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In Reply:

Department of Human Genetics, Medical Oncology and Pathology, University Medical Center Nijmegen, Nijmegen, the Netherlands

Adem et al review three studies on breast pathology in patients with hereditary breast cancer. They conclude that the available data support their previous claim that breast cancer progression from benign breast disease to invasive cancer is more rapid in BRCA mutation carriers [1]. They list the following arguments: 1) A low prevalence (2-2.5%) of high-risk lesions in prophylactically removed breasts from BRCA-mutation carriers, and 2) a high incidence of cancer in BRCA-mutation carriers. This model may be true. On the other hand, our study [2] and the Memorial Sloan-Kettering Cancer Center study [3] found a much higher prevalence of high-risk lesions (43% and 46%, respectively). Both these studies used more extensive breast tissue sampling protocols and therefore achieved higher sensitivity. Thus, the hypothesis that BRCA mutation carriers have a higher prevalence of high-risk lesions cannot be discarded. In fact, our data and that from the Memorial Sloan-Kettering Cancer Center study seem to favor increased incidence of lesions over rapid progression [2,3]. We agree that future studies are required to resolve whether progression or incidence of high-risk lesions is more important or whether other factors are involved. We note that irrespective of the underlying biologic model, the data argue for prophylactic removal of the breasts in BRCA1 and BRCA2 mutation carriers [4]. We also note that the prevalence of high-risk lesions was even higher in non-BRCA linked high-risk families in our study (Table 1). Thus the absence of a mutation in the BRCA1 or BRCA2 genes in such a family should not be taken to indicate low risk.

The authors indicated no potential conflicts of interest.

REFERENCES

1. Adem C, Reynolds C, Soderberg CL, et al: Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers. Cancer 97:1-11, 2003[CrossRef][Medline]

2. Hoogerbrugge N, Bult P, de Widt-Levert LM, et al: High prevalence of premalignant lesions in prophylactically removed breasts from women at hereditary risk for breast cancer. J Clin Oncol 21:41-45, 2003[Abstract/Free Full Text]

3. Kauff ND, Brogi E, Scheuer L, et al: Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations. Cancer 97:1601-1608, 2003[CrossRef][Medline]

4. Meijers-Heijboer H, van Geel B, van Putten WLJ, et al: Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 345:159-164, 2001[Abstract/Free Full Text]

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