Lani

Breast cancer classification has evolved from descriptions of the appearance of the tumor on a slide (inflammatory, ductal, etc) to being based on which general group of similarly delineated genes are detected on multigene arrays. The subtypes of infiltrating ductal carcinoma are called Luminal A, Luminal B, Normal, Her2neu and Basal. The last two are estrogen receptor negative. THE BIG QUESTION IS WHERE DO THE her2neu positive, hormonal receptor positive tumors fit in?? This question is still unanswered. Most researchers feel they do not fit into any of the three hormonal positive subgroups -- perhaps they need their own subtype. Stefanie Jeffreys of Stanford University gave a talk in Molde, Norway in June (only the abstract available so far) describing several different subsets of her2+hormonal+ tumors by results of multigene array each with a different natural history and prognosis(which implies they may need different treatments).
I am including two abstracts, the first from a paper by Charles Perou and Laszlo Pusztai, who have written a lot on the topic of the Luminal vs Normal vs Her2 vs Basal groups, and discusses how the different groups vary in their response to chemotherapy, and the latter from the Dutch group who described the 70 gene signature of breast cancer (apparently much better than OncoDx test to predict prognosis of a particular breast cancer tumor, but not yet clinically available) showing that the subtype by multigene array does not differ between primary and metastasis.


PURPOSE: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. EXPERIMENTAL DESIGN: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. RESULTS: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. CONCLUSIONS: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.
Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer.

Weigelt B, Hu Z, He X, Livasy C, Carey LA, Ewend MG, Glas AM, Perou CM, Van't Veer LJ.

Divisions of Experimental Therapy and Diagnostic Oncology, The Netherlands Cancer Institute, The Netherlands .

Microarray analysis has been shown to improve risk stratification of breast cancer. Breast tumors analyzed by hierarchical clustering of expression patterns of "intrinsic" genes have been reported to subdivide into at least four molecular subtypes that are associated with distinct patient outcomes. Using a supervised method, a 70-gene expression profile has been identified that predicts the later appearance or absence of clinical metastasis in young breast cancer patients. Here, we show that distant metastases display both the same molecular breast cancer subtype as well as the 70-gene prognosis signature as their primary tumors. Our results suggest that the capacity to metastasize is an inherent feature of most breast cancers. Furthermore, our data imply that poor prognosis breast carcinomas classified either by the intrinsic gene set or the 70 prognosis genes represent distinct disease entities that seem sustained throughout the metastatic process.

As always, you ask one question it leads to several more...

Hope this helped anyway