Effect of intraoperative use of low-dose dexmedetomidine on the prognosis of patients undergoing breast cancer surgery

doi:10.3969/j.issn.1674-8115.2023.02.008

Abstract

Abstract:

Objective ·To investigate the influence of intraoperative dexmedetomidine infusion on the recurrence-free survival (RFS) and overall survival (OS) rate of patients undergoing breast cancer surgery. Methods ·A retrospective analysis was performed on patients who underwent breast cancer surgery at the Breast Disease Diagnosis and Treatment Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from July 2013 to June 2014. Patients were divided into dexmedetomidine group and control group according to whether dexmedetomidine was injected intraoperatively at 0.7?0.8 ìg/kg. After correcting the confounding factors between the two groups by using the propensity score matching method, the factors affecting the prognosis and survival of patients undertaking breast cancer surgery were investigated by univariate and multivariate analysis, and the Kaplan-Meier survival curve was further used to analyze the effect of intraoperative dexmedetomidine on RFS and OS after five years of breast cancer surgery. Results ·There were significant differences in age, progesterone receptor (PR) positive ratio, proliferating cell nuclear antigen (Ki67) expression score, American Society of Anesthesiologists (ASA) grade, and anesthesia duration between the two groups before propensity score matching. After propensity score matching, a total of 239 pairs were successfully matched, and there was no significant difference in baseline data and perioperative data between the two groups (P>0.05). Univariate analysis showed that age (P=0.032), postoperative radiotherapy (P=0.041), Ki67 score (P=0.021), and tumor TMN stage (P=0.029) were significantly correlated with postoperative five-year OS. The results of multivariate analysis showed that postoperative radiotherapy, Ki67 score, and tumor TMN stage were significantly correlated with postoperative five-year OS (P<0.05). Intraoperative low-dose dexmedetomidine infusion was not a risk factor for postoperative five-year OS (P>0.05). Compared with the control group, the five-year postoperative RFS and OS in dexmedetomidine group did not decrease significantly (P>0.05). Conclusion ·Intraoperative use of low dosage of dexmedetomidine (0.7?0.8 μg/kg) has no significant effect on RFS and OS in patients undergoing breast cancer surgery at five years postoperatively, providing theoretical reference for the rational selection of anesthetics for tumor patients. The effect of higher dosage of dexmedetomidine needs to be further confirmed by prospective multicenter randomized controlled studies.

Key words: dexmedetomidine, breast cancer, overall survival, recurrence-free survival

CLC Number:

R614.2

YANG Xiaoxuan, ZHU Shan, QIAN Cheng, CHU Xiaoying. Effect of intraoperative use of low-dose dexmedetomidine on the prognosis of patients undergoing breast cancer surgery[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 194-200.

