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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