Examining the Role Genetics Plays in Breast Cancer Onset 

A Conversation with Olufunmilayo I. Olopade, MD, FACP


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We hear about the celebrities having prophylactic mastectomies, but what’s missing in the media reports are stories of regular women who are going about their lives and asking their doctors to help them manage their risk factors. This is where ASCO can come into the discussion and help doctors give women good information regarding their specific risks.

—Olufunmilayo I. Olopade, MD, FACP

Internationally known for her research in the molecular genetics of cancer, Olufunmilayo I. Olopade, MD, FACP, first became interested in oncology during medical school in Nigeria, where she cared for patients with Burkitt’s lymphoma. After moving to Chicago in 1983 to continue her medical education, Dr. Olopade became interested in the fundamental biology of cancer, especially solid tumors, and in finding ways to translate research in genetics to the development of more effective therapies for patients.

In the early 1980s, Dr. Olopade was the recipient of ASCO’s Conquer Cancer Foundation Young Investigator Award, which she used to study chromosomal abnormalities in brain tumors. She later concentrated her research on the molecular genetics of breast cancer in diverse populations, cancer risk assessment, personalized approaches to prevention, and disparities in health outcomes. In 2005, she received a MacArthur Foundation Genius Grant, and the following year, was the recipient of the American Association for Cancer Research–Minorities in Cancer Research Jane Cooke Wright Memorial Lectureship Award.

Dr. Olopade is the Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, Associate Dean for Global Health, and Director of the Center for Clinical Cancer Genetics at the University of Chicago Medicine. Her current laboratory research is focused on using whole-genome technologies and bioinformatics to develop novel approaches to risk assessment and precision cancer medicine.

The ASCO Post spoke with Dr. Olopade about her research in tumor-suppressor genes, the treatment of breast cancer in women at high risk—especially young women—and the development of better strategies for earlier detection and prevention of breast and ovarian cancers.

African–African American Connection

Why did you become interested in studying the genetics of breast cancer?

I’ve been fortunate to work in an area of the South Side of Chicago where the population is predominantly African American, and I was able to look at how genetics can be distributed across populations. I realized how much we know about cancer in majority populations and how little we know about cancers in minority and underserved populations. And as far back as 1997, when we started thinking about the role of genetics in the clinic, I felt that until we could get in-depth knowledge about minority populations, we would not know what to do with all the genetic variations that could potentially impact cancer outcomes.

So part of my interest in researching the genetics of breast cancer came from the connection I was making between early-onset breast cancer in the young women coming into my clinic in Chicago and the women I saw in Nigeria. I asked a simple question: Were these cancers due to inherited gene mutations?

Early-onset Breast Cancer

Does early-onset breast cancer affect more African American women than Caucasian women?

Yes, early-onset breast cancer affects not only more African American women, but more Hispanic women as well. If you look at the global distribution of cancer in women, the disease affects greater numbers of younger women in populations that have a lower incidence of breast cancer in general. So anywhere around the world where populations have not adopted a Western lifestyle, you are going to see that the face of breast cancer is that of a young woman.

How do genetic mutations like BRCA1 and BRCA2 contribute to early-onset breast cancer?

We really haven’t had the tools to determine both the genetic contribution and the role of lifestyle and other environmental factors in the development of breast cancer. But we know that genes are influenced by lifestyle, culture, what you eat, and the environment. So as much as we need to study how these factors interact with one another, we also need to ask, What is driving this cancer, is it the genetic mutation that is acquired, and how are those mutations acquired? Is it that the genetic mutations you were born with predispose you to getting cancer?

We are finally now in a position to understand these questions, because we can do testing on the germ line and testing on the tumors and figure out which one is driving the development of the cancer.

Sequencing the Genome

What led to the development of BROCA, the genetic screening panel that now includes BRCA1 and BRCA2 (since the Supreme Court ruling that human genes may not be patented)?

After investigators found the BRCA1 gene mutation in 1994 and BRCA2 mutation in 1995, we began looking for the unexplained inherited factors that contributed to breast cancer. We were expecting to find BRCA3, but we didn’t. What we did find were other altered genes that contributed to breast cancer risk. We now know there are about 18 genes that can be altered and thereby contribute to breast cancer risk, but we may learn about more genes in the future.

