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High Prevalence of Premalignant Lesions in Prophylactically Removed Breasts From Women at Hereditary Risk for Breast Cancer

N. Hoogerbrugge, P. Bult, L.M. de Widt-Levert, L.V. Beex, L.A. Kiemeney, M.J.L. Ligtenberg, L.F. Massuger, C. Boetes, P. Manders, H.G. Brunner

From the Hereditary Cancer Clinic, Departments of Human Genetics, Medical Oncology, Pathology, Surgery, Epidemiology and Biostatistics, Gynecology, and Radiology, University Medical Center Nijmegen, the Netherlands.

Address reprint requests to N. Hoogerbrugge, MD, Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands; email: n.hoogerbrugge{at}antrg.azn.nl.

Purpose: Women with a hereditary predisposition for breast cancer have an extremely high risk of developing invasive breast carcinoma, and many women consider prophylactic mastectomy to avoid this risk. The use of prophylactic mastectomy is still debated. Identification of frequent premalignant lesions in mastectomy specimens would support the preventive concept of prophylactic mastectomy.

Patients and Methods: We performed a prospective study of breast specimens from 67 women at extremely high genetic risk of breast cancer, with or without previous breast cancer, who were undergoing prophylactic mastectomy (66% were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by radiographic and macroscopic examination of 5-mm tissue slices, with subsequent histology of suspicious lesions and random samples from each quadrant of the breast and the nipple area.

Results: In 57% of the women, one or more different types of high-risk histopathologic lesions were present: 37% atypical lobular hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and 15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one woman with ductal carcinoma-in-situ. None of these lesions was detected at palpation or mammography, which were performed before the mastectomy. The presence of high-risk lesions was independently related to age older than 40 years (odds ratio, 6.6; P = .01) and to bilateral oophorectomy before prophylactic mastectomy (odds ratio, 0.2; P = 0.02).

Conclusion: Many women at high risk of hereditary breast cancer develop high-risk histopathologic lesions, especially after the age of 40 years. Surveillance does not detect such high-risk histopathologic lesions.

Both N. Hoogerbrugge and P. Bult contributed equally to this work.

Related Correspondence

• High-Risk Lesions in High-Risk Women: A High-Risk Formalin-Based Biology!
  Camilo Adem, Robert B. Jenkins, Frédérique Capron, and Dominique Stoppa-Lyonnet
  JCO 2004 22: 1159-1161 [Full Text]

Related Reply

• In Reply:
  Nicoline Hoogerbrugge, Peter Bult, and Han Brunner
  JCO 2004 22: 1161-1162 [Full Text]

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