History Of Oral Contraceptive Use Research Articles

Abstract 4431: Steroid hormone metabolites and mammographic breast density in premenopausal women

Abstract Background: Steroid hormones influence breast tissue development and play a role in breast carcinogenesis. Their associations with mammographic breast density (MBD), an established risk factor for breast cancer, are less clear. We, therefore, investigated the associations of steroid hormone metabolites with MBD in premenopausal women. Methods: Our study population consists of 705 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. We assessed volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV) using Volpara. We assayed 54 steroid hormone metabolites from fasting blood samples at Metabolon. Linear regression models were used, after adjusting for covariates, to estimate the least square means of VPD, DV, and NDV across tertiles (T) of each metabolite. Sensitivity analysis was performed among the subset of participants with a history of oral contraceptive use (OCP). We used the Benjamini-Hochberg procedure to correct for multiple tests to control the false discovery rate (FDR) at a 5% level. Results: Five androgen metabolites (androstenediol (3beta,17beta) monosulfate 2, androstenediol (3beta,17beta) disulfate 1, 5alpha-androstan-3alpha,17beta-diol monosulfate 2, 5alpha-androstan-3alpha,17beta-diol disulfate, and 5alpha-androstan-3beta,17beta-diol disulfate) and two corticosteroid metabolites (tetrahydrocortisone glucuronide 5, and cortolone glucuronide 1) were inversely associated with VPD. Androstenediol (3beta,17beta) disulfate 1, and 5alpha-androstan-3alpha,17beta-diol disulfate displayed the strongest associations with VPD. The mean VPD decreased across tertiles of androstenediol (3beta,17beta) disulfate 1 from 9.0% in T1 to 8.5% in T2, and 7.5% in T3 (FDR p-value=0.02). Similarly, the mean VPD decreased from 8.8% in T1 to 8.4% in T2, and 7.6% in T3 of 5alpha-androstan-3alpha,17beta-diol disulfate (FDR p-value=0.03). Progestin steroid metabolites appeared to be positively associated with VPD but only 5alpha-pregnan-3beta,20alpha-diol monosulfate 2 was marginally significant after FDR correction (7.5% in T1, 8.3% in T2, and 8.8% in T3; FDR p-value=0.06). Four metabolites (three corticosteroids and one androgenic steroid) were positively associated with NDV. No metabolite was associated with DV. In sensitivity analysis limited to OCP users, mean VPDs were lower but the directions of associations were similar to those observed in the overall analysis. Conclusion: We report novel associations of corticosteroids and androgen metabolites with breast density in premenopausal women. Our findings shed important new insights into hormonal biomarkers and MBD. Citation Format: Kayode A. Matthew, Girish K. Vanapali, Kayla R. Getz, Myung S. Jeon, Chongliang Luo, Xingyi Guo, Jingqin Luo, Adetunji T. Toriola. Steroid hormone metabolites and mammographic breast density in premenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4431.

Early preterm abdominal pregnancy: A case report

Background: Abdominal pregnancies, a rare form of ectopic pregnancy, pose significant risks to themother and fetus. The severity of complications depends on the gestational age at presentation,abdominal pregnancy location, and attachment to abdominal organs.Case presentation: A 38-year-old, para 3+0 gravida 4 presented with abdominal pain and moderatepallor at 30 weeks gestational age, extrapolated from obstetric ultrasound due to an unknown last normalmenstrual period. She was HIV-positive and on highly active antiretroviral therapy. She had a history oforal contraceptive use before conception. Ultrasound revealed a viable intraabdominal pregnancy at 30weeks with the placenta attached to the mesentery in the right upper quadrant with a nongravid uterus.She was transfused with four units of packed red blood cells before elective laparotomy. Intraoperatively,the gestational sac in the upper quadrants and membranes were ruptured. A live male infant wasdelivered, weighing 990g, Apgar scores of 8 at 1 and 9 at 5. The placenta, which was attached to the leftfallopian tube and the broad ligament was extracted. The infant was admitted to the newborn unitbecause of prematurity. The postoperative period was uneventful, and the mother and baby were doingwell at the writing of this abstract.Conclusion: Early preterm abdominal pregnancy should be managed by elective laparotomy to optimizeoutcomes for both the mother and fetus. Cases with limited attachment to the viscera tend to havefavorable outcomes. Neonatal outcome primarily depends on gestational age at delivery.

