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Breast Cancer Beginnings
March 15, 2001

These human mammary epithelial cells are in the second of two growth spurts, during which their chromosomes become abnormal and begin to look like those seen in the earliest stage of breast cancer.
image: University of California - San Francisco

Breast cancer is a devastating disease which will strike approximately 192,000 women this year, according to the American Cancer Society. Researchers have come a long way in understanding and treating it, but they are still trying to find out why this type of cancer is so common.

Now they may have an answer. Scientists at the University of California in San Francisco have found that certain cells in the breast may behave in a unique way that makes them more susceptible to cancer.

Keeps on growing

Breast cancer is the second most common cancer among women (next to non-melanoma skin cancers), and the second leading cause of cancer death in women. According to the American Cancer Society, the risk of breast cancer for women over 40 is so great that they recommend an annual screening mammogram to catch tumors as early as possible.

But mammograms can miss as many as 15 percent of breast cancers, and right now there is no better screening tool. [See stn2’s Beyond Mammography for more on the status and future of breast cancer detection] So instead of trying to catch tumors, some researchers have turned their attention to studying when and why they form.

In a paper published in last month’s journal Nature, scientists at the University of California in San Francisco (UCSF) announced their finding that mammary epithelial cells, which form the lining of the milk ducts, behave differently than other cells. "We take cells from the body and grow them in tissue culture plates," says Thea Tlsty, professor of pathology at UCSF and one of the paper’s authors. "And what most cells do…is grow for a period of time and then stop growing, and it is said that they enter senescence, which is a barrier to cell division." While mammary epithelial cells also enter senescence, in their case it turns out that it’s reversible. These cells emerge from senescence and then continue to grow.

Deadly changes

These intact, healthy-looking chromosomes from young human mammary epithelial cells (blue) have normal-looking, long telomeres (red).
image: University of California - San Francisco
Old Epithelial Cell Telomeres
These chromosomes (blue) from old human mammary epithelial cells (HMECs) appear fragmented and have short telomeres (red) when compared to their counterparts from young HMECs.
image: University of California - San Francisco

This has major implications for understanding cancer. "What’s exciting about mammary epithelial cells growing beyond senescence is that they accumulate genetic changes, the same changes we see in the earliest stages of breast cancer," says Tlsty.

Fibroblasts, the supporting cells under the epithelial cells which don’t form cancer, stay in senescence, which is in effect a protective barrier against cancer. But when epithelial cells continue to grow past this barrier, it sets the stage for disease. "When they go on to grow and enter the second plateau, it’s a condition, a situation where the cells are dividing, they are dying…and they’re also accumulating genetic changes," explains Tlsty. "In essence they are ripping their chromosomes apart. As the cells enter that second plateau almost 100 percent of the cells now have chromosomal abnormalities. Those chromosomal abnormalities are the same ones that are detected in the earliest lesions of breast cancer."

Cells are normally able to go past senescence only if they’re infected by a virus or other carcinogen, but this research shows that mammary epithelial cells do this on their own. This means they don’t have protective mechanisms in place, so if they are exposed to environmental mutagens, they accumulate the chromosomal changes that are the earliest signs of breast cancer, Tlsty says. "If the observations that we made in tissue culture can be extended to human beings, then that would suggest that every woman has the beginnings of breast cancer and that we would be able to detect it," she says.

Revealing this mechanism in mammary cells may give researchers a new tool for understanding cancer in other parts of the body. It could also help them identify markers that could eventually lead to earlier detection and treatment of breast cancer. If they can find a way to stop such cells from continuing to grow, it could even help to prevent it.

Elsewhere on the web

Beyond Mammography (

The evolution of senescence

All about breast cancer

Understanding your breast cancer pathology report

Types of breast cancer

by Jill Max

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