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The breast cancer susceptibility gene, BRCA2 on chromosome 13q12-13, was recently isolated. Mutations in BRCA2 are thought to account for as much as 35% of all inherited breast cancer as wall as a proportion of inherited ovarian cancer. Many BRCA2-linked families also contain cases of male breast cancer. We have analysed germline DNA from 50 males with breast cancer (unselected for family history) and 26 individuals from site-specific female breast and breast-ovarian cancer families for mutations in BRCA2. All 17 breast-ovarian cancer families have been screened for BRCA1 coding region mutations and none were detected. Conformation-sensitive gel electrophoresis (CSGE) analysis of PCR-amplified DNA followed by direct sequencing was used to detect sequence variants. Three of eleven individuals carry the same mutation, all are of Ashkenazi Jewish descent, supporting the observation by Neuhausen et al. in this issue that there is a common mutation in this population. Eleven truncating mutations and nine polymorphisms were identified -- all were coding region variants. No loss-of-transcript mutations were identified in the sixteen samples for which this analysis was possible. Seven of the nine disease-associated mutations were detected in the 50 men with breast cancers; for thus in our series, BRCA2 mutations account for 14% of male breast cancer, all but one of which had a family history of male and/or female breast cancer.

Background. Some growth factors may promote tumor growth by affecting tumor angiogenesis. The angiogenic growth factor, pleiotrophin, was demonstrated previously in human breast carcinoma tissues; however, the pattern of pleiotrophin expression in normal breast tissues has not been established. Methods. The expression of pleiotrophin and the related growth factor, midkine, was examined by polymerase chain reaction amplification of reverse transcriptase copies of RNA transcripts (RT‐PCR) from freshly resected normal and malignant human breast tissues. Northern blot analysis of midkine expression was performed on a limited number of the specimens and on human and canine breast carcinoma cell lines. Clinicopathologic variables from the breast cancer patients were examined in relation to the growth factor expression patterns. Results. The majority of both malignant and normal breast tissues expressed pleiotrophin. In contrast, midkine was expressed frequently in the malignant breast tissues but in only one of the normal specimens. Northern blot analysis of the breast carcinoma cells lines showed that they commonly expressed midkine transcripts. The only correlation of the growth factor expression patterns with the other clinical variables was the finding that the three midkine‐negative breast carcinoma specimens also had low estrogen receptor levels. Conclusions. By this analysis, the expression of pleiophin was equivalent in both malignant and normal human breast tissues. Midkine, on the other hand, exhibited increased expression in the breast carcinomas but showed much lower expression in the normal breast tissue. Although the cellular source of the midkine expression was not determined by the RT‐PCR assay, the Northern blot analysis showed that isolated populations of breast cancer cells commonly express this growth factor. This is the first example of a tissue simultaneously expressing high amounts of both pleiotrophin and midkine, a finding of unclear pathophysiologic significance.

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Granulomatous mastitis is an uncommon inflammatory disease that typically presents with painful breast lesions. Recent publications have brought to light a specific subset of granulomatous mastitis patients with a distinct histological pattern of disease termed, “cystic neutrophilic granulomatous mastitis” (CNGM). Although many cases of granulomatous lobular mastitis have been thought to be idiopathic, this rare subset of an uncommon disease has been linked to infections with Corynebacterium species. Herein, a cohort of CNGM patients from a large, tertiary care, North‐American, academic medical center is presented. Correlative demographic, clinical, radiographic, pathologic, microbiologic, management, and outcomes data are provided. Collaborative communication between specialists to accurately diagnose and manage these patients is essential to decreasing potential morbidity.