Connections between reproductive health and cognitive aging among women enrolled in the HCHS/SOL and SOL-INCA.

Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women. Participants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence). Younger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence. Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Clinical, histological features, and predictors of relapse in patients with idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis is a benign, inflammatory disease of breasts characterized by non-caseating granulomas. Our study aims to identify distinguishing clinical and histopathological features of relapsing disease compared to those in complete remission. We queried databases at our institution (1990-2021) to include females ≥18 years with biopsy-proven diagnosis of idiopathic granulomatous mastitis, excluding patients with breast cancer, lymphoproliferative disorders, solid organ malignancy, foreign body reaction in breast, plasma cell mastitis, and ductal ectasia. Remission was defined as a 3-month period without recurrence of symptoms or imaging findings. Relapse was defined as recurrence after 3 months of remission. Clinical and histopathological features were compared using 2-sample t tests and chi-squared tests. Of the 27 patients that met our inclusion criteria, the mean age at diagnosis was 35.8 years (± standard deviation 9.4 years) with a mean body mass index of 31.7 kg/m2 (± standard deviation 6.7 kg/m2). 11 (41%) were Hispanic, 25 (93%) had at least one previous full-term pregnancy prior to diagnosis and 8 (30%) were on oral contraceptives. Remission was seen in 18 patients (66%) and 9 (33%) had relapse. Six of these patients received steroids after antibiotics, while 5 patients received methotrexate. Three (33%) patients with relapse and 14 (77%) with remission, had abscess formation confirmed on histopathology (P = .04). Patients with remission had a higher number of abscesses on histopathology and history of oral contraceptive use was associated with more relapse. By identifying key clinical and histopathological findings in this population may guide prognosis and treatment of these patients.

Association of Cumulative Lifetime Exposure to Female Hormones With Cerebral Small Vessel Disease in Postmenopausal Women in the UK Biobank.

Rates of cerebrovascular disease increase after menopause, which is often attributed to the absence of hormones. It remains unknown whether the cumulative exposure to hormones across a female person's premenopausal life extends the window of cerebrovascular protection to the postmenopausal period. To investigate this, we examined the relationship between lifetime hormone exposure (LHE) and cerebral small vessel disease in more than 9,000 postmenopausal women in the UK-Biobank. The cohort consisted of women (aged 40-69 years) who attended one of 22 research centers across the United Kingdom between 2006 and 2010. Women were excluded if they were premenopausal when scanned, had missing reproductive history data, self-reported neurologic disorders, brain cancer, cerebral vascular incidents, head or neurologic injury, and nervous system infection. Endogenous LHE (LHEEndo) was estimated by summing the number of years pregnant (LHEParity) with the duration of the reproductive period (LHECycle = age menopause - age menarche). Exogenous LHE (LHEExo) was estimated by summing the number of years on oral contraceptives and hormone replacement therapy. Cerebral small vessel disease was determined by estimating white matter hyperintensity volume (WMHV) from T2-fluid-attenuated inversion recovery brain MRI (acquired between 2014 and 2021), normalized to intracranial volume and log-transformed. Multiple linear regressions were used to assess the relationship between LHEEndo on WMHV adjusted for age, cardiovascular risk factors, sociodemographics, and LHEExo. A total of 9,163 postmenopausal women (age 64.21 ± 6.81 years) were retained for analysis. Average LHEEndo was 39.77 ± 3.59 years. Women with higher LHEEndo showed smaller WMHV (adj-R 2 = 0.307, LHEEndo β = -0.007 [-0.012 to -0.002], p < 0.01). LHEParity and LHECycle were independent contributors to WMHV (adj-R 2 = 0.308, p << 0.001; LHEParity β = -0.022 [-0.042 to -0.002], p < 0.05; LHECycle β = -0.006 [-0.011 to -0.001], p < 0.05). LHEExo was not significantly related to WMHV (LHEExo β = 0.001 [-0.001 to 0.002], p > 0.05). Women with more prolonged exposure to endogenous hormones show relatively smaller burden of cerebral small vessel disease independent of the history of oral contraceptive use or hormone replacement therapy. Our results highlight the critical role endogenous hormones play in female brain health and provide real-world evidence of the protective effects premenopausal endogenous hormone exposure plays on postmenopausal cerebrovascular health.

Extremely giant liver hemangioma: a case beyond the norms.

