Marker predicts breast cancer recurrence.

Marker predicts breast cancer recurrence

A mysterious protein whose function has for years eluded scientists -- and whose very existence has remained doubtful to some -- appears useful as a strong predictor of breast cancer recurrence.

The mystery substance, called haptoglobin-related protein (Hpr), becomes the most recent addition to a growing list of cellular and genetic markers that scientists can use to help predict the likelihood that a cancer has invisibly spread, or metastasized, to distant sites. Physicians and patients need such clues as they decide whether to augment surgical treatment with chemotherapy. Cancer researchers additionally hope such tests may shed light on the cellular mechanisms responsible for metastasis and lead to novel therapies.

Researchers caution they must investigate the new test further to confirm its apparent value. But when applied to preserved tissue specimens from 70 women diagnosed with breast cancer between 1977 and 1985, it proved a potent tool for predicting which of the women would go on to experience a cancer recurrence.

"Women with breast cancer who have this marker are almost fourfold more likely to recur than women who don't have the marker," says Gary R. Pasternack of the Johns Hopkins University School of Medicine in Baltimore, who with Francis P. Kuhajda and Steven Piantadosi performed the research.

Moreover, says Pasternack, "when you combine [the test] with progesterone receptor status, you gain even more predictive power." The absence of receptors for the hormone progesterone has remained by itself only weakly associated with cancer recurrence. But in their retrospective analysis, the researchers found that 92 percent of women whose cancerous breast tissue tested both positive for Hpr and negative for progesterone receptors experienced a cancer recurrence. Only 20 percent of Hpr-negative women had a recurrence, irrespective of progesterone receptor status.

For years, scientists have remained baffled by the discovery of a human gene whose sequence suggests it codes for a variant form of haptoglobin, but whose protein product long went undiscovered. Normal haptoglobin circulates in the blood, where it mops up hemoglobin leaking from aging red blood cells so the body can recycle the iron in that oxygen-transporting compound. Kuhajda and co-workers finally isolated the variant haptoglobin, called haptoglobin-related protein, earlier this year and made antibodies to it. Their new work, published in the Sept. 7 NEW ENGLAND JOURNAL OF MEDICINE, shows that antibodies to Hpr bind preferentially to breast cancer cells with a propensity to metastasize.

The researchers caution that their antibodies may be binding to an Hpr-like protein rather than to Hpr itself. So while the test appears valuable as a diagnostic aid, it may not tell much about Hpr's true function.

Nonetheless, comments Lance A. Liotta, a metastasis researcher at the National Cancer Institute in Bethesda, Md., "we can see in the future there will be a number of these tests and they'll all be incorporated into a panel of markers" to predict metastasis.