Effect of anaesthetic technique on immune cell infiltration in breast cancer: a follow-up pilot analysis of a prospective, randomised, investigator-masked study.
BACKGROUND
Live animal studies using an inoculation model of breast cancer indicate that anaesthetic drugs and techniques differentially affect cancer metastasis, inversely related to Natural Killer (NK) cell and T lymphocyte levels. Clinical histological studies demonstrate that the distribution of these immune cells and macrophages in intra-tumoral cancer tissue can predict prognosis and response to therapy. No study has evaluated whether the anaesthetic technique influences human breast cancer immune cell infiltration.


METHODS
Excised breast cancer specimens from patients previously enrolled in an ongoing, prospective, randomised trial (NCT00418457) investigating the effect of anaesthetic technique on long-term breast cancer outcome were immunohistochemically stained to enable a colour deconvolution technique to summate marked immune cell infiltration: CD56 (NK cells), CD4 (T helper cells), CD8 (T suppressor cells) and CD68 (macrophages). Patients were randomised to receive either a propofol-paravertebral anaesthetic with continuing analgesia (PPA, n=12) or a balanced general anaesthesia with opioid analgesia (GA, n=16) for 24 h postoperatively. Investigators were masked to group allocation.


RESULTS
Normalised positive intensity values, (median (interquartile range (IQR)), for CD56 were lower in GA121 (116-134) versus 136 (132-142), p=0.015. CD4 was also lower in GA10.9 (5.5-27.8) versus PPA 19.7 (14.4-83.5), p=0.03 but CD8 5.5 (4.0-9.75) versus 13.0 (5.0-14.5) respectively, p=0.24 and CD 68 infiltration 5.8 (3.25-8.75) versus 8.0 (3.0-8.75), p=0.74 were not significantly different.


CONCLUSIONS
PPA induces increased levels of NK and T helper cell infiltration into breast cancer tissue compared with GA but not T suppressor cells or macro phages. This is consistent with the hypothesis that the anaesthetic technique may affect perioperative immune function conducive to resisting breast cancer recurrence and metastasis.
Department of Anaesthesia, Mater Misericordiae University Hospital and School of Medicine & Medical Science, University College Dublin, Dublin, Ireland.
Fiona
F
Desmond
Digital Core Pathology Laboratory, Mater Misericordiae University Hospital and School of Medicine & Medical Science, University College Dublin, Dublin, Ireland.
Janet
J
McCormack
Department of Pathology, Mater Misericordiae University Hospital and School of Medicine & Medical Science, University College Dublin, Dublin, Ireland.
Niall
N
Mulligan
Department of Surgery, Mater Misericordiae University Hospital and School of Medicine & Medical Science, University College Dublin, Dublin, Ireland.
Maurice
M
Stokes
Department of Anaesthesia, Mater Misericordiae University Hospital and School of Medicine & Medical Science, University College Dublin, Dublin, Ireland Outcomes Research Consortium, Cleveland Clinic, Cleveland, OH, U.S.A. donal.buggy@ucd.ie.
Donal J
DJ
Buggy
D000328:Adult; D000368:Aged; D000758:Anesthesia / Q000379:methods*; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001943:Breast Neoplasms / Q000276:immunology*; D019002:CD56 Antigen / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019002:CD56 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C522918:NCAM1 protein, human
Anaesthetic technique; breast cancer immune cell infiltration; randomised grial