A 68-year-old overweight woman with no history of oral contraceptive use presented a large liver mass of 40 cm on abdominal ultrasound without associated symptoms. Complete blood count, coagulation study, and liver biochemistry were unremarkable. Abdominal contrast-enhanced CT revealed a 33x24 cm lesion with discontinuous peripheral globular uptake and centripetal fill-in, consistent with an extremely giant hemangioma. It affected all segments of the right lobe, compressing the right suprahepatic vein and displacing all intra-abdominal structures, with a deviation of the midline structures (stomach and pancreas) to the left. Given the hemangioma size and its significant mass effect, surgery was discussed but declined by the patient, who remains asymptomatic 3 years later. Extremely giant liver hemangiomas (>10 cm) are rare, and the approach to asymptomatic patients is debated. Some advocate for prophylactic excision due to the potential for internal bleeding, growth, or rupture, while others suggest intervention for hemangiomas near major vascular structures. The American College of Gastroenterology recommends surgical intervention in such cases, but the European Association for the Study of the Liver suggests a conservative approach for most patients. This case highlights a successful "watch-and-wait" strategy, bringing attention to this unusual condition and its controversial management.

Villoglandular Adenocarcinoma of the Uterine Cervix: A Case Report.

Cervical adenocarcinomas constitute for approximately 10%-20% of all invasive cervical cancers. Villoglandular adenocarcinomas (VGAs) are a rare subtype of cervical adenocarcinoma, representing approximately 5% of all cases of cervical adenocarcinomas. Herein, we report the case of a 49-year-old perimenopausal woman successfully treated for VGA. The patient presented to the hospital with a primary complaint of vaginal discharge persisting for 7 months with worsening symptoms. She had no underlying medical conditions or history of oral contraceptive use. A punch biopsy revealed an adenocarcinoma, and a human papillomavirus (HPV) test indicated positive for HPV-16. The patient underwent a radical hysterectomy with bilateral pelvic lymph node dissection, and a pathological diagnosis of VGA was established. After surgery, the patient underwent a 6-week course of concurrent chemoradiotherapy with cisplatin. During the 42 months of follow-up, no signs of disease recurrence or metastasis were observed. Because of the limitations of specimen acquisition, achieving a precise diagnosis through cervicovaginal cytology and punch biopsy is challenging. Instead, conization should be considered to prevent misdiagnosis.

Carcinoma cervix: A single institute experience from Kashmir, Northern India.

Carcinoma cervix is the fourth most commonly diagnosed cancer worldwide, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Carcinoma cervix is an uncommon malignancy in Kashmir. In this retrospective study, we have tried to find clinicopathological characteristics of carcinoma cervix along with the survival rates at our tertiary care hospital. Case records of cervical cancer patients registered from January 1, 2015, to January 1, 2019, were retrieved. A total of 138 patients was registered. 22 had undergone surgery, and out of these 17 had received postoperative radiotherapy. 109 patients were treated with definitive chemoradiation and 13 with palliative radiotherapy. Descriptive statistics were used to summarize patient and treatment-related variables, and Kaplan-Meier analysis was performed for survival analysis. A total of 138 cases that were registered from 2015 to 2019 were included in this study. The median age at the presentation was 56 years. Most of the patients had a performance status of 1 (98 patients (71.01)). Most of the patients 110 (79.71%) were married before 20 years of age, only 1 patient was unmarried, and 85 (61.59) patients were multiparous in our study group. Only 14 (10.14%) patients in our study group had a history of oral contraceptive use and most of them were non-smokers [124 (89.80%)]. Multiple marriages were present in 8 (5.79%) patients only. The most common presenting symptom was bleeding per vagina (78.26%), and the maximum number of patients fall in the post-menopausal group (67.39%). 116 patients had squamous cell carcinoma histology while 10 patients had adenocarcinoma histology. Most of the patients had stage II and stage III disease (85 patients). At last, follow up out of 138 patients 75 (54.35) were alive. 3 year disease-free survival was 54.34% and 3-year overall survival was 72.46%. Carcinoma cervix is an uncommon malignancy in Kashmir because of different socio-cultural and religious practices but the response to treatment, toxicity profile, and survival are similar to the rest of the world.

