Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

The other day I clicked on a link someone shared on Twitter about new findings in breast cancer genes, which sounded really cool and interesting.  On clicking through it turned out to be a rather disappointing Reuters release on several fronts:

  1. Where's the link to the original article (in these days of social sharing leaving it out is plain lazy)?
  2. What/where are the "five common genetic factors" exactly?  No mention is made of them.
  3. What does this finding actually mean?
  4. What's the 'wow' factor here rather than the 'so what' factor?

I don't know about anyone else, but daily press releases and assaults in the media about identification of yet more gene blah blah that may or may not be relevant becomes anaesthetising after a while.

After a while, I finally tracked down the actual article in Nature Genetics myself to see what the data actually said (reference below with link to the paper for those interested).

What the researchers did was interesting; they conducted a large genome-wide study (GWAS) in around 8,000 people, approx. half of whom had a family history of breast cancer and half did not (controls). They then studied the DNA of another 24,000 women, with and without breast cancer.  By analysing over half a million SNP's, they were able to identify new 5 loci on chromosomes 9, 10 and 11 which if present, represent an increased risk of developing breast cancer.  This is in addition to 13 gene variations already identified in previous research.

Many of you will be aware of two high risk genes which are more likely to be defective in someone with breast cancer, known as BRCA1 and BRCA2.  These genes often confer higher risk of breast or ovarian cancers and can be tracked in families to try and pick up the cancer earlier. More recently, they have become targets for therapeutic intervention with PARP inhibitors such as AstraZeneca's olaparib in BRCA-positive breast and ovarian cancers.  More on this in another post. 

But what if these 5 new gene variations are also important and early identifiers of increased risk?

The reason that these findings are important is that as Prof Bert Vogelstein of Johns Hopkins never tires of pointing out at AACR meetings, most cancers, including breast cancer, are often diagnosed relatively late in their development and people die from the last 3 years of metastatic disease because the cancer went undetected for 20 odd years. 

GWAS as a field is also becoming more relevant, highlighting distinct subsets of
patients who can then be evaluated for prognosis, biomarkers, efficacy
and tolerability differences.

We still have very few methods of efficient and effective early detection, but what GWAS may allow us to do in future when we have more complete information (and gene testing is cheap, reliable and more widely available) is to potentially run screens to identify those most at risk for cancer.  These people could then be monitored more closely and watched diligently for early signs of cancer appearing.  Early stage cancer is potentially curable with surgery.  Inevitably, preventative studies could also be considered for high risk groups in future.

So these findings will have little immediate impact now, but in future if replicated, they could form the backbone of a comprehensive strategy to identify those people most at risk from developing cancer.  If we think about it, the enormous cost of end of life medical care massively dwarfs what the cost of earlier intervention and potential cure via surgery with or without neoadjuvant therapy would be.  Ultimately, we need this kind of data to move to a wellness model rather than a palliative model.

I would like to acknowledge my buddy Scott Hensley at NPR Health for prodding me into explaining the rationale behind my grump on Twitter about the flood of 'so what' rather than 'oh wow' gene data that constantly abounds daily.  If you're not following him on Twitter or listening to his awesome NPR Health podcasts on iTunes or the web, you should consider it!
Turnbull, C., Ahmed, S., Morrison, J., Pernet, D., Renwick, A., Maranian, M., Seal, S., Ghoussaini, M., Hines, S., Healey, C., Hughes, D., Warren-Perry, M., Tapper, W., Eccles, D., Evans, D., Hooning, M., Schutte, M., van den Ouweland, A., Houlston, R., Ross, G., Langford, C., Pharoah, P., Stratton, M., Dunning, A., Rahman, N., & Easton, D. (2010). Genome-wide association study identifies five new breast cancer susceptibility loci Nature Genetics DOI: 10.1038/ng.586

6 Responses to “Are we becoming immune to daily gene announcements?”

  1. Carmen

    Hmmm… BUT my (personal, that is, non-institutional) questions (concerns, I guess) is that in identifying all of these “at risk” people – because it seems like that could be a heck of a lot of people, and assuming of course that you can validate all of these genetic changes that signal increased risk – how intense (and expensive) will the monitoring have to be, and will you be able to identify the points at which an intervention of some type is required? I have other questions on the subject, of course, but these are among the most pressing! 😀

  2. MaverickNY

    Howdy Carmen! Great to finally meet you in person at AACR last month. Great questions and ones that I suspect the NIH and NCI will be thinking about too.
    Monitoring need not be that expensive, or at least any more than it is now. For example, many women who have a history of breast or ovarian cancers via BRCA1/2 are routinely followed by their PCP’s via either annual mammograms or MRI’s if they are considered to be high risk and the women themselves perhaps check for symptoms more diligently than most.
    Let’s assume that these new loci might also turn out to be familial like BRCA. From memory, hereditary breast cancer is rare and only around one in 20 of all breast cancers are due to inherited faults in breast cancer genes, so the numbers may turn out to be quite small.
    That said, if we could more easily identify and catch just these cancers early that would allow earlier and more effective intervention. There is so much research yet to be done in this field and many answers to be found.
    In this respect, I think the future is really about:
    1. How can we identify those most at risk for cancer prognostically?
    2. What is the best way to efficiently monitor them?
    3. What early prevention strategies/therapeutics could be employed?
    4. How can we mitigate the risk with more healthy strategies?
    5. If cancer is detected earlier, how can we collect and summarise this body of data to show that detection and monitoring is viable?
    The list goes one. Maybe more researchers and policy makers will think more strategically going forward. We’ve made great progress but there is still a lot of work to go.
    Ultimately, we have to balance the risk-benefits of early detection and cure vs long term cost of treating stage IV disease (v expensive).

  3. SBE

    Hi Sally,
    First, I think you did a great job explaining this article. One item I would mention is that this is a GREAT GWAS article in a sea of underpowered & overinterpreted studies. As you have implied, each of these mutations confers a small effect on your risk of developing cancer.
    What your list above is missing is a list of the genes that have been identified and how each of those genes affects your individual risk. I think this is a sub-bullet of #1 (that you implied but did not state).
    I personally have tired of reading gene announcements because there are so many poorly-conducted studies out there just like the SNP reporting in the late 90s and early 2000s. Articles like this get me jazzed up again, but only until OBR comes out and I see a new crappy article…
    On a similar note, I am also tired of food/additive/diet associations with cancer risk.

  4. MaverickNY

    Hi Brandon,
    Yes, I agree the missing 13 should be added, I was irritated enough that the new 5 were not stated in much of the press on it so went and found them myself.
    My original intent was to include them in the article but got distracted by phone calls coming in while making sure I had the right ones and then forgot!
    I’ll add them to the blog post as an update at the end for those interested unless you have them all to hand and would like to add them in a comment? 😉

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