Olufunmilayo Olopade, MD, discusses her research on genomic sequencing and breast cancer, which has led to insights into how the disease progresses—and how it can be prevented. What's key, she says, is that one-size-fits-all screening shouldn't be recommended.

Genomic sequencing is becoming increasingly central to cancer treatment, used by oncologists to develop—and match patients to—therapies that target specific alterations. However, Olufunmilayo Olopade, MD, of the University of Chicago Medicine in Illinois, argues that genomic testing should play a more significant role at earlier stages of cancer. “We really need to integrate genetics into all aspects of oncology care,” Olopade says. “I'm impatient to go beyond waiting to treat advanced cancer to using genomics to prevent cancer, and also to give people the opportunity for early detection.” To this end, Olopade cofounded CancerIQ, which provides oncology centers with a “cancer risk clinic in a box” that includes tools such as screening questionnaires and a digital platform for ordering genetic tests and managing high-risk patients (www.canceriq.com).

In an interview with Cancer Discovery's Catherine Caruso, Olopade spoke about her broad vision for genomic sequencing in breast cancer, including how it can improve risk assessment and lead to better cancer detection and prevention. She will delve further into her work at the American Association for Cancer Research (AACR) Annual Meeting 2020 in San Diego, CA, April 24–29.

What are your main areas of research?

I am a practicing oncologist, but my research is focused on getting a deeper understanding of the genetic basis of cancer progression, especially in individuals with inherited cancer susceptibility. I think we're on the cusp of routinely using germline alterations to identify those at high risk and intercept cancer—and using genetics for population risk stratification. If everybody knew their risk of cancer, people could be more proactive in reducing their risk. But we haven't pushed genomic testing for risk assessment far enough.

I'm also interested in population genetics. We have such a diverse population in the United States, and that genetic diversity means that we should have diversity in the research that we do. My work has spanned studying breast cancer progression in Nigerian women, as well as in women on the South Side of Chicago and in women of African ancestry in the diaspora. We're learning a lot about how cancers evolve to become resistant to therapy and become metastatic in these different populations. We can better intercept metastases if we know how these cancers progress.

What insights have you gained from your work?

When we started finding families with BRCA1/2 mutations, everybody thought the only thing you could do was recommend that these women have their breasts removed to avoid cancer. We began a program of research on women who didn't want to have their breasts removed prophylactically but wanted to be screened. We looked at MRI to see if we can have better resolution and better screening. Over two decades, we've shown that you can pick up inherited cancers very early if you use MRI [Clin Cancer Res 2019;25:1786–94]. For decades, women have been going in for mammograms, but if we can better predict risk, we can assign women to get MRI, a technology that keeps getting better and cheaper.

But questions remain: How many people don't know they have a BRCA mutation? How do we get them in for genomic testing? Can we prevent breast cancer outright if we know the risk? We have interventions that work, we just have not been able to implement them across the board—every cancer center and community practice should be able to develop a strategy for preventive oncology.

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“We should not be recommending one-size-fits-all screening,” Olopade says.

How does breast cancer progress in different populations? How can this knowledge inform screening?

At the population level, in the Nigerian Breast Cancer study we found that Nigerian women were getting breast cancer in their 30s and 40s, for reasons that were poorly understood [J Clin Oncol 2018;36:2820–5]. More than any other population we have studied, we found these women were more likely to develop triple-negative breast cancer—a form of breast cancer that tends to develop earlier in life. We found that it's because they are more likely than other populations to have mutations in BRCA1/2 and other genes involved in DNA repair. By sequencing the tumors of these young women, we're beginning to understand that the trajectory of cancer is different than what we previously thought. The classic cancer biology textbook says it takes 20 years for you to go from one cell to cancer, but that's not true. We see women who have a perfectly normal MRI come back in 6 months and have a 6 mm breast cancer blossoming—and if they waited another 6 months it would be in the lymph nodes. So, the way we thought about cancer's trajectory has been turned on its head, and sometimes the trajectory of your cancer may be related to your genetic ancestry—and so we should not be recommending one-size-fits-all screening.

How has studying different populations shaped your views on the importance of diversity in cancer research?

The whole biomedical research enterprise has not really addressed diversity and equity, so at the AACR Meeting, I will talk about some of the newer insights we've been able to gain looking at diverse cancer genomes thanks to our collaborators in Nigeria. The scientific community has to see that cancer research must be global for us to make the kind of progress we need to make. We need to embrace diversity and inclusion—diversity in the types of questions we ask and in the populations we study—because we don't know where the cures are going to come from.

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©2020 American Association for Cancer Research.
2020
American Association for Cancer Research.