体重指数与年龄交互作用对乳腺癌患者预后影响的研究

doi:10.19401/j.cnki.1007-3639.2022.08.007

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (8): 719-726.doi: 10.19401/j.cnki.1007-3639.2022.08.007

体重指数与年龄交互作用对乳腺癌患者预后影响的研究

肖佳龙¹()(), 莫淼¹, 周昌明¹, 王泽洲¹, 沈洁¹, 袁晶¹, 余科达², 柳光宇², 吴炅², 沈镇宙², 邵志敏², 郑莹¹()()

1.复旦大学附属肿瘤医院肿瘤预防部,复旦大学上海医学院肿瘤学系,上海 200032
2.复旦大学附属肿瘤医院乳腺外科,复旦大学上海医学院肿瘤学系,上海 200032

收稿日期:2022-05-05 修回日期:2022-07-19 出版日期:2022-08-30 发布日期:2022-09-19
通信作者: 郑莹 E-mail:19211230035@fudan.edu.cn;zhengying@fudan.edu.cn
作者简介:肖佳龙（ORCID: 0000-0002-6361-7329）,硕士,E-mail: 19211230035@fudan.edu.cn。

The effect of the interaction between body mass index and age on the prognosis of breast cancer

XIAO Jialong¹()(), MO Miao¹, ZHOU Changming¹, WANG Zezhou¹, SHEN Jie¹, YUAN Jing¹, YU Keda², LIU Guangyu², WU Jiong², SHEN Zhenzhou², SHAO Zhimin², ZHENG Ying¹()()

1. Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
2. Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Received:2022-05-05 Revised:2022-07-19 Published:2022-08-30 Online:2022-09-19
Contact: ZHENG Ying E-mail:19211230035@fudan.edu.cn;zhengying@fudan.edu.cn

摘要/Abstract

摘要：

背景与目的： 目前已有研究表明体重指数（body mass index,BMI）是乳腺癌患者预后的影响因素。本研究旨在分析不同年龄段的乳腺癌患者的BMI与其死亡风险的关联。方法： 回顾性收集2008年1月1日—2016年12月31日在复旦大学附属肿瘤医院住院治疗的25 629例初诊乳腺癌患者的临床特征和生存状况,经调整主要预后影响因素,以限制性立方样条Cox比例风险回归模型分析在不同年龄亚组中BMI与乳腺癌患者预后的关联。结果： BMI与年龄均为乳腺癌预后的影响因素,且存在显著的交互作用。不同年龄组患者的死亡风险与BMI的关联模式有所不同。在年龄小于35岁组观察到死亡风险与BMI呈现“J”型的关联,BMI为20.16 kg/m²的患者死亡风险最低;在年龄35 ~ 60岁组观察到BMI在23 kg/m²以下的患者死亡风险随着BMI的增加没有明显变化,BMI在23 kg/m²以上的患者死亡风险随着BMI的增加而增加;而在年龄大于60岁组观察到死亡风险与BMI呈现“U”型的关联,BMI为23.86 kg/m²的女性死亡风险最低。年龄小于35岁组患者的死亡风险对BMI变化的敏感程度相较于年龄35 ~ 60岁组和大于60岁组更高。结论： 在校正了相关预后因素后,BMI与年龄对乳腺癌患者预后的影响有显著的交互作用,不同年龄组患者的死亡风险与BMI的关联模式有所不同,对于年轻患者,死亡风险最低对应的诊断时BMI约为20 kg/ m²,而对于60岁以上患者,死亡风险最低对应的诊断时BMI约为24 kg/m²。

关键词: 体重指数, 年龄, 交互作用, 乳腺癌

Abstract:

