“The GSK grant funding to undertake mutational profiling of breast cancer in Uganda allows us to describe the biology of our cancers and to take advantage of advancements in therapeutics of breast cancer and improve survival in our patients,” said the UCI’s Orem.
In the U.S. and other high-income countries, for example, breast tumors are analyzed to see whether they express certain receptors for the hormones estrogen and progesterone and for human epidermal growth factor. Targeted therapies (in addition to surgery, chemotherapy and radiation) are available for tumors that express those receptors.
Tumors that express none of those receptors are called triple negative. In the U.S., African-American women are more likely to be diagnosed with triple-negative breast cancer and have a 40 percent higher death rate than European-American women. Triple negative breast cancer is particularly aggressive and has a poorer prognosis than other breast cancers, in part because there are no targeted therapies, underscoring the need for more research into this type of cancer and the importance of including different races and ethnicities in clinical trials.
No one now knows which tumor receptors are prevalent in sub-Saharan Africa because in most countries, reliable analysis is not done. Two small studies in Uganda have shown conflicting results.
‘There’s something different’
Part of the problem is a lack of resources and training to do the analysis. The gold standard for determining receptor status, at least in developed countries, is known as an immunohistochemistry test. However, barriers to testing include costs, inexperience in preparing specimens properly and a dearth of pathologists trained to reliably interpret the results.
The UCI-Fred Hutch study will test an alternative diagnostic tool — reverse transcription polymerase chain reaction, or RT-PCR — which already is used throughout the continent as part of international and regional efforts to test and treat HIV. Smaller studies have compared RT-PCR testing against immunohistochemistry to test for breast cancer receptor status. The two tests resulted in identical results about 90 percent of the time.
The study will enroll 100 Ugandan women with newly diagnosed breast cancer to undergo additional analysis of receptor status. Their tumor samples will be processed in the laboratories of the UCI-Fred Hutch Cancer Centre in Kampala, a state-of-the-art facility that opened in 2015 with outpatient clinics, laboratories and classrooms for training researchers and clinicians. The Kampala lab will ship frozen tissue samples to Seattle, and the study will compare the results of samples tested in Kampala using RT-PCR and in Seattle using immunohistochemistry.
In addition, the next-generation sequencing done at King’s Seattle laboratory by study co-investigator Dr. Eric Konnick — also using samples processed by the UCI-Fred Hutch laboratories in Kampala — will seek to understand at the molecular level why breast cancer in Uganda is so aggressive and why it so often affects young women. Konnick will focus on the exome, or the small percentage of the billions of nucleotides in the human genome that have the potential to be “expressed,” or translated into proteins.
“We do know that breast cancer tends to be more aggressive in Uganda,” Menon said. “But there are other differences too. The average age of a breast cancer patient at UCI is in the 40s, where in the U.S., it is 61. There’s likely something different in the pathogenesis of the disease. Hopefully this study will help to clarify some of the differences.”
Testing an oral chemotherapy regimen
In addition to establishing whether RT-PCR is an effective alternative to immunohistochemistry, the study will also test the feasibility of a chemotherapy regimen already shown to be effective for estrogen-positive breast cancers. Of the 100 women enrolled in the trial, 25 with receptor-positive early or locally advanced stage breast cancer will be invited to participate in this part of the study.