On studying the expression of basal markers in different morphological tumor types, we found that tumors of special type were either absolutely negative or expressed these markers in a small proportion of cases. We found that invasive grade 3 carcinomas of no special type had a basal phenotype and were estrogen receptors negative. The same finding has been reported in a previous study (20).These findings are in keeping with two previous reports that reported a high prevalence of the basal phenotype in ductal carcinoma with extensive necrosis and their aggressive behavior (21). Overall, tumors expressing the basal phenotype were more often grade 3 tumors and estrogen receptors negative with poor outcome. A previous genetic study on grade 3 carcinoma of no special type with basal phenotype identified specific genetic alterations and the aggressive nature of that subset (22).

It has been reported previously that molecular subclassification of breast cancer was associated with efficacy of postoperative and preoperative chemotherapy (12,13,14,38). In our study, the group of patients who received standard-based adjuvant chemotherapy, DFS was found to be significantly shorter in the basal phenotype. Nearly 8% of the patients that were HER2 positive received trastuzumab therapy, and this fact could have influenced the good prognostic of HER2 phenotype in our series.

Despite differences in taxonomy, there is a consistent trend across all studies confirming the relatively poor prognosis of the triple-negative or basal-like breast cancer subgroup (27). The majorities of triple-negative breast cancer tumors overexpress the EGFR (16) and might be candidates for anti-EGFR and/or anti–vascular endothelial growth factor therapies (28). Tumors in women with BRCA1 germ-line mutations have similarities to basal-like breast cancers (29). In vitro chemosensitivity studies have found that human cells lacking BRCA1 may be sensitive to cisplatin and to other drugs that cause double-strand breaks in DNA (30). Thus, agents such as cisplatin or carboplatin may prove to be effective treatments for the basal like group.

Despite the complexity of expression of the markers used in the present study, we were able to identify four profiles: luminal, HER2, basal and null/no expression. This supports the finding of studies that have, similarly, reported cases of breast cancer with null/no expression markers (31,32,33).Two previous studies have reported cases of breast cancer which were negative for both the luminal and basal markers (33,34). Both studies used frozen section material in which immunoreactivity was optimally preserved. One could argue that cases having no demonstrable phenotype may be a consequence of loss of reaction due to differences in tissue handling. However, all cases in our study were handled in a similar way and optimally fixed in formalin.

In conclusion, we found that expression of basal phenotype was associated with poor prognostic in the context of randomized phase III trials. The high rates of distal recurrence and the low incident of local recurrence, suggest that these patients have a tendency to develop visceral metastases early in the course of their disease. Standard adjuvant chemotherapy seems to be less effective in these tumors and new therapeutic approaches are indicated. The majorities of triple-negative breast cancer tumors overexpress the EGFR (16) and might be candidates for anti-EGFR and/or anti–vascular endothelial growth factor therapies (28). In this respect, different clinical trials are now under way, like GEICAM/2006-03 clinical trial were neoadyuvant based carboplatin chemotherapy is used in basal phenotype. This trial and others will answer these questions in the near future.

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