a new kind of her2neu +er= breast cancer type--baso-luminal!

[Lani]

with an even shorter disease-free and overall survival than triple-negative!

1: Clin Cancer Res. 2006 Jul 15;12(14):4185-91. Links
Basoluminal carcinoma: a new biologically and prognostically distinct entity between Basal and luminal breast cancer.

Laakso M,
Tanner M,
Nilsson J,
Wiklund T,
Erikstein B,
Kellokumpu-Lehtinen P,
Malmstrom P,
Wilking N,
Bergh J,
Isola J.
Authors' Affiliations: Department of Pathology, Seinajoki Central Hospital, Seinajoki, Finland.
PURPOSE: Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that is typically hormone receptor negative and shows a distinct gene expression profile. Based on variable basal cytokeratin immunostaining patterns, we hypothesized that the "basal phenotype" tumor group may comprise more than one biological entity. EXPERIMENTAL DESIGN: Basal cytokeratins 5 and 14 (CK5/14) were stained by immunohistochemistry and the percentage of positive cells was defined by image analysis. The results thus obtained were compared with clinicopathologic characteristics and relapse-free survival. RESULTS: Of the 506 breast tumors, 53 (10.5%) showed immunoreactivity for CK5/14. Basal cytokeratin expression showed up as two microscopically distinguishable subtypes, i.e., a uniformly positive type ("basal") and a partially positive type ("basoluminal") often displaying a checkerboard-type intratumoral heterogeneity. These subgroups could also be separated with a third basal cytokeratin (CK17, P < 0.0001). Both basal and basoluminal subtypes were hormone receptor negative and of high grade, but differed with respect to the Ki-67 labeling index (P = 0.0014), vimentin (P = 0.005), and c-kit (P = 0.02), which were more frequently expressed in basal than in basoluminal tumors. In contrast, the amplification of HER-2 was found almost exclusively in the basoluminal subgroup (P = 0.009). Compared with the basal tumors, basoluminal tumors associated with significantly shorter relapse-free survival (P = 0.01), which was not explained by their more frequent HER-2 amplification. CONCLUSIONS: We conclude that the intratumoral heterogeneity in basal cytokeratin expression can be used to define two distinct breast cancer subtypes, basal and basoluminal, with distinctive features related to proliferation activity, oncogene and biomarker status, and patient survival.
PMID: 16857790 [PubMed - in process]

The more they look, the more subtypes they find. Hopefully they will delineate markers for targetted therapies of each type.

[Christine MH-UK]

Unfortunately, they are a rather different four:

From Harold J. Burstein, The Distinctive Nature of Her2-Positive Breast Cancers:

Hormone receptors, HER2, and increasingly, genomic profiles distinguish at least four major classes of breast cancer: HER2-positive tumors; HER2-negative, hormonereceptor–positive tumors, which can be divided into two classes, favorable and unfavorable, on the basis of genomic and pathobiologic features; and basal-like tumors that express neither HER2 nor hormone receptors.

I am not sure what the fifth type would be, although I remember some postings suggesting that slightly her2 cancers were perhaps another subtype.

Another four possibilities come from the "Defeat Cancer" project website:
http://www.worldcommunitygrid.org/pr...HdcResearch.do

Subclasses of Cancer
"Within broad categories of cancer – such as breast, liver, or lung, there are subclasses of cancer. Breast cancer, for example, is a broad category that consists of a number of subclasses (including intraductal, lobular, medullary, colloid), which exhibit variation in terms of aggressiveness and which require specific treatments and drug regimens. So rather than looking at breast cancer as a single disease, doctors must treat it as a multitude of diseases, each requiring targeted therapies."

I suspect that the five types are just a start anyway. Part of the purpose of the Help Defeat Cancer project is to figure out the genetic commonalities that distinguish different cancer subtypes and what existing treatments have been most effective (similar to the recent finding that FEC is much better than CMF for her2positive breast cancer). The project is relying on donated computer time to analyze hundreds of thousands of breast cancer and head and neck cancer samples over the next three months and the hope is that this will enable the faster development of better targeted therapies.

The only disappointing thing about the project is that it requires 750MB of RAM to participate in the cancer project, although there are also less memory intensive biomedical projects running on the World Community Grid involving folding proteins relevant to disease and screening potential AIDS drugs. All of the knowledge developed remains in the public domain.

[Christine MH-UK]

I meant to post that as the reply to something in the Main her2 forum.