Abstract PO4-02-14: Parity and age first full term pregnancy affects the odds of different breast cancer subtypes defined by estrogen receptor and human epidermal growth factor receptor-2
Authors: Liu Zhao , Zhang Jiumeng , Van Baelen Karen , Vangoitsenhoven Maja , Wildiers Hans , Soubry Adelheid , Neven Patrick 
Published: May 2024

Background:

A rising trend in the incidence of estrogen receptor (ER)-positive subtype over time is observed in several high-income countries, while the incidence of ER-negative subtype is decreasing in some areas. It has been found that decreased parity and late age at 1st full-term pregnancy (FTP1) can increase the risk of breast cancer (BC). This study aims at investigating the association between two reproductive factors, parity and FTP1, and the odds of BC subtypes in premenopausal and postmenopausal patients.

Patients and method:

This study included patients diagnosed with early-stage BC after the age of 34, who were treated in UZ Leuven between January 2000 and November 2020. The patients were classified into four subtypes defined by ER and human epidermal growth factor receptor-2 (HER2). ER positivity was defined as &gt;1% of cells staining positive while HER2 positivity was based on fluorescence in situ hybridization (FISH) testing of samples with immunohistochemistry score of 2+ or 3+. Baseline-category logit models with subtype as the response (ER+/HER2- as the baseline) and adjusted for age at diagnosis and BMI, were performed for premenopausal and postmenopausal patients separately. First, we exclude nulliparous patients. Parity (1-2 or ≥3) and FTP1 (continuous) were included in the models as the covariates of interest in the first model. To evaluate the effects of reproductive patterns compared to nulliparity, a new variable reproductive pattern was created by taking intersection of parity groups and FTP1 groups (&lt; 27, ≥27). Reproductive pattern was set as the covariate of interest in the second model.

Result:

After imputing the missing values, we included 9606 patients in the study. 8125 of them were parous. In parous patients, high FTP1 was associated with low odds of ER-/HER2- BC relative to ER+/HER2- BC for both premenopausal and postmenopausal patients (table 1). In postmenopausal patients, low parity was associated with low odds of ER-/HER2- BC and high odds of ER+/HER2+ BC relative to ER+/HER2- BC. There was no evidence that parity affects the odds of subtypes in premenopausal patients.

When investigating the effect of different reproductive patterns compared to nulliparity on the odds of subtypes, there was no evidence that reproductive patterns will affect the odds of subtypes in premenopausal patients. Postmenopausal patients who had FTP1 before 27 years old and had at least three children tended to have higher odds of ER-/HER2- BC relative to ER+/HER2- BC compared to nulliparous patients.

Conclusion:

In parous patients, increased FTP1 was associated with reduced odds of ER-/HER2- relative to ER+/HER2- BC. In postmenopausal patients, patients with at least three children tended to have low odds of ER-/HER2- BC and high odds of ER+/HER2+ BC relative to ER+/HER2- BC. When compared to nulliparity, the combination of having at least three children and having the first child before 27 years old increased the odds of ER-/HER2- BC relative to ER+/HER2- BC in postmenopausal patients.

Table 1 Effect of FTP1, parity on subtype odds Menopause Subtype Effect Odds ratio (95%CI) p-value pre ER-/HER2- FTP1 (continuous) 0.960 (0.935, 0.985) 0.0021 post 0.969 (0.948, 0.990) 0.0047 pre ER-/HER2+ 0.992 (0.952, 1.034) 0.7166 post 1.005 (0.977, 1.034) 0.7081 pre ER+/HER2+ 0.976 (0.949, 1.004) 0.0962 post 1.015 (0.992, 1.039) 0.1969 pre ER-/HER2- Parity 1-2 vs ≥3 1.194 (0.899, 1.585) 0.2200 post 0.784 (0.648, 0.949) 0.0124 pre ER-/HER2+ 1.152 (0.723, 1.834) 0.5521 post 0.896 (0.684, 1.173) 0.4228 pre ER+/HER2+ 1.080 (0.795, 1.469) 0.6220 post 1.300 (1.022, 1.654) 0.0329 The baseline category is ER+/HER2- subtype Effect of age at first full-term pregnancy and parity on subtype odds

Citation Format: Zhao Liu, Jiumeng Zhang, Karen Van Baelen, Maja Vangoitsenhoven, Hans Wildiers, Adelheid Soubry, Patrick Neven. Parity and age first full term pregnancy affects the odds of different 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 PO4-02-14.