BROCA, which was developed by Mary-Claire King, PhD, Tom Walsh, PhD, and their colleagues at the University of Washington School of Medicine, is a new way of sequencing the genome to find out how these genes can be altered and lead to cancer. The test currently detects mutations in about 40 genes, with a focus on mutations associated with breast and ovarian cancers.

Genetic Screening

When should oncologists recommend genetic testing for their patients with breast cancer or ovarian cancer?

ASCO has issued recommendations for when genetic counseling and testing should be offered to patients.1 In general, there are three reasons why oncologists may want to offer their patients genetic screening: To predict the risk of cancer for the patient and to help family members understand their own risk factors, because now we can actually do something about managing those risks. Increasingly, genetic test results can also influence choice of treatment after a cancer diagnosis.

For example, a study we presented at this year’s ASCO Annual Meeting showed that magnetic resonance imaging (MRI) surveillance of women at high risk for breast cancer every 6 months is effective in early detection of aggressive breast cancer by detecting tumors less than 1 cm in diameter.2 Moreover, using MRI imaging eliminates exposing young women to excessive amounts of radiation in mammography screenings. This makes me much more optimistic that for many of these aggressive cancers, we can now do better risk assessments and use genetics to identify women at high risk for specific subtypes of breast cancer. We can then tailor strategies to manage that risk.

Prophylactic Mastectomy

Are more women coming to your practice asking about prophylactic mastectomies since the actress Angelina Jolie went public with her decision to have a bilateral mastectomy? How are you advising those patients?

Even before Ms. Jolie’s announcement, we had been seeing an epidemic of women coming into our clinic and asking to have a prophylactic mastectomy. Everybody still has a fear of getting cancer, and that’s why I’m excited about our research—because we know that having a genetic mutation doesn’t mean that the person will get cancer. A lot of work we are doing gives women more options, including regular MRI surveillance.

We hear about the celebrities having prophylactic mastectomies, but what’s missing in the media reports are stories of regular women who are going about their lives and asking their doctors to help them manage their risk factors. This is where ASCO can come into the discussion and help doctors give women good information regarding their specific risks, so they are not getting their information from the media.

Aggressive Treatment

A study presented at the ASCO Annual Meeting showed that most women 40 or younger diagnosed with breast cancer are choosing mastectomy rather than lumpectomy plus radiation, and most of those choosing mastectomy also elect to have their noncancerous breast removed.3 Why do you think more women are choosing such aggressive treatment?

We have failed in presenting these patients with alternative viewpoints. Women come to my clinic after being told by their oncologist, “If you don’t want to get cancer, why don’t you have both breasts removed?” At our cancer genetics education presentation at the ASCO meeting, we said it is important that we tell these patients they have options and that having a genetic mutation doesn’t mean they will definitely get cancer.

We want women to know about their risk for breast cancer and how to manage that risk. Cancer prevention is going to be increasingly emphasized, because we can’t tell every woman to remove every body part. Let’s give women options and tell them that cancer is curable when picked up early and cancer is preventable. As ASCO members, all of us have to make sure that women get that message.

Supreme Court Decision

What was your reaction to the Supreme Court ruling in June that human genes could not be patented?

It was a victory for genetic justice. And now the price for genetic testing will be less expensive and available to more people. As someone who is interested in health disparities, I feel that the Supreme Court got it right by supporting the most vulnerable of all. People with a genetic burden who need our help should not face unnecessary emotional and financial burden because they can’t afford the genetic test. ■

Disclosure: Dr. Olopade reported no potential conflicts of interest

References

1. Robson ME, Storm CD, Weitzel J, et al: American Society of Clinical Oncology policy statement update: Genetic and genomic testing for cancer susceptibility. J Clin Oncol 28:893-901, 2010.

2. Guindalini RSC, Huang Y-C, Obeid E, et al: Breast cancer surveillance in high-risk women with magnetic resonance imaging every 6 months. 2013 ASCO Annual Meeting. Abstract 1506. Presented June 3, 2013.

3. Rosenberg SM, Sepucha K, Ruddy KJ, et al: Choosing mastectomy over lumpectomy. 2013 ASCO Annual Meeting. Abstract 6507. Presented June 3, 2013.



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