Abstract A89: HER2-overexpressing tumors and time since last pregnancy
Authors: Cruz Giovanna I. , Bondy Melissa , Daneri-Navarro Adrian , Meza-Montenegro Maria Mercedes , Gutiérrez-Millan Luis Enrique , Martínez María Elena , Thompson-Carino Patricia 
Published: December 2010

Background: Risk of dying from breast cancer is higher among Hispanic women compared to non-Hispanic whites (NHW) despite lower overall incidence rates and a more favorable risk factor profile. Part of the observed disparity can be explained by aggressive tumor biology although unequal access to care is also a key factor. A recent pooled case-only study suggests Hispanic women are more likely to be diagnosed with HER2-positive tumors compared to NHWs. Given the high parity rates among Hispanics and recent interest in the differential effect of reproductive factors on breast tumor subtypes, we investigated the relative correlation between reproductive factors and tumor phenotype stratified on HER2 status.

Methods: A total of 459 women of Mexican origin from the case-only ELLA Binational Breast Cancer Study were classified into hormone receptor (HR) positive cases (estrogen or progesterone-receptor positive, HER2-negative) and HER2-overexpressing cases (HER2+, HR-). Women negative for all three markers (triple negative) were not considered in these analyses. Reproductive factors considered in the analysis include age at first full-term pregnancy, total number of full-term pregnancies, ever breastfeeding, breastfeeding after last pregnancy, and time since last pregnancy. Time to diagnosis since last pregnancy was classified as either ≤10 years or &gt;10 years. We conducted separate analyses for women diagnosed at ≤ 40 years (n=72) and at &gt;40 years of age (n=386). Differences were tested using a Pearson chi-square test or Student's t-test. We calculated case-case odds ratios (OR) and 95% confidence intervals (CI) using logistic regression to estimate the relative correlation between time since last pregnancy and HER2+ tumors in reference to HR+ tumors. Models included age at diagnosis, recruitment site, age at first pregnancy, number of pregnancies and breastfeeding.

Results: Out of 459 women, 338 (74%) were HR+ and 121 (26%) HER2+. No significant differences were observed in the proportion of HR+ tumors among women ≤ 40 and those &gt; 40 (79% vs. 73%, respectively; p=0.22). HER2+ cases were younger at diagnosis compared to HR+ cases (mean age 51.8 vs. 53.1, respectively; p= 0.30). HER2+ cases were more likely to be diagnosed after the age of 40 compared to HR+ cases (OR 4.37; 95% CI: 1.84,10.40) and were more likely to occur within the 10-year period following the last pregnancy (OR=3.99; 95% CI: 1.95,8.16). No difference was observed for age at first full-term pregnancy (OR 0.99; 95% CI: 0.95,1.03), number of full-term pregnancies (OR 0.95; 95% CI: 0.84,1.07) or ever breastfeeding (OR 0.98; 95% CI: 0.59,1.62). A significant interaction was observed between time since last pregnancy and age at diagnosis (p=0.03). Stratified results suggest the relationship between time since last pregnancy and tumor phenotype is stronger in the &gt;40 age group (OR 3.68; 95% CI: 1.60,8.44) compared to those ≤40 (OR 2.68; 95% CI: 0.19,37.16).

Conclusions: HER2+ tumors were more likely to be diagnosed in the 10-year period after the last pregnancy compared to HR+ tumors, independent of age. These findings suggest a relationship between HER2+ breast cancer and pregnancy history that differs from that with HR+ tumors, supporting the presence of etiologic heterogeneity in these subtypes.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A89.