The Antidote

Counterspin for Health Care and Health News

Tuesday, June 12, 2007

The fog of medicine

Baffling news from the recent American Society for Clinical Oncology meeting, about which the public should probably not yet make too much of a fuss; however, the NY Times chose to report on it, so there you are. Here's my take on what I've read in today's article.

Researchers presented an analysis of pathology samples from a study that had previously shown that breast cancer patients classified as positive for the HER-2 gene allowed them to benefit from treatment with trastuzumab (Herceptin). Another look at the HER-2 positive samples showed that 20% of them were actually HER-2 negative - and yet half of those women benefited from treatment with trastuzumab, a drug that specifically targets HER-2.

This could mean any (or more than one) of three things, none of which we have enough information at this point to be confident:

- the tests (immunohistochemistry - for the protein - and fluorescence in situ hybridization - for the gene) are worse than we thought
- the threshold for classifying a patient as HER-2 positive is wrong
- trastuzumab is not as specific to HER-2 as we thought (suggesting that women with HER-2 negative tumors could also benefit)

The studies described are small, and even those at the meeting (including the Times writer) did not have the benefit of all the methodological and data details we would in a peer-reviewed, published paper. In other words, these findings are meant to be chatter amongst investigators, and to suggest directions for more definitive research: for example, why did the women in the early studies test positive for HER-2, and negative now? were there other genes involved that could affect the results of the tests and/or the activity of trastuzumab? I'm not a molecular biologist, or an oncologist, so I'll stop there.

Regarding the NYTimes story itself, if it had fallen clearly into the excitement-of-science category, perhaps - perhaps - I'd have been OK with it, but there's a little too much hype offered up front by a National Cancer Institute scientist, suggesting that the results are potentially "practice-changing."


At 9:45 AM, Anonymous bev M.D. said...

Hi DB;

I saw your blog once before referenced on a Sermo post, but I forgot to add it to my favorites! So that's why I am commenting on a non-recent post!

As a pathologist I can add just a little clarity to the NY Times article, which I have not read. As far as classifying patients as positive or negative for HER-2neu; this is not an exact science. In fact, I heard a recent presentation indicating that an "outside" (e.g. pathologist not involved in a given clinical trial) pathologist's classification of this receptor as either + or - was found to be often in error. Like many things in pathology, it's not black and white - if one uses immunohistochemistry, it's a matter of estimating how many cells stain brown, how they stain brown, and then calling it 1+, 2+ or 3+. You can see how irreproducible that might be. There is also an immunofluorescence test called FISH which is somewhat better, but more expensive and prone to its own problems.

The bottom line is, I would look at reliability of classification first when trying to explain these seeminly aberrant results. That said, there may be something else going on in addition.

At 9:48 AM, Anonymous bev M.D. said...

Oops, wrong blog name; sorry!! I was scrolling through several recommended blogs and forgot I had switched from DB's Medical Rants.
But I'm adding you to my favorites anyhow!! (:

At 9:57 PM, Blogger Emily DeVoto, Ph.D., said...

Hi Bev,

I was momentarily confused, but your comment was right on, so no problem. Thanks for the insight about HER-2. I might like to write a general piece about the pitfalls of pathology someday... I was always intrigued by a study I heard about once re. the vast disagreement among a dozen or so pathologists who were assigning melanoma diagnoses on a series of slides.


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