Triple Negative Breast Cancers: Outcome Correlation with Immunohistochemical Expression of Basal Markers
PH Tan, A Thike, PY Cheok. Singapore General Hospital, Singapore, Singapore
Background: Triple negative (TN) breast cancers are defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and c-erbB2 expression. Oncologic management options for this group of aggressive tumors are limited. Our data on 653 TN cancers disclosed 84% to be basal-like based on an immunohistochemical tripanel of CK14, EGFR and 34βE12. In this study, we evaluate their disease free and overall survivals (DFS, OS) in correlation with immunohistochemical expression of basal markers (CK5/6, CK14, CK17, 34βE12), SMA, p63, CD117 and EGFR.
Design: The study cohort comprised 653 TN breast cancers previously interrogated using antibodies to CK5/6, CK14, CK17, 34βE12, p63, CD117 and EGFR applied to sections cut from tissue microarray (TMA) blocks, using the streptavidin-biotin method. Follow-up was obtained from casenotes. DFS and OS were defined as time from diagnosis to recurrence or death respectively, and correlated with protein immunohistochemical expression. A p value <0.05 defined statistical significance.
Results: Median age was 52 years. Majority (82%) were Chinese, 8% Malay, 5% Indian, and 5% of other ethnic origins. Tumor size ranged from 0.9 to 20 cm (mean 2.9 cm, median 2.5 cm). Infiltrative ductal carcinoma was the commonest subtype (92%). Histologic grade 3 tumors predominated (77%). Node positivity occurred in 40%. CK5/6, CK14, CK17, 34βE12, SMA, CD117, p63 and EGFR were expressed in 6%, 48%, 50%, 70%, 25%, 45%, 22% and 30% of TN breast cancers respectively. Follow-up ranged from 1 to 185 months (mean 84, median 88 months). Recurrences occurred in 20% and deaths in 24% of women. Recurrences constituted local disease recrudescence (20%), distant metastases (49%), and both (6%), while contralateral breast cancer occurred in 25%. Both DFS and OS were statistically associated with CK5/6, CK17, 34βE12, p63, CD117 protein reactivity in an adverse manner, while SMA appeared to implicate a more favorable prognosis.
Conclusions: TN breast cancers in our study were usually high grade T2 tumors, with basal-like phenotype in up to 84%. Protein expression of CK5/6, CK17, 34βE12, p63 and CD117 is accompanied by more frequent recurrences and deaths, indicating that basal-like features as reflected by these markers are prognostic, and may support a need for their routine evaluation in TN cases. The presence of SMA, a marker of myoepithelial differentiation, in implicating a better OS, and the possibility of CD117 as a therapeutic target, require further study.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 47, Tuesday Morning