Debbie L.
12-03-2013, 08:36 PM
I'm moving this from the DCIS thread (which was already a thread Elizabeth had moved -- this is a fertile tree).
AussieGirl touched on how complex the idea of knowing the subtype of a tumor can be:
"Luminal A and B refer to oncotype DX type analysis and are ER+ subtypes. Luminal B is higher grade than luminal A and may require adjuvant chemo + anti-ER therapy. Don't worry about it. This primarily a research tool and if your are HER2 positive you are in the HER2 encriched group. "Luminal B/ HER2+ category is ER+ HER2+ high grade invasive carcinoma. Use of this particular category (as opposed to just HER2+ cancer) is always accepted as a category."
For years, we've heard they've identified 5 molecular subtypes of breast cancer (luminal A and B, Her2, basal, and "normal-like"). Here's the famous green/red graph we see over and over: Gene Expression Profiling (http://cancerres.aacrjournals.org/content/65/6/2170/F2.large.jpgamp)
There are probably many more subtypes than just 5, and there has been research published in the last few years naming, for example, 10 of them: Cancer Research UK (http://www.nhs.uk/news/2012/04april/Pages/breast-cancer-genetic-diversity-mapped.aspx)
But back to that heat map graph of gene expression that sorts all those tumors into one of the 5 subtypes. If you look at the handy black-and-white area at the top, you'll begin to notice, for example -- that not all TNBC is "basal" nor is all basal cancer ER negative. There are HER2+ cancers in every subtype except basal (but I've heard there are HER2+ tumors of the basal type so maybe they were too rare to make it into this set). Some luminal B's are HER2+ but some HER2+ subtypes are ER+. Argg! So confusing.
Oncotype DX does not, as far as I know, name cancers by subtype (as luminal A or B). I think that's extrapolated by some as meaning that anything in the high risk range is probably luminal B.
But right now we're in this muddy area. All that most people know about a tumor are the basic 3 markers (ERPR and HER2) plus some information about proliferation (grade, Ki67, S-phase assays, etc). One can make guesses about which subtype a tumor might be in, using that information -- but again, as we see by looking closely at the heat map -- that guess may not be accurate. Which right now doesn't really matter much (the inaccuracy). We still treat mostly by those 3 markers, and sometimes the Oncotype, because -- so far that's all we have evidence to support.
But don't you think we must be on the edge of a transition zone? Where soon all research will look at all possible genetic information from a tumor -- perhaps using for now the 5 subtypes but having the details stored so that as more subtypes are identified and validated, they can go back and look retrospectively at even more subtypes -- looking at the behavior of each type, and most-importantly, its response to many different treatments. Perhaps eventually looking not just at the tumor's pedigree but also at the heterogeneity and the immune environment in which it lives. So that eventually (we are far from there, yet) -- there will truly be individualized treatment. Then, not only will we treat (stop) cancers most effectively, but we will save people from the many toxicities of treatments that do not stop their cancer.
So that was an extremely long no-anwer to Roz's question about what subtype her cancer might be. We don't know, from the information given. And even if we did know, we wouldn't know what to do with that information (yet).
Debbie Laxague
AussieGirl touched on how complex the idea of knowing the subtype of a tumor can be:
"Luminal A and B refer to oncotype DX type analysis and are ER+ subtypes. Luminal B is higher grade than luminal A and may require adjuvant chemo + anti-ER therapy. Don't worry about it. This primarily a research tool and if your are HER2 positive you are in the HER2 encriched group. "Luminal B/ HER2+ category is ER+ HER2+ high grade invasive carcinoma. Use of this particular category (as opposed to just HER2+ cancer) is always accepted as a category."
For years, we've heard they've identified 5 molecular subtypes of breast cancer (luminal A and B, Her2, basal, and "normal-like"). Here's the famous green/red graph we see over and over: Gene Expression Profiling (http://cancerres.aacrjournals.org/content/65/6/2170/F2.large.jpgamp)
There are probably many more subtypes than just 5, and there has been research published in the last few years naming, for example, 10 of them: Cancer Research UK (http://www.nhs.uk/news/2012/04april/Pages/breast-cancer-genetic-diversity-mapped.aspx)
But back to that heat map graph of gene expression that sorts all those tumors into one of the 5 subtypes. If you look at the handy black-and-white area at the top, you'll begin to notice, for example -- that not all TNBC is "basal" nor is all basal cancer ER negative. There are HER2+ cancers in every subtype except basal (but I've heard there are HER2+ tumors of the basal type so maybe they were too rare to make it into this set). Some luminal B's are HER2+ but some HER2+ subtypes are ER+. Argg! So confusing.
Oncotype DX does not, as far as I know, name cancers by subtype (as luminal A or B). I think that's extrapolated by some as meaning that anything in the high risk range is probably luminal B.
But right now we're in this muddy area. All that most people know about a tumor are the basic 3 markers (ERPR and HER2) plus some information about proliferation (grade, Ki67, S-phase assays, etc). One can make guesses about which subtype a tumor might be in, using that information -- but again, as we see by looking closely at the heat map -- that guess may not be accurate. Which right now doesn't really matter much (the inaccuracy). We still treat mostly by those 3 markers, and sometimes the Oncotype, because -- so far that's all we have evidence to support.
But don't you think we must be on the edge of a transition zone? Where soon all research will look at all possible genetic information from a tumor -- perhaps using for now the 5 subtypes but having the details stored so that as more subtypes are identified and validated, they can go back and look retrospectively at even more subtypes -- looking at the behavior of each type, and most-importantly, its response to many different treatments. Perhaps eventually looking not just at the tumor's pedigree but also at the heterogeneity and the immune environment in which it lives. So that eventually (we are far from there, yet) -- there will truly be individualized treatment. Then, not only will we treat (stop) cancers most effectively, but we will save people from the many toxicities of treatments that do not stop their cancer.
So that was an extremely long no-anwer to Roz's question about what subtype her cancer might be. We don't know, from the information given. And even if we did know, we wouldn't know what to do with that information (yet).
Debbie Laxague