Background and purpose: Currently, several studies have demonstrated that body mass index (BMI) is a prognostic factor in breast cancer. The study aimed to assess the association pattern of BMI with mortality risk among patients of different age groups. Methods: This retrospective cohort study included the clinical characteristics and survival status of 25 629 patients diagnosed with breast cancer and subsequently hospitalized in Fudan University Shanghai Cancer Center between January 1, 2008 and December 31, 2016. The association between BMI and prognosis of breast cancer patients in different age subgroups was analyzed using Cox proportional hazards regression model with restricted cubic splines adjusting the main prognostic factors. Results: BMI and age were both influencing factors of breast cancer prognosis, and there was a significant interaction (P = 0.011). The pattern of association between risk of death and BMI differed among different age groups. A "J-shaped" association between risk of death and BMI was observed in the patients younger than 35 years, with a BMI of 20.16 kg/m² corresponding to the lowest risk of death. In the age group of 35-60 years, no significant change in the risk of death was observed in patients with BMI below 23 kg/m², and the risk of death in patients with BMI above 23 kg/m² increased with increasing BMI; A "U-shaped" association between risk of death and BMI was observed in the patients older than 60 years, with a BMI of 23.86 kg/m² being the lowest. The risk of death was more sensitive to changes in BMI in patients aged less than 35 years than in those aged 35-60 years and those aged more than 60 years. Conclusion: BMI and age have a significant interaction in the prognosis of breast cancer when adjusted for potential confounding factors. The association pattern between the risk of death and BMI of patients in different age groups is different. For patients under 35 years old, the lowest risk of death corresponds to BMI at diagnosis of about 20 kg/m², while for patients over 60 years old, the lowest risk of death corresponds to a BMI at diagnosis of about 24 kg/m².

Key words: BMI, Age, Interaction, Breast cancer

中图分类号:

R737.9

肖佳龙, 莫淼, 周昌明, 王泽洲, 沈洁, 袁晶, 余科达, 柳光宇, 吴炅, 沈镇宙, 邵志敏, 郑莹. 体重指数与年龄交互作用对乳腺癌患者预后影响的研究[J]. 中国癌症杂志, 2022, 32(8): 719-726.

