Breast cancer categories

[AlaskaAngel]

I've seen it mentioned in different sources that it currently is believed that there are 5 or 6 different major types of breast cancer, and I know that one of these types is a mixture of BRCA1's and others who recur fairly rapidly, but... does anyone have any idea what the proposed characteristics are for the other 4 or 5 types? Is HER2-positive a separate group in itself, or is it found in all 5 or 6, or ????

A.A.

[al from Canada]

AA,
I would consider HER2 a totally separate cancer
Al

[Lolly]

Here's a link to a web page which lists the MANY classifications of breast cancer...wow, I didn't know there were so many. According to this site, HER/2 neu is a characteristic of a breast cancer, not a seperate type.

Classification of Breast Cancer
http://www-medlib.med.utah.edu/WebPa...ST/BREAST.html

<3 Lolly

Breast cancer classification has evolved from descriptions of the appearance of the tumor on a slide (inflammatory, ductal, etc) to being based on which general group of similarly delineated genes are detected on multigene arrays. The subtypes of infiltrating ductal carcinoma are called Luminal A, Luminal B, Normal, Her2neu and Basal. The last two are estrogen receptor negative. THE BIG QUESTION IS WHERE DO THE her2neu positive, hormonal receptor positive tumors fit in?? This question is still unanswered. Most researchers feel they do not fit into any of the three hormonal positive subgroups -- perhaps they need their own subtype. Stefanie Jeffreys of Stanford University gave a talk in Molde, Norway in June (only the abstract available so far) describing several different subsets of her2+hormonal+ tumors by results of multigene array each with a different natural history and prognosis(which implies they may need different treatments).
I am including two abstracts, the first from a paper by Charles Perou and Laszlo Pusztai, who have written a lot on the topic of the Luminal vs Normal vs Her2 vs Basal groups, and discusses how the different groups vary in their response to chemotherapy, and the latter from the Dutch group who described the 70 gene signature of breast cancer (apparently much better than OncoDx test to predict prognosis of a particular breast cancer tumor, but not yet clinically available) showing that the subtype by multigene array does not differ between primary and metastasis.


PURPOSE: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. EXPERIMENTAL DESIGN: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. RESULTS: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. CONCLUSIONS: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.
Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer.

Weigelt B, Hu Z, He X, Livasy C, Carey LA, Ewend MG, Glas AM, Perou CM, Van't Veer LJ.

Divisions of Experimental Therapy and Diagnostic Oncology, The Netherlands Cancer Institute, The Netherlands .

Microarray analysis has been shown to improve risk stratification of breast cancer. Breast tumors analyzed by hierarchical clustering of expression patterns of "intrinsic" genes have been reported to subdivide into at least four molecular subtypes that are associated with distinct patient outcomes. Using a supervised method, a 70-gene expression profile has been identified that predicts the later appearance or absence of clinical metastasis in young breast cancer patients. Here, we show that distant metastases display both the same molecular breast cancer subtype as well as the 70-gene prognosis signature as their primary tumors. Our results suggest that the capacity to metastasize is an inherent feature of most breast cancers. Furthermore, our data imply that poor prognosis breast carcinomas classified either by the intrinsic gene set or the 70 prognosis genes represent distinct disease entities that seem sustained throughout the metastatic process.

As always, you ask one question it leads to several more...

Hope this helped anyway

Fascinating.

It is the way forward including pretesting for the best treatment options.

RB

[AlaskaAngel]

Lani, bless you -- you knew exactly what I was asking about. I don't save everything I read, and then I can't quite put a finger later on things that I want to go back to. From what I do remember, the BRCA1-mixed-with-others-that-recur-early was the basal type. I am reconsidering being tested late for BRCA1/2 to try to decide about ovariectomy (an aunt died of ovarian CA) and so was curious as to where BRCA2 fit in as well as where HER2 fit in, but I didn't know that the HER2+/HR+'s are a puzzle. Thanks very much.

A.A.

basal type are the triple negatives ie, her2- as well as hormone negatives, but as you know her2negatives can metastasize as her2 positive--I guess the thinking is that the her2 testing was not done well or isn't as accurate as when you look for the gene on a multigene array chip. Some think they originate in basal( myoepithelial) cells a different cell type than ductal cells. Others just think they represent a different set of progenitor cells from a breast cancer stem cell. The real mystery continues ie, what characteristics does a breast cancer stem cell have ie, is her2 expressed, are hormonal receptors expressed?

Triple negative breast cancer has been tied to one of the two BRCA genes, I do not remember which at this moment--and everytime I go to look something up I lose everything I have typed in my post--this is still relatively preliminary thinking as described at ASCO and not written in stone.

Perhaps someone can instruct me how to save my posts while I go gather additional information. Sorry to be so computer illiterate.

Hope this helps,
Lani

[AlaskaAngel]

Lani, I don't know if this is the answer for you but this is what I do: You can minimize the current screen (in my case, internet explorer showing HER2 Support Group Forums), then either open a new internet explorer screen, or google, or a document, and find what you are looking for, and then minimize that, and then maximize the original screen that shows HER2support. Then you can bounce back and forth between them by minimizing or maximizing without closing. Does that work for you?

A.A.

I have tried something similar, but as I am on an Apple MacIntosh-type computer I think the strategy must be something slightly different as I always lose all my post. I have to go to a word processing program start a new document save it, go get the info, copy and paste it, change the save as ...
and hope by the time I get back to the post I haven't screwed something up.

Oh well!

Thanks again,
Lani

Lani,
If you are using the Apple Safari browser, and switching windows within that browser is not working for you, you could add Firefox as an additional browser http://www.apple.com/downloads/macos...lafirefox.html
Then you should be able to toggle back and forth (maximizing and minimizing the browser windows as you wish) and hopefully not lose any info. I do this all the time on my Mac. I don't know if the Operating System no. would make a difference -- I have OS X (panther).)We can't let you get stymied by a technology glitch -- your input is too valuable!

Lani,
Full address to get Firefox:

http://www.apple.com/downloads/macos...lafirefox.html

Good luck.

[Lolly]

http://mednews.wustl.edu/news/page/normal/6358.html

I already had downloaded firefox, but didn't really know how to utilize it to "bounce back and forth" while writing "posts" I will try to utilize it next time I post. Wish me luck!

Thanks again,
Lani

Interesting post Lolly.

There seem to be more and more articles acknowledging limitations with traditional staging.

Hopefully as gene array become more economic and accepted people will get treatments that are applicable to them rather than what appears in the past to be a blanket based approach.

It seems to me that this is particulary important for early diagnosis of younger fertile sufferers who have to make decisions on chemo treatments that impact on long fertility etc.

RB