SAN ANTONIO, Dec. 15 -- Benign breast disease in young women, especially atypical hyperplasia, significantly increases the risk of a malignancy, but by how much varies according to histology and other factors, researchers reported here.
- Explain to patients that benign breast disease increases the risk of breast cancer in young women.
- Point out that type of benign disease, family history, and other factors influence the magnitude of breast cancer risk.
- Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Women with atypical hyperplasia had a seven-fold increased risk of breast cancer, irrespective of family history, Karthik Ghosh, M.D., of the Mayo Clinic in Rochester, Minn., said at the San Antonio Breast Cancer symposium.
Proliferative disease without atypia doubled the risk of cancer, whereas nonproliferative breast disease was associated with a risk increase in the absence of a positive family history.
Several previous studies demonstrated that biopsy-confirmed benign breast disease increases the risk of a malignancy. More recently, research at the Mayo Clinic showed an inverse association between lobular involution and breast cancer risk.
Given that breast cancer is the leading cause of death in women ages 25 to 49, Dr. Ghosh and colleagues examined the impact of three factors on breast cancer risk in young women with benign breast disease:
- Benign breast disease histology
- Family history of breast cancer
- Extent of lobular involution
The investigators also assessed the risk conferred by combinations of risk factors and the influence of risk factors on ipsilateral versus contralateral breast cancer.
The study included women ages 18 to 49 who had benign breast disease documented by excisional biopsy from Jan. 1, 1967 to Dec. 31, 1991. The same pathologist reviewed all tissue specimens for the study.
Benign breast disease was classified as nonproliferative, proliferative disease without atypia, or atypical hyperplasia. From questionnaires and a chart review, the investigators determined whether the study participants had no family history of breast cancer, a weak family history, or a strong family history.
Lobular involution was classified as none, partial (1% to 74%), or complete (≥75%).
Breast cancer cases documented during follow-up were compared with expected rates of breast cancer as derived from the NCI Surveillance, Epidemiology, and End Results (SEER) database.
The review identified 4,460 women younger than 50 who were followed for a median of 20 years after diagnosis of benign breast disease. A majority of the women (57%) were ages 40 to 49, followed by 30 to 39 (26%), and 18 to 29 (17%). Dr. Ghosh reported that 62% of the patients had no family history of breast cancer, 21% had a weak family history, and 17% had a strong history.
Nonproliferative disease accounted for 72% of the benign disease, followed by proliferative disease without atypia (26%), and atypical hyperplasia (2%). About a third of the biopsies revealed no lobular involution, partial involution in 61%, and complete involution in 5%.
During the follow-up period, 326 (7%) breast cancers were diagnosed. Analysis of breast cancer cases by benign breast disease histology revealed a risk ratio of 1.2 for nonproliferative disease, 2.02 for proliferative disease without atypia, and 6.92 for atypical hyperplasia (P=0.001).
Analysis of breast cancer risk by family history yielded a risk ratio of 1.32 for patients with no family history, 2.12 for a weak family history, and 2.19 for a strong family history. Breast cancer risk by lobular involution status ranged from 1.72 for no involution to 0.68 for complete involution (P=0.001).
"The impact of lobular involution on risk, even in young women with benign breast disease, is an interesting finding," said Dr. Ghosh. "It suggests that future research could potentially think about ways of promoting lobular involution as a means to reduce breast cancer risk."
The combination of benign breast disease histology and family history resulted in a graded breast cancer risk for patients with nonproliferative disease that ranged from 1.01 to 1.90. In contrast, the highest cancer risk for patients with proliferative disease without atypia and for atypical hyperplasia was observed in patients with a weak family history (3.27 and 11.2, respectively).
Combining involution and benign disease histology showed an inverse association with increasing involution for all three histologic types.
The side of breast cancer occurrence varied with increasing length of follow-up. Ipsilateral breast cancer predominated within the first five years after diagnosis of benign breast disease (65%), whereas contralateral breast cancer accounted for 52% of cases that occurred five years or more after diagnosis of benign breast disease (P=0.03).
"The increased proportion of ipsilateral breast cancers within the first five years suggests the possibility that precursors might be present," said Dr. Ghosh.