Referral, Genetic Counselling, and BRCA Testing in the Manitoba High-Grade Serous Ovarian Cancer Population, 2004–2019

(1) Background: The primary objective of this study was to examine the rate of genetic referral, BRCA testing, and BRCA positivity amongst all patients with high-grade serous ovarian cancers (HGSOC) from 2004-2019. The secondary objective was to analyze secondary factors that may affect the rates of referral and testing. (2) Methods: This population-based cohort study included all women diagnosed with HGSOC using the Manitoba Cancer Registry, CervixCheck registry, Medical Claims database at Manitoba Health, the Hospital Discharge abstract, the Population Registry, and Winnipeg Regional Health Authority genetics data. Data were examined for three different time cohorts (2004-2013, 2014-2016; 2017-2019) correlating to practice pattern changes. (3) Results: A total of 944 patients were diagnosed with HGSOC. The rate of genetic referrals changed over the three timeframes (20.0% → 56.7% → 36.6%) and rate of genetic testing increased over the entire timeframe. Factors found to increase rates of referral and testing included age, histology, history of oral contraceptive use, and family history of ovarian cancer. Prior health care utilization indicators did not affect genetic referral or testing. (4) Conclusion: The rate of genetic referral (2004-2016) and BRCA1/2 testing (2004-2019) for patients with a diagnosis of HGSOC increased over time. A minority of patients received a consultation for genetics counselling, and even fewer received testing for a BRCA1/2. Without a genetic result, it is difficult for clinicians to inform treatment decisions. Additional efforts are needed to increase genetics consultation and testing for Manitoban patients with HGSOC. Effects of routine tumour testing on rates of genetic referral will have to be examined in future studies.

S1346 Is the Mutational Landscape of Hepatocellular Adenoma Distinct in the Setting of Oral Contraceptive Use?

Introduction: Hepatocellular adenomas (HCA) are benign tumors with possible complications of bleeding and malignant transformation. Oral contraceptive us in women of childbearing are most frequently associated with hepatocellular development. This study investigates the multifactorial role of oral contraceptive use and its effect on mutation frequency, mutation count, and nodule size in patients with HCA. Methods: Using the cBioPortal platform and systematic bioinformatical analysis of the Cancer Genome Atlas (INSERM) Cancer Cell 2014 data for hepatocellular adenoma, 30 HCA patients were included in this study. Of which twenty-one patients had used oral contraception for greater than two years, four patients < 2 years, and five patients had no reported history of oral contraceptive use. Results: The mutational landscape of the lack of oral contraceptive use associated with HCA was distinct with statistically significant alterations in ACY1, APOA1, APOB, ARHGAP22, ARNTL2, BICRAL, C3ORF70, CASR, CD247, CDH9 mutation frequency (See Figure). Further, the mutation count was statistically significant as patients with oral contraceptive use < 2 years had the lowest mutation count of 6, (See Table). Additionally, the nodule size (mm) in patients with HCA was statistically significant as patients with a history of oral contraceptive use < 2 years had the smallest median nodule size of 37.5 mm (See Table). Conclusion: The findings in this study highlight the complex multifactorial role of oral contraceptive use in HCA. Further studies are essential for understanding the molecular and pathophysiologic impact of oral contraceptive use on functions of critical genes that exert carcinogenic potential.Figure 1.: The mutational landscape among oral contraceptive use in hepatocellular adenoma Table 1. - Mutation count and nodule size in hepatocellular adenoma with relation to oral contraceptive use No OCP use OCP < 2 years OCP use > 2 years P-value Mutation count 19 6 11 0.03 Nodule size (mm) 70 mm 37.5 mm 70 mm 0.03

Prevalence and Risk Factors Associated With Gestational Diabetes Mellitus Among Pregnant Women: A Cross-Sectional Study in Ghana.

