predicting complete pathological response ie,chemoworking, by molecular subtype here?

Lani · 09-20-2007, 08:43 AM

Definitely getting closer! This study was just based on immunohistochemistry available now for paraffin embedded specimens, not expensive not yet available multigene array chips. Subtypes based on ER, PR, her2 status mainly, with a few other markers thrown in for fine tuning.

ABSTRACT: Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy [Cancer]
Background: The molecular classification system categorizes invasive breast carcinomas according to their key driving biomarkers. In the current study, the authors evaluated whether response to neoadjuvant chemotherapy was correlated with the molecular classification groups.
Methods: Using immunohistochemistry, the molecular classification group (luminal-A, luminal-B, HER-2-variant, HER-2-classic, and basal phenotype) was retrospectively determined in 68 breast cancer patients who received neoadjuvant treatment.
Results: A total of 28 carcinoma patients (41.2%) achieved a compete pathologic response (CPR), including 2 of 15 patients classified as having luminal-A (13.3%), 4 of 16 patients classified as having luminal-B (25.0%), 10 of 12 patients classified as having HER-2-classic (83.3%), none of the 4 patients classified as having HER-2-variant, and 12 of 21 patients classified as having basal phenotype (57.1%) neoplasms. The CPR rate among patients with the HER-2-classic and basal neoplasms was 67% (22 of 33 neoplasms), compared with 17.1% (6 of 35 neoplasms) in the non-HER-2-classic/basal combined group (P < .001). Eleven carcinomas were initially diagnosed as invasive lobular carcinomas (pleomorphic and classic), 4 of which were luminal-A, 4 of which were luminal-B, 2 of which were HER-2-classic, and 1 of which was basal. On review, only 3 of these 11 cases remained classified as classic lobular carcinoma, all of which were classified as luminal-A, and none of these patients achieved a CPR. Four of the other 8 patients achieved a CPR.
Conclusion: The molecular classification system is useful for identifying carcinoma patients who are most likely and those who are least likely to achieve a CPR. In the current study, all the morphologically classic lobular carcinomas were classified as luminal-A neoplasms, which may explain the low rate of CPR reported.

Becky · 09-20-2007, 10:29 AM

Dear Lani

What is the difference between Her2 classic vs variant? Also, any idea of the type of chemo used?

Thank you in advance

Hopeful · 09-20-2007, 11:11 AM

Lani,

What is the source for this abstract?

Thanks,

Hopeful

KellyA · 09-20-2007, 12:46 PM

Lani-
Ok, so what is ER/PR-, Her2 +?

Kelly

Lani · 09-20-2007, 04:39 PM

yours is the easiest question--according to this paper her2+er-pr- is classic
her2.

They used a variety of chemos, which makes the study less meaningful.

I was expecting her2 variant to be her2+er+pr+ or pr- but it wasn't!

I will try to post the link so others can peruse it.

Lani · 09-20-2007, 04:41 PM

http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum

KellyA · 09-20-2007, 06:01 PM

Thank you Lani- I can never understand these abstracts. I do really appreciate your efforts in educating all of us with the newest information available.

Love, Kelly

Becky · 09-20-2007, 07:05 PM

Lani

Before I even asked about variant forms of Her2, I was thinking the same as you - that the classic is ER-/PR-. And that is even simplified. You got me curious. The classic form is the NORMAL form of Her2 (regardless of hormone status). There are many rare variants but the variant we all know about (although these threads are old) is the p95 truncated version of the extra cellular domain. Apparently besides this variant, there are 4 other even rarer variants identified.

So, classic is just the normal version, period. Variants are the "mutated" or "deformed" forms of Her2.

Lani · 09-20-2007, 08:44 PM

but I am disappointed in the article as many details are not addressed.

The variants of her2 eg the truncated version are genetic variants....I believe this addresses the variant of the "her2" molecular subtype ie, the grouping based on multigene array chip profiles of multitude of genes.
This study is out of William Beaumont Hospital in Michigan and the numbers of tumors studied was limited.

They did not test for many of the biomarkers I would have found interesting eg her3, phospo-her2, etc.

Dr. Charles Perou who was instrumental in naming the 5 molecular subtypes of breast cancer believes her2+ER+ breast cancers fall within the luminal B group, as do many other authors. This paper does not specify where they believe her2+ER+ tumors fall--despite two readings I have yet to find it even referred to and yet they constitute around 45% OF HER2+ breast cancers in many studies.

I will investigate further and let you know.