Intraductal approach to the detection of intraductal lesions of the breast.

Bloody nipple discharge is a clue in the detection of ductal carcinoma of the breast that do not display a mass. Since sensitivity of discharge cytology is not sufficiently high and mammary ductendoscopy (MS) contributes to the diagnosis of intraductal lesions. We set out to determine whether the intraductal approach is effective for detection of ductal carcinoma. We performed 445 MS procedure in 323 patients who had nipple discharge but no overt mass. The diagnostic accuracy rates of discharge cytology and intraductal breast biopsy (IDBB) were studied in detecting malignancy. The therapeutic value of IDBB for intraductal papillomas was studied in 73 patients. Out of 323 patients, 80 had breast cancer and 155 had intraductal papilloma. MS detected intraductal tumors in 47 cases (58.8%). IDBB was performed in 35 of these 47 cases. The sensitivity was 37.1% by touch cytology, 68.6% by IDBB, and 82.8% by directed ductal lavage cytology. Of the 73 intraductal papilloma patients who were followed for more than 3 years, the therapeutic effectiveness of IDBB was recognized in 57 (78.1%). Directed ductal lavage cytology was the most sensitive method in detecting malignancy. MS and IDBB were benefit in the treatment of intraductal papilloma.

Evaluation of sensitivity to 5-FU on the basis of thymidylate synthase (TS)/dihydropyrimidine dehydrogenase (DPD) activity and chromosomal analysis in micro tissue specimens of breast cancer.

BACKGROUND: Preoperative assessment of the anticancer drug sensitivity of tumors plays an important role in the selection of therapy. If evaluation of the 5-FU sensitivity of microtissue specimens obtained by techniques such as core needle biopsy could be performed, the addition of fluorouracil to adriamycin and cyclophosphamide may further enhance response rates. In order to evaluate a simple sensitivity test for the anti-tumor agent 5-fluorouracil (5-FU), we examined whether an assay of a small sample could measure mRNA to predict the activities of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In addition, gene abnormalities on chromosomes 1 and 18 corresponding to DPD, TS and the relationships between the gene abnormalities and the amount of mRNA and activity were examined. METHOD: TS and DPD activity were measured using the fluorodeoxyuridine monophosphate ligand binding assay and radio enzymatic assay, respectively, while mRNA levels were assayed by real-time polymerase chain reaction. Chromosome 1 and 18 aberrations were investigated by fluorescence in situ hybridization (FISH) with centromere probes. RESULTS: TS mRNA and TS activity showed a positive correlation (r=0.518, p=0.0017). TS activity and TS mRNA were significantly higher in the nuclear grade 3 group than in the other groups (p=0.04, p=0.0072, respectively). TS activity and mRNA in tumor tissue tended to decrease in the progesterone receptor positive groups (p=0.059, p=0.066, respectively). There was no correlation between DPD mRNA and DPD activity in tumor tissue (r=0.139, p=0.4423). DPD mRNA was measured as 282.88+/-170.68 copies/cell in tumor tissue and 635.88+/-310.04 copies/cell in normal tissue, and was thus significantly higher in normal tissue (p<0.001). CONCLUSIONS: TS mRNA showed a positive correlation with TS activity, suggesting that this method of using small amounts of tissue can replace anti-cancer drug sensitivity tests.