Better genetic diagnostics in Ugandan breast cancer patients

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Published: 29 May 2020
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Dr Julie Gralow - University of Washington School of Medicine, Seattle, USA

Dr Julie Gralow speaks to ecancer online about her ASCO 2020 virtual presentation which discussed the profiling of breast cancer patients in Sub Saharan Africa, specifically Uganda.

Joint with the Ugandan Cancer Institute, researchers in Seattle are looking at using RT-PCR instead of a more complex and expensive IHC approach, (using resources and capacity developed during the HIV pandemic).

Dr Gralow explains that using this technique is almost as good and specific as the more complex IHC methods - which would greatly improve the diagnosis, personalisation, and availability of breast cancer treatment in Sub Saharan Africa.

We did a very interesting study with our colleagues at the Uganda Cancer Institute looking at a more reproducible and reliable way of doing oestrogen receptor, progesterone receptor and HER2 testing in breast cancers that are diagnosed at the Uganda Cancer Institute. The Fred Hutchinson Cancer Research Centre has a long-standing relationship with the Uganda Cancer Institute that started based on HIV-associated malignancies and now has really expanded across malignancies. Breast cancer is the most common cancer in women who present at the Uganda Cancer Institute followed closely by cervical cancer.

So we have several clinical trials ongoing in partnership with our Ugandan colleagues and this was a trial looking at instead of doing classic immunohistochemistry, which is what we typically do for oestrogen receptor, progesterone receptor, HER2, and then following up with fluorescence in-situ hybridisation for the two pluses by HER2. Instead of doing that, which takes a lot of manpower, a lot of reagents, a lot of equipment and skill, could we use this automated PCR cartridge-based system that’s widely used throughout Africa for HIV and TB? It’s a system that they already know how to use and it’s in place and available. Could we use that and do ER/PR/HER2 testing by RT-PCR? So we compared that, using the Cepheid machine and an assay called the STRAT4 Breast Cancer Gene Expert assay, could we use that? And we compared it to the gold standard of immunohistochemistry actually done in Seattle by our group.
What we show in this presentation is that actually it’s pretty reliable. The ER and PR in particular were quite highly correlated. The HER2 was a little bit less but we’re really investigating that because that seems to be in the two pluses which we did not go on and do FISH because the RT-PCR doesn’t have that capacity, they don’t have that capacity at the Uganda Cancer Institute. But I do think we could tweak that and figure out the three pluses who were most likely to respond to HER2-based therapy, we can probably reliably identify with this technique.

So we’re going to continue to do this. This was in the first thirty-some patients out of a hundred planned and we’re starting to look at how can we get HER2 therapy in Uganda. It’s expensive but it really works in appropriately selected patients and so this is part of a project to try to get adjuvant trastuzumab in HER2 patients in Uganda so that we can decrease recurrences and deaths. If we could figure out how to get the therapies that we have in our high income countries, just the ones we know about right now, if we could get them into patients in low and middle income countries tomorrow we would be saving tens, if not hundreds, of thousands of lives overnight without any further research other than how do we implement these things and how do we afford them.

So I think this is a fascinating study and leapfrogging, not teaching them all how to do immunohistochemistry but moving on to a machine that they know how to use, they have in place. I think this is where we need to go with this, what we call, leapfrog technology where they don’t need to do it the same way that we do it if we can do it reliably.