Abstract PO4-02-13: Parity and age first full term pregnancy affects the age of breast cancer diagnosis in breast cancer subtypes defined by estrogen receptor and human epidermal growth factor receptor 2
Authors: Zhang Jiumeng , Liu Zhao , Van Baelen Karen , Vangoitsenhoven Maja , Wildiers Hans , Soubry Adelheid , Neven Patrick 
Published: May 2024

Abstract
Background: Reproductive factors like parity and age at first full term pregnancy (FTP1) are found to have an impact on the occurrence of breast cancer (BC) in many epidemiological studies. Importantly, since the 70s, an ongoing trend to postpone FTP1 and have less children is observed. Additionally, there is an increasing trend for breast cancer incidence in young women in the past several decades, which may match the changing exposures to reproductive factors over time. To our knowledge, few studies focus on the association between parity, FTP1 and the age of breast cancer diagnosis. In this study, we aimed at studying the association between age at breast cancer diagnosis and reproductive factors (parity and FTP1) in each of the four breast cancer subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).
Patients and method: We considered patients who were &gt;34 years old and were diagnosed and/or treated for early BC in University Hospitals Leuven between January 2000 and November 2020. Patient and tumor characteristics were extracted from the patient files. Missing values were filled in by multiple imputation. A linear mixed model with birth cohorts as random effects was built for premenopausal and postmenopausal patients separately to investigate the association between two reproductive factors (parity and age at first full term pregnancy) and age at diagnosis in each of four breast cancer subtypes defined by ER and HER2. ER positivity was defined as &gt;1% of cells staining positive and reflex fluorescence in situ hybridization (FISH) testing was performed for samples that immunohistochemically (IHC) stained for HER2 with IHC score of 2+ or 3+. Parous women are classified into low parity (1 or 2 children) and high parity (≥ 3 children) and FTP1 was divided into &lt; or ≥ 27 years of age. BMI was considered a possible confounder and was corrected for. We first excluded nulliparous people and compared the mean ages at diagnosis in different parity groups and FTP1 groups separately. We created new variable reproductive patterns by taking intersection of parity categories and FTP1 categories. Then the mean ages at diagnosis in parous groups could be compared with the mean age at diagnosis in nulliparous patients. Step down Bonferroni procedure is applied to correct for multiple comparisons.
Result: 3039 premenopausal patients and 6569 postmenopausal patients at breast cancer diagnosis were included in the study. Patients with early age at FTP1 have older age at diagnosis in case of ER+HER2+ BC in both premenopausal and postmenopausal group as compared to patients with late FTP1 (Table 1). For premenopausal patients with ER-HER2+, early age at FTP1 was associated with older age at diagnosis in comparison to late age at FTP1. Premenopausal patients with ER+HER2- BC that had low parity and late FTP1 were diagnosed 0.66 years later than nulliparous patients (p= 0,01).
Conclusion: In both premenopausal and postmenopausal parous patients with early FTP1, an older age at diagnosis was observed in HER2+ cases only. When compared to nulliparous patients, the combination of low parity and late FTP1 was associated with older age at diagnosis for premenopausal patients with ER+ HER2- BC.

Table 1 Differences in mean age at diagnosis between FTP1 groups in parous patients Menopause Subtype Comparison Estimate (difference in mean age at diagnosis) p-value pre ER+HER2+ &lt;27 vs &gt;=27 1,2030 0,0045 ER+HER2- &lt;27 vs &gt;=27 -0,0548 0,7468 ER-HER2+ &lt;27 vs &gt;=27 1,3519 0,0334 ER-HER2- &lt;27 vs &gt;=27 0,4023 0,3326 post ER+HER2+ &lt;27 vs &gt;=27 1,1764 0,0175 ER+HER2- &lt;27 vs &gt;=27 0,0743 0,7069 ER-HER2+ &lt;27 vs &gt;=27 -0,3750 0,6023 ER-HER2- &lt;27 vs &gt;=27 0,3862 0,3815
Citation Format: Jiumeng Zhang, Zhao Liu, Karen Van Baelen, Maja Vangoitsenhoven, Hans Wildiers, Adelheid Soubry, Patrick Neven. Parity and age first full term pregnancy affects the age of breast cancer diagnosis in breast cancer subtypes defined by estrogen receptor and human epidermal growth factor receptor 2 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-13.