Gestational diabetes mellitus (GDM) is a global public health issue that have serious consequences on mother and her child's health. However, limited data is available on the prevalence of GDM and its associated risk factors in Ghana. This study investigated the prevalence and associated risk factors of GDM among women attending selected antenatal clinics in Kumasi, Ghana. This cross-sectional study included 200 pregnant women who attended antenatal clinics from Three-selected health facilities in the Ashanti Region, Ghana. Women already diagnosed of GDM were identified through their medical records and were confirmed based on the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG), which uses a fasting blood glucose of ≥ 5.1 mmol/L. A well-structured questionnaire was used to collect data on socio-demographic, obstetric, clinical and lifestyle risk factors. Multivariate logistic regression models were used to determine the independent risk factors of GDM. The overall prevalence of GDM among study participants was 8.5%. GDM was prevalent among age 26 and 30 years (41.2%), married participants (94.1%) with basic education (41.2%) and being Akan by ethnicity (52.9%). Previous history of oral contraceptive use (aOR: 13.05; 95% CI: 1.43-119.23, p=0.023), previous history of preeclampsia (aOR: 19.30; 95% CI: 2.15-71.63; p=0.013) and intake of soda drinks (aOR: 10.05, 95% CI: 1.19-84.73, p=0.034) were found to be independent risk factors of GDM. The prevalence of GDM was found to be 8.5% and this was associated with the previous use of oral contraceptives, history of preeclampsia and intake of soda drinks. Public health education and dietary lifestyle modification may be required for pregnant women who are at risk of GDM.

Breast tuberculosis: analysis of 24 patients

Introduction: Breast tuberculosis is a disease that is difficult to diagnose with its clinical appearance and can be confused with breast abscesses and breast carcinomas. In this study, we aimed to analyze 24 patients diagnosed with breast tuberculosis, followed up and treated.&#x0D; Material and Method: Among 4489 patients examined in the breast diseases outpatient clinic between January 2012 and December 2020, patients diagnosed with breast tuberculosis were evaluated retrospectively. Demographic, clinical features, radiological findings, histopathological and microbiological findings of the patients were recorded. Diagnosis, treatment protocols and treatment outcomes were evaluated.&#x0D; Results: A total of 24 breast tuberculosis cases were analyzed in the study. The mean age was 41.6 (28-64 years) and all patients were diagnosed for the first time. There was a history of oral contraceptive use in 10 patients. Among patients, 19 of them were in the reproductive age, and five patients were in the postmenopausal period. Four patients were in lactating period. On physical examination, breast mass was detected in 16 (67%) patients, abscess was present in 5 patients (20.8%), and sinus and discharge were evident in three patients (12.5%). Breast ultrasonography revealed a breast mass in 16 patients (67%), abscess in eight patients (33%), and axillary lymphadenopathy in six patients (25%). The diagnosis was made by core biopsy in 10 (41.6%) patients, fine-needle aspiration biopsy in three patients (12.5%), and incisional biopsy in 11 patients (45.8%). All patients were given quadruple antituberculosis therapy in the first 2 months for 9 months, and double antituberculosis therapy for 7 months. In addition to antituberculosis treatment, mass excision was performed in three patients (12.5%), segmental mastectomy in one patient (4.1%), simple mastectomy in one patient (4.1%), and abscess drainage were completed in eight patients (33.3%). Cure was achieved in all patients after treatment.&#x0D; Conclusion: Breast tuberculosis is a rare disease that can be difficult to diagnose unless the disease itself is suspected. As the diagnosis of the disease is delayed, the disease becomes complicated and the need for surgical treatment increases as well as medical treatment. Although there are different opinions about the duration of the treatment, in our study, cure was achieved with 9 months of treatment and no recurrence was observed in the 1-year follow-up. Since 10 patients had a history of oral contraceptive use, further research is needed to understand whether oral contraceptive use is a predisposing factor in the development of breast tuberculosis.

Association of oral contraceptives and tubal ligation with antimüllerian hormone.

Oral contraceptives (OCs) and tubal ligation are commonly used methods of contraception that may impact ovarian function. Few studies have examined the association of these factors with antimüllerian hormone (AMH), a marker of ovarian aging. We examined the association of OC use and tubal ligation with AMH in the Nurses' Health Study II prospective cohort among a subset of 1,420 premenopausal participants who provided a blood sample in 1996-1999. History of OC use and tubal ligation were reported in 1989 and updated every 2 years until blood collection. We utilized generalized linear models to assess whether mean AMH levels varied by duration of and age at first use of OCs and history, age, and type of tubal ligation. In multivariable models adjusted for smoking, reproductive events, and other lifestyle factors, we observed a significant, inverse association between duration of OC use and mean AMH levels (P for trend = 0.036). Compared to women without a tubal ligation, AMH levels were significantly lower when the procedure included a clip, ring, or band (1.04 ng/ml vs 1.72 ng/ml, P < 0.01). AMH levels were not associated with age at first use of OCs or age at tubal ligation. Our analysis found an association between duration of OC use and certain types of tubal ligation with mean AMH levels. Further research is warranted to confirm the long-term association of these widely used contraceptive methods with AMH.

