Abstract

Abstract Background: The impact of reproductive factors on breast cancer has proven to be complex. The risk for estrogen receptor positive/HER2-negative (ER+/HER2-) breast cancer is estimated to be transiently augmented in the years after giving birth (up to 20 years) while later in life high parity and early first full-term pregnancy (1st FTP) seem to protect against ER+/HER2- breast cancer (BC). Invasive lobular carcinomas (ILC) represents the second most common histological subtype of BC and >90% are ER+/HER2-. In this study, we aimed at investigating whether parity and age at 1st FTP are associated with: 1) the prevalence of ER+/HER2- pure ILC (i.e., not mixed) in an ER+/HER2- BC cohort (overall and according to the age at breast cancer diagnosis), and, 2) standard clinical and pathological features of pure ILC. Patients and methods: We performed a single center retrospective study in UZ Leuven, Belgium of patients diagnosed with non-metastatic ER+/HER2- breast cancer between January 2000 and November 2020. Both patient and tumor characteristics were collected from clinical files. Firth’s logistic regression was performed to investigate the association of BC histology (pure ILC vs all other BC histological subtypes = control group) with parity (yes vs. no and nulliparous, 1 child, 2 children, >2 children) in univariable models and multivariable models adjusted for age group at diagnosis (< 30, 31-40, 41-50, 51-60, 61-70, >70), age at 1st FTP (continuous and per age group: < 21, 21-25, 26-30, >30), Interval between 1st FTP and diagnosis (continuous), year of birth and BMI. Analyses were done in the overall group as well as per age group at diagnosis. Similarly, regression analyses were performed in patients with ER+/HER2- ILC to assess the association of parity (yes vs. no and nulliparous, 1 child, 2 children, >2 children) with the following variables: age at diagnosis, BMI, histological grade, tumor size, nodal involvement and progesterone receptor positivity. Results: 7360 patients were included of which 1121 (15.2%) were diagnosed with pure ER+/HER2- ILC, the remaining 6239 (84.8%) patients were considered as the control group. Overall, in multivariable analyses, parity with >2 children was associated with a higher prevalence of pure ILC as compared to uniparous patients (odds ratio, OR 1.257, 95CI 1.039-1.521, p= 0.019). No significant association was seen for age at 1st FTP and interval 1st FTP – diagnosis. The subgroup analyses per age group are summarized in Table 1. Only for the age group 41-50, an increased age 1st FTP was associated with an increased prevalence of pure ILC. In patients with pure ER+/HER2- ILC, nulliparous women were less likely to have a progesterone receptor (PR)-positive tumor as compared to parous women (OR 0.477, 95CI 0.224-0.907, p= 0.022). No other significant associations were seen for clinicopathological features between nulliparous and parous women, and between uniparous and multiparous women in the overall cohort nor any age group. Conclusions: Within an ER+/HER2- breast cancer cohort, higher parity seems to be associated with a higher prevalence of pure ILC, which is especially seen in the patients diagnosed with breast cancer between the age of 51 and 60. Increased age at the 1st FTP only seems to increase the incidence of ILC in the age group 41-50. With the exception of nulliparous women having less PR positive tumors, parity does not seem to affect the clinicopathological features of ER+/HER2- pure ILC. Table 1: subgroup analyses per age group of association of histology (pure ILC vs control group) with parity, age 1st FTP and interval 1st FTP – diagnosis Citation Format: Karen Van Baelen, Ha-Linh Nguyen, François Richard, Maja Vangoitsenhoven, Giuseppe Floris, Hans Wildiers, Kevin Punie, Ann Smeets, Ines Nevelsteen, Frédéric Amant, Sileny Han, Thaïs Baert, Patrick Neven, Christine Desmedt. The impact of parity and age of first full term pregnancy on the prevalence of invasive lobular carcinoma in patients with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-35.

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