Triple negative breast tumors in African-American and Hispanic/Latina women are high in CD44+, low in CD24+, and have loss of PTEN

Abstract

Background: African-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status.

Methods: A total of N=318 African-American and Hispanic/Latina women, with clinically-annotated information within the inclusion criteria were included. Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques. Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival (DFS).

Results: The triple-negative-breast-cancer (TNBC) receptor-subtype was more prevalent among premenopausal women, and the Hormonal Receptor (HR) positive subtype was most common overall. TNBC tumors were more likely to have loss of PTEN, express high Ki67, and have increased CD44+/CD24- expression. TNBC was also associated with higher plasma-IGF-I levels. HR-/HER2+ tumors showed high pAkt, decreased FOXO1, and high CD24+ expression. The loss of PTEN impacted DFS significantly in African Americans, but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors. The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS, but were not independent predictors for DFS. HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment.

Conclusions: TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles. Our study also shows for the first time that TNBC was significantly associated with PTEN loss, high Ki67 and the CD44+/CD24- phenotype. The loss of PTEN impacts DFS significantly in African Americans.

Figure 1. Expression pattern of CD44 and CD24 in breast cancer tissue.

Breast tissues were double-stained with antibodies specific for CD44 and CD24. CD44 was detected with Permanent Red and CD24 was detected using diaminobenzidene (DAB brown). The white arrow indicates CD44+ cells (a and b), the yellow arrow indicates CD24+ cells (a, c, d), and the red arrow indicates CD44+/CD24+ cells (c).

Figure 2. Disease Free Survival (DFS) and breast cancer subtypes.

Kaplan-Meier was used to compare the 5-year DFS among cancer subtypes in: (A) African-Americans; (B) Hispanic/Latinas. (C) low Ki67; (D) high Ki67; (E) CD44+/CD24- vs. CD44-/CD24-; (F) CD24+/CD44- vs. CD24-/CD44-; (G) PTEN in African-Americans; and (H) PTEN in Hispanic/ Latinas. Log-rank test was used to determine the significance between the curves.