XIAO Jialong, MO Miao, ZHOU Changming, WANG Zezhou, SHEN Jie, YUAN Jing, YU Keda, LIU Guangyu, WU Jiong, SHEN Zhenzhou, SHAO Zhimin, ZHENG Ying. The effect of the interaction between body mass index and age on the prognosis of breast cancer[J]. China Oncology, 2022, 32(8): 719-726.

图/表 4

表1

不同BMI分组乳腺癌患者的临床病理学特征分布情况"

Item	BMI (kg/m²)				χ²	P value
Item	<18.5	18.5≤BMI<24.0	24≤BMI<28.0	≥28.0	χ²	P value
Age/year					981.443	<0.001
<35	187 (18.44%)	1 112 (7.70%)	222 (3.05%)	50 (2.79%)
35-59	637 (62.82%)	10 575 (73.24%)	4 800 (65.99%)	1 046 (58.37%)
≥60	190 (18.74%)	2 751 (19.05%)	2 252 (30.96%)	696 (38.84%)
Menopause					715.483	<0.001
No	585 (57.69%)	7 690 (53.26%)	2 766 (38.03%)	538 (30.02%)
Yes	429 (42.31%)	6 748 (46.74%)	4 508 (61.97%)	1 254 (69.98%)
Side^*					7.092	0.069
Right	464 (46.03%)	6 889 (48.09%)	3 392 (46.90%)	805 (45.38%)
Left	544 (53.97%)	7 437 (51.91%)	3 841 (53.10%)	969 (54.62%)
Invasive					19.340	<0.001
In situ	92 (9.07%)	1 215 (8.42%)	528 (7.26%)	109 (6.08%)
Invasive	922 (90.93%)	13 223 (91.58%)	6 746 (92.74%)	1 683 (93.92%)
Multi^#					0.788	0.852
No	971 (95.76%)	13 865 (96.04%)	6 980 (95.98%)	1 727 (96.37%)
Yes	43 (4.24%)	572 (3.96%)	292 (4.02%)	65 (3.63%)
Ki-67^△					2.167	0.539
Low	289 (35.68%)	4 552 (37.62%)	2 327 (38.20%)	560 (37.38%)
High	521 (64.32%)	7 549 (62.38%)	3 764 (61.80%)	938 (62.62%)
ER^▲					8.950	0.030
Negative	293 (30.05%)	3 957 (28.17%)	1 959 (27.55%)	448 (25.34%)
Positive	682 (69.95%)	10 088 (71.83%)	5 152 (72.45%)	1 320 (74.66%)
PR^**					13.627	0.003
Negative	388 (39.75%)	4 956 (35.30%)	2 480 (34.88%)	579 (32.82%)
Positive	588 (60.25%)	9 082 (64.70%)	4 630 (65.12%)	1 185 (67.18%)
HER2^##					15.476	0.001
Negative	622 (70.52%)	9 191 (71.86%)	4 837 (73.53%)	1 247 (75.53%)
Positive	260 (29.48%)	3 600 (28.14%)	1 741 (26.47%)	404 (24.47%)
T^△△					179.136	<0.001
T₀	17 (1.99%)	255 (1.99%)	189 (2.85%)	42 (2.58%)
T_is	92 (10.77%)	1 215 (9.48%)	528 (7.96%)	109 (6.70%)
T₁	465 (54.45%)	6 887 (53.72%)	3 149 (47.47%)	748 (45.95%)
T₂	249 (29.16%)	4 183 (32.63%)	2 612 (39.37%)	684 (42.01%)
T_3-4	31 (3.63%)	279 (2.18%)	156 (2.35%)	45 (2.76%)
N^▲▲					73.100	<0.001
N₀	641 (67.19%)	9 242 (66.29%)	4 423 (63.01%)	1 014 (59.68%)
N₁	210 (22.01%)	2 895 (20.77%)	1 510 (21.51%)	372 (21.90%)
N₂	61 (6.39%)	1 120 (8.03%)	647 (9.22%)	195 (11.48%)
N₃	42 (4.40%)	684 (4.91%)	439 (6.25%)	118 (6.95%)
M					17.461	0.001
M₀	992 (97.83%)	14 256 (98.74%)	7 165 (98.50%)	1 750 (97.66%)
M₁	22 (2.17%)	182 (1.26%)	109 (1.50%)	42 (2.34%)

