Abstract 5569: Ki67 is an independent prognostic marker in breast cancer even after accounting for molecular subtype
Authors: Abeer M. Mahmoud, Virgilia Macias, Umaima Al-alem, Jacob K. Kresovich, Galina Khramtsova, Andre Kajdacsy-Balla, Elizabeth L. Wiley, Garth H. Rauscher
Journal: Cancer Research (2014)

Abstract Ki67 labeling index (LI) has been demonstrated to be a prognostic marker in invasive breast cancer; a high Ki67 LI is associated with poorer survival among breast cancer patients. The goal of these analyses was to examine the extent to which Ki67 was associated with specific breast cancer subtypes, and whether it could serve as an additional prognostic marker above and beyond breast cancer subtype, in an ethnically diverse sample of 287 patients (86 Non-Hispanic White, 84 Hispanic and 116 African American). IHC analysis was performed on tissue microarrays constructed from invasive breast cancer samples obtained from the Breast Cancer Care in Chicago study (patients diagnosed between 2005-2008). Tissue samples were tested for the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR and CK5/6. From these results, breast cancers were classified as Luminal A (ER+/PR+/HER2-), Luminal B (ER+/PR+/HER2+), HER2 enriched (ER-/PR-/HER2+), and triple negative (TN) (ER-/PR-/HER2-). TN tumors were subclassified into basal like (BL) if they expressed either EGFR or CK5/6 or otherwise classified as unspecified (US) if negative for both EGFR and CK5/6. Ki67 LI was classified as low (&amp;lt;14%) or high (≥14%). We used multivariable logistic regression to examine associations between Ki67, breast cancer subtype, and histological grade, controlling for race/ethnicity and age at diagnosis in all models. In adjusted models, the proportion of tumors with a high Ki67 LI was much lower for luminal A (28%) than for luminal B, HER2, TN-US, and TN-BL subtypes (91,66, 77 and 89%, respectively, p&amp;lt;0.0001). The proportion of tumors that were high histologic grade was also much lower for luminal A (29%) than for luminal B, HER2, TN-US, and TN-BL subtypes (85, 86, 94 and 68%, respectively, p&amp;lt;0.0001). Before accounting for subtype, 68% of high Ki67 tumors were high grade, compared with only 26% of low Ki67 tumors (p&amp;lt;0.0001); after controlling for breast cancer subtype these percentages were 58% and 37%, respectively, p=0.001). In this multi-ethnic sample of breast cancer patients, we found that Ki67 was a significant independent predictor of more aggressive, higher grade disease, even after accounting for molecular subtype. Ki67 might serve as a useful additional marker for the classification of breast cancer into molecular subtypes. Citation Format: Abeer M. Mahmoud, Virgilia Macias, Umaima Al-alem, Jacob K. Kresovich, Galina Khramtsova, Andre Kajdacsy-Balla, Elizabeth L. Wiley, Garth H. Rauscher. Ki67 is an independent prognostic marker in breast cancer even after accounting for molecular subtype. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5569. doi:10.1158/1538-7445.AM2014-5569