新辅助化疗对乳腺癌患者血脂影响及因素分析

doi:10.3877/cma.j.issn.1674-0793.2019.01.004

目的

研究新辅助化疗（NAC）对乳腺癌患者血脂水平的影响及相关因素，为降低乳腺癌患者心血管疾病相关死亡率和改善乳腺癌预后提供诊疗依据。

方法

收集整理青岛大学附属医院乳腺诊疗中心299例完成4~6周期化疗的乳腺癌患者临床病理资料及血脂水平结果，分析患者接受NAC前后的血脂水平变化及相关影响因素。

结果

接受NAC后乳腺癌患者血清三酯甘油（TG）、总胆固醇（TC）及低密度脂蛋白胆固醇（LDL-C）水平均显著高于术前，而高密度脂蛋白胆固醇（HDL-C）水平低于术前，差异均有统计学意义[（2.26±1.77）mmol/L vs（1.47±1.13）mmol/L、（5.81±1.20）mmol/L vs （5.17±1.07）mmol/L、（3.42±0.89）mmol/L vs （2.87±0.77）mmol/L、（1.28±0.33）mmol/L vs （1.45±0.32）mmol/L，t=-10.02、-9.80、-9.36、9.28，均P<0.01]。单因素分析提示患者肿瘤病理类型（χ²=7.676，P=0.022）及化疗方案（χ²=10.747，P=0.005）是接受NAC后血清TG水平升高的相关因素；患者年龄（χ²=4.065，P=0.044）及是否绝经（χ²=5.134，P=0.023）与NAC后血清LDL-C水平升高相关；血清HDL-C的降低与患者年龄（χ²=7.284，P=0.007）、分子分型（χ²=8.626，P=0.003）及是否绝经（χ²=9.608，P=0.002）有关，而体质量指数（BMI）和化疗疗效与各血脂水平变化无关。多因素分析显示病理类型为浸润性非特殊癌（OR=3.624，P=0.008）及蒽环类联合紫衫类化疗方案（OR=3.508，P=0.001）是影响TG水平升高的独立危险因素；未绝经（OR=2.237，P=0.017）、分子分型为三阴性（OR=3.184，P=0.001）是影响HDL-C水平降低的独立危险因素。

结论

NAC后乳腺癌患者各血脂水平的变化对心血管系统及肿瘤复发、转移等预后不利，临床医师应重视患者血脂代谢变化及相关危险因素，定期检测并及时给予指导干预，降低癌症患者心血管疾病的死亡率并改善预后。

关键词: 乳腺肿瘤, 肿瘤辅助疗法, 血脂异常, 心血管疾病

Objective

To study the effect of neoadjuvant chemotherapy (NAC) on blood lipid level in patients with breast cancer and to analyze the related factors in order to provide diagnostic and therapeutic basis for reducing the mortality of cardiovascular diseases and improving the prognosis of breast cancer.

Methods

The clinicopathological data and blood lipid levels of two hundred and ninety-nine patients with breast cancer with 4 to 6 cycles of chemotherapy were collected and analyzed. The changes of blood lipid levels and related factors after NAC were analyzed.

Results

The levels of serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in breast cancer patients after NAC treatment were significantly higher than those before NAC, while the levels of high density lipoprotein cholesterol (HDL-C) were lower than those before NAC treatment [(2.26±1.77) mmol/Lvs (1.47±1.13) mmol/L, (5.81±1.20) mmol/L vs (5.17±1.07) mmol/L, (3.42±0.89) mmol/L vs (2.87±0.77) mmol/L, (1.28±0.33) mmol/L vs (1.45±0.32) mmol/L, t=-10.02, -9.80, -9.36, 9.28, all P<0.01]. Univariate analysis showed that pathological type of tumors (χ²=7.676, P=0.022) and chemotherapy regimen (χ²=10.747, P=0.005) were correlated with increased serum TG level after NAC treatment. Age (χ²=4.065, P=0.044) and menopause (χ²=5.134, P=0.023) were correlated with increased serum LDL-C level after NAC treatment. The decrease of serum HDL-C was related to age (χ²=7.284, P=0.007), molecular typing (χ²=8.626, P=0.003) and menopause (χ²=9.608, P=0.002), but BMI and chemotherapy efficacy were not related to the changes of blood lipid levels. Multivariate analysis showed that pathological type of non-specific cancer (OR=3.624, P=0.008) and anthracycline combined paclitaxelt chemotherapy (OR=3.508, P=0.001) were independent risk factors for the increase of TG level; premenopause (OR=2.237, P=0.017) and triple-negative molecular typing (OR=3.184, P=0.001) were independent risk factors for the decrease of HDL-C level.

