Circulating killer cells in women undergoing needle-directed excisional breast biopsy

Needle-directed excisional breast biopsy (NDBB) is performed on many women having suspicious mammograms. Only a small subset of these women (approximately 20%) will be found to have breast cancer. The goal of this study was to test the hypothesis that presence (or absence) of circulating lymphocytes able to kill cultured breast cancer-derived cell lines would discriminate the subset of women with early forms of breast cancer from those with benign breast disease. The immune status of over 200 women undergoing NDBB was ascertained at the time of biopsy from a peripheral blood sample. Use of a standard surface immunophenotyping panel able to discriminate a variety of both natural killer cells and cytotoxic T lymphocytes revealed no significant differences when compared to a group of healthy volunteers or to the normal ranges established for our laboratory. Functional assays (cytotoxicity studies) were performed in a blinded fashion on peripheral blood lymphocytes from a subset (N = 31) of these women using a panel of target cell lines. Target cells included the NK sensitive K562; the NK resistant Daudi; and two breast cancer-derived cell lines, the hormone sensitive MCF7 and MDA-MB-435 which has been shown to metastasize in immunocompromised mice. No differences were apparent among the groups with respect to ability to kill either K562 or Daudi. All individuals undergoing NDBB had an enhanced ability to kill the breast cancer-derived cell lines compared to healthy donors. Individuals with breast cancer killed, on average, twice as many MCF7 cells as than did individuals with benign breast disease whereas both groups killed approximately three times as many MDA-MB-435 cells as did healthy donors. Further, a higher proportion of the women undergoing NDBB (2-3x) had relatively high cytotoxic ability directed against the breast cancer-derived lines than was found among healthy donors. These data expand earlier observations (Hamilton et al., 1988) that women with stage I breast cancer had elevated ability to kill MCF7 to include a substantial subset of all women with suspicious mammograms.