Summary of Research Findings

An important finding of our studies concerns the relationship between proliferative breast disease and breast cancer. (New England Journal of Medicine, January 17, 1985.) Proliferative disease is characterized by abnormal numbers of glandular breast cells. Thirty-one percent of women who have benign breast biopsies have proliferative breast disease. These women have a mild elevation in breast cancer risk. A rare type of proliferative disease called atypical hyperplasia is associated with a moderate elevation in this risk. As with complex fibroadenoma, the importance of this finding is enhanced in women with a family history of breast cancer. Women with atypical hyperplasia are particularly well advised to undergo mammographic screening and counseling for breast cancer risk.

Another important recent finding concerns a type of benign breast tumor called fibroadenoma. Fibroadenomas are the most common type of breast tumor found in women under thirty, and account for twenty percent of all benign breast biopsies. Our study of these tumors was published in the July 7, 1994 issue of the New England Journal of Medicine. We found that breast cancer risk in these women varied with the type of fibroadenoma. Fibroadenomas with microscopic changes we call "complex" were associated with a mild elevation in breast cancer risk. This risk was larger in women who also had a mother or sister who had developed breast cancer. In contrast, two-thirds of our fibroadenoma patients had simple tumors and no family history of breast cancer. These women were no more likely to develop breast cancer than other women from the general population of the same age. This study suggests that women with simple fibroadenomas need not be concerned about having an elevated breast cancer risk. On the other hand, women with a family history of breast cancer who also have complex fibroadenomas would be well advised to start undergoing mammographic screening by age thirty-five or forty.

Selected publications Kasami M, Vnencak-Jones CL, Manning S, Dupont WD, and Page DL: "Loss of heterozygosity and microsatellite instability in breast hyperplasia: No obligate correlation of these genetic alterations with subsequent malignancy. American Journal of Pathology, 1997; 150(6):1925–1932.

Page DL, Salhany KE, Jensen RA, and Dupont WD: "Subsequent breast carcinoma risk after biopsy with atypia in a breast papilloma." Cancer, 1996; 78(2):258–266.

Page DL, Dupont WD, and Jensen RA: "Papillary apocrine change of the breast: Associations with atypical hyperplasia and risk of breast cancer." Cancer Epidemiology, Biomarkers & Prevention, 1996; 5(1):29–32.

Page DL, Dupont WD, Rogers LW, Jensen RA, and Schuyler PA: "Continued local recurrence of carcinoma 15 – 25 years after a diagnosis of low grade ductal carcinoma in-situ of the breast treated only by biopsy." Cancer, 1995; 76(7):1197–1200.

Roodi N, Bailey LR, Kao WX, Verrier CS, Yee CJ, Dupont WD, and Parl FF: "Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer." Journal of the National Cancer Institute, 1995; 87(6):446–451.

O’Malley FP, Vnencak-Jones CL, Dupont WD, Parl F, Manning S, and Page DL: "p53 mutations are confined to the comedo type ductal carcinoma in-situ of the breast: Immunohistochemical and sequencing data." Laboratory Investigation, 1994; 71:67–72.

Simpson JF, O’Malley FP, Dupont WD, and Page DL: "Heterogeneous expression of nm23 gene product in non-invasive breast carcinoma". Cancer, 1994; 73(9):2352–2358.

Dupont WD, Page DL, Parl FF, Vnencak-Jones CL, Plummer WD Jr., Rados MS, and Schuyler PA: "Long-term breast cancer risk in women with fibroadenoma." New England Journal of Medicine, 1994; 331(1):10–15.

Caleffi M, Teague MW, Jensen RA, Vnencak-Jones CL, Dupont WD, and Parl FF: "p53 gene mutations and steroid receptor status in breast cancer: Clinicopathologic correlations and prognostic assessment." Cancer, 1994; 73(8):2147–2156.

O’Malley FP, Page DL, Nelson EH, and Dupont WD: "Ductal carcinoma in-situ of the breast with apocrine cytology: Definition of a borderline category." Human Pathology, 1994; 25(2):164–168.

Dupont WD, Parl FF, Hartmann WH, Brinton LA, et al.: "Breast cancer risk associated with proliferative breast disease and atypical hyperplasia." Cancer, 1993; 71(4):1258–1265.

Dupont WD and Page DL: "Risk factors for breast cancer in women with proliferative breast disease." New England Journal of Medicine, 1985; 312:146–151.

Topic revision: r1 - 29 Mar 2004, DalePlummer

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