Biologic markers of risk in nipple aspirate fluid are associated with residual cancer and tumour size

We previously demonstrated that nipple aspirate fluid (NAF) can be obtained from virtually all non-Asian women between the ages of 30 and 72. The focu s of this report is to (1) determine the association of candidate markers o f breast cancer risk in NAF obtained from fresh mastectomy specimens with r esidual breast carcinoma, and (2) evaluate the association of the markers w ith breast tumour progression. Nipple aspiration was performed on 97 specim ens. Cytology, DNA index (including % hypertetraploid cells), cell cycle pa rameters (S phase fraction, % cells in G2/M), prostate-specific antigen (PS A), epidermal growth factor (EGF), testosterone, carcinoembryonic antigen ( CEA) and prostaglandin D synthase (PGDS) were evaluated in NAF for their as sociation with (1) residual ductal carcinoma in situ (DCIS) or invasive can cer, and (2) pathologic tumour size. NAF was obtained from 99% (96/97) of s pecimens. Atypical and malignant NAF cytology were significantly associated with residual DCIS or invasive cancer (P = 0.001) and with larger tumours (P = 0.004). One hundred per cent and 88% of subjects with malignant and at ypical NAF cytology, respectively, had residual carcinoma. The percentage o f cells in G2/M and DNA index were associated both with risk of residual ca rcinoma (P = 0.01 for each) and larger tumour size (DNA index, P = 0.03; G2 /M, P = 0.05), although neither biomarker improved the ability of NAF cytol ogy, to predict residual breast cancer. Higher DNA index was associated wit h atypical cytology (P = 0.0001). In summary, atypical and malignant NAF cy tology are associated with larger tumour size, and are highly predictive of residual carcinoma after needle or excisional biopsy of the breast. (C) 19 99 Cancer Research Campaign.