Conclusions

The changes of blood lipid levels of the patients after neoadjuvant chemotherapy are unfavorable for the prognosis of cardiovascular system and tumor recurrence and metastasis. Clinicians should pay attention to the changes of blood lipid metabolism, regularly detect and give guidance in time to reduce the mortality of cardiovascular diseases and improve the prognosis of breast cancer patients.

Key words: Breast neoplasms, Neoadjuvant therapy, Dyslipidemias, Cardiovascular diseases

表1 299例乳腺癌患者NAC前后血脂水平比较（mmol/L，）

项目	TG	TC	LDL-C	HDL-C
化疗前	1.47±1.13	5.17±1.07	2.87±0.77	1.45±0.32
化疗后	2.26±1.77	5.81±1.20	3.42±0.89	1.28±0.33
t值	-10.02	-9.80	-9.36	9.28
P值	<0.001	<0.001	<0.001	<0.001

表1 299例乳腺癌患者NAC前后血脂水平比较（mmol/L，）

项目	TG	TC	LDL-C	HDL-C
化疗前	1.47±1.13	5.17±1.07	2.87±0.77	1.45±0.32
化疗后	2.26±1.77	5.81±1.20	3.42±0.89	1.28±0.33
t值	-10.02	-9.80	-9.36	9.28
P值	<0.001	<0.001	<0.001	<0.001

表2 影响299例乳腺癌患者NAC前后血脂变化的单因素分析[例(%)]

因素		例数	TG升高	χ²值	P值	TC升高	χ²值	P值	LDL-C升高	χ²值	P值	HDL-C降低	χ²值	P值
年龄(岁)
	≤45	101	76(75.2)	0.241	0.623	73(72.3)	2.501	0.114	75(74.3)	4.065	0.044^a	59(58.4)	7.284	0.007^a
	>45	198	154(77.8)	0.241	0.623	125(63.1)	2.501	0.114	124(62.6)	4.065	0.044^a	146(73.7)	7.284	0.007^a
BMI(kg/m²)
	<24	114	90(78.9)	0.425	0.514	75(65.8)	0.015	0.901	77(67.5)	0.081	0.776	81(71.1)	0.530	0.466
	≥24	185	140(75.7)	0.425	0.514	123(66.5)	0.015	0.901	122(65.9)	0.081	0.776	124(67.0)	0.530	0.466
是否绝经
	否	191	150(78.5)	0.773	0.379	134(70.2)	3.663	0.056	136(71.2)	5.134	0.023^a	119(62.3)	9.608	0.002^a
	是	108	80(74.1)	0.773	0.379	64(59.3)	3.663	0.056	63(58.3)	5.134	0.023^a	86(79.6)	9.608	0.002^a
分子分型
	三阴性	41	28(68.3)	1.994	0.158	29(70.7)	0.432	0.511	25(61.0)	0.665	0.415	20(48.8)	8.626	0.003^a
	非三阴性	258	202(78.3)	1.994	0.158	169(65.5)	0.432	0.511	174(67.4)	0.665	0.415	185(71.7)	8.626	0.003^a
病理类型
	特殊癌	26	20(76.9)	7.676	0.022^a	22(84.6)	5.612	0.060	18(69.2)	0.986	0.611	17(65.4)	2.771	0.250
	非特殊癌	249	197(79.1)			158(63.5)			163(65.5)			175(70.3)
	混合型癌	24	13(54.2)			18(75.0)			18(75.0)			13(54.2)
化疗方案
	蒽环类为主	39	22(56.4)	10.747	0.005^a	26(66.7)	0.293	0.864	26(66.7)	0.061	0.970	28(71.8)	1.469	0.480
	蒽环+紫衫类	252	202(80.2)			166(65.9)			168(66.7)			173(68.7)
	紫衫类为主	8	6(75.0)			6(75.0)			5(62.5)			4(50.0)
疗效
	无效	53	43(81.1)	0.643	0.423	37(69.8)	0.371	0.542	36(67.9)	0.054	0.816	41(77.4)	2.313	0.128
	有效	246	187(76.0)	0.643	0.423	161(65.4)	0.371	0.542	163(66.3)	0.054	0.816	164(66.7)	2.313	0.128

表2 影响299例乳腺癌患者NAC前后血脂变化的单因素分析[例(%)]

