for all you her2+ ER+s, THEY KEEP SEARCHING FOR A MOLECULAR SUBTYPE FOR YOU

[Lani]

some ignore the type, others lump it into Luminal B.
Here is another approach:
Int J Clin Exp Pathol. 2009;2(5):444-55. Epub 2009 Feb 9.

Prevalence, morphologic features and proliferation indices of breast carcinoma molecular classes using immunohistochemical surrogate markers.

Bhargava R, Striebel J, Beriwal S, Flickinger JC, Onisko A, Ahrendt G, Dabbs DJ.
Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center Pittsburgh, PA, USA.
There is dearth of studies that provide a practical working formulation of breast cancer gene expression analysis for the surgical pathologist. ER, PR, HER2 were used as surrogate markers to classify 205 breast carcinomas into molecular classes. Ki-67 labeling index was calculated using an image analysis system. The data was analyzed for molecular class prevalence, and inter-relationships amongst morphologic parameters, Ki-67 index, and molecular classes. Of the 205 tumors, 113 (55%) were classified as luminal A (strong ER+, HER2 negative), 34 (17%) as luminal B (weak to moderate ER+, HER2 negative), 32 (15%) as triple negative (negative for ER/PR and HER2), 8 (4%) as ERBB2 (negative for ER/PR but HER2+), 10 (5%) as luminal A-HER2 hybrid (strong ER+ and HER2+), and 8 (4%) as luminal B-HER2 hybrid (weak to moderate ER+ and HER2+). The average Ki-67 index was lowest in luminal A (15.8%), intermediate for ERBB2 (27.8%) and highest for triple negative tumors (>50%). Multivariate logistic regression analyses found the following associations: ERBB2 tumors with apocrine differentiation (p=0.0031); Triple negative tumors with high Ki-67 index (p<0.0001) and CK5 positivity (p<0.0001); HER2 negative-low receptor positive tumors (luminal B) with increased lymph node involvement (p=0.0141). The immunohistologic criteria were validated on a different set of 359 cases treated with neoadjuvant chemotherapy, which showed a pathologic complete response predominantly in ERBB2 and triple negative tumors. Immunohistochemistry is a reliable surrogate tool to classify breast carcinoma according to the gene expression profile classification.
PMID: 19294003

[Laurel]

Hmmm, so what's a "luminal A-Her2 hybrid" supposed to think?

[sassy]

Lani, can you translate for these Luminal A-her2 hybrid girls?

[suzan w]

ditto!! translate! :)

[Lani]

several years ago based on gene array studies done on fresh frozen biopsy samples these were

basal usually, but not always triple negative
her type HER2+ ER-
Luminal A ER+her2- with good prognosis
Luminal B those ER+s who don't have as good a prognosis--various researchers argued about where her2+ER+ fit in here, some thought about 50% of these were her2+ ER+ others didn't know if they fit in at all
some also described a Normal type (a lot like normal breast tissue)

If you want to follow articles on this, the major ones have been by Chuck Perou of North Carolina, Sotirou of France/Belgium (?) and Laszlo Pusztai
(sp?) of MD Anderson.

This study is trying to see if using immunochemistry (cheap, more readily available than Affymetrix multigene arrays and able to be done on formal fixed paraffin embedded tumor specimens rather than fresh frozen ones, thus testable on everyone world wide and on old archival tissues) for three
main markers plus a measure of proliferation couldn't tell us a lot about how different tumors behave (prognosis-wise)ie, a poor man's version. They did also look for cytokeratin (CK)5 , a marker of triple negative~basal.

In their system, they identified her2 tumors as being divided into 3 types

(1) her2+ER- which they said constituted 4% of all breast cancers

(2) Her2+ strong ER+ which constitute 5% of all bc

(3) her2+ weak to moderate ER+ which constitute 4% of all bc

her2+ bc is usually felt to represent 20-25% of breast cancer (and these only add up to 13% so the method me not be so good, the IHC testing not so good, or their population scewed) --with roughly half being ER+ and half ER-, but those that are ER+ are usually dumped into the luminal B group because they just didn't know where they belonged.

The interesting news here is that the ERBB2 group (those which are ER+) and the triple negatives had the best results with neoadjuvant therapy (where you can see the results right away) If they keep dividing the her2+ ER+s this way, maybe they can study how neoadjuvant herceptin plus hormonal treatment with or without chemo does to determine whether chemo is necessary for these groups.

Hope this helps!

[schoolteacher]

Lani,

When I had my neoadjuvant Herceptin and Taxol, I asked the doctor about putting me on an estrogen suppress because my cancer was 70 or more estrogen driven. He would not.

It will be interesting to see the results of any studies adding Herceptin and an estrogen suppressor.

Amelia