Rethinking Breast Cancer

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How often does that happen? Statisticians estimate that 20 of every 100 women who get only mastectomy (or lumpectomy plus radiation) for a 2-cm tumor that has not spread to the lymph nodes would, all other things being equal, suffer a recurrence sometime in the next five to 10 years. Fourteen of those tumors would have come back regardless of whether any additional therapies had been tried. The remaining six would have been prevented by chemotherapy. "For a 6% improvement, that's a lot of women who have to accept chemotherapy," says Dr. Gralow at the Fred Hutchinson Cancer Research Center in Seattle. But there is no way to figure out in advance which six tumors actually needed to be treated.

That may change as scientists learn more about the genetic alterations that transform a normal cell into a malignant one. Last month a group of scientists from the U.S. and the Netherlands published a paper in the research journal Nature describing a molecular test they have developed that may predict, at the time of surgery, which cancers will be likely to metastasize--and therefore might benefit from chemotherapy. Using so-called DNA microarrays, the researchers analyzed some 25,000 genes from the breast cancers of 100 women. By winnowing the number of relevant markers to about 70 genes, they produced a DNA profile that correlated closely with the women's actual outcomes. "There's not much that stands in the way of this test being used clinically," says Stephen Friend, one of the paper's authors and a co-founder of the biotech firm Rosetta Inpharmatics. Clinical trials could begin, he believes, within the year.

Such a test might prove particularly helpful in determining what to do about the so-called micrometastases that pathologists are starting to discover in some women's lymph nodes. Once again, better detection techniques have revealed minute clumps of cancer--0.2 mm or 0.008 in. across--that are smaller than anyone had ever seen before.

Until recently, the presence of any cancer in a lymph node would be a clear signal that chemotherapy was required. But at the upcoming meeting of the American Society of Clinical Oncology in May, a group of cancer experts will recommend that these minute malignancies be left alone, as long as the original breast tumor is small. "We used to seek out and destroy every cell," says Dr. Eva Singletary, a breast surgeon at the M.D. Anderson Center in Houston, who chairs the expert panel. "Now we try to target and control our treatment."

Ideally, Singletary would like to be able to tailor each woman's treatment to the characteristics of her particular tumor. Already scientists have identified a biological marker called the HER2 receptor, whose presence usually signifies a very aggressive cancer. For the past four years, a drug called Herceptin has been given to women with metastatic tumors that make a lot of the HER2 protein. Now trials are being conducted to see if Herceptin, which may have some deleterious effects on the heart, will nonetheless help other women with smaller tumors that haven't yet spread.