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Benign Breast Disease Linked to Increased Breast Cancer Risk (dateline December 30, 1999)

The results of a study published in the December 15, 1999 issue of the Journal of the National Cancer Institute revealed that women who are diagnosed with epithelial hyperplasia lesions lacking atypia (EHLA) may be at higher risk for developing breast cancer than women without EHLA. EHLA is a benign (non-cancerous) breast condition often referred to as "usual duct hyperplasia." Researchers have known for some time that atypical hyperplasia (a dangerous increase in abnormal breast cells) is a marker for increased breast cancer risk, but this study marks the first time usual hyperplasia (a general increase in the number of breast cells) has been also been identified as a risk factor. EHLA is found in nearly 25% of benign breast biopsy samples but usually goes untreated because most physicians do not believe it indicates breast cancer.

In the study, the Nashville Breast Study Cohort research group focused on the chemical messenger, transforming growth factor beta (TGFb), which regulates cell division. Normally, TGFb attaches to the TGFb receptor on the surface of breast cells, signaling them not to divide. However, if a breast cells lacks the TGFb receptor, the TGFb cannot attach itself to the cell wall, and consequently, cannot stop the cell from dividing. Eventually, the breast cells may divide and multiply out of control, causing breast cancer. The researchers found that women with EHLA are less likely to have TGFb receptors on their breast cells.

The group studied 54 women whose breast biopsies revealed EHLA and who later developed invasive breast cancer. These women were compared to a control group of 115 women with EHLA who did not develop breast cancer. In observing all 169 women, the researchers found that when TGFb receptors were present on less than 25% of breast cells, women were three times as likely to develop invasive breast cancer than when TGFb receptors were present on more than 75% of cells. More than two-thirds of the EHLA women (104) studied were lacking TGFb receptors on more than 75% of their breast cells.

This is the first time researchers have found credible evidence of a biologic marker of increased breast cancer risk in women with benign breast disease, said William Dupont, Professor of Preventive Medicine at Vanderbilt University School of Medicine. Breast disease may be thought of as a continuum:

Breast Disease "Continuum"

normal arrow_wingding.gif (76 bytes) hyperplasia (increase in number of cells) arrow_wingding.gif (76 bytes) atypical hyperplasia (dangerous increase in number of abnormal cells, a marker for breast cancer) arrow_wingding.gif (76 bytes) ductal carcinoma in situ arrow_wingding.gif (76 bytes) invasive cancer

It is important to note that not all breast lesions progress in a step-wise fashion through each phase before becoming significant. In general, anything farther to the right than atypical hyperplasia may need surgical removal. Researchers have already shown that atypical hyperplasia increases a woman’s risk of breast cancer, but until now, usual hyperplasia has not been linked to a higher risk.

Though the Nashville Breast Cohort research group’s study is small and needs further confirmation, the results indicate that women with EHLA should be aware of their possible increased risk for breast cancer. The American Cancer Society has recommended a set of guidelines women should follow to help detect breast cancer at an early stage:

  • Women over 20 years of age should practice monthly breast self-examination and have clinical breast exams at least every three years.
  • Women over 40 should have yearly mammograms  in addition to yearly clinical breast exams and monthly breast self-examination.
  • Many physicians also recommend that women who have a high risk of breast cancer and/or family history begin receiving annual screening mammograms between the ages of 30 and 40.
  • Woman at a very high risk of breast cancer (such as those have tested positive for the BRCA1 and BRCA2 cancer genes) should speak with their physician about beginning annual mammograms as early as age 25.

If further studies confirm the link between EHLA and breast cancer, women with usual hyperplasia may wish to consider engaging in preventive measures to reduce their risk of developing breast cancer (such as taking the drug tamoxifen). Tamoxifen is already being used to prevent breast cancer in women with atypical hyperplasia and lobular carcinoma in situ (LCIS), a condition marked by abnormal cells in the lobules of the breast. In a study of 2,000 women with LCIS or atypical hyperplasia, those who took tamoxifen were 66% to 86% less likely to develop breast cancer within five years, compared with those who a placebo (an inactive pill).

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