Premalignant lesions in breast, ovary and Fallopian tube in prophylactically removed tissue from women at hereditary high risk for breast and ovarian cancer

B Hermsen MD^a, S von Mensdorff-Pouilly MD PhD^a, P van Diest MD PhD^b, F Menko MD PhD^c, J Piek MD^a, H Fabry MD^d, P Kenemans MD PhD^a, RHM Verheijen MD PhD^a

^aDepartment of Obstetrics and Gynaecology, ^bDepartment of Pathology, ^cDepartment of Clinical and Human Genetics, ^dDepartment of Surgery; VU University Medical Centre, Amsterdam, Netherlands

AIM To analyse the frequency of premalignant lesions occurring in breast, ovarian and Fallopian tube tissue removed at prophylactic surgery from women at hereditary high risk of breast/adnexal cancer. METHODS Prophylactically removed tissues were obtained from 85 women who underwent bilateral salpingo-oophorectomy (pBSO) and from 59 women who underwent mastectomy (pM). A total of 28 patients underwent both pBSO and pM. Control tissue samples were obtained from women undergoing breast reduction surgery (N = 99) or adnexal surgery for benign reasons (Fallopian tube tissue, N = 72; ovarian tissue, N = 18). Specimens were studied by microscopic examination of 4 mm thick H&E stained sections for the presence of premalignant and malignant lesions. RESULTS Premalignant lesions were found in 32 out of 85 (38%) of women undergoing pBSO. The lesions consisted of dysplasia of the ovary (N = 8, 9%), dysplasia of the Fallopian tube in 27 (32%) cases (p < 0.0001) and one case of tubal carcinoma. Seventy-seven percent of cases with tubal dysplasia and the one case of tubal carcinoma occurred in women with a BRCA1/2 mutation. Premalignant lesions were present in 28 out of 59 (47%) women undergoing pM. Ductal hyperplasia was found in 24 (41%) cases (p = 0.08), atypical lobular hyperplasia in 2 cases, and only one case of atypical ductal hyperplasia was detected. Further, we found one ductal carcinoma in situ (DCIS), two lobular carcinoma in situ (LCIS), and three cases of invasive ductal carcinoma. No correlation was found between the occurrence of premalignant lesions in breast and adnexal tissues. In the control group ductal hyperplasia was found in 27/99 (27%) women and no advanced hyperplasia. No premalignant lesion were detected in the adnexal tissue samples. CONCLUSIONS Hereditary high risk of breast/ovarian cancer is associated with a high frequency of dysplastic lesion of the Fallopian tube, leading to the hypothesis that ovarian carcinoma may originate in tubal mucosa cells. These dysplastic lesions did not correlate with premalignant or malignant lesions of the breast.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 897 (Precursor lesions).