An international
scientific collaborative led by the Harvard Stem Cell Institute’s Kornelia
Polyak has discovered why women who give birth in their early 20s are less
likely to develop breast cancer eventually than women who don’t, triggering a
search for a way to confer this protective state on all women.
The researchers are now testing p27, a mammary gland
progenitor marker, on tissue samples collected from thousands of women over
decades — women whose medical histories have been followed extremely closely —
to see if it is an accurate breast cancer predictor in a large population. If
the hypothesis is confirmed, which appears likely within a few months, Polyak
says the commercial development of a clinical test for breast cancer risk would
follow.
In a paper just published in the journal Cell Stem Cell, the researchers describe
how a full-term pregnancy when a woman is in her early 20s reduces the relative
number and proliferative capacity of mammary gland progenitors — cells that
have the ability to divide into milk-producing cells — making them less likely
to acquire mutations that lead to cancer.
By comparing numerous breast tissue samples, the scientists
found that women at high risk for breast cancer, such as those who inherit a
mutated BRCA1 or BRCA2 gene, have higher-than-average numbers of mammary gland
progenitors. In general, women who carried a child to full term had the lowest
populations of mammary gland progenitors, even when compared with cancer-free
women who had never been pregnant. In addition, in women who gave birth
relatively early but later developed breast cancer, the number of mammary gland
progenitors was again observed to be higher than average.
Research shows that two trends are contributing to an
increase in the number of breast cancer diagnoses, a rise in obesity and the
ever-increasing number of women postponing childbearing. The scientists’
long-range goal is to develop a treatment that would mimic the protective
effects of early childbearing.
The research, which took five years to complete, began with
conversations between Polyak and Saraswati Sukumar, a professor at Johns
Hopkins University School of Medicine. The two scientists formed collaborations
with clinicians at cancer centers that see large numbers of high-risk women, in
order to obtain breast tissue samples. They also worked with genomics experts
and bioinformaticians to analyze gene expression in different breast cell
types. At times, Polyak and Sukumar had trouble gaining cooperation for the
study, which is unique in the breast cancer field for its focus on risk
prediction and prevention.
Source: news.havard.edu
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