表1

表2

图1

表3

参考文献 24

[1]	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492
[2]	ROCK C L, DOYLE C, DEMARK-WAHNEFRIED W, et al. Nutrition and physical activity guidelines for cancer survivors[J]. CA Cancer J Clin, 2012, 62(4): 243-274.
[3]	PROTANI M, COORY M, MARTIN J H. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis[J]. Breast Cancer Res Treat, 2010, 123(3): 627-635. doi: 10.1007/s10549-010-0990-0
[4]	CHAN D S M, VIEIRA A R, AUNE D, et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies[J]. Ann Oncol, 2014, 25(10): 1901-1914. doi: 10.1093/annonc/mdu042
[5]	ZHANG M L, CAI H, BAO P P, et al. Body mass index, waist-to-hip ratio and late outcomes: a report from the Shanghai Breast Cancer Survival Study[J]. Sci Rep, 2017, 7(1): 6996. doi: 10.1038/s41598-017-07320-7
[6]	CHLEBOWSKI R T, AIELLO E, MCTIERNAN A. Weight loss in breast cancer patient management[J]. J Clin Oncol, 2002, 20(4): 1128-1143. doi: 10.1200/JCO.2002.20.4.1128
[7]	RYU S Y, KIM C B, NAM C M, et al. Is body mass index the prognostic factor in breast cancer? A meta-analysis[J]. J Korean Med Sci, 2001, 16(5): 610-614. doi: 10.3346/jkms.2001.16.5.610
[8]	MOON H G, HAN W, NOH D Y. Underweight and breast cancer recurrence and death: a report from the Korean Breast Cancer Society[J]. J Clin Oncol, 2009, 27(35): 5899-5905. doi: 10.1200/JCO.2009.22.4436
[9]	CHOLLET-HINTON L, OLSHAN A F, NICHOLS H B, et al. Biology and etiology of young-onset breast cancers among premenopausal African American women: results from the AMBER consortium[J]. Cancer Epidemiol Biomarkers Prev, 2017, 26(12): 1722-1729. doi: 10.1158/1055-9965.EPI-17-0450
[10]	赵翠翠, 刘红. 年轻乳腺癌的分子生物学发病机制[J]. 肿瘤防治研究, 2020, 47(3): 213-217.
	ZHAO C C, LIU H. Molecular biological pathogenesis of young breast cancer[J]. Cancer Res Prev Treat, 2020, 47(3): 213-217.
[11]	AZIM H A Jr, NGUYEN B, BROHÉE S, et al. Genomic aberrations in young and elderly breast cancer patients[J]. BMC Med, 2015, 13: 266. doi: 10.1186/s12916-015-0504-3
[12]	周昌明, 莫淼, 袁晶, 等. 以医院登记为基础的20万例恶性肿瘤患者生存报告[J]. 中国癌症杂志, 2020, 30(1): 11-24.
	ZHOU C M, MO M, YUAN J, et al. Report on 200 thousand cancer patients' survival from a hospital-based cancer registry database[J]. China Oncol, 2020, 30(1): 11-24.
[13]	中国年轻乳腺癌诊疗与生育管理专家共识专家委员会. 年轻乳腺癌诊疗与生育管理专家共识[J]. 中华肿瘤杂志, 2019, 41(7): 486-495.
	Expert Committee of Consensus on Diagnosis and Treatment of Young Breast Cancer and Fertility Management in China. Chinese consensus guideline for breast cancer in young women: clinical practice and fertility preservation[J]. Chin J Oncol, 2019, 41(7): 486-495.
[14]	ORGANIZATION W H. World Health Day 2012: ageing and health: toolkit for event organizers[J]. World Health Organization, 2012.
[15]	陈春明, 孔灵芝, 主编. 中华人民共和国卫生部疾病控制司编著. 中国成人超重和肥胖症预防控制指南[M]. 北京: 人民卫生出版社, 2006.
	CHEN C M, KONG L Z, editor-in-chief. Edited by the Department of Disease Control of the Ministry of Health of the People's Republic of China guidelines for the prevention and control of overweight and obesity in Chinese adults[M]. Beijing: People's Health Publishing House, 2006.
[16]	EDGE S B, BYRD D R, COMPTON C C, et al. AJCC cancer staging manual[M]. New York, NY: Springer New York, 2010.
[17]	KAWAI M, MINAMI Y, NISHINO Y, et al. Body mass index and survival after breast cancer diagnosis in Japanese women[J]. BMC Cancer, 2012, 12: 149. doi: 10.1186/1471-2407-12-149
[18]	DE VISSER K E, EICHTEN A, COUSSENS L M. Paradoxical roles of the immune system during cancer development[J]. Nat Rev Cancer, 2006, 6(1): 24-37. doi: 10.1038/nrc1782
[19]	MUELLER M M, FUSENIG N E. Friends or foes-bipolar effects of the tumour stroma in cancer[J]. Nat Rev Cancer, 2004, 4(11): 839-849. doi: 10.1038/nrc1477
[20]	DENARDO D G, JOHANSSON M, COUSSENS L M. Immune cells as mediators of solid tumor metastasis[J]. Cancer Metastasis Rev, 2008, 27(1): 11-18. doi: 10.1007/s10555-007-9100-0
[21]	CUNNINGHAM-RUNDLES S, MCNEELEY D F, MOON A. Mechanisms of nutrient modulation of the immune response[J]. J Allergy Clin Immunol, 2005, 115(6): 1119-1128; quiz1129. doi: 10.1016/j.jaci.2005.04.036
[22]	SCHOLZ C, ANDERGASSEN U, HEPP P, et al. Obesity as an independent risk factor for decreased survival in node-positive high-risk breast cancer[J]. Breast Cancer Res Treat, 2015, 151(3): 569-576. doi: 10.1007/s10549-015-3422-3
[23]	TANG B, HAN C T, ZHANG G M, et al. Waist-hip ratio (WHR), a better predictor for prostate cancer than body mass index (BMI): results from a Chinese hospital-based biopsy cohort[J]. Sci Rep, 2017, 7: 43551. doi: 10.1038/srep43551
[24]	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2021年版)[J]. 中国癌症杂志, 2021, 31(10): 954-1040.
	The Society of Breast Cancer China Anti-Cancer Association. Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2021 edition)[J]. China Oncol, 2021, 31(10): 954-1040.

