I had a somewhat mixed reaction to Genetic Technologies’ (ASX : GTG) recent, rather breathless update about the progress of its BREVAGenplus breast cancer risk test (the product website is worth a read for basic background). There can be little doubt that we are entering the era of genetic testing in order to improve the economics of healthcare through better decision-making. While there are plenty of risks and ethical issues to still be ironed out, there are also plenty of potential benefits if we can get it right.
It has taken me a while to look past GTG’s rather underwhelming and mostly rubbish past to try to understand and convince myself that there is something of real clinical credibility here. It wasn’t much helped by their recent highly-technical and jargonish paper (full text available) that, while probably containing some very interesting analysis, imparts few clearly discernible messages for someone that doesn’t have a Ph.D in biostatistics. After a few reads, I came to the conclusion that this soundbite (on page 587) is probably the most important:
For each of the risk prediction models, the combined risk score resulted in approximately 40 % of African American cases moving into a higher risk category and approximately 10 % of controls moving into a lower risk category. For Hispanics, over 20 % of cases moved into a higher risk category, and 6 % of controls moved into a lower risk category when using BCRAT and 17 % when using IBIS. These values are higher than the two previous studies of Caucasian cohorts which identified between 3 and 10 % of cases moving to a higher risk category.
Followed by :
The AUC value for BCRAT obtained for Hispanic women is lower than that previously reported . Whilst the IBIS model is widely used across ethnicities in the US it has only been validated for Caucasian populations , and both the ORs and AUC derived here for the model alone are low for both African American and Hispanic women. For the present analysis, information was not available for second degree relatives or for family history of ovarian cancer and it is not immediately clear whether this has impacted on the IBIS model performance. In addition to ethnicity differences and reduced pedigree inputs, the low values may reflect that IBIS was developed using data from studies of predominately postmenopausal women and is intended for use with high-risk populations.
Did they really use the word “pedigree” here? Hmmmm…
The problem is that the library of single nucleotide polymorphisms (SNPs) or “genetic mutations” that form the basis of the BREVAGenplus test have almost entirely been identified from Caucasian (i.e. white) women with breast cancer. Moreover, the risk predictor tests that are made more “discriminatory” by the BREVAGenplus test are also, on the whole, most validated in Caucasian (i.e. white) women with breast cancer. Therefore, although the fact that the SNP panel appears to confer some discriminatory benefit on the standard models of breast cancer risk, there is really very little evidence at this stage that the BREVAGenplus test is going to confer benefit on African and Hispanic women (i.e. non-white women), including reclassification to a higher risk category.
In fact I would argue from an ethics vantage that if a “diagnostic” test, without any meaningful genetic basis in minority patient populations, results in a % of women in minority populations to be reclassified as lower risk (and therefore potentially ineligible for augmented screening), then this test should be strenuously avoided. Why? Because it means that populations of women that are already underserved could be yet further marginalised, without a fully validated reason for it. By simply calibrating a “white” breast cancer risk score (using “white” genetic profiling no less) I don’t think we do anything positive for these women at all, and in fact it might be a dangerous reason for our already socio-economically biased healthcare systems to spend even less on these patient populations.
And therein lies the rub.
My personal interpretation of all of this malarkey is that the purpose of this exercise is really to eliminate an implied racial ineligibility for the BREVAGenplus test. This isn’t so much about increasing the market opportunity for the test, which is what our asinine market apparently thought by giving the “reward” of a bump in GTG’s stock price. Rather it is about removing a potentially racially polarising label for the product. Nothing damages marketability more than a product indication for a breast cancer test that reads “this product is not suitable for women of African or Hispanic origin.” I realise this is not a terribly positive interpretation, but it is really the only substantiated one.
At the end of the day, GTG talks a lot about physicians doing “good” for patients but it is measurable patient outcomes and healthcare reimbursement that matters (with paltry revenues and no specific reimbursement angle, let’s just ignore commercial success for the moment). For lack of actual genetic profiling in African/Hispanic patient populations, GTG has done the next best thing to make sure that its product has the broadest possible applicability, and that’s fine. But in doing so it may actually do its bit to ensure that fewer already underserved women get access to more advanced forms of screening.
Oh, and until BREVAGenplus gets properly reimbursed (i.e. not under a catch-all “misc” code), some people are going to have to pay for the test out of pocket. This is also less likely to happen in poorer “minority” populations.
It’s kind of a can of worms.