因素		例数	TG升高	χ²值	P值	TC升高	χ²值	P值	LDL-C升高	χ²值	P值	HDL-C降低	χ²值	P值
年龄(岁)
	≤45	101	76(75.2)	0.241	0.623	73(72.3)	2.501	0.114	75(74.3)	4.065	0.044^a	59(58.4)	7.284	0.007^a
	>45	198	154(77.8)	0.241	0.623	125(63.1)	2.501	0.114	124(62.6)	4.065	0.044^a	146(73.7)	7.284	0.007^a
BMI(kg/m²)
	<24	114	90(78.9)	0.425	0.514	75(65.8)	0.015	0.901	77(67.5)	0.081	0.776	81(71.1)	0.530	0.466
	≥24	185	140(75.7)	0.425	0.514	123(66.5)	0.015	0.901	122(65.9)	0.081	0.776	124(67.0)	0.530	0.466
是否绝经
	否	191	150(78.5)	0.773	0.379	134(70.2)	3.663	0.056	136(71.2)	5.134	0.023^a	119(62.3)	9.608	0.002^a
	是	108	80(74.1)	0.773	0.379	64(59.3)	3.663	0.056	63(58.3)	5.134	0.023^a	86(79.6)	9.608	0.002^a
分子分型
	三阴性	41	28(68.3)	1.994	0.158	29(70.7)	0.432	0.511	25(61.0)	0.665	0.415	20(48.8)	8.626	0.003^a
	非三阴性	258	202(78.3)	1.994	0.158	169(65.5)	0.432	0.511	174(67.4)	0.665	0.415	185(71.7)	8.626	0.003^a
病理类型
	特殊癌	26	20(76.9)	7.676	0.022^a	22(84.6)	5.612	0.060	18(69.2)	0.986	0.611	17(65.4)	2.771	0.250
	非特殊癌	249	197(79.1)			158(63.5)			163(65.5)			175(70.3)
	混合型癌	24	13(54.2)			18(75.0)			18(75.0)			13(54.2)
化疗方案
	蒽环类为主	39	22(56.4)	10.747	0.005^a	26(66.7)	0.293	0.864	26(66.7)	0.061	0.970	28(71.8)	1.469	0.480
	蒽环+紫衫类	252	202(80.2)			166(65.9)			168(66.7)			173(68.7)
	紫衫类为主	8	6(75.0)			6(75.0)			5(62.5)			4(50.0)
疗效
	无效	53	43(81.1)	0.643	0.423	37(69.8)	0.371	0.542	36(67.9)	0.054	0.816	41(77.4)	2.313	0.128
	有效	246	187(76.0)	0.643	0.423	161(65.4)	0.371	0.542	163(66.3)	0.054	0.816	164(66.7)	2.313	0.128

表3 多因素分析影响NAC前后TG变化的危险因素

危险因素		Wals值	OR值	95%CI	P值
病理类型
	浸润性特殊癌	2.709	2.938	0.820~10.526	0.100
	浸润性非特殊癌	7.003	3.624	1.455~9.023	0.008
化疗方案
	蒽环联合紫衫类	11.646	3.508	1.706~7.214	0.001
	紫衫类为主	1.183	2.655	0.457~15.427	0.277

表3 多因素分析影响NAC前后TG变化的危险因素

危险因素		Wals值	OR值	95%CI	P值
病理类型
	浸润性特殊癌	2.709	2.938	0.820~10.526	0.100
	浸润性非特殊癌	7.003	3.624	1.455~9.023	0.008
化疗方案
	蒽环联合紫衫类	11.646	3.508	1.706~7.214	0.001
	紫衫类为主	1.183	2.655	0.457~15.427	0.277

表4 多因素分析影响NAC前后HDL-C变化的危险因素

危险因素	Wals值	OR值	95%CI	P值
≤45岁	1.160	1.389	0.764~2526	0.281
未绝经	5.741	2.237	1.158~4.324	0.017
三阴性乳腺癌	10.305	3.184	1.158~4.324	0.001

表4 多因素分析影响NAC前后HDL-C变化的危险因素

危险因素	Wals值	OR值	95%CI	P值
≤45岁	1.160	1.389	0.764~2526	0.281
未绝经	5.741	2.237	1.158~4.324	0.017
三阴性乳腺癌	10.305	3.184	1.158~4.324	0.001

表5 多因素分析影响NAC前后LDL-C变化的危险因素

危险因素	Wals值	OR值	95%CI	P值
≤45岁	1.028	1.379	0.741~2.684	0.311
未绝经	1.922	1.505	0.844~2.566	0.166

表5 多因素分析影响NAC前后LDL-C变化的危险因素

危险因素	Wals值	OR值	95%CI	P值
≤45岁	1.028	1.379	0.741~2.684	0.311
未绝经	1.922	1.505	0.844~2.566	0.166

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Influencing factor analysis of neoadjuvant chemotherapy on blood lipid in patients with breast cancer

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Influencing factor analysis of neoadjuvant chemotherapy on blood lipid in patients with breast cancer