Clinical Research News

Biological Markers in Breast Cancer

Ductal carcinoma in situ (DCIS) refers to cancer of the cells lining the milk ducts. Left untreated, DCIS may begin to spread into the breast tissue surrounding the ducts, becoming invasive breast cancer. Although only some women with DCIS will develop invasive breast cancer, it is not possible to predict who will develop this more serious form.

This study will determine whether there is a difference in estrogen receptor status between African American and white women with ductal carcinoma in situ (DCIS), and if so, whether that difference impacts recurrence and survival rates.

African American women have the highest mortality rates for breast cancer compared to other women, and although they do not develop breast cancer as frequently as white women, African American women face a 32% higher risk of dying from the disease than other women in the U.S.—even when they have access to excellent health care. Are behavioral, physiological, or genetic differences between populations responsible for this disparity? Tumor biology may hold some of the answers, according to Kathie-Ann Joseph, MD, MPH, Assistant Professor of Surgery at NewYork-Presbyterian Hospital/Columbia University Medical Center. In her clinical practice and research efforts, Dr. Joseph is seeking new strategies to reduce disparities between African American women and others diagnosed with breast cancer.

It has been well documented that among women diagnosed with invasive breast cancer, which can become deadly unless treated early, tumors are estrogen (ER)-negative in 40% of African American women, compared to 23% in white women. ER-negative tumors are associated with a worse outcome and an increased risk of recurrences—and they are not responsive to tamoxifen, which is an antiestrogenic therapy. Yet because tamoxifen was developed before the role of hormone receptors was identified, early studies of its effectiveness overlooked this important factor. And while physicians now routinely test ER status in women with invasive breast cancer, ER testing has not been routine practice for women with ductal carcinoma in situ (DCIS), or cancer located just in the cells lining the milk ducts of the breasts.

Dr. Joseph is now working to determine whether ER-negativity also plays a parallel role in DCIS. Like invasive breast cancer, DCIS may be ER-positive or ERnegative. If the tumors of African American women with DCIS are found to be frequently ER-negative (as they are in invasive cancer), this discovery will have important ramifications for the diagnosis and treatment of DCIS.

"Women who have DCIS are at an increased risk of developing invasive cancer later in life. Many hospitals still do not test the tumors of patients with DCIS to see whether they are ERpositive or negative, however. If we find that a high proportion of African American women are ER-negative, routine testing really needs to become the standard of care. It also means that researchers will need to develop other treatments besides chemotherapy and radiation, strategies that are not hormonally dependent." she states. In the DCIS study, Dr. Joseph is collaborating with several other New York hospitals to compare tissue samples from African American women with those of white women. About 160 samples, half from each population, will be analyzed to determine the rate of ER-negativity in the two populations. She will also investigate whether other biological markers associated with worse prognosis, such as P21, BCL2, and Her-2, may be predictors of tumor recurrence and survival rates.