Differential effects of serum from patients administered distinct anaesthetic techniques on apoptosis in breast cancer cells in vitro: a pilot study.
In vitro and retrospective clinical studies suggest an association between anaesthetic technique during primary breast cancer surgery and cancer outcome. Apoptosis is an important step in the mechanism of breast cancer metastasis, but whether it is influenced by anaesthetic technique is unknown. Using serum from breast cancer surgery patients randomized to receive distinct anaesthetic techniques, we investigated its effect on apoptosis in oestrogen receptor (ER)-negative breast cancer cells in vitro.
Women with biopsy-proven breast cancer were randomized to receive either propofol general anaesthesia with paravertebral analgesia (PPA) or standard sevoflurane general anaesthesia with opioid analgesia (SGA) in an ongoing, prospective clinical trial (NCT 00418457). Serum from a randomly selected subset of these patients (10 PPA and 10 SGA) who had donated 20 ml venous blood immediately before anaesthetic induction and at 1 h after operation was exposed to ER-negative MDA-MB-231 cells. Apoptosis was measured using ApoLive-Glo Multiplex Assay™.
Exposure of MDA-MB-231 cells to postoperative serum of PPA patients resulted in higher luminescence ratio (apoptosis) than SGA patients, median (25-75%), 0.40 (0.35-0.43) compared with 0.22 (0.21-0.30), respectively (P=0.001). The luminescence ratio of postoperative serum from SGA was reduced compared with preoperative SGA 0.22 (0.21-0.30) compared with 0.3 (0.25-0.35) (P=0.045).
Serum from patients given sevoflurane anaesthesia and opioids for primary breast cancer surgery reduces apoptosis in ER-negative breast cancer cells to a greater extent than serum from patients given propofol-paravertebral anaesthesia. Anaesthetic technique might affect the serum milieu in a manner that impacts cancer cell apoptosis, and thereby tumour metastasis.
Jaura AI
，Flood G
，Gallagher HC
，Buggy DJ
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Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study.
Animal models and retrospective clinical data suggest that certain anaesthetic techniques can attenuate immunosuppression and minimize metastasis after cancer surgery. Natural killer (NK) T cells are a critical component of the anti-tumour immune response. We investigated the effect of serum from women undergoing primary breast cancer surgery, randomized to propofol-paravertebral block (PPA) or sevoflurane-opioid (GA) anaesthetic techniques, on healthy human donor NK cell function and cytotoxicity against oestrogen and progesterone receptor-positive breast cancer cells (HCC1500).
Ten subjects who donated serum before operation and 24 h after operation in an ongoing randomized prospective trial (NCT 00418457) were randomly selected. Serum from PPA (n=5) and GA (n=5) subjects was co-cultured with HCC1500 and healthy primary NK cells. NK cell activating receptors (NKp30, NKp44, NKp46, 2b4, CD16, NKG2D), cytokine production, NK CD107a expression, and cytotoxicity towards HCC1500 were examined.
Serum from PPA subjects did not alter normal NK marker expression or secretion of cytokines. Serum from GA subjects reduced NK cell activating receptor CD16 [from mean (sem), 82 (2)% to 50 (4)%, P=0.001], IL-10 [from 1700 (80) to 1200 (92) pg ml(-1), P=0.001], and IL-1β [from 68 (12) to 19 (4) pg ml(-1), P=0.01]. An increase in NK cell CD107a [23 (2)% to 37(3)%, P=0.007] and apoptosis of HCC1500 [11 (1)% to 21 (2)%, P=0.0001] was observed with PPA serum, but not GA serum, treated NK cells.
Serum from women with breast cancer undergoing surgical excision who were randomized to receive a PPA anaesthetic technique led to greater human donor NK cell cytotoxicity in vitro compared with serum from women who received GA.
NCT 041857.
Buckley A
，McQuaid S
，Johnson P
，Buggy DJ
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Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial.
Three perioperative factors impair host defence against recurrence during cancer surgery: the surgical stress response, use of volatile anaesthetic, and opioids for analgesia. All factors are ameliorated by regional anaesthesia-analgesia. We tested the primary hypothesis that breast cancer recurrence after potentially curative surgery is lower with regional anaesthesia-analgesia using paravertebral blocks and the anaesthetic propofol than with general anaesthesia with the volatile anaesthetic sevoflurane and opioid analgesia. A second hypothesis was that regional anaesthesia-analgesia reduces persistent incisional pain.
We did a randomised controlled trial at 13 hospitals in Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore, and the USA. Women (age <85 years) having potentially curative primary breast cancer resections were randomised by computer to either regional anaesthesia-analgesia (paravertebral blocks and propofol) or general anaesthesia (sevoflurane) and opioid analgesia. The primary outcome was local or metastatic breast cancer recurrence. The secondary outcome was incisional pain at 6 months and 12 months. Primary analyses were done under intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT00418457. The study was stopped after a preplanned futility boundary was crossed.
Between Jan 30, 2007, and Jan 18, 2018, 2132 women were enrolled to the study, of whom 24 were excluded before surgery. 1043 were assigned to regional anaesthesia-analgesia and 1065 were allocated to general anaesthesia. Baseline characteristics were well balanced between study groups. Median follow-up was 36 (IQR 24-49) months. Among women assigned regional anaesthesia-analgesia, 102 (10%) recurrences were reported, compared with 111 (10%) recurrences among those allocated general anaesthesia (hazard ratio 0·97, 95% CI 0·74-1·28; p=0·84). Incisional pain was reported by 442 (52%) of 856 patients assigned to regional anaesthesia-analgesia and 456 (52%) of 872 patients allocated to general anaesthesia at 6 months, and by 239 (28%) of 854 patients and 232 (27%) of 852 patients, respectively, at 12 months (overall interim-adjusted odds ratio 1·00, 95% CI 0·85-1·17; p=0·99). Neuropathic breast pain did not differ by anaesthetic technique and was reported by 87 (10%) of 859 patients assigned to regional anaesthesia-analgesia and 89 (10%) of 870 patients allocated to general anaesthesia at 6 months, and by 57 (7%) of 857 patients and 57 (7%) of 854 patients, respectively, at 12 months.
In our study population, regional anaesthesia-analgesia (paravertebral block and propofol) did not reduce breast cancer recurrence after potentially curative surgery compared with volatile anaesthesia (sevoflurane) and opioids. The frequency and severity of persistent incisional breast pain was unaffected by anaesthetic technique. Clinicians can use regional or general anaesthesia with respect to breast cancer recurrence and persistent incisional pain.
Sisk Healthcare Foundation (Ireland), Eccles Breast Cancer Research Fund, British Journal of Anaesthesia International, College of Anaesthetists of Ireland, Peking Union Medical College Hospital, Science Fund for Junior Faculty 2016, Central Bank of Austria, and National Healthcare Group.
Sessler DI
，Pei L
，Huang Y
，Fleischmann E
，Marhofer P
，Kurz A
，Mayers DB
，Meyer-Treschan TA
，Grady M
，Tan EY
，Ayad S
，Mascha EJ
，Buggy DJ
，Breast Cancer Recurrence Collaboration
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