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HOME > PAST ISSUE > March-April 2007 > Article Detail

MARGINALIA

By Any Other Name

By giving tumors their right names, scientists gain power over them

Robert L. Dorit

Identity Crisis

So what makes breast cancer "breast cancer"? Part of the answer surely is, to borrow the realtor's mantra, location, location, location. Breast cancer describes tumors that, in both men and women, occur in breast tissue. But is that enough to give all tumors of the breast the same name? Their occurrence in the same part of the body may indeed reflect a deeper underlying similarity, a lifelong and irreversible identity shaped by the neighborhood in which the tumor cells grew up. But location could instead be a superficial similarity—an address that groups together unrelated conditions and obscures connections to tumors in other parts of the body. And the riddle deepens.

The progenitor cell of a breast tumor may have once been a well-defined cell in the lining of a milk duct. At that point, the progenitor cell would have been keenly aware of its location in space, of its age, of its identity and responsibilities as a duct cell. But cells that begin to grow uncontrollably, as they do in a tumor, lose their bearings, shun their roots and even appear to move back in time, undoing the process of differentiation that made them what they are. A pathologist scrutinizing cells from a biopsy looks for those cells that have lost their way, that have forgotten what they are. So what are we to call these tumor cells that are in the breast but no longer of the breast?

Perhaps the answer consists in not being fooled by looks, but instead in attending to some prominent feature of cellular behavior. Yet behavior, too, may be misleading. Much of the biology and epidemiology of breast cancer can be understood by focusing on the interaction between breast tumors and a single circulating hormone: estrogen. Estrogen is a powerful message for cells, prompting those who heed it to divide.  The increased risk of breast cancer associated with obesity in post-menopausal women reflects the ability of fat tissue to produce estrogen, increasing a woman's lifetime exposure to estrogen. The protective effect of early childbearing and extended breastfeeding on breast cancer risk stems from the suppression of ovulation and the consequent reduction in lifetime estrogen exposure. Even one of the best bits of recent news in this field, the eight percent decline in breast cancer incidence seen in the United States in 2003, is connected to the decline in hormone-replacement therapy (which includes estrogen) as a treatment for menopausal symptoms. Given all of this, surely estrogen sensitivity is the hallmark of breast cancer, the one empirical feature that unites all breast tumors?

Surprisingly, no. A third of breast tumors turn out to be deaf to estrogen, having lost the ability to make and position estrogen receptors (ERs) on the surfaces of their cells. These ER-negative tumors may not be able to hear the command of estrogen to divide, but unfortunately they miss the meaning of declining estrogen levels: stop dividing. As a result, these tumors are more dangerous than their attuned counterparts—faster spreading, harder to treat, more likely to recur. Based on functional criteria, ER-negative tumors may well deserve their own separate name. By the same token, many ovarian tumors are keenly sensitive to levels of circulating estrogen, accounting for the frequent co-occurrence of ovarian and breast tumors in certain patient populations. Do all estrogen-responsive tumors deserve their own label too, regardless of what piece of human real estate they despoil?




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