January 10, 2003

Breast cancer risk clarified at VUMC

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Dr. Raymond DuBois is internationally known as an investigator in the link between colon cancer, arthritis drugs and an enzyme called cyclooxygenase-2 (COX-2). (photo by Dean Dixon)

Breast cancer risk clarified at VUMC

Women diagnosed with a specific form of benign breast disease called atypical lobular hyperplasia (ALH) are at increased risk of developing breast cancer, but the risk is not the same for both breasts, Vanderbilt researchers report this week.

The findings, reported in the British medical journal The Lancet, challenge the long-held belief that the risk for breast cancer in women with this diagnosis was the same in both breasts, an assumption that could be used as an argument for double mastectomy to prevent cancer. Instead, the researchers found that women with this type of abnormality were three times more likely to develop breast cancer than are women without this diagnosis, and that three-fourths of subsequent breast cancers occurred in the same breast.

“For me, this is awfully exciting because it challenges the ‘all-or-nothing’ argument,” said Dr. David L. Page, professor of Pathology and Preventive Medicine.

“What I hope is that this is the beginning of a discussion about the appropriate way to reduce the risk for these women. It may be that we can remove part of the breast and remove most of the risk.”

This work is an extension of the Nashville Breast Studies, a large cohort of women who have undergone breast biopsies at Vanderbilt, Baptist and St. Thomas hospitals since 1950. Through study of this cohort, Page and his colleagues have reported a number of important findings about the complexities of benign breast disease and breast cancer risk.

In this study, 252 women were identified with the abnormal cells known as ALH (sometimes called lobular carcinoma in situ) and treated by biopsy alone. Not considered were women who underwent mastectomy because of their ALH diagnosis.

Fifty breast cancers developed among these women; the side was known for 48 of them. Of those, 36 cancers, or 75 percent, occurred in the same breast as the previous biopsy.

Benign lesions associated with increased cancer risk have been thought to be either a marker of something in the breast environment that favored cancer development or a precursor that would itself become malignant if not removed.

“These findings show that atypical lobular hyperplasia is somewhere in the middle,” said co-investigator William D. Dupont, Ph.D., professor of Preventive Medicine. “ A statistically significant proportion of women develop breast cancer in the same breast, though by no means all. I think the take-home message should be one of calm caution. It’s not grounds for an emergency but it is grounds for a woman and her physician to pay attention and be diligent about breast screening in the future.”

Atypical lobular hyperplasia is diagnosed in up to 4 percent to 5 percent of biopsies. Incidence is increasing as mammography becomes more sensitive and the diagnosis is made more frequently at centers like Vanderbilt where pathologists have an interest in the disease and are trained to diagnose it. (Page noted that the definition of ALH used for this study is the same one used by the researchers following the large nurses’ cohort based at Harvard University).

In an accompanying editorial, Dr. Sunil Lakhani of the Institute of Cancer Research and Royal Marsden Hospital in London writes that “now is the time for an awakening about atypical lobular hyperplasia.”

Dr. Mark Kelley, chief of Surgical Oncology and medical director of the Vanderbilt Breast Center, noted the importance of the findings in challenging traditional teaching.

“This raises interesting questions about the pathophysiology of ALH — is it a risk marker or a pre-malignant condition or a hybrid of the two?” Kelley said.

Susan Caro, director of the Vanderbilt-Ingram Cancer Center’s Family Cancer Risk Service agreed. “This adds important information for counseling women who have this diagnosis about their risk for breast cancer and how they might manage that risk,” Caro said.

Noting the size of the cohort of women in the Nashville Breast Studies — more than 7,500 women who underwent biopsies between 1950 and 1985 — Page said the researchers are grateful for the women who have agreed to participate in the effort. “Since 1973, we have been working on this research using more than half the women in Nashville who have undergone breast biopsies,” Page said. “The region deserves a big pat on the back because the rate of cooperation has been phenomenal.”

In addition to Page and DuPont, co-authors are nurse and study coordinator Peggy A. Schuyler; Dr. Roy A. Jensen, associate professor of Pathology and Cancer Biology; Walton D. Plummer, who coordinated the data and contributed to the statistical analysis; and Dr. Jean F. Simpson, professor of Pathology

The National Cancer Institute funded the work.