DIfferent subtypes of her2+ breast cancer with different prognoses being identified

[Lani]

I have opined for a long while that her2+ breast cancer can be divided into several groups which may have different prognoses and may require different treatments(just like breast cancer as a whole can be divided into several types with different prognoses and which respond better to different treatments.

Although this is far from "the whole story"...at least they are looking at it!


Ann Surg Oncol. 2011 Aug 31. [Epub ahead of print]
Prognostic Value of Basal Phenotype in HER2-overexpressing Breast Cancer.
Bagaria SP, Ray PS, Wang J, Kropcho L, Chung A, Sim MS, Shamonki JM, Martino S, Cui X, Giuliano AE.
Source
Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA, USA.
Abstract
BACKGROUND:
Primary breast cancers that overexpress human epidermal growth factor receptor 2 have variable biological features and clinical outcomes. A subgroup of HER2-overexpressing tumors that express basal-like immunohistochemical markers-the so-called basal-HER2+ subtype-is associated with poor prognosis. We investigated the clinical relevance of this basal-HER2+ subtype within HER2-overexpressing breast tumors.

METHODS:
Database review identified consecutive patients with HER2-overexpressing breast cancer. Archival tumor specimens from these patients were immunostained for estrogen receptor (ER), HER2, and basal cytokeratin (CK) expression, then subtyped as luminal-HER2+ (ER positive and basal CK negative), HER2+ (ER negative and basal CK negative), and basal-HER2+ (ER negative and basal CK positive). Subtypes were correlated with clinicopathologic features and overall survival.

RESULTS:
Immunohistochemical assessment of 131 HER2-overexpressing breast tumors identified 79 (60%) luminal-HER2+ tumors, 40 (31%) HER2+ tumors, and 12 (9%) basal-HER2+ tumors. There was no difference in the use of adjuvant trastuzumab and chemotherapy among patients with these subtypes. Five-year overall survival was 65% for patients with basal-HER2+ tumors versus 94% (P = 0.0035) and 96% (P = 0.0031) for patients with luminal-HER2+ and HER2+ tumors, respectively. The basal-HER2+ subtype was associated with the worst prognosis after adjusting for age, tumor size, lymph node status, and adjuvant treatment (hazard ratio 5.06, 95% confidence interval 1.1-23.2, P = 0.037).

CONCLUSIONS:
The basal-HER2+ subtype highlights the heterogeneous biology of HER2-overexpressing breast cancer. The basal-HER2+ subtype is independently associated with poor survival and may provide insight into breast cancer cell response to anti-HER2 therapy.

PMID: 21879270

[pibikay]

Thanks Lani for the info

[Debbie L.]

This is a really interesting one, Lani. The more I think about it, the more questions I have. Does anyone have access to full text? I'd definitely like to see more information than 5 year overall survival, for example. Many of those in the both groups may have had recurrences but still be living with cancer, at 5 years.

They didn't break the luminals into A and B. Are they assuming that all HER2+ luminals are Bs? With such good stats, maybe it doesn't matter?

I thought that some ER+/HER2+ tumors WERE of the HER2+ subtype, yet they didn't have any further assay to find those. Although as above, with such good stats, does it matter for this focus? It seems they were mainly trying to separate the basals from everything else.

It would be especially interesting to see if Herceptin made any difference at all for the basal HER2+ subtype. Of course, they can't test that now but perhaps they can mine old data, if assays were done to categorize basal HER2+, or if tissue is available.

Debbie Laxague

[Trish]

Thanks Lani. Is basal cytokeratin expression testing done as a clinical standard as is the FISH test? And is it possible to have ER + basal+?
Trish

[kykeon22]

I too was wondering if ER + can be ck positive, or all ER + are ck negative.

[Lani]

there are different cytokeratins they check for as I recall CK 5 is the one specific to to triple negatives, not sure if only those that are basal or the others too. Will have to review.

Cytokeratins are not routinely tested for except 18/19 if they are looking for epithelial cells from breast cancer in the bone marrow.

The definition of the different subtypes of bc is still in flux but at least they are looking for the subtypes of her2 to try to determine which treatment is best for which subtype.