Unexpected Populations for Deep Vein Thrombosis: Presentation in an Endurance Athlete

This case presents an athletic 40-year-old female marathon runner who presented with a headache secondary to dural venous sinus thrombosis and right calf deep vein thrombosis (DVT). Though this is outside of the typical image we portray of a common DVT patient, athletes too experience hypercoagulable risk factors and medical issues, just as their less in-shape peers. This patient’s history of oral contraceptive use, Lynch syndrome, colon cancer, and pregnancy indicates potential risk factors for DVT. Even without these though, it is important to note that every endurance athlete experiences hemoconcentration, dehydration, and inflammation during exercise, training, and competition events. This case demonstrates the need for an increased index of suspicion in endurance athletes. The case exemplifies an all-too-frequent occurrence of allowing our differential to be skewed away from potentially life-threatening conditions like DVT, and their thrombotic sequelae, because of the “textbook population” descriptions of a given disease state. We hope this case will shed needed light on the phenomenon and lead to more controlled research on the probability and pathophysiology for thrombotic events in this broadened population so that its incidence and prevalence in endurance athletes can be accurately reported in the literature.

The causal effect and impact of reproductive factors on breast cancer using super learner and targeted maximum likelihood estimation: a case-control study in Fars Province, Iran

ObjectivesThe relationship between reproductive factors and breast cancer (BC) risk has been investigated in previous studies. Considering the discrepancies in the results, the aim of this study was to estimate the causal effect of reproductive factors on BC risk in a case-control study using the double robust approach of targeted maximum likelihood estimation.MethodsThis is a causal reanalysis of a case-control study done between 2005 and 2008 in Shiraz, Iran, in which 787 confirmed BC cases and 928 controls were enrolled. Targeted maximum likelihood estimation along with super Learner were used to analyze the data, and risk ratio (RR), risk difference (RD), andpopulation attributable fraction (PAF) were reported.ResultsOur findings did not support parity and age at the first pregnancy as risk factors for BC. The risk of BC was higher among postmenopausal women (RR = 3.3, 95% confidence interval (CI) = (2.3, 4.6)), women with the age at first marriage ≥20 years (RR = 1.6, 95% CI = (1.3, 2.1)), and the history of oral contraceptive (OC) use (RR = 1.6, 95% CI = (1.3, 2.1)) or breastfeeding duration ≤60 months (RR = 1.8, 95% CI = (1.3, 2.5)). The PAF for menopause status, breastfeeding duration, and OC use were 40.3% (95% CI = 39.5, 40.6), 27.3% (95% CI = 23.1, 30.8) and 24.4% (95% CI = 10.5, 35.5), respectively.ConclusionsPostmenopausal women, and women with a higher age at first marriage, shorter duration of breastfeeding, and history of OC use are at the higher risk of BC.

Abstract PS8-21: The impact of exogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC)

Abstract Background: Oral contraceptives (OC) and hormone replacement therapy (HRT) are well-established risk factors for ER positive breast cancer. Infertility is associated with an increased breast cancer risk and there is conflicting data on the influence of fertility treatments on breast cancer risk. The impact of exogenous estrogen exposure on breast cancer characteristics is not well described. Methods: A single center retrospective cohort study comprising all women with ER positive, human epidermal growth factor receptor 2 (HER2) negative, EBC whose tumors were sent to OncotypeDX analysis and were treated in our institute between 2005 and 2012. Data on exogenous estrogen exposure were collected including: OC and HRT use and prior fertility treatments. The impact of these exposures was assessed on pre-specified histopathological features including: tumor size, nodal status, ER and progesterone receptor (PR) staining, grade, Oncotype recurrence score (RS), ki67, lymphovascular and perineural invasion. Results: A total of 620 women were included, 79% (Num) were postmenopausal. Prior exposure to OC, HRT and fertility treatments was documented in 19% (103), 30% (136) and 11% (62), respectively. OC use was associated with smaller (≤1cm) tumors (30% vs. 20%, p=0.023) and were less likely to have grade 3 disease (10% vs. 19%, p=0.049). No other associations were found between exogenous estrogen exposures and tumor characteristics (Table). Conclusions: Use of OC may be associated with breast cancer with a distinct features compared to women with luminal breast cancer without history of OC use. Large scale studies are needed to better characterize these findings. Fertility treatmentHRT ≥ 2 yearsHRTOCPNo (%)Yes(%)PNo(%)Yes (%)PNo (%)Yes (%)PNo(%)Yes(%)0.1722254252165150.7002355222057240.7002255232456200.023205723304426T≤1 cm 1&amp;lt;T≤2 T&amp;gt;2 cm0.85917180.09815200.09815210.6671815Node positive0.06479138891100.29982126761590.29982135771590.207791488795IDC ILC Other0.1671864181473130.5001667181664190.5001667171762210.049186319187310Grade 1 230.18922078329680.70811781122770.70811781221780.7392227732275ER intensity≤1 1&amp;lt;ER⇐2 ER&amp;gt;20.1121470.67116150.67116140.103148PR Negative1.000530.455520.455530.28252PNI present0.772670.351780.351570.056105LVI present0.18620290.36222190.36223180.5282218Ki67 &amp;gt;20%0.85917180.78718160.78717180.5701816Oncotype RS&amp;gt;25 Citation Format: Orly Yariv, Rinat Yerushalmi, Assaf Moore, Tzippy Shohat, Ofer Rotem, Yasmin Korzets Ceder, Hadar Goldvaser. The impact of exogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-21.

