her2 borderline--a new type of breast cancer???
 

ABSTRACT: Pathology of borderline HER-2/neu breast carcinoma: a biologically distinct phenotype [Breast Cancer Research and Treatment]
Purpose: The significance of HER-2/neu results obtained by immunohistochemical analyses (IHC) which are neither negative nor strongly positive is controversial. The incidence of fluorescence in situ hybridization (FISH) positivity in these tumors is small and the implication is that these borderline results represent laboratory misclassification. We analyzed the tumor characteristics of these HER-2/neu borderline tumors to determine if they represent a unique tumor type.

Methods: HER-2/neu status was determined by image analysis (IA) of IHC sections in 669 cases of invasive breast cancer. Borderline cases were reflexed to FISH to determine gene status. HER-2/neu results were compared to tumor morphology and other tumor markers.

Results: HER-2/neu was negative, borderline and positive in 69.5, 15.8, and 14.6% of cases, respectively. HER-2/neu amplification was present in 17.3% of borderline cases. The borderline group is significantly different from the HER-2/neu positive group for all parameters studied except Ki-67. Compared to the HER-2/neu negative group, the borderline group showed a significantly higher HER-2/neu gene copy number and a trend towards lower progesterone receptor expression (p=0.058). Compared to the HER-2/neu negative group, the HER-2/neu borderline/FISH-negative group showed significantly lower PR expression. Compared to the HER-2/neu positive group, the HER-2/neu borderline/FISH positive group showed significant differences with multiple parameters.

Conclusion: Borderline HER-2/neu tumors are a unique tumor type and do not represent laboratory imprecision. Hormone receptor alterations are associated with early changes in HER-2/neu expression. While IA is capable of detecting these changes, current FISH methodology is not.

Lani;

I am HER-2/neu borderline/FISH positive and am curious about what you think this study means. When stated that my group shows "significant differences with multiple parameters" I am confused.

I have read an interesting article which discussed a study done on RNA samples of 360 primary breast cancer tumors where probes for 160 distinct genes in the 17Q chromosomal region were arrayed in the order of their location along the chromosome. These tumors with similar patterns of gene expression, including elevated her2 expression were clustered together by a computer and grouped. In the array of genes where her2 RNA was elevated expression of closely linked genes mapping to both sides of the gene was also elevated. "This reflects the fact that the unit of DNA amplification -- the amplicon -- almost always included a stretch of chromosomal DNA that was far longer than the erbB2/neu/HER2 gene itself., leading to co-amplification of these neighboring genes. Among these genes are several that may also psoitvely influence cell proliferation and survival, including GRB7 and PPARB whose protein products interact with ErbB2 and with the apoptosis cicuitry, respectively. Hence, in such cases, a number of co-amplified genes may be collaborating to orchestrate the malignant phenotype of human breast cancer cells, and it becomes difficult to ascribe specific cancer cell phenotypes to the elevated expression of only a single gene, such as erbB2/neu/HER2."

I wonder if Her2 borderlines are not tumors whose genes express more of these borderline/neighboring genes ....such as GRB7 or PPARB than erbB2 in fact. This, to me, suggests that for us borderlines, perhaps other treatments might be more effective.....I wonder about lapatinib?

Cathy

HER2+/HER2++ Clinical trial
 

A clinical trial I posted recently under the clinical trial section is intended for advanced bc/mets HER2+ or HER++.

A.A.

Cathya
 

I think when they refer to the amplicon it refers to the stretch of DNA that includes her2AND something else. There were some people who suspected GRB7 was the culprit and not her2 itself. GRB7 is one of the components of the OncoDx test. Another close-lying gene in the amplicon is topoII I believe from I talk I heard Dr. Slamon give in San Antonio (for some reason I think cmyc may be too, but I am quite unsure if that is so or where I read/heard it)

Her2 may not be the whole story. If you have her1 (egfr or erbb1) positive and/or her3 positive, those may also make the difference as they join with her2 to produce the same effect.

Targeted molecular diagnostics tests for EGFR and her3. I am still waiting for the publishing of the paper on what lab tests predict tykerb efficacy. Did any members of this board listen to that talk/see that poster?

If you see my other posts from today. I opine that there are several types of her2 + breast cancer. A paper given in Molde, Norway by Dr. Stepanie Jeffreys of Stanford discusssed several different types of her2+ ER+ breast cancer--still unable to find the info published.

The mystery is unfolding. I hope we can speed it up by helping loosen the restrictions on researchers regarding stem cell use, medical privacy rules, access to specimens etc...

Will get off my soap-box for now!
Lani

Thank you, Lani, for the good information. Please do post the papers as you find them and I will do the same.

Scientists have long used categorization or nosology to group things into categories in order to study them. But the map is not the territory. I surmise that many different cancers exist that are potentially as unique as each individual. Meanwhile, I had the ER/PR/HER2/TOPA2 positive type.