5 ms·

What hard evidence is there that genomics is relevant to cancer treatment, as proven by survival rates? Color me skeptical.

tom_b 11y ago
Hmmm? Genomic breast cancer subtypes that each respond to different chemotherapies? http://www.nature.com/nature/journal/v490/n7418/full/nature11412.html http://www.nature.com/nature/journal/v490/n7418/full/nature1...
- a8da6b0c91d 11y ago
  That doesn't really say anything about proven treatment efficacy.
  - tom_b 11y ago
    Some information is hidden away in supplemental table 6, which points out candidate drugs to affect different biological pathways for different mutations. You could also skim http://www.nature.com/nature/journal/v406/n6797/full/406747a0.html http://www.nature.com/nature/journal/v406/n6797/full/406747a... for more information about genomic classification of breast cancer. From a treatment prespective, I would say that just glancing at http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.htm... would provide information on treatment decisions generally made by finding appropriate subtype classifications. I think that it is pretty clear that genomic sequencing of patient normal and tumor tissue to find mutations is going to be standard-of-care sooner rather than later, but it is fair to point out that genomic sequencing is not currently standard-of-care. However, I know of studies currently underway that look at variant calls and the possibility of taking action on those calls in ways the involve specifically adding those results back into the patient medical record. I am struggling a bit with how to phrase this, but I don't think you can argue against (1) different subtypes of breast cancer are separate diseases and can be classified by genomic sequencing and (2) treatments for these separate diseases are different and have different efficacies.
dudurocha 11y ago
Look for BRCA1 and BRCA2 genetic testing and therapy.
davecap1 11y ago
Cancer is a disease of genetics. You need to know what kind of cancer someone has in order to choose the treatment. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032883/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032883/
nl 11y ago
Oh look! Watson can answer that question: https://youtu.be/UFF9bI6e29U?t=2670 https://youtu.be/UFF9bI6e29U?t=2670 (ok, it's not exactly that question, but you can see how it works)
Gatsky 11y ago
You are right to say this. I treat breast cancer, and I'm doing a PhD on breast cancer genomics, and there is no evidence that high throughput data of any kind, whether it is genomics, transcriptomics, epigenomics, proteomics, metabolomics etc-omics actually helps patients. At the moment, a small panel of biomarkers using technology that is at least 20 years old is all we use to make treatment decisions. Is it adequate? Certainly not, but there is a HUGE amount of carefully collected data in many thousands of patients backing it up. Not sure who is downvoting you, but they seem to have swallowed the hype wholesale. At the risk of sounding gratuitously negative, I find the discussion of medicine on HN to be of very poor quality, markedly below the general standard.
- tom_b 11y ago
  I think there is a distinction to be made here in questioning patient outcomes and questioning the relevance of genomic sequencing in treatment decisions. Don't you think it is fair to say that high throughput data (whole genome sequencing with variant calling) is still in a state of being evaluated to measure its effectiveness in aiding the treatment decision process but that early results seems to lean towards it becoming part of the standard diagnostic approach? Genomic sequencing and patient outcomes is a thornier question. My non-practitioner take is that it is too early to tell scientifically, but that there will probably be some benefit to early identification of specific cancer types and choosing treatment. But I think many people would have made a similar statement about mammography and early detection, and absolute mortality appears to not be reduced by adding mammography to the diagnostic procedures, right? The research value of genomic sequencing seems high enough to make it worthwhile. At least, when I sit in on molecular tumor board reviews (the oncologists at a table looking at called variant results for a specific patient), I hear them commenting about possibly new and unknown variants being of research value. I am really looking forward to your reply - Internet message boards in general have to be almost the worst way to discuss medicine, but having participation from researchers and practioners like you is tremendously illuminating!
  - Gatsky 11y ago
    I define genomics as the unbiased interrogation of the genome using high throughput technology. Sequencing one mutant locus using Sanger sequencing does not fall under this definition - I don't think IBM's business model is using Watson to interpret that. So when other people point out that HER2 is a useful genomic marker they are missing the point - HER2 can be determined with immunohistochemistry for example which has been around for 50 years. I'm not sure what your question is... genomics has research value, for sure, it's great. Is it worth trying to incorporate it into routine care? Yes, probably, if you have enough cash. Should a hospital pay for a black box machine learning algorithm to make recommendations from a highly polluted, often erroneous and hugely incomplete literature corpus? The alternative put forward by people actually doing the science is that we should try and develop large open source databases/repositories about the significance of genomic findings, and then collect the data about what happens to the patients.
dekhn 11y ago
Herceptin. Trastuzumab inhibits the effects of overexpression of HER2. If the breast cancer doesn't overexpress HER2, trastuzumab will have no beneficial effect (and may cause harm). he original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) breast cancer from 20.3 to 25.1 months.[1] In early stage breast cancer, it reduces the risk of cancer returning after surgery by an absolute risk of 9.5%, and the risk of death by an absolute risk of 3% however increases serious heart problems by an absolute risk of 2.1% which may resolve if treatment is stopped.[2]

tom_b 11y ago

Hmmm? Genomic breast cancer subtypes that each respond to different chemotherapies? http://www.nature.com/nature/journal/v490/n7418/full/nature11412.html http://www.nature.com/nature/journal/v490/n7418/full/nature1...