Abstract PO029: Oral contraceptive use and postmenopausal sex steroid hormone metabolism

Abstract OBJECTIVE: Oral contraceptive (OC) use is common in the United States and high-profile articles have renewed research interest in OC use and cancer risk. Several mechanisms have been proposed to explain how OC use influences postmenopausal cancer risk; one of the leading hypotheses is that OC use fundamentally alters feedback in the hypothalamic-pituitary-gonad axis, leading to long term changes in sex steroid hormone metabolism. However, women who use OCs are also unique with respect to factors that may affect both hormone metabolism and cancer risk. No studies have comprehensively commented on hormone levels in postmenopausal women who did and did not use OCs. DESIGN: We examined differences in circulating markers of sex steroid hormone metabolism associated with prior use of OCs among a subcohort of postmenopausal women from the Women’s Health Initiative Observational Study (983 women with at least one intact ovary and not currently using menopausal hormone therapy). MATERIALS AND METHODS: Using highly sensitive liquid chromatography–tandem mass spectrometry assays, we measured over 30 markers of estrogen and androgen metabolism in study serum samples. We used linear regression (adjusted and weighted) to estimate geometric mean hormone levels, which were then converted into relative percent differences. We controlled for potential confounders and stratified by: lifetime ovulatory cycles, body mass index, and parity (the focus of this abstract). RESULTS: Women with a history of OC use (n=346) had lower levels of estrogen metabolites than women who never used OCs (n=637), particularly when limiting this comparison among parous women (n=158 nulliparous women, n=825 parous women). In parous women, OC use was associated with reductions in total estrone (-18.5%, 95% confidence interval [CI] -31.1, -3.7%) and in estrogen metabolism overall: 2-hydroxylation metabolites were reduced by -18.5% (CI -28.2, -7.7%), 4-hydroxylation metabolites by -19.9% (CI -29.4, -9.1%), and 16-alpha-hydroxylation metabolites by -24.0% (CI -34.2, -12.2%). Hormone differences associated with OC use among nulliparous women were imprecise. When we made comparisons to nulliparous women who did not use OCs, women who both used OCs and were parous had lower testosterone (-21.2%, CI -33.1, -7.2%) and higher dihydrotestosterone relative to testosterone (its metabolic precursor; 16.5%, CI% -0.6, 36.6). However, aside from lower total estrone (-25.5%, CI -44.6, 0.2%), estrogen metabolism was not different between these groups. CONCLUSIONS: We saw evidence suggesting estrogen metabolism, as reflected in circulating markers, may be lower in postmenopausal women who previously used OCs. These effects were strongest among parous women, likely due to sufficient sample size, rather than any synergistic effect attributable to both using OCs and giving birth. These results support the idea that OC users have lower estrogen levels, but this should be evaluated in other age groups, as differences in hormone metabolism early in the lifecourse may lead women to use OCs. Citation Format: Kara A. Michels, Sally B. Coburn, Garnet Anderson, Louise A. Brinton, Chu Chen, Roni T. Falk, Margery L. Gass, Ashley M. Geczik, JoAnn E. Manson, Ruth M. Pfeiffer, Kerryn Reding, Gloria E. Sarto, Nicolas Wentzensen, Robert A. Wild, Xia Xu, Britton Trabert. Oral contraceptive use and postmenopausal sex steroid hormone metabolism [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO029.