Figures/Tables 4

TrendMD

References 18

1	BALASUBRAMANIAN R, ROLPH R, MORGAN C, et al. Genetics of breast cancer: management strategies and risk-reducing surgery[J]. Br J Hosp Med (Lond), 2019, 80(12): 720-725.
2	WANG Y L, XU X F, LIU H, et al. Effects of dexmedetomidine on patients undergoing radical gastrectomy[J]. J Surg Res, 2015, 194(1): 147-153.
3	CATA J P, SINGH V, LEE B M, et al. Intraoperative use of dexmedetomidine is associated with decreased overall survival after lung cancer surgery[J]. J Anaesthesiol Clin Pharmacol, 2017, 33(3): 317-323.
4	WANG C Y, DATOO T, ZHAO H L, et al. Midazolam and dexmedetomidine affect neuroglioma and lung carcinoma cell biology in vitro and in vivo[J]. Anesthesiology, 2018, 129(5): 1000-1014.
5	LAVON H, MATZNER P, BENBENISHTY A, et al. Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers[J]. Br J Anaesth, 2018, 120(1): 188-196.
6	SZPUNAR M J, BURKE K A, DAWES R P, et al. The antidepressant desipramine and α₂-adrenergic receptor activation promote breast tumor progression in association with altered collagen structure[J]. Cancer Prev Res (Phila), 2013, 6(12): 1262-1272.
7	LIU Y, SUN J X, WU T, et al. Effects of serum from breast cancer surgery patients receiving perioperative dexmedetomidine on breast cancer cell malignancy: a prospective randomized controlled trial[J]. Cancer Med, 2019, 8(18): 7603-7612.
8	VON MINCKWITZ G, SCHMITT W D, LOIBL S, et al. Ki67 measured after neoadjuvant chemotherapy for primary breast cancer[J]. Clin Cancer Res, 2013, 19(16): 4521-4531.
9	CHEN X S, ZHU S J, FEI X C, et al. Surgery time interval and molecular subtype may influence Ki67 change after core needle biopsy in breast cancer patients[J]. BMC Cancer, 2015, 15: 822.
10	CHEN W Q, ZHENG R S, BAADE P D, et al. Cancer statistics in China, 2015[J]. CA A Cancer J Clin, 2016, 66(2): 115-132.
11	FLANDERS C A, ROCKE A S, EDWARDSON S A, et al. The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies[J]. Crit Care, 2019, 23(1): 402.
12	VÁZQUEZ S M, MLADOVAN A G, PÉREZ C, et al. Human breast cell lines exhibit functional α₂-adrenoceptors[J]. Cancer Chemother Pharmacol, 2006, 58(1): 50-61.
13	XIA M, TONG J H, ZHOU Z Q, et al. Tramadol inhibits proliferation, migration and invasion via α₂-adrenoceptor signaling in breast cancer cells[J]. Eur Rev Med Pharmacol Sci, 2016, 20(1): 157-165.
14	ZHENG L H, ZHAO J, ZHENG L K, et al. Effect of dexmedetomidine on perioperative stress response and immune function in patients with tumors[J]. Technol Cancer Res Treat, 2020, 19: 1533033820977542.
15	LAVON H, KRIGMAN R, ELBAZ E, et al. The perioperative use of the sedative dexmedetomidine in cancer patients may have detrimental effects[J]. Brain Behav Immun, 2015, 49: e29.
16	MANNE G R, UPADHYAY M R, SWADIA V. Effects of low dose dexmedetomidine infusion on haemodynamic stress response, sedation and post-operative analgesia requirement in patients undergoing laparoscopic cholecystectomy[J]. Indian J Anaesth, 2014, 58(6): 726-731.
17	SIOBAL M S, KALLET R H, KIVETT V A, et al. Use of dexmedetomidine to facilitate extubation in surgical intensive-care-unit patients who failed previous weaning attempts following prolonged mechanical ventilation: a pilot study[J]. Respir Care, 2006, 51(5): 492-496.
18	温润耀. TCH新辅助化疗方案对HER2阳性乳腺癌的疗效及对患者ER、PR、HER2表达的影响[J]. 中国医学创新, 2021, 18(13): 15-19.
	WEN R Y. Influence of efficacy and levels of ER, PR, HER2 in HER2 positive breast cancer by TCH neoadjuvant chemotherapy regimen[J]. Medical Innovation of China, 2021, 18(13): 15-19.

Item	DEX group (n=385)	Control group (n=273)	P value
Age/year	54.5±0.6	52.1±0.7	0.004
BMI/(kg·m^-2)	23.2±0.2	23.3±0.2	0.002
Chemotherapy/n(%)	259 (67.3)	180 (65.9)	0.742
Radiotherapy/n(%)	176 (45.7)	127 (46.5)	0.871
Hormonal therapy/n(%)	236 (61.3)	177 (64.8)	0.365
ER+/n(%)	224 (58.2)	171 (62.6)	0.258
PR+/n(%)	155 (40.3)	140 (51.3)	0.011
HER2+/n(%)	94 (24.4)	61 (22.3)	0.576
Ki67/n(%)	209 (54.3)	151 (55.3)	0.812
ASA classification/n(%)			0.000
Ⅰ	206 (53.5)	91 (33.3)
Ⅱ	179 (46.5)	182 (66.7)
TMN stage/n(%)			0.937
0	50 (13.0)	31 (11.4)
Ⅰ	155 (40.3)	106 (38.8)
ⅡA	101 (26.2)	77 (28.2)
ⅡB	36 (9.3)	28 (10.3)
Ⅲ	43 (11.2)	31 (11.4)
Type of surgery/n(%)			0.891
Breast-conserving surgery	111 (28.8)	80 (29.3)
Mastectomy	274 (71.2)	193 (70.7)
Duration of anesthesia/min	64.8±1.1	61.1±0.9	0.023
Remifentanil/μg	707.7±17.2	692.6±19.6	0.563
Sufentanyl/μg	34.5±0.5	34.2±0.6	0.638
Propofol/mg	142.0±1.2	138.6±1.4	0.074
Cisatracurium/mg	19.7±0.2	19.4±0.3	0.301
Inhalable anesthetic/n(%)			0.169
Sevoflurane	183 (47.5)	115 (42.1)
Desflurane	202 (52.5)	158 (57.9)
VAS score when leaving PACU	0.6±0.0	0.6±0.0	0.342
Propensity score	0.31±0.08	0.25±0.06	0.006