a8da6b0c91d 11y ago
That doesn't really say anything about proven treatment efficacy.
- tom_b 11y ago
  Some information is hidden away in supplemental table 6, which points out candidate drugs to affect different biological pathways for different mutations. You could also skim http://www.nature.com/nature/journal/v406/n6797/full/406747a0.html http://www.nature.com/nature/journal/v406/n6797/full/406747a... for more information about genomic classification of breast cancer. From a treatment prespective, I would say that just glancing at http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.htm... would provide information on treatment decisions generally made by finding appropriate subtype classifications. I think that it is pretty clear that genomic sequencing of patient normal and tumor tissue to find mutations is going to be standard-of-care sooner rather than later, but it is fair to point out that genomic sequencing is not currently standard-of-care. However, I know of studies currently underway that look at variant calls and the possibility of taking action on those calls in ways the involve specifically adding those results back into the patient medical record. I am struggling a bit with how to phrase this, but I don't think you can argue against (1) different subtypes of breast cancer are separate diseases and can be classified by genomic sequencing and (2) treatments for these separate diseases are different and have different efficacies.

dudurocha 11y ago

Look for BRCA1 and BRCA2 genetic testing and therapy.

davecap1 11y ago

Cancer is a disease of genetics. You need to know what kind of cancer someone has in order to choose the treatment. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032883/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032883/

nl 11y ago

Oh look! Watson can answer that question: https://youtu.be/UFF9bI6e29U?t=2670 https://youtu.be/UFF9bI6e29U?t=2670 (ok, it's not exactly that question, but you can see how it works)

Gatsky 11y ago

You are right to say this. I treat breast cancer, and I'm doing a PhD on breast cancer genomics, and there is no evidence that high throughput data of any kind, whether it is genomics, transcriptomics, epigenomics, proteomics, metabolomics etc-omics actually helps patients. At the moment, a small panel of biomarkers using technology that is at least 20 years old is all we use to make treatment decisions. Is it adequate? Certainly not, but there is a HUGE amount of carefully collected data in many thousands of patients backing it up. Not sure who is downvoting you, but they seem to have swallowed the hype wholesale. At the risk of sounding gratuitously negative, I find the discussion of medicine on HN to be of very poor quality, markedly below the general standard.

tom_b 11y ago
I think there is a distinction to be made here in questioning patient outcomes and questioning the relevance of genomic sequencing in treatment decisions. Don't you think it is fair to say that high throughput data (whole genome sequencing with variant calling) is still in a state of being evaluated to measure its effectiveness in aiding the treatment decision process but that early results seems to lean towards it becoming part of the standard diagnostic approach? Genomic sequencing and patient outcomes is a thornier question. My non-practitioner take is that it is too early to tell scientifically, but that there will probably be some benefit to early identification of specific cancer types and choosing treatment. But I think many people would have made a similar statement about mammography and early detection, and absolute mortality appears to not be reduced by adding mammography to the diagnostic procedures, right? The research value of genomic sequencing seems high enough to make it worthwhile. At least, when I sit in on molecular tumor board reviews (the oncologists at a table looking at called variant results for a specific patient), I hear them commenting about possibly new and unknown variants being of research value. I am really looking forward to your reply - Internet message boards in general have to be almost the worst way to discuss medicine, but having participation from researchers and practioners like you is tremendously illuminating!
- Gatsky 11y ago
  I define genomics as the unbiased interrogation of the genome using high throughput technology. Sequencing one mutant locus using Sanger sequencing does not fall under this definition - I don't think IBM's business model is using Watson to interpret that. So when other people point out that HER2 is a useful genomic marker they are missing the point - HER2 can be determined with immunohistochemistry for example which has been around for 50 years. I'm not sure what your question is... genomics has research value, for sure, it's great. Is it worth trying to incorporate it into routine care? Yes, probably, if you have enough cash. Should a hospital pay for a black box machine learning algorithm to make recommendations from a highly polluted, often erroneous and hugely incomplete literature corpus? The alternative put forward by people actually doing the science is that we should try and develop large open source databases/repositories about the significance of genomic findings, and then collect the data about what happens to the patients.

dekhn 11y ago

Herceptin. Trastuzumab inhibits the effects of overexpression of HER2. If the breast cancer doesn't overexpress HER2, trastuzumab will have no beneficial effect (and may cause harm). he original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) breast cancer from 20.3 to 25.1 months.[1] In early stage breast cancer, it reduces the risk of cancer returning after surgery by an absolute risk of 9.5%, and the risk of death by an absolute risk of 3% however increases serious heart problems by an absolute risk of 2.1% which may resolve if treatment is stopped.[2]