A Multicentre Observational Study on Risk Factors for Breast Cancer.

Breast cancer is the most common malignancy in Indian women. There is scant data from Indian hospital-based populations on the prevalence of risk factors of this disease. We performed this study to quantify and analyze various epidemiological risk factors in Indian breast cancer patients. This was a multicenter collaborative study wherein breast cancer patients older than 18years were served a structured questionnaire after informed consent. Patients or their relatives were required to fill out the questionnaire and those who were unable to read and write were excluded. Data were abstracted from case record forms and variables were descriptively analyzed. Between January 2015 and February 2016, 800 patients were screened, of whom 736 patientswith a mean age of 50.13years were enrolled in the study. The mean number of pregnancies was 2.75 (0-11), the number (percentage) of women who had breastfed for more than 6months was 628 (85.3) and 406 (55.1%) patients were post-menopausal at the time of breast cancer diagnosis. Of the enrolled patients, 91 (12.8%) had history of exposure to passive smoke, 13 (1.8%) had partners who were heavy smokers, 27(3.7%) had history of oral contraceptive use, 4 (0.5%) had history of hormone replacement therapy, and 103 (14%) had undergone hysterectomy with oophorectomy. Our study contributes to the descriptive prevalence of some known risk factors in Indian breast cancer patients.

The impact of exogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC).

e12606 Background: Oral contraceptives (OC) and hormone replacement therapy (HRT) are well-established risk factors for ER positive breast cancer. Infertility is associated with an increased breast cancer risk and there is conflicting data on the influence of fertility treatments on breast cancer risk. The impact of exogenous estrogen exposure on breast cancer characteristics is not well described. Methods: A single center retrospective cohort study comprising all women with ER positive, human epidermal growth factor receptor 2 (HER2) negative, EBC whose tumors were sent to OncotypeDX analysis treated in our institute between 2005 and 2012. Data on exogenous estrogen exposure were collected including: OC and HRT use and prior fertility treatments. The impact of these exposures was assessed on pre-specified histopathological features including: tumor size, nodal status, ER and progesterone receptor (PR) staining, grade, Oncotype recurrence score (RS), ki67, lymphovascular and perineural invasion. Results: A total of 620 women were included, 79% were postmenopausal. Prior exposure to OC, HRT and fertility treatments was documented in 19% (103), 30% (136) and 11% (62), respectively. OC use was associated with smaller (≤1cm) tumors (30% vs. 20%, p = 0.023) and were less likely to have grade 3 disease (10% vs. 19%, p = 0.049). No other associations were found between exogenous estrogen exposures and tumor characteristics (Table). Conclusions: Use of OC may be associated with breast cancer with a distinct features compared to women with luminal breast cancer without history of OC use. Large scale studies are needed to better characterize these findings. [Table: see text]

Expression analysis of growth arrest specific 8 and its anti-sense in breast cancer tissues

The Growth arrest specific 8 (GAS8) and its anti-sense transcript (GAS8-AS1) are located in a genomic region that is frequently mutated in breast cancer. These transcripts have established tumor suppressor effects in some human malignancies. In the current investigation, we aimed at identification of the role of GAS8 and GAS8-AS1 in breast cancer. We measured gene expression of GAS8 and GAS8-AS1 in paired tumoral and non-tumoral tissues obtained from 88 breast cancer patients by means of real time PCR. No significant differences were identified in expressions of GAS8 and GAS8-AS1 in tumoral samples compared with non-tumoral tissues (Fold changes = 1.53 and 1.71; P values = .28 and 0.14 respectively). Transcript levels of GAS8-AS1 was significantly correlated with estrogen receptor (ER) status (P = .01). Expression of GAS8 gene was associated with history of oral contraceptive use (P = .04). The similar expressions of GAS8 and GAS8-AS1 genes in tumoral and non-tumoral tissues of breast in spite of previous reports regarding their fundamental tumor suppressor roles in other tissues show that these genes are not involved in the pathogenesis of breast cancer. So, these genes have distinct roles in diverse tissues.