Item	DEX group (n=385)	Control group (n=273)	P value
Age/year	54.5±0.6	52.1±0.7	0.004
BMI/(kg·m^-2)	23.2±0.2	23.3±0.2	0.002
Chemotherapy/n(%)	259 (67.3)	180 (65.9)	0.742
Radiotherapy/n(%)	176 (45.7)	127 (46.5)	0.871
Hormonal therapy/n(%)	236 (61.3)	177 (64.8)	0.365
ER+/n(%)	224 (58.2)	171 (62.6)	0.258
PR+/n(%)	155 (40.3)	140 (51.3)	0.011
HER2+/n(%)	94 (24.4)	61 (22.3)	0.576
Ki67/n(%)	209 (54.3)	151 (55.3)	0.812
ASA classification/n(%)			0.000
Ⅰ	206 (53.5)	91 (33.3)
Ⅱ	179 (46.5)	182 (66.7)
TMN stage/n(%)			0.937
0	50 (13.0)	31 (11.4)
Ⅰ	155 (40.3)	106 (38.8)
ⅡA	101 (26.2)	77 (28.2)
ⅡB	36 (9.3)	28 (10.3)
Ⅲ	43 (11.2)	31 (11.4)
Type of surgery/n(%)			0.891
Breast-conserving surgery	111 (28.8)	80 (29.3)
Mastectomy	274 (71.2)	193 (70.7)
Duration of anesthesia/min	64.8±1.1	61.1±0.9	0.023
Remifentanil/μg	707.7±17.2	692.6±19.6	0.563
Sufentanyl/μg	34.5±0.5	34.2±0.6	0.638
Propofol/mg	142.0±1.2	138.6±1.4	0.074
Cisatracurium/mg	19.7±0.2	19.4±0.3	0.301
Inhalable anesthetic/n(%)			0.169
Sevoflurane	183 (47.5)	115 (42.1)
Desflurane	202 (52.5)	158 (57.9)
VAS score when leaving PACU	0.6±0.0	0.6±0.0	0.342
Propensity score	0.31±0.08	0.25±0.06	0.006

Item	DEX group (n=239)	Control group (n=239)	P value
Age/year	54.3±0.8	52.9±0.8	0.212
BMI/(kg·m^-2)	23.1±0.2	23.0±0.2	0.681
Chemotherapy/n(%)	168 (70.3)	161 (67.4)	0.548
Radiotherapy/n(%)	119 (49.8)	108 (45.2)	0.357
Hormonal therapy/n(%)	116 (48.5)	109 (45.6)	0.582
ER+/n(%)	125 (52.3)	141 (59.0)	0.174
PR+/n(%)	158 (66.1)	140 (58.6)	0.113
HER2+/n(%)	60 (25.1)	58 (24.3)	0.916
Ki67/n(%)	129 (54.0)	141 (59.0)	0.308
ASA classification/n(%)			0.082
Ⅰ	109 (45.6)	129 (54.0)
Ⅱ	130 (54.4)	110 (46.0)
TMN stage/n(%)			0.531
0	24 (9.9)	21 (8.5)
Ⅰ	103 (43.3)	100 (41.9)
ⅡA	75 (31.2)	79 (33.1)
ⅡB	10 (4.3)	12 (5.1)
Ⅲ	27 (11.1)	27 (11.4)
Type of surgery/n(%)			0.176
Breast-conserving surgery	6 (25.8)	58 (24.3)
Mastectomy	177 (74.2)	181 (75.7)
Duration of anesthesia/min	64.6±1.3	62.2±1.0	0.162
Remifentanil/μg	680.5±20.7	704.7±21.6	0.416
Sufentanyl/μg	34.0±0.7	34.2±0.7	0.781
Propofol/mg	141.9±1.5	138.2±1.4	0.073
Cisatracurium/mg	19.4±0.3	19.1±0.3	0.367
Inhalable anesthetic/n(%)			0.564
Sevoflurane	83 (34.8)	76 (32.1)
Desflurane	156 (65.2)	163 (67.9)
VAS score when leaving PACU	0.6±0.0	0.7±0.1	0.125
Propensity score	0.29±0.07	0.30±0.06	0.331

