For decades, researchers have tried to understand why breast cancer in younger black women is such a significant public health problem.

Black women have fewer breast cancers than white women, but their mortality is worse. Black women under the age of 50 have a 77 percent higher mortality rate from breast cancer than white women of the same age.

Results of a study led by scientists from the University of North Carolina at Chapel Hill schools of Public Health and Medicine and the UNC Lineberger Comprehensive Cancer suggest one reason for these differences.

When younger, premenopausal, black women get breast cancer, they are more than twice as likely as older women, black or white, to get an aggressive breast cancer subtype, the study found. They are also much less likely to get the least aggressive type. A report of the research appears in the June 7 issue of the Journal of the American Medical Association.

“The present study adds an important piece to a large puzzle,” said senior study author Dr. Robert Millikan. “Previous studies showed that many breast tumors in younger African American women are very fast-growing and hard to treat.

“We found something new: Younger African American breast cancer patients show a high frequency of one of the aggressive subtypes of breast cancer called basal-like,” said Millikan, associate professor of epidemiology at the UNC School of Public Health, a UNC Lineberger member and principal investigator of the Carolina Breast Cancer Study (CBCS). The CBCS, one of the largest black breast cancer databases in the United States, is a population-based case-control study that enrolled women with breast cancer from 24 counties of North Carolina as cases, and an equal number of women without breast cancer as controls. Women who consented to the study were interviewed about their histories, and their tumor tissue was collected. The study required extensive cooperation from all of the women who participated in the study, their physicians and pathologists, and a large number of hospitals in North Carolina.

According to JAMA study lead author Dr. Lisa A. Carey, associate professor of medicine in the hematology-oncology division at UNC’s School of Medicine, modern technologies such as microarray analysis can reveal the molecular characteristics of cancers and have shown that breast cancer is not one disease. “It is a family of diseases that are biologically different from each other, some more aggressive than others,” Carey said. “In this study, using the Carolina Breast Cancer Study, we were looking at how frequently these different subtypes occur in a given population.”

DNA microarray analysis allows scientists to determine the expression levels of thousands of genes simultaneously. This can reveal gene expression patterns, which, in turn, enable genomic profiling of tumor cells.

UNC School of Medicine study co-author Dr. Charles M. Perou, assistant professor of genetics, pathology & laboratory medicine, and a Lineberger member, is a pioneer in microarray technology. “Gene expression analysis using DNA microarrays has identified several breast cancer subtypes, including luminal A, luminal B, basal-like and HER2-plus/estrogen receptor-negative,” said Perou. “These studies were based on limited sample sets. We wanted to see if we could identify the presence of these subtypes through a population-based study and to find out if they correlate with factors such as age, menopausal status and race.”

But microarray analysis requires freshly frozen tumor tissue specimens, and the tissue available from the CBCS was collected between 1993 and 2001. Fortunately, the CBCS had many tumor tissue samples in blocks of paraffin.

To use these, Perou, along with study co-authors Dr. Torsten O. Nielsen and Dr. Maggie C. U. Cheang of the University of British Columbia in Vancouver, Canada, had developed in 2004 an antibody test to identify the main breast cancer subtypes that they validated in a large (930 cases) tissue microarray study.

The test involves immunohistochemistry (IHC) profiling, which is the testing of sections of tissue for specific proteins by attaching them to specific antibodies, and then looking for the antibodies through the enzymes to which they were connected. This IHC test was refined for the JAMA study, which was the first time the IHC method was used to examine breast cancer subtypes in a population-based study.

“And this had the surprising finding that the basal-like subtype was more than twice as frequent in younger African American women with breast cancer versus everyone else,” Perou said. Among premenopausal African Americans with breast cancer, this type makes up 39 percent compared with postmenopausal African Americans (14 percent) or Caucasians of any age (16 percent).”

The JAMA report notes that the high prevalence of basal-like breast tumors anda lower prevalence of a subtype associated with a more favorable outlook for survival, luminal A, could contribute to the higher breast cancer mortality in younger black women.

There are treatment implications of these findings.

As Carey, medical director of the UNC Breast Center and a Lineberger clinical faculty member, points out, “Right now, the only available treatment for basal-like breast cancer is chemotherapy. Fortunately, while there are no targeted treatments yet for basal-like breast tumors, some of the newer chemotherapies tend to benefit this subtype more than other subtypes. “In addition, there are many new drugs that we will be evaluating in clinical trials to try to provide a targeted treatment for patients with this subtype of breast cancer.”

Millikan said, “This is important information to know, since it means that African American women, like all breast cancer patients, need the best possible diagnostic workups and access to the latest clinical trials. It will be extremely important for these findings to be validated in other patient populations, and to engage breast cancer advocacy groups to ensure that the findings are translated into better care and access to clinical trials for all breast cancer patients.”

“My advice for young African American women,” added Carey, “is the same as my advice for all women: get regular health care.”

Dr. Jorge Gomez of the National Cancer Institute said a particular kind of grant, the Specialized Programs of Research Excellence (SPORE) grant, was crucial in moving this research forward. SPORE grants “are dedicated to transitioning laboratory discoveries to the clinic or clinical observations to the lab. This collaborative project exemplifies the multidisciplinary nature of the SPORE Program,” Gomez said.

Study co-authors from the UNC School of Medicine are Dr. Chad A. Livasy, department of pathology and laboratory medicine; Lynn G. Dressler and David Cowan, department of medicine; and Dr. H. Shelton Earp, Lineberger professor of cancer research, professor of medicine and pharmacology and UNC Lineberger director. Other co-authors include Dr. Kathleen Conway and Dr. Melissa A. Troester from the UNC School of Public Health’s department of epidemiology; Dr. Patricia G. Moorman from the Duke University Medical Center’s department of family medicine; and Dr. Joseph Geradts, a former UNC Lineberger member now at Roswell Park Cancer Institute in Buffalo, N.Y.

http://www.med.unc.edu