Stress-related hormonal suppression of natural killer activity does not show menstrual cycle variations: implications for timing of surgery for breast cancer.
BACKGROUND
Evidence exists that prognosis in breast cancer may be related to the timing of primary surgery. Fluctuations in natural killer (NK) cells and/or their sensitivity to surgical stress hormones could mediate this phenomenon. We sought to establish, firstly, if there are any numerical or functional changes in NK cells during the course of the menstrual cycle and, secondly, if their prior in vitro incubation with cortisol and adrenaline produced functional change that was more pronounced at a particular point in the cycle.


METHODS
Normally menstruating females (n = 10) were sampled at two points (mid-follicular and mid-luteal) during two cycles. NK cell numbers were determined by flow cytometry. Natural killer cell activity (NKA) (unstimulated and following a 2-hour pre-incubation with cortisol and adrenaline) was determined using chromium-51 release assays from peripheral blood mononuclear cells (PBMCs) prepared from cryopreserved samples from the second cycle.


RESULTS
NK cell numbers (expressed as a percentage of a standard lymphgate) were significantly higher at the mid-luteal point compared to the mid-follicular point (8.45 +/- 3.71 vs. 6.85 +/- 2.80, p < 0.05, data pooled from both cycles). Corresponding changes in NKA were observed, although these did not reach statistical significance. The mean inhibitory effects of cortisol (67%) and adrenaline (12%) on NKA were significant, but this phenomenon was uninfluenced by cycle point.


CONCLUSIONS
This study supports the role of menstrual cycle-induced alterations in NK cells as a putative mediator of improved survival when surgery for breast cancer is carried out in the follicular phase. However there is no evidence of the cyclical sensitivity of NK cells to the principal surgical stress hormones.
Garland
Malcolm
M
Education and Research Centre, St. Vincent's University Hospital, Conway Institute, University College Dublin, Dublin 4, Ireland. mgarland@ireland.com
Doherty
Derek
D
Golden-Mason
Lucy
L
Fitzpatrick
Patricia
P
Walsh
Noel
N
O'Farrelly
Cliona
C
D000328:Adult; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000601:surgery*; D002452:Cell Count; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005498:Follicular Phase / Q000276:immunology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008183:Luteal Phase / Q000276:immunology*
D006854:Hydrocortisone; D004837:Epinephrine