Dramatic difference between breast cancers in US and Africa

A study comparing, for the first time, breast cancers from Nigeria, Senegal and North America has found that women of African ancestry are more likely to be diagnosed with a more virulent form of the disease than women of European ancestry.

Researchers from the University of Chicago, working with colleagues at the University of Calabar in Nigeria and the University of North Carolina, found that breast cancers in African women produce a different pattern of gene expression. Tumors from African women -- from three locations in Nigeria and one in Senegal -- are more likely to originate from a different group of cells within the breast and often do not present the molecular targets that form the basis of many standard therapies.

"We have known for a long time that breast cancer is not one disease and that it may be somehow different in Africa," said study author Funmi Olopade, M.D., professor of medicine and director of the Center for Clinical Cancer Genetics at the University of Chicago. "But there was no real sense of how much of that was biology and how much was environment. Now we have clear evidence that nature plays an important role. These tumors are biologically quite different in ways that make this a worse disease."

"The discovery means we have to rethink how soon and how often we screen for breast cancer in women at risk for the most aggressive type of breast cancer, as well as how we prevent it and how we treat it," she added. "The guidelines were developed based on our deep knowledge of breast cancer in older women of European ancestry, but our results mean that much of the U.S. and European data simply do not apply to the types of breast cancer we most commonly see in African women."

The researchers studied the pattern of gene expression -- a measure of which genes were turned on and active -- in breast cancer tissue from 378 women in Nigeria and Senegal. They compared the results with a database of breast cancer tissue from 930 Canadian women compiled by Charles Perou and colleagues in North Carolina and British Columbia.

They found three significant differences:

• First, breast cancers in African women were more likely to arise from basal-like cells, rather than the inner milk-secreting luminal cells, which are the most common source of breast cancers for U.S. and European women. (This type of basal-like breast cancer is also observed among women with inherited BRCA1 mutations). Tumors that arise from basal cells have a worse prognosis, regardless of race.

• Second, African breast cancers often lacked estrogen receptors. Although 80 percent of breast cancers in Caucasian women have estrogen receptors, only 23 percent of African tumors did. These tumors do not depend on estrogen and thus will not respond to drugs, such as tamoxifen, that prevent estrogen from reaching the cancer cells.

• Third, cancers from African women were slightly less likely to express the cell-surface marker HER2. HER2 is the target for the drug Herceptin, which was recently approved for metastatic breast cancer. It is over-expressed in about 23 percent of Caucasians and 19 percent of Africans.

Breast cancer strikes fewer women in Africa, "but it hits earlier and harder," said Olopade. In America, most breast cancer occurs after menopause, usually in the late 50s or 60s. In Africa, it most often strikes women in their 40s. The average age of the African women in this study was 44.

Studies suggest that 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 Caucasians but earlier onset and worse prognosis. African American women under the age of 35 have a 50 percent greater risk of developing breast cancer than Caucasians. This risk levels off by around age 50 and African Americans over 50 have less risk than Caucasians.

Most of the screening guidelines in this country are based on studies that primarily looked at Caucasians, said Olopade. "We need to reconsider how to screen for a disease that is less common but starts sooner and moves faster. Obviously an annual mammogram beginning at 50 is not the best route to early detection in African women, who get the disease and die from it in their 40s, and it also needs to be adjusted in African Americans and high-risk women in all racial/ethnic groups."

Olopade is one of four principal investigators in a large-scale, multi-year, cross-disciplinary effort based at the University of Chicago to sort out the genetic and environmental factors that contribute to breast cancer. The study will look at the genes, lifestyle, socioeconomic status, and social interactions of women in the United States and Africa and their relationship to breast cancer.

She combines expertise in cancer risk and genetics with a close African connection. Olopade grew up in Nigeria, retains close ties with cancer specialists there and returns frequently to teach, for research -- and to visit. She worked with Nigerian researcher Francis Ikpatt, who is completing a three-year post-doctoral fellowship in Olopade's laboratory, to gather the tumor samples from three regions of Nigeria, and later from Senegal. The gene expression analysis was performed in Olopade's laboratory at the University of Chicago.

"We now have the world's largest collection of tumor samples from Africa," said Olopade. "Francis did most of that over the course of one year. That should give you some idea of how neglected this continent is by cancer researchers."

The Breast Cancer Research Foundation and the National Women's Cancer Research Alliance funded the study, which was presented April 18, 2005, at the 96th annual meeting of the American Association for Cancer Research.

Also contributing were Jinhua Xu and Audrey Kramtsov from Chicago; Roland Ndoma-Egba of the University of Calabar in Nigeria; Kauode Adelusola from the University of Ife, Nigeria; Jean Marie Dangou from Senegal; and Charles Perou of the University of North Carolina.