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01-28-2006, 12:33 PM

This is a question of classification of tumors which reflects how the knowledge regarding cancer has progressed and yet how the majority of dcotors still use our old classification systems originated at a time when we had much more limited knowledge(based on the ability to examine things under the microscope but an inability to know what genes or gene products might cause any particular tumor type to act the way it does).

The old classification system(still in use) was based on microscopic appearance of the tissues. They were graded 1,2, or 3 based on how undifferentiated (abnormal, out-of-control) looking the cells looked under the microscope. This had to do with abnormal and varying size of cells, abnormal appearances of nucleii of cells, how many cell divisions were seen, etc.

A recent paper claims there are no Grade II infiltrating ductal tumors and these should be reclassified using more recent means of classification. So even if some members answer that their tumor was Stage II it might today be re-classified as Stage III.

The most recent classification (not yet in wide clinical use and not expected to be for at least 5 years) is based on multigene arrays(usually done on Affymetrix chips). Tumors are classified into Luminal, Normal, Basal and her2 groups--the her2 group being ER-PR-. Those with her2+ER+PR+ do not yet have a group to fully explain them and they may be about half of her2+ tumors!

Oncologist say that higher grade tumors are more amenable to chemo because they have more rapidly dividing cells (although Ki67 is a much better measure of that I understand) and chemo works by (hopefully) affecting rapidly dividing cells more than normal less rapidly dividing cells.

There seems to be a population of dormant, slowly dividing cells which hides out in the bone marrow especially which researchers call "stem cells"
These tend to be resistant to chemotherapy as they only divide once in a blue moon.

These are like mildew in that they can sit there in small amounts quietly causing no problem, but under the right circumstances (like humidity for mildew) start to divide quickly. Just like mildew they are hard to kill because they only reproduce very infrequently.

Chemo also tends to work best in ER-PR- tumors, but as more and more is learned about breast cancer, it seems they will find that there are subset which do or do not respond to chemo vs therapy x vs therapy y. It was serendipity that they continued to test Herceptin whent initial results were not promising because they were trying to treat too many patients with something which only a few would respond to. Luckily a test was available to work out which subset was the one which was likely to respond.

Hopefully they will in the next few years sort out which genes make which tumor respond to which therapies and treat only those people who need it with only those treatments which are likely to work.

Volunteering for a neoadjuvant chemo clinical trial helps that day come closer, because by serially testing with biopsies and MRIs or other imagine during the course of treatment they can correlate what characteristics each tumor has and which characteristics predicted response to which treatment.
Unfortunately the way clinical trials work is that they have to give the old approved treatment PLUS the new one, making it hard to figure out if it was necessary or if there are better treatments.

If your reason for raising this question is because you still have lingering doubts as to whether you really needed chemo and if it indeed will do what you wanted it to, there are tests available and in the works to help you know that, even if it is now water under the bridge. The OncoDX test is a general test which puts you in one of three categories--low, medium and high risk if your tumor was Stage I and your lymph nodes were negative. There is a 70 gene test in the works in Holland (not clinically available) and
Robin P has pointed out a company called Therapeutic Molecular Diagnostics which can go back, sample your tumor sample embedded in paraffin and look at various markers such as Ki67 (which reflects the speed with which your tumor was growing), topoisomerase II (which Dr. Slamon says reflects whether anthracyclines like doxirubicin are needed besides a taxane to be effective) as well as many others, the implications of which they are not yet sure of.

Will get off the soapbox--again I raise the topic for discussion: Would you rather know that they don't know for sure or be given a dogmatic answer that you later learn was wrong?

01-28-2006, 12:33 PM	#7
Unregistered. Guest Posts: n/a	Tumor Grading felt to be an old-fashioned classification having outlived its utility This is a question of classification of tumors which reflects how the knowledge regarding cancer has progressed and yet how the majority of dcotors still use our old classification systems originated at a time when we had much more limited knowledge(based on the ability to examine things under the microscope but an inability to know what genes or gene products might cause any particular tumor type to act the way it does). The old classification system(still in use) was based on microscopic appearance of the tissues. They were graded 1,2, or 3 based on how undifferentiated (abnormal, out-of-control) looking the cells looked under the microscope. This had to do with abnormal and varying size of cells, abnormal appearances of nucleii of cells, how many cell divisions were seen, etc. A recent paper claims there are no Grade II infiltrating ductal tumors and these should be reclassified using more recent means of classification. So even if some members answer that their tumor was Stage II it might today be re-classified as Stage III. The most recent classification (not yet in wide clinical use and not expected to be for at least 5 years) is based on multigene arrays(usually done on Affymetrix chips). Tumors are classified into Luminal, Normal, Basal and her2 groups--the her2 group being ER-PR-. Those with her2+ER+PR+ do not yet have a group to fully explain them and they may be about half of her2+ tumors! Oncologist say that higher grade tumors are more amenable to chemo because they have more rapidly dividing cells (although Ki67 is a much better measure of that I understand) and chemo works by (hopefully) affecting rapidly dividing cells more than normal less rapidly dividing cells. There seems to be a population of dormant, slowly dividing cells which hides out in the bone marrow especially which researchers call "stem cells" These tend to be resistant to chemotherapy as they only divide once in a blue moon. These are like mildew in that they can sit there in small amounts quietly causing no problem, but under the right circumstances (like humidity for mildew) start to divide quickly. Just like mildew they are hard to kill because they only reproduce very infrequently. Chemo also tends to work best in ER-PR- tumors, but as more and more is learned about breast cancer, it seems they will find that there are subset which do or do not respond to chemo vs therapy x vs therapy y. It was serendipity that they continued to test Herceptin whent initial results were not promising because they were trying to treat too many patients with something which only a few would respond to. Luckily a test was available to work out which subset was the one which was likely to respond. Hopefully they will in the next few years sort out which genes make which tumor respond to which therapies and treat only those people who need it with only those treatments which are likely to work. Volunteering for a neoadjuvant chemo clinical trial helps that day come closer, because by serially testing with biopsies and MRIs or other imagine during the course of treatment they can correlate what characteristics each tumor has and which characteristics predicted response to which treatment. Unfortunately the way clinical trials work is that they have to give the old approved treatment PLUS the new one, making it hard to figure out if it was necessary or if there are better treatments. If your reason for raising this question is because you still have lingering doubts as to whether you really needed chemo and if it indeed will do what you wanted it to, there are tests available and in the works to help you know that, even if it is now water under the bridge. The OncoDX test is a general test which puts you in one of three categories--low, medium and high risk if your tumor was Stage I and your lymph nodes were negative. There is a 70 gene test in the works in Holland (not clinically available) and Robin P has pointed out a company called Therapeutic Molecular Diagnostics which can go back, sample your tumor sample embedded in paraffin and look at various markers such as Ki67 (which reflects the speed with which your tumor was growing), topoisomerase II (which Dr. Slamon says reflects whether anthracyclines like doxirubicin are needed besides a taxane to be effective) as well as many others, the implications of which they are not yet sure of. Will get off the soapbox--again I raise the topic for discussion: Would you rather know that they don't know for sure or be given a dogmatic answer that you later learn was wrong?