Estrogen-Only Treatment Does Not Increase Breast Cancer Risk

Postmenopausal women who have had hysterectomies and undergone long-term therapy with estrogen were not found to have an increased risk of developing breast cancer, according to a study published in the April 12 Journal of the American Medical Association. The study was sponsored by the National Heart, Lung, and Blood Institute (NHLBI).

The finding came from the Women's Health Initiative (WHI) Estrogen-Alone Trial of more than 10,000 healthy women who received either estrogen or placebo. After an average 7 years of follow-up, the study found slightly lower rates of breast cancer in the estrogen group compared with the placebo group, although the differences were not statistically significant. The women receiving estrogen did experience greater rates of abnormal mammography findings and biopsies than the placebo group.

This is in contrast to earlier results from the WHI Estrogen plus Progestin study, which was stopped in 2002 because of an increased risk of breast cancer. The WHI Estrogen-Alone Trial was stopped in 2004 because of increased stroke risk, but the effects on invasive breast cancer were deemed uncertain at the time. Subsequent analyses concluded that treatment with estrogen alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy.

"Longer follow-up is needed to fully explain the reduced number of breast cancers in women taking estrogen," said NHLBI and WHI Director Dr. Elizabeth G. Nabel. "However, this new analysis does not alter the overall conclusion from the WHI that hormones, including estrogen alone and estrogen plus progestin, should not be used for the prevention of chronic disease" such as coronary heart disease, cancer, or osteoporosis.

Discovery Shows How Kaposi's Sarcoma Virus Enters Cells

Researchers have discovered a protein on the surface of some human cells that is used by the Kaposi's sarcoma herpesvirus (KSHV) to enter the cells. This virus is a necessary factor in the development of Kaposi's sarcoma, a cancer that occurs most often in people with HIV/AIDS and certain types of lymphoma. The newly identified protein is called xCT.

Drs. Johnan Kaleeba and Edward A. Berger of the National Institute of Allergy and Infectious Disease found that KSHV can infect a broad range of cell types in different species. The researchers hypothesized the existence of a protein on the cell surface that is distinct from molecules previously implicated in the attachment and entry process of KSHV infection.

After identifying xCT, Drs. Kaleeba and Berger confirmed its role in KSHV infection experimentally. They showed first that antibodies against xCT prevented the virus from entering cells that would normally allow entry. They also showed that stimulating the production of xCT in cells that were otherwise not susceptible to infection resulted in infection, according to findings in the March 31 Science.

An intriguing finding noted in the Science paper is the possibility that xCT is part of a pathogenic mechanism by which KSHV induces or exploits physiologic responses in human cells to its own benefit. For instance, the virus might influence a cell's production of xCT to allow itself greater access to the cell.

Inadequate Screening Is Linked to Breast Cancer Disparities

A study published April 18 in the Annals of Internal Medicine confirms that the higher incidence of advanced breast tumors among African American women compared with white women may be explained in part by inadequate mammographic screening - the women were 55 or older the first time they were screened, or they had waited more than 42 months between mammograms, or they had never been screened. African American women with the same screening history as other women were no more likely to have large or advanced-stage tumors.

Previous research based on women's recollections suggested that minority women tend to have higher mortality from breast cancer because they are less likely to get mammograms and they get them later than white women. In the current study, the researchers used data collected through the NCI-funded Breast Cancer Surveillance Consortium to ascertain the mammographic history and cancer outcomes of more than a million women over the age of 40. All women had at least one mammogram during the period analyzed.

Though there were no differences in stage and tumor size among African American and other women when screening history was the same, there were differences within tumors themselves. The researchers found that African American women had a disproportionate number of high-grade tumors compared with white women, regardless of screening frequency. The nonwhite women in the study also were more likely to receive inadequate screening before their breast cancer diagnosis: 34 percent of African American, 24 percent of Hispanic, and 27 percent of Native American women, compared with 18 percent of white women.

"This is an example where the story is more complicated than we would like; the higher risk of breast cancer mortality among African American women can be partially addressed by increased screening, but we need to know more about the biology as well," says Dr. Rachel Ballard-Barbash, associate director of the Applied Research Program in NCI's Division of Cancer Control and Population Sciences and co-author of the study.