WHY it is exceedingly important not to let hospitals throw away tumor specimens!!!!

[Lani]

the following is an exceedingly pertinent and helpful article by scientists at MIT who have examined specimens from patients treated with surgery and radiation therapy only (ie, no antihormonals, no chemotherapy)

The describe not only the usual subsets of breast cancer by molecular classification, ER+ luminal A and luminal B (which they describe subsets of) and basal (triple negative) but also define the her2 set differently.

It seems it does not consist of those her2+s which are ER-, leaving her2+ER+s in the limbo of being difficult to classify, but rather finds there are two main subsets of her2+ breast cancer, divided into those with two very different prognoses. What divides the groups it turns out is not ER status, but rather genes associated with lymphocytes (ie, those whose immune systems are better able to cope with and fight them, and those whose immune systems are not up to the job)

By microgene array they found genes for these lymphocytes greatly increased, but as not everyone has specimens amenable to making a microgene array, more importantly they found a difference which can be seen simply on a microscopic slide without high tech means--the presence of lymphocytes in the tumor specimen!

Thus, if this pans out, and those associated with it are no slouches, having a pathologist go back and look at several sections/slides of the original tumor specimen for lymphocytic infiltration could serve perhaps better than an OncoDXtest --which does not divide her2+ER+ tumors into those with different behaviors, just putting them all in a high risk category as two of the 15 main genes examined (6 are "housekeeping genes" are located on the her2 amplicon, her2 and GRB7), thus scewing her2+ tumors de facto towards high recurrence scores--to predict prognosis and perhaps to guide treatment (more intensive for those with worse prognosis). And for those who are ER- , oncoDx was never validated in your tumor type anyway!

Here is the abstract--I recommend the full article:

: Cancer Res. 2007 Nov 15;67(22):10669-76. Links
High expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence rates.

Alexe G, Dalgin GS, Scanfeld D, Tamayo P, Mesirov JP, DeLisi C, Harris L, Barnard N, Martel M, Levine AJ, Ganesan S, Bhanot G.
The Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
Gene expression analysis has identified biologically relevant subclasses of breast cancer. However, most classification schemes do not robustly cluster all HER2+ breast cancers, in part due to limitations and bias of clustering techniques used. In this article, we propose an alternative approach that first separates the HER2+ tumors using a gene amplification signal for Her2/neu amplicon genes and then applies consensus ensemble clustering separately to the HER2+ and HER2- clusters to look for further substructure. We applied this procedure to a microarray data set of 286 early-stage breast cancers treated only with surgery and radiation and identified two basal and four luminal subtypes in the HER2- tumors, as well as two novel and robust HER2+ subtypes. HER2+ subtypes had median distant metastasis-free survival of 99 months [95% confidence interval (95% CI), 83-118 months] and 33 months (95% CI, 11-54 months), respectively, and recurrence rates of 11% and 58%, respectively. The low recurrence subtype had a strong relative overexpression of lymphocyte-associated genes and was also associated with a prominent lymphocytic infiltration on histologic analysis. These data suggest that early-stage HER2+ cancers associated with lymphocytic infiltration are a biologically distinct subtype with an improved natural history.
PMID: 18006808 [PubMed - indexed for MEDLINE]