004. At the time, women were included in the pre-menopause who had a breast lump with the triple diagnosis of positive benignity and eumenorrheic during the last six months. The study project was analyzed and approved by the Research Ethics Committee of UNIFESP-EPM, under number CEP 1182/06. The patients underwent excision of the breast lumps and adjacent normal breast tissue fragments which were fixed in 10% buffered formalin. 31 patients were excluded and 87 patients were analyzed. The patients were divided into two groups: group A (with COC) consisted of 42 women who used an COC cycle composed of 30μg of EE and 150μg of LNG, group B (without COC) consisted of 45 women with natural cycles. The immunohistochemical reaction was performed in an automation device and the following antibodies were used: ERα antibody clone SP1 titer 1:500 and PR antibody clone PgR636 titer 1:400. The histological slides were read using conventional optical microscopy. After identifying the epithelial areas, 7 fields with 40X magnification were evaluated. Statistical analysis for parity was performed using Fisher's exact test. At age the Students t-Test was applied. ERα and PR counts were evaluated in the Generalized Estimation Equation (EEG) model. In order to compare the total ERα and PR counts by evaluation and group moments, we used the Analysis of Variance (ANOVA) and the Kolmogorov-Smirnov test. Statistical analyzes were performed using the programs SPSS 20.0 and STATA 12. For all statistical tests the significance level of 5% (p ≤ 0.05) was adopted. Results: The control group (without COC) had a higher mean age of 23.7 ± 5.9 years compared to the study group (with COC) with a mean age of 20.5 ± 5.1 years. Regarding parity, the study group (with COC) had 83.9% of nulliparous versus 73.3% in the control group (without COC). From the EEG model a statistically significant mean difference in ERα expression was observed in the fourth week in the study group (with COC) compared to the control group (without COC) with p <0.001. The comparison of PR expressions in the control group (without COC) in the fourth week or in the late luteal phase (LLP) with the ERα expressions, also in the fourth week (LLP) of the control group (without COC) the mean PR expression was higher and statistically significant than ERα expression with p <0.001. The group of women using COC showed higher average percentages of ERα (p <0.001) and PR (p <0.001) when compared to women in the control group (without COC). Conclusions: The average of expressions of the ERα and PR in users of an COC cycle composed of 30 µg EE and 150 µg LNG higher percentages of ERα (p <0.001) and PR (p <0.001) when compared to women from the control group (without COC). The ERα expression in the study group (with COC) in the fourth week (pause) was higher than the ERα expression in the fourth week (LLP) of the control group (without COC), a statistically significant difference (p <0.001). The expression PR in the fourth week of the control group (without COC) or LLP was higher than the ERα and this difference was statistically significant (p <0.001). Citation Format: Weekly evaluation of α estrogen and progesterone receptors in women´s breast epithelium after oral combined hormonal contraceptive use for one month [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-18.

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