Is It Possible to Optimize Neoadjuvant Chemotherapy Response by EGFR and CK5/6 Expression Status in Breast Cancer Patients?

We examined the expression of ER, HER2, Ki-67, CK5/6 and EGFR by immunohistochemistry in breast tumors from patients who underwent neoadjuvant chemotherapy (NAC).

88 breast cancer patients who received NAC and surgery at our institute between January 2008 and March 2013 were enrolled. Staining results of ER, HER2, CK5/6, EGFR and Ki-67 were quantitated by automated immunostaining analysis. Patients were stratified into four grades (0, 1+, 2+, 3+) by ER status. Ki-67 index and nuclear grade were compared between a CK5/6- and/or EGFR-positive cohort and a CK5/6- and EGFR-negative cohort for each ER status grade. We also assessed response to chemotherapy according to ER, CK5/6 and EGFR status in a HER2 negative cohort.

The percentage of CK5/6- and/or EGFR-positive tumors decreased inversely with increasing degree of ER expression. In the ER0 cohort, the CK5/6- and/or EGFRpositive cohort had a higher Ki-67 index (p=.0875) and nuclear Grade 3 (p=.0036) than a CK5/6- and EGFR-negative cohort. A CK5/6- and/or EGFR-positive cohort showed a higher tumor reduction rate of clinical effect than a CK5/6- and EGFR-negative cohort (mean=57.3% and 24.6%, respectively, p=.2053) in an ER0 cohort. In the CK5/6- and/or EGFR-positive cohort, two of nine showed Grade 3 and seven showed Grade 2a or more of pathological effect. In cohorts of ER2+ or ER3+, there was no correlation between CK5/6 and EGFR status and response to chemotherapy.

In triple negative breast cancer (TNBC), CK5/6 and EGFR expression can be utilized as markers that differentiate the effect of NAC.

Keywords: CK5/6, EGFR, Estrogen receptor, Ki-67, Triple negative breast cancer.