Item	DEX group (n=239)	Control group (n=239)	P value
Age/year	54.3±0.8	52.9±0.8	0.212
BMI/(kg·m^-2)	23.1±0.2	23.0±0.2	0.681
Chemotherapy/n(%)	168 (70.3)	161 (67.4)	0.548
Radiotherapy/n(%)	119 (49.8)	108 (45.2)	0.357
Hormonal therapy/n(%)	116 (48.5)	109 (45.6)	0.582
ER+/n(%)	125 (52.3)	141 (59.0)	0.174
PR+/n(%)	158 (66.1)	140 (58.6)	0.113
HER2+/n(%)	60 (25.1)	58 (24.3)	0.916
Ki67/n(%)	129 (54.0)	141 (59.0)	0.308
ASA classification/n(%)			0.082
Ⅰ	109 (45.6)	129 (54.0)
Ⅱ	130 (54.4)	110 (46.0)
TMN stage/n(%)			0.531
0	24 (9.9)	21 (8.5)
Ⅰ	103 (43.3)	100 (41.9)
ⅡA	75 (31.2)	79 (33.1)
ⅡB	10 (4.3)	12 (5.1)
Ⅲ	27 (11.1)	27 (11.4)
Type of surgery/n(%)			0.176
Breast-conserving surgery	6 (25.8)	58 (24.3)
Mastectomy	177 (74.2)	181 (75.7)
Duration of anesthesia/min	64.6±1.3	62.2±1.0	0.162
Remifentanil/μg	680.5±20.7	704.7±21.6	0.416
Sufentanyl/μg	34.0±0.7	34.2±0.7	0.781
Propofol/mg	141.9±1.5	138.2±1.4	0.073
Cisatracurium/mg	19.4±0.3	19.1±0.3	0.367
Inhalable anesthetic/n(%)			0.564
Sevoflurane	83 (34.8)	76 (32.1)
Desflurane	156 (65.2)	163 (67.9)
VAS score when leaving PACU	0.6±0.0	0.7±0.1	0.125
Propensity score	0.29±0.07	0.30±0.06	0.331

Influencing factor	Univariate analysis		Multivariate analysis
Influencing factor	HR(95%CI)	P value	HR(95%CI)	P value
Age	1.02 (1.00, 1.03)	0.032	1.01 (0.99, 1.04)	0.062
BMI	1.01 (0.98, 1.03)	0.891	1.00 (0.99, 1.01)	0.603
Chemotherapy	0.98 (0.95, 1.00)	0.063	0.98 (0.95, 1.11)	0.062
Radiotherapy	0.54 (0.24, 1.47)	0.041	0.55 (0.26, 1.54)	0.033
Hormonal therapy	1.10 (0.56, 1.48)	0.732	0.93 (0.65, 1.33)	0.562
ER+	0.98 (0.45, 1.54)	0.087	1.12 (0.66, 1.69)	0.118
PR+	1.09 (0.53, 1.44)	0.228	1.22 (0.64, 1.73)	0.215
HER2+	1.02 (0.51, 1.49)	0.198	1.12 (0.58, 1.63)	0.115
Ki67	1.15 (1.01, 1.22)	0.021	1.13 (1.09, 1.18)	0.033
ASA classification	0.97 (0.95, 1.01)	0.067	1.01 (0.97, 1.04)	0.632
TMN stage		0.029		0.032
0	0.99 (0.95, 1.05)		1.25 (0.74, 2.09)
Ⅰ	1.15 (0.64, 1.71)		1.24 (0.46, 2.12)
ⅡA	1.09 (0.52, 1.51)		0.96 (0.62, 1.38)
ⅡB	1.16 (0.88, 1.23)		1.21 (1.01, 1.58)
Ⅲ	1.23 (0.74, 1.74)		1.26 (0.87, 1.84)
Type of surgery		0.781		0.593
Breast-conserving surgery	1.09 (0.84, 1.52)		1.08 (0.73, 1.59)
Mastectomy	0.98 (0.91, 1.15)		1.02 (0.79, 1.69)
Duration of anesthesia	1.02 (0.85, 1.36)	0.232	0.99 (0.69, 1.23)	0.312
Remifentanil	0.69 (0.34, 1.89)	0.538	0.74 (0.49, 1.09)	0.381
Sufentanyl	0.87 (0.39, 1.41)	0.667	0.98 (0.71, 1.29)	0.769
Propofol	1.01 (0.88, 1.29)	0.517	1.10 (0.89, 1.31)	0.487
Cisatracurium	1.05 (0.91, 1.25)	0.473	1.08 (0.88, 1.27)	0.388
Inhalable anesthetic	0.94 (0.73, 1.27)	0.081	0.92 (0.87, 1.08)	0.057
VAS score when leaving PACU	1.02 (0.81, 1.19)	0.790	1.10 (0.81, 1.19)	0.682
Dexmedetomidine	1.15 (0.62, 2.16)	0.626	1.17 (0.62, 2.20)	0.673