An Attempt Towards A Novel Classification Of Triple Negative Breast Cancer Using Immunohistochemical Markers

Objective Intense efforts have been made to gain a better understanding ofheterogeneity of triple-negative breast cancers from molecular to genomic levels. Inthis study, we aimed to bridge gene expression subtypes of triple-negative breastcancers to a clinically accessible classification by virtue of immunohistochemicalmarkers.Methods There were total of2407breast cancer patients received surgeries atChina-Japan Union Hospital of Jilin University between January2006andNovember2014. Among these cases,1646cases that had informativeimmunohistochemical results were included in the study. Out of the1646patients,154were triple negative breast cancer. Using immunohistochemical analysis, wecategorized154triple-negative breast cancers into three main subtypes. Differencesin the frequencies of basic characteristics and clinicopathological parametersbetween breast cancer subtypes were examined using chi-square tests. Relapse-freesurvival (RFS) was defined as the time from the date of diagnosis to the date ofrelapse of breast cancer, including locoregional recurrence and/or distant metastasis.Breast cancer-specific survival (BCSS) was defined as the date of a woman’sdiagnosis of breast cancer until her date of death. Survival times were censored if theprimary or underlying cause of death was not breast cancer, or if the patient was stillalive on December30,2014(the date when the outcome data were collected).Survival curves were obtained using Kaplan-Meier method and differences insurvival among the breast cancer subtypes were assessed by the log-rank test.Prognostic analyses used the Cox regression method. Univariate analyses testedclassical clinicopathological features: Age (＞50vs≤50), pathological tumor size(pT2-3vs pT1), lymph node status (positive vs negative), histological grade (2,3vs 1), necrosis(marked vs minimal or absent), Ki67(＞30%vs≤30%), adjuvantchemotherapy (done vs not done). The findings were analyzed using the statisticalsoftware SPSS for Windows, Version18. All statistical tests were two-sided at the5%level of significance.Results We defined three main groups in154triple-negative cases, basal-likegroup expressed CK5/6and/or CK14(86cases), AR(+) group showed positivity forandrogen receptor (18cases), and the other group exhibited CD44+CD24-/lowphenotype (42cases). There were3overlapped cases between basal-like subgroupand CD44+CD24-/lowphenotype subgroup, and11unclassified cases. In this newimmunohistochemical classification of triple-negative breast cancers, multiplecomparisons showed that as for histological grade and tumor necrosis, statisticaldifferences existed between any two of the three groups, whereas at age and tumorsize, differences only lied between AR (+) and Basal-like group. Compared with AR(+)group, both Basal-like and CD44+CD24-/lowgroups had higher Ki67scores.Survival analyses detected differences between two groups: AR (+) and Basal-like(Log-rank P=0.044for Breast cancer-specific survival), whereas within the caseswithout chemotherapy, remarkable distinction was among three groups (Log-rankP=0.008for Breast cancer-specific survival). Significant protective effect ofchemotherapy was observed only in Basal-like group (HR0.18,95%CI0.09-0.65,P<0.001). Basal-like group showed undistinguishable clinicopathologicalcharacteristics versus CK5/6and/or CK14positive tumors that were nottriple-negative. Same with CD44+CD24-/lowgroup versus non–triple negative tumorsthat had CD44+CD24-/lowphenotype; and AR (+) group versus luminal subtype.Conclusions Our study is a preliminary attempt to bridge gene expressionsubtypes to a practical and clinically-accessible diagnostic test. We useimmunohistochemistry methodology to see how we can perhaps break down TNBCinto its components. We successfully distinguished three subtypes exhibiting diverseclinicopathological and prognostic characteristics with the minimum use ofimmunohistochemical markers.