Objectives: This study examined the association between reproductive factors and risk of breast cancer (BC) according to the expression of hormone receptors (HR) in women from three Colombian cities. Methodology: 316 cases were recruited between 2012 and 2019 from major general or cancer-dedicated hospitals were women diagnosed with first primary invasive breast cancer confirmed with a biopsy with a clinical staging according to the international tumor-node-metastasis (TNM) classification and residents for at least 3 years in the cities of Barranquilla, Cali, and Medellin. Controls were selected from the general population residing in the same city district as the case for at least 3 years using a multilevel sampling frame. They were matched to cases on age (± 3 years) and city district of residence. Cases and controls were recruited and interviewed by trained health staff, and provided blood samples and tumor tissues, prior to any treatment. Socioeconomic (education level and type of health insurance), anthropometric (weight, height, waist circumference, and body mass index), family history of BC, history of benign breast disease, lifestyle and reproductive (age at menarche, pregnancy ever, parity,. breastfeeding, and its duration) variables were considered. A conditional logistic regression model was used to estimate Odds Ratios (OR) and 95% confidence intervals (95% CI) and evaluate the association of reproductive factors. The final multivariate models were adjusted for factors that changed the risk estimate by more than 10%, including level of education, history of benign breast disease, and health insurance. P values <0.05 were considered statistically significant. Results: Pregnancy ever (OR = 0.48; 95% CI, 0.26-0.90), parity (OR = 0.89; 95% CI, 0.79-0.99 per child), breastfeeding (OR = 0.97; 95% CI, 0.95-0.99) and its longer duration (OR = 0.35; 95% CI, 0.18-0.71 > 12 months) were associated with a decrease in the risk of BC. When combining the reproductive variables, in women who had more than 2 children and breastfed (OR 0.25 95% CI 0.13-0.50), whose last pregnancy was less than 19 years (OR = 0.32 95% CI, 0.17-0.63) and with age at first full-term pregnancy (FFTP) older than 21 years (OR = 0.33 95% CI, 0.17-0.63), the reduction in BC risk was greater than when evaluating the variables individually. The risk of ER+ BC was inversely related to parity (OR = 0.78 95% CI, 0.63-0.95), having breastfed (OR = 0.47 95% CI, 0.26-0.87) and the use of oral contraceptives (OR = 0.56 95% CI, 0.32 -0.99). Although an increased risk for ER- and TN tumors was observed with the use of oral contraceptives, this was not significant probably due to insufficient sample size. Conclusions: As has been observed in other studies in this Colombian population, reproductive factors and the use of hormonal contraceptives were differentially associated with the BC risk. Our data can be useful to identify risk groups to design prevention measures tailored to the specific population. Conflict of interest: None of the authors declare that they have a conflict of interest. Table 1.Odds ratios and 95% confidence intervals of association between breast cancer and reproductive factors and combination of reproductive variables.FactorNMatchedap-valueaMultivariatebp-valuebCases/ControlsOR (95% CI)cOR (95% CI)cEducation levelPrimary school or less119/1371.001.00High School140/1411.34 (0.88-2.03)0.167750.90 (0.60-1.34)0.5901Above High School57/382.27 (1.24-4.04)0.007831.29 (0.74-2.26)0.3710Health Insurance (Contributive)241/1942.24(1.49, 3.38)<0.00011.72 (1.14-2.59)0.0104History of benign breast disease (Yes)158/2314.5 (7.64-27.52)<0.000112.18 (7.5-19.9)<0.0001Pregnancy ever (Yes)263/2960.34 (0.20-0.59)0.00010.48 (0.26-0.90)0.0226Parityd (per child)0.78 (0.69-0.87)<0.00010.89 (0.79-0.99)0.0414Nulliparous61/211.001.001 child68/610.43 (0.24-0.79)0.005970.44 (0.22-0.88)0.019932 children83/970.29 (0.16-0.53)<0.00010.41 (0.21-0.80)0.00849≥3 children104/1370.23 (0.12-0.42)<0.00010.34 (0.17-0.65)0.00119Breastfeeding ever (Yes)75/1200.47 (0.32-0.68)<0.00010.50 (0.34-0.75)0.00089Duration of breastfeeding (months)d0.97 (0.95-0.99)0.01380.97 (0.95-0.99)0.01263Never114/701.001.00≤12155/1610.86 (0.46-1.61)0.64200.66 (0.35-1.19)0.17976>1247/850.41 (0.20-0.84)0.01470.35 (0.18-0.71)0.00328Combination: Parity and breast feedingNulliparous61/211.001.00≥1 children, never breastfeed181/1750.37 (0.21-0.63)0.00020.47 (0.25-0.87)0.01711 child, ever breastfeed13/200.25 (0.11-0.60)0.00190.32 (0.12-0.86)0.0238≥ 2 children, ever breastfeed61/1000.19 (0.10-0.35)<0.00010.25 (0.13-0.50)<0.0001Combination: Parity and time since last birthNulliparous61/211.001.001 child, < 19 years since last birth49/410.46 (0.27-0.90)0.02250.47 (0.22-0.99)0.04611 child, ≥ 19 years since last birth19/200.31 (0.13-0.78)0.01300.36 (0.14-0.94)0.0376≥ 2 children, < 19 years since last birth79/1060.25 (0.13-0.47)<0.00010.32 (0.17-0.63)0.0009≥ 2 children, ≥ 19 years since last birth108/270.27 (0.14-0.52)<0.00010.42 (0.22-0.81)0.0097Combination: Parity and age at FFTPeNulliparous61/211.001.001 Child, age at FFTP <2115/140.48 (020-1.14)0.094440.33 (0.12-0.92)0.03471 child, age at FFTP >2152/470.40 (0.21-0.76)0.005460.47 (0.23-0.97)0.0413>2 Children, age at FFTP <21100/1160.28 (0.15-0.50)<0.00010.43 (0.22-0.82)0.0110>2Children, age at FFTP >2181/1170.25 (0.14-0.45)<0.00010.33 (0.17-0.63)0.0008aConditional logistic regression matched on age, Location, bConditional logistic regression matched on age, Location and adjusted for education level, history of benign breast disease and Health Insurance. cORs are given for both continuous (unit of change) and catrgorical variables. dParous women only; FFTP: first full-term pregnancy, eFFTP: First full-term pregnancy, median age = 21 Table 2.Association of breast cancer and reproductive factors by hormone receptor statusReproductive variablesER+ vs Control (n = 208)ER- vs Control (n = 94)TN vs Control (n = 56)ORa (95% CI)p-valuebORa (95% CI)p-valuebORa (95% CI)p-valuebPregnancy ever0.29(0.11-0.80)0.020.55 (0.16-1.94)0.360.64 (0.2-2.8)0.55Parityd0.78(0.63-0.95)0.010.86 (0.66-1.1)0.240.94 (0.66-1.34)0.72Breastfeeding everc0.47(0.26-0.87)0.010.59 (0.26-1.4)0.220.62 (0.2-1.93)0.41Hormonal contraceptive use0.54(0.29-1.01)0.051.37 (0.5-3.5)0.511.61 (0.46-5.67)0.46Pills0.56(0.32-0.99)0.041.25 (0.51-3.1)0.621.81 (0.53-6.17)0.34aORs are given for continuous variables (unit change). bConditional logistic regression matched on age, Location, and adjusted for education level, history of benign breast disease and Health Insurance. cParous women only. dParity: number of childbirths Citation Format: Juanvilson A Zambrano, SM, Maria Del Mar Idarraga, SM, Samuel Agudelo, BSc, William Arias, MSc, Yina Zambrano, BsC, Karen Cardenas, MSc, Daniel Jurado, M. Sc, Maria C Agudelo, PhD(c), Emanuel Vasco, MD, Alison Mondul, PhD, Laura Rozek, PhD, Andres Ossa, MD, Mauricio Borrero, MD, Fernando Herazo, MD, Edgar Navarro, MD, Roberto Jaramillo, MD, Isabelle Romieu, PhD, Sabina Rinaldi, PhD and Gloria I Sánchez, PhD. Reproductive factors and molecular subtypes of breast cancer in premenopausal and postmenopausal women from 3 Colombian cities: PRECAMA & POSCAMA studies [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 P3-12-28.