Differences in gene activity underlie the heterogeneity (or variations) in breast cancer. Drawings of microscope images show four types of noninvasive breast cancer (confined to the milk ducts, left) and four types of invasive breast cancer (right). Researchers haven't yet concluded how many types of breast cancer may exist altogether. (Courtesy J. Dirk Iglehart, MD)
Diversity
Scientists have also conducted microarray studies of HER-2/neu-positive and ER-positive cells to learn if any subcategories of these forms of breast cancer exist. The results so far are intriguing. "Researchers have found some diversity within the HER-2/neu group, and a great deal within the ER-positive group," Dr. Iglehart reports. "It appears there are at least two genetically different types of tumors that are ER-positive."
Recently, a group of researchers led by Dana-Farber's Sridhar Ramaswamy, MD, found that some breast tumors have a metastasis signature," a pattern of gene activity that predicts whether they are likely to spread to other parts of the body. Since most cancer deaths are caused by tumors that have metastasized from their original site, the discovery raises hopes that doctors will soon be able to pinpoint such vagabond cancers before they have a chance to spread.
As researchers make ever-finer distinctions among breast cancers, the challenge will be to devise practical ways of identifying them in patients. At the same time, scientists will seek to discover which treatments are most effective against which forms of the disease.
Dr. Iglehart notes that until the early 1970s, young women with breast cancer all underwent oophorectomies — surgical removal of the ovaries — on the theory that without estrogen supplied by the ovaries, breast cancers would be deprived of their growth stimulant. The therapy helped the more than 70 percent of patients with ER-positive tumors, but failed for the 30 percent with ER-negative cancers.
"Understanding the diversity within breast cancer cases will help us more closely match therapies with patients," says Dr. Iglehart. "To illustrate, not all HER-2/neu-positive breast cancers respond well to Herceptin. We need to find what it is about the other tumors that renders Herceptin ineffective."
Perhaps because breast cancer has been so intensely studied, researchers know more about its various guises than they do of any other form of cancer. "By viewing breast cancer as a collection of diseases rather than a single, monolithic one," says Dr. Iglehart, "we're establishing a paradigm for the treatment of other solid tumors as well."
