Normal aging of breast tissue lessens breast cancer risk, reports a new study by Mayo Clinic Cancer Center researchers published in the Nov. 15 issue of the Journal of the National Cancer Institute.
As most women get older, and especially after menopause, the milk-producing glands (lobules) shut down -- a process known as lobular regression, or involution. Since breast cancer is thought to originate in the lobules, their reduced size and number decreases the chance of cancer formation. Women who experience complete involution have half the risk of developing breast cancer of those who do not.
"The risk of breast cancer increases among women who have no breast involution as they age," says Lynn Hartmann, M.D., Mayo Clinic oncologist and lead investigator of the study. "This study identifies specific groups of women who are at lower or higher risks of breast cancer due to their extent of involution and factors such as age, family cancer history, reproductive history and types of benign breast disease."
Breast cancer is a significant threat to women. The American Cancer Society reports that more than 250,000 women will be diagnosed in the United States this year with breast cancer, and at least 40,000 will die from it. Dr. Hartmann's team is working to better understand the steps that precede breast cancer and which of them can be recognized in benign breast tissue. In a previous study, published in the New England Journal of Medicine in 2005, they showed that certain types of benign breast disease increase the risk of breast cancer.
The current study contributes to Mayo's emerging model that seeks to define individual women's risk more precisely and thus be able to tailor screening and risk-reducing measures to women depending on their individual risks.
The investigators found that among women with benign breast disease and little or no breast tissue involution, risk for developing breast cancer was twice that of women whose breast glandular tissues had been replaced completely with connective and fatty tissue (53 percent had complete involution as they aged beyond 70 years).
The study included 8,736 women who had breast biopsies at Mayo Clinic that were benign during a 25-year period starting in 1967. Breast tissue samples from this Mayo Clinic Benign Breast Disease cohort were evaluated to determine extent of involution. As a group, the Mayo cohort was at 40 percent increased risk of breast cancer compared to a larger population of presumably healthy women who comprise the Iowa Surveillance, Epidemiology and End Results (SEER) registry. This increased risk has been seen in other cohorts of women with benign breast tissue. However, those in the Mayo cohort who had complete breast lobular involution had no more risk of developing breast cancer than the baseline established in the Iowa SEER cohort.
The researchers found that hormone replacement therapy and prior pregnancies play a role in progression of involution. Hormonal replacement therapy had a slight impact on amount of involution. More women (22.9 percent) who never took hormone replacement had complete involution of mammary tissue than women (20.3 percent) who were treated with estrogen, progesterone or combinations of these two female hormones. Women who gave birth to more than three children retained a greater number of breast lobules. More women (27 percent) who had no children had complete involution, while only 18 percent of women with four children completed mammary involution. Breast-feeding of children had no impact on extent of involution.
"The research community has not focused on breast involution in recent years, nor has this natural process previously been linked to breast cancer risk," reports Dr. Hartmann. "Our study is the first to establish that the extent of breast involution relates directly to risk for breast cancer." She also says that women who would otherwise be considered at high risk (such as those with atypia) appear to have reduced risk when greater degrees of involution are present.
By documenting involution status in a woman's background breast tissue, cancer physicians have another important variable to aid in predicting a woman's risk, at least in women with benign breast tissue. This information can be considered with epidemiological background, individual factors such as age and reproductive history. Ultimately, it is hoped that biomarkers will be defined that contribute to the risk of breast cancer, and these will be integrated into a comprehensive Mayo model for breast cancer risk assessment.
Dr. Hartmann added that by appraising an individual's personal information within a complete, integrated model for predicting risk, every woman's breast cancer risk can be determined with precision and accuracy, leading to the patient's optimal peace of mind based on accurate risk assessment and the appropriate level of preventive intercession and awareness.
Other Mayo researchers included the study's lead author, Tia Milanese, a Mayo medical student; Marlene Frost, Ph.D.; Robert Vierkant; Shaun Maloney; V. Shane Pankratz, Ph.D.; Amy Degnim, M.D.; L. Joseph Melton III, M.D.; and Ellen Goode, Ph.D. Collaborators from other institutions included Daniel Visscher, M.D., and Thomas Sellers, Ph.D, M.D.
The research was supported in part by a Department of Defense Center of Excellence Grant, the National Cancer Institute, the Susan G. Komen Breast Cancer Foundation, Andersen Foundation, the Breast Cancer Research Foundation and the Regis Foundation for Breast Cancer Research.
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