| Breast cancer is a highly heterogeneous disease from clinical, genetic and phenotypic points of view. It brought many difficulties to the diagnosis and treatment of breast cancer. One of those is, to many of the same type of clinical or pathological characters of patients, the clinical outcome is quite defferent from using the same or similar treatment. Since the beginning of this century, Gene expression analysis has identified several breast cancer subtypes, including luminal A, luminal B, triple negative and HER2- subtypes. According to the conventional histological type, molecular subtype could provide more reliable and accurate prognostic and predictive evidence and could be stronge guidance to individual treatment of breast cacer patients. While molecular and genetic testing is very expensive and not yet widely available for clinical prognostic and predictive, The IHC classification provides both therapeutic and prognostic information with inexpensive and readily available. For the current study a Her2 neu result of 2+ is considered a negative result unless verified by fluorescent in-situ hybridization (FISH). In recent years, the molecular subtypes of breast cancer clinical features and prognostic factors of population-based study of are rare, espiacialy for Asian and Chinese wemen. By some objective conditions, breast cancer in China, some clinical features and epidemiological characteristics are very different from those of west world country. This study evaluates clinical and pathologic features and survival of the four molecular subtypes in patients from Hospital of Jilin University with IHC and FISH makers.Materials and Methods:A retrospective analysis of all women diagnosed with breast cancer from 2000 to 2007, who had assessable data for ER, PR, and HER2 status. Molecular subtype classification was done based on IHC surrogates for ER, PR, and HER2 status obtained from Department of Breast Surgery tumor registry for each patient.63 patients with HER2 express "++" were verified by FISH test. The molecular subtypes were defined as:Luminal A (ER/PR+, HER2-), Luminal B (ER/PR+, HER2+), triple negative (ER-, PR-, Her2-) and HER2+(ER+, PR+, HER2+). The patients were aged 25to 84years, with a mean age of 49.5±10.7 years. Premenopause were 551 (46.3%) and postmenopause 640 (53.7%). Follow-up data were obtained to Jan 10th,2011, Follow-up duration was calculated from the date of surgery to the date of last follow-up, or death. The median follow-up, based on censoring distribution, was 64±29.5 months.969 (81.4%) patients were alive,222 (18.6%) patients were died.Result:Final analysis included 1191 breast cancer subjects,835 (70.1%) were the luminal A subtype,124 (10.4%) were luminal B subtype,148 (12.4%) were triple negative subtype, and 84 (7.1%) were HER2+ subtype. There were no significantly diffences by age (P=0.38), location (P=0.63), axillary lymph node status at time of diagnosis (P=0.84), histology group (P=0.60), patients'district (P=0.16), and radiotherapy condition (P=0.13). The proportion of patients with Luminal A subtype and Luminal B subtype seemed more postmenopause than patients with triple negative and HER2+(P=0.004). According to others subtypes, the proportion of patients with Luminal A subtype were more likely to have smaller tumor size (P=0.011), earlier AJCC stage (P=0.007) and better histologic differentiated (P<0.001). Compared with the patients with luminal A subtype, patients with triple negative subtype were more like premenopause women (OR,2.7; 95% CI,1.5-4.9), patients with Luminal B (OR,1.9; 95%CI,1.2-3.2) and triple negative (OR,2.41; 95% CI,1.5-3.7) subtype were more "later stage breast cancer" than patients with Luminal A. Patients with Luminal B subtype were 2.2 times more likely to be poorly histology stage (P=0.004; 95%CI,1.3-4.5) than those of Luminal A, patients with triple negative subtype were 1.8 times(P=0.04;95%CI,0.9-3.1). A total of 190(15.9%) cases with LR/DM, of these subjects 59 (31%) had local recurrence and the remaining had distance metastasis were:12 cases for multi-organ metastasis(6.3%),51 in bone (26.8%),25 with liver (13.2%),22 with lung (11.6%),11 with brain (5.8%) and mediastinal lymph nodesor other sites were 10 (5.2%).Overall survival rate for all cases was 81.4% and 3-year,5-year and 10-year overall survival rate were 88.9%,82.4% and 63.4%.Luminal A subtype has the highest overall survival (86.3%),3-year survival was (92.2%),5-year survival was (87.6%) and 10-year survival was (68.6%). Second place was HER2+ subtype with 77.4%(overall),86.3% (3-yea),82.9%(5-year),55.6%(10-year). Survival status with Luminal B subtypes was 72.6% for overall,84.8% for 3-year,73.2% for 5-year and 53.1% for 10-year. The triple negative subtype has the lowest overall survival (62.8%),3-year survival was (75.3%),5-year survival was (61.8%) and 10-year survival was (48.2%). There were significantly differences in survival status among four breast cancer subtypes (P<0.001). We analysised the survival status for the different levels of age type,tumor size, AJCC stage status, lymph node status, histologic stage and chemotherapy status with four breast cancer subtypes, There were significantly difference in survival status among four breast cancer subtypes (P<0.05). The disease free survival status with four subtypes was similar with that of overall survival rate.Compare with the Luminal A subtype, the triple negative sutype has the lowest overall survival (RR,2.12; 95% CI,1.41-3.19) and disease free survival(RR,2.29; 95% CI, 1.57-3.38). By Cox multivariate analysis, breast cancer subtype (RR,1.35;95% CI 1.21-1.52), AJCC stage (RR,1.91; 95%CI 1.34-2.72), status of axillary lymph node (RR,1.62; 95%CI 1.15-1.86), histologic stage (RR,3.19; 95%CI 2.39-4.251), adjuvant chemotherapy (RR.1.79; 95%CI 1.55-2.09) and LR/DM status (RR,7.72; 95%CI 3.81-17.62)were maintained its significance as risk foctors of overall survival and disease free survival.Conclusion:The Luminal A subtype has the highest overall survival, disease free survival and clinical outcome, triple negative subtype has the lowest clinical outcome but the patients with this kind of subtype could be benefited much more from adjuvant chemotherapy than the other subtypes. There were significantly differences in survival status among four breast cancer subtypes for the different level of age type, tumor size, AJCC stage status, lymph node status, histologic stage and chemotherapy status. The risk foctors of overall survival and disease free survival were breast cancer subtype, AJCC stage, status of axillary lymph node, histologic stage, adjuvant chemotherapy and LR/DM status.According to the similar reports from west world countries, further confirmatory studies are necessary to refine IHC classification. We support IHC classification as a clinical tool as ER/PR and HER2 testing is widely available at a reasonable cost, is a clinically-used, therapeutically informative classification of breast cancer based on immunophenotype and biologic phenotypes, and is prognostic as well as somewhat predictive. For the current study a HER2 result of "++" is verified by FISH test for accurate result. |
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