and FINALLY a reexamination of prior studies taking into account different subtypes

[Lani]

of her2+ breast cancer.

I have said for years that her2+bc needed to be subdivided into subtypes in order to know the best treatment for each --now they have done so using PAM50. I am not sure this is the best way to divide the subtypes, compared to other ways (by active pathways, genomics, proteomics, epigenomics, etc) but it is a practical way, based on the fact it can be done comparatively inexpensively and on FFPE specimens (which everyone gets) rather than fresh frozen speciments(which only a few get)

As you can see from Dr. Ellis' disclosures he has quite a few potential conflicts of interest, especially concerning PAM50, nevertheless I think the general approach is the right one ie, subdividing to conquer, just as is being done with breast cancer in general.. THe article this commentary is commenting on comes from Chuck Perou and Lisa Carey and bears Jose Baselga's name as well. The former two are from Uof No caroline, the latter the director of Memorial Sloane Kettering .

I was especially pleased that they will be trying to do a subgroup analysis to see if the recent negative results of the ALTTO trial are in fact valid .

link to Dr Ellis' commentary:

http://jnci.oxfordjournals.org.conte....full.pdf+html

The article itself is interesting in that they found that, in general, being her2+ does not confer that much worse of a prognosis than others in the subgroup (but this all depends on whether treated with herceptin or not) and that her2+ bc can be Lum A (very small % of lum A), lum B, her2 enriched (obviously) or even basal. It shows a new way which should be used to look at old trials although I remain unsure that it is the right or ultimate way to divide to conquer-- this will be shown by reeamination of the old trials by these subgroups, and new trials which hopefully will lead the way to tailor treatment to those who will respond best with the least side effects and allow expenisve new drugs like pertuzumab to be used just for those who will benefit.

http://www-ncbi-nlm-nih-gov./pubmed/25139534

J Natl Cancer Inst. 2014 Aug 19;106(8). pii: dju152. doi: 10.1093/jnci/dju152. Print 2014 Aug.
Molecular Features and Survival Outcomes of the Intrinsic Subtypes Within HER2-Positive Breast Cancer.
Prat A1, Carey LA2, Adamo B2, Vidal M2, Tabernero J2, Cortés J2, Parker JS2, Perou CM2, Baselga J2.
Author information

Abstract
BACKGROUND:
The clinical impact of the biological heterogeneity within HER2-positive (HER2+) breast cancer is not fully understood. Here, we evaluated the molecular features and survival outcomes of the intrinsic subtypes within HER2+ breast cancer.
METHODS:
We interrogated The Cancer Genome Atlas (n = 495) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets (n = 1730) of primary breast cancers for molecular data derived from DNA, RNA and protein, and determined intrinsic subtype. Clinical HER2 status was defined according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines or DNA copy-number aberration by single nucleotide polymorphism arrays. Cox models tested the prognostic significance of each variable in patients not treated with trastuzumab (n = 1711).
RESULTS:
Compared with clinically HER2 (cHER2)-negative breast cancer, cHER2+ breast cancer had a higher frequency of the HER2-enriched (HER2E) subtype (47.0% vs 7.1%) and a lower frequency of Luminal A (10.7% vs 39.0%) and Basal-like (14.1% vs 23.4%) subtypes. The likelihood of cHER2-positivity in HER2E, Luminal B, Basal-like and Luminal A subtypes was 64.6%, 20.0%, 14.4% and 7.3%, respectively. Within each subtype, only 0.3% to 3.9% of genes were found differentially expressed between cHER2+ and cHER2-negative tumors. Within cHER2+ tumors, HER2 gene and protein expression was statistically significantly higher in the HER2E and Basal-like subtypes than either luminal subtype. Neither cHER2 status nor the new 10-subtype copy number-based classification system (IntClust) added independent prognostic value to intrinsic subtype.
CONCLUSIONS:
When the intrinsic subtypes are taken into account, cHER2-positivity does not translate into large changes in the expression of downstream signaling pathways, nor does it affect patient survival in the absence of HER2 targeting.
© The Author 2014. Published by Oxford University Press.
PMID: 25139534 [PubMed - in process] Free full text

remember I am not so good at posting links so if I erred, please correct….got to go!