Editor's Note:
In the United States, breast cancer tumor characteristics -- including hormone receptor status and histology -- differ by race/ethnicity, and both biological and lifestyle factors are thought to contribute to these differences.[1] Although genetic testing has enabled the identification of women at risk for the development of breast cancer, and it is now possible to identify different forms of breast cancer for which therapy can be individualized, differential access to and utilization of genetic counseling and cancer care exists among racial and ethnic minorities and remains to be addressed.[2]
Following the 2007 Breast Cancer Symposium, held in San Francisco, California, in September, Medscape's Jill Chamberlain, Editorial Director, Hematology-Oncology, spoke about these issues with Olufunmilayo I. Olopade, MD, Professor of Hematology/Oncology, Department of Medicine, Pritzker School of Medicine; Walter L. Palmer Distinguished Service Professor, Department of Medicine and Human Genetics; and Director, Center for Clinical Cancer Genetics, University of Chicago Medical Center, Chicago, Illinois. Dr. Olopade's research has focused on biological differences in breast cancer across diverse populations within and outside of the United States.
Medscape: How has the genomic revolution impacted the diagnosis and treatment of breast cancer?
Dr. Olopade: It wasn't until the genomic revolution occurred that it was realized that physicians have treated breast cancer as a single disease when, in fact, from 5 to 7 categories of breast cancer exist. Today, because of the genomic revolution, our focus is on individualizing breast cancer treatment and learning more about individuals and their specific cancers using genomic analyses. An important goal is to identify breast cancer while it is local and curable, thus decreasing morbidity and costs.
Medscape: During your presentation at the 2007 Breast Cancer Symposium, you pointed out that race and area of origin are different factors that influence breast cancer. Would you explain that premise?
Dr. Olopade: As scientists, when we consider race, we should be thinking not only about color, but also about ancestry. For example, a patient may be African American, but her genetic material may be more European than African. Thus, we need to turn to a patient's ancestry, not race, to provide reliable information about genetic material and breast cancer risk.
I often use the example of Ashkenazi Jewish women, an ethnic population that is white but of eastern European descent. The prevalence of BRCA1 germline mutations is greater in the Ashkenazi Jewish population than in the general North American population.[3] BRCA1 tumors have a distinct phenotype and are associated with a significantly lower level of HER-2/neu amplification. Thus, it is possible that BRCA1-associated and HER-2/neu highly amplified tumors progress through distinct molecular pathways. We are now using tumor phenotype and ancestry to identify individuals likely to benefit from BRCA1 testing.[4]
Medscape: What is known about breast cancer in women of African descent?
Dr. Olopade: Women of African ancestry are more likely to be diagnosed with estrogen receptor-negative breast cancer than women of European ancestry. In a recent collaborative study in which gene expression was determined in breast cancer tissue from 378 women in Nigeria and Senegal and compared with a database of breast cancer tissue from more than 900 Canadian women, we found that breast cancers in African women were more likely to be estrogen receptor-negative.
Whereas in the United States, breast cancer typically occurs after menopause and usually affects women in their late 50s or early 60s, in Africa, breast cancer most commonly occurs in women in their late 40s. The rate and genetic profiles of breast cancers in African American women are likely to fall somewhere in between, with a slightly lower lifetime incidence of breast cancer than white women, but earlier onset and worse prognosis. African American women under the age of 35 have a 50% greater risk of developing breast cancer than white women of the same age group. This risk plateaus around the age of 50, and African American women over the age of 50 have less risk of developing breast cancer than white women.
Medscape: It is well known that triple-negative breast cancer has aggressive features and that patients with this form of the disease have a worse outcome than those with other breast cancer types. What are the population differences in triple-negative breast cancer?
Dr. Olopade: A number of studies have shown that triple-negative breast cancer is overrepresented in young African American women. In the Carolina Breast Cancer Study,[5] a population-based, case-control study that oversampled premenopausal and African American women, triple-negative breast cancer was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non-African American women (15%) of any age (P < .001). In a study[6] in which racial/ethnic differences in breast cancer incidence and outcome were examined in a large cohort of postmenopausal women who participated in the Women's Health Initiative, about 32% of African American women had triple-negative and poorly differentiated disease compared with rates of 10% to 17% in other ethnic groups.
Medscape: What are the clinical implications of these findings?
Dr. Olopade: Since most of the breast cancer screening guidelines used in the United States are based on studies that primarily included white women, we need to individualize breast cancer screening recommendations, inasmuch as current guidelines may not be optimal for African American women in whom breast cancer is less common but may develop earlier and progress rapidly. The practice of an annual mammogram beginning at age 50 may need to be adjusted based on individual risk assessment for women in all racial/ethnic groups.
In addition, since we know that all breast cancer is not the same, it is more critical for patients likely to develop aggressive types of breast cancer to have access to care than it is for those with more indolent forms of the disease. The practicing oncologist or radiologist -- or anyone else who cares for women with breast cancer -- should begin to focus on whether the individual patient has been diagnosed with a rapidly growing type of breast cancer, and treatment should not be unnecessarily delayed. A better understanding of breast cancer biology is crucial to developing and delivering tailored therapy to all patients. There's an intersection between biology and ensuring that oncologists aggressively treat certain forms of breast cancer rather than viewing the disease as a garden-variety cancer that can wait for treatment.
Medscape: How has the development of multigene assays facilitated the individualization of breast cancer treatment?
Dr. Olopade: The ability to examine thousands of genes using multigene assays has allowed us to learn that breast cancer is not one disease but rather multiple diseases. We are now using multigene assays for decision making in patients with breast cancer. We also know from genomic analysis that a certain proportion of outcome in a patient with breast cancer is contributed by that patient's genetic material as well as the genetic material from the tumor. Thus, it is important to know how the tumor develops within the patient.
Whenever a new genetic test is introduced, it is very important to determine how it performs in different populations. These newer multigene assays increasingly will be utilized and in the future will impact how oncologists practice. That is why it is important to educate both clinicians and patients about these tools and also to conduct more studies in diverse populations.
Medscape: As genomic research continues, what is likely to be the next advance?
Dr. Olopade: Right now, investigators are focusing on different treatments based on the results of genomic analysis. For example, we now know that women with HER2-positive breast cancer should receive trastuzumab because it is effective for that subgroup. However, there remain many different types of breast cancer for which we do not have specific drugs. In the near future, I believe that clinicians will have access to many new drugs targeted to different types of breast cancer. When that occurs, we will need to rely on genomic analysis to define which drug(s) should be given to the individual patient based on the breast cancer type and the toxicities they are expected to have.
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