Characteristic	HR (95% CI)	P value
Age		<0.001
<35	1
≥35 and <60	0.831 (0.597-1.158)	0.274
≥60	1.746 (1.233-2.473)	0.002
BMI (kg/m²)		0.002
<18.5	1.166 (0.521-2.609)	0.709
≥18.5 and <24	1
≥24 and <28	1.329 (0.721-2.450)	0.361
≥28	4.247 (2.054-8.778)	<0.001
BMI (kg/m²) ^* age		0.011
BMI (≥18.5 and <24)^*age (<35)	1
BMI (<18.5)^*age (≥35 and <60)	0.842 (0.367-1.932)	0.686
BMI (≥24 and <28)^*age (≥35 and <60)	0.704 (0.277-1.789)	0.461
BMI (≥28)^*age (≥35 and <60)	0.299 (0.106-0.842)	0.022
BMI (<18.5)^*age (≥60)	0.777 (0.314-1.923)	0.586
BMI (≥24 and <28)^*age (≥60)	0.524 (0.193-1.424)	0.205
BMI (≥28)^*age (≥60)	0.193 (0.064-0.580)	0.003

BMI implication	BMI value (kg/m²)	Age<35		35≤age<60		Age≥60
BMI implication	BMI value (kg/m²)	HR (95% CI)^*	HR (95% CI)^#	HR (95% CI)^*	HR (95% CI)^#	HR (95% CI)^*	HR (95% CI)^#
1st percentile	17.19	1.258 (0.674-2.347)	2.016 (1.059-3.836)	0.921 (0.652-1.301)	1.005 (0.826-1.222)	1.482 (0.976-2.250)	1.497 (1.003-2.236)
Cut-off of underweight and normal	18.50	0.825 (0.500-1.362)	1.322 (0.996-1.755)	0.924 (0.737-1.157)	1.008 (0.727-1.398)	1.333 (0.993-1.788)	1.347 (1.013-1.791)
Cut-off of normal and overweight	24.00	1.181 (1.082-1.289)	1.893 (1.095-3.274)	1.054 (0.984-1.129)	1.150 (0.694-1.906)	0.990 (0.914-1.072)	1.000 (0.989-1.012)
Cut-off of overweight and obesity	28.00	1.816 (1.145-2.881)	2.911 (1.669-5.076)	1.334 (1.142-1.559)	1.456 (0.880-2.409)	1.145 (0.921-1.422)	1.157 (0.975-1.372)
99th percentile	31.25	2.493 (1.056-5.884)	3.996 (1.836-8.695)	1.634 (1.192-2.240)	1.783 (0.980-3.243)	1.405 (1.001-1.974)	1.420 (0.999-2.019)

体重指数与年龄交互作用对乳腺癌患者预后影响的研究

The effect of the interaction between body mass index and age on the prognosis of breast cancer

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 4

参考文献 24

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张景臣, 李新, 李江涛, 李海平, 陈艳丽, 牛冰, 祁川川, 叶贝贝. LINC02163靶向miR-338-3p影响乳腺癌细胞增殖、侵袭及迁移[J]. 中国癌症杂志, 2022, 32(9): 818-826.
[2]	中国抗癌协会乳腺癌专业委员会, 中国医师协会外科医师分会乳腺外科医师委员会, 上海市抗癌协会乳腺癌专业委员会. 乳腺肿瘤整形与乳房重建专家共识（2022年版）[J]. 中国癌症杂志, 2022, 32(9): 836-924.
[3]	肖玉铃, 朱秀之, 江一舟, 邵志敏. 三阴性乳腺癌精准治疗研究的新进展与未来展望[J]. 中国癌症杂志, 2022, 32(8): 669-679.
[4]	邱鹏飞, 王永胜. 前哨淋巴结时代乳腺癌的精准区域处理：演进与展望[J]. 中国癌症杂志, 2022, 32(8): 680-687.
[5]	张羽, 刘强. 液体活检在乳腺癌精准治疗中的应用进展及展望[J]. 中国癌症杂志, 2022, 32(8): 688-697.
[6]	周文斌, 谢晖, 丁强, 王水. 在乳腺癌局部精准治疗中的新进展：联合免疫治疗未来可期[J]. 中国癌症杂志, 2022, 32(8): 698-704.
[7]	刘燚铭, 范蕾, 莫淼, 邵志敏, 余科达. 卵巢功能抑制治疗雌激素受体阳性早期乳腺癌的短期效应和长期生存的影响因素分析[J]. 中国癌症杂志, 2022, 32(8): 705-711.
[8]	陈安莉, 沈浩元, 阳仕雄, 邓春燕, 胡超华, 刘汉忠, 王舒, 钱芳. 血浆长链非编码RNA H19对乳腺癌新辅助治疗效果的预测价值[J]. 中国癌症杂志, 2022, 32(8): 727-735.
[9]	刘强, 方仪, 王靖. 单细胞测序技术在乳腺癌研究中的应用进展[J]. 中国癌症杂志, 2022, 32(7): 635-642.
[10]	钱瑶(综述), 刘锋(审校). 乳腺癌新辅助内分泌治疗的研究进展及展望[J]. 中国癌症杂志, 2022, 32(7): 643-649.
[11]	贾晓青, 孙晓寅, 蒋蓓琦, 梅章懿, 傅韵, 莊志刚. 类泛素化neddylation修饰调控乳腺癌中核纤层蛋白lamin B1的表达[J]. 中国癌症杂志, 2022, 32(6): 535-541.
[12]	刘建兰, 陈黛诗, 胡泓, 周冬仙, 胡锦涛. HER2阳性浸润性乳腺癌新辅助治疗反应的预测因子及治疗前后HER2状态变化的评估[J]. 中国癌症杂志, 2022, 32(5): 417-426.
[13]	章倩, 方晓燕, 刘娟, 刘进, 程蕾蕾, 孙菁. 早期左侧乳腺癌保乳术后大分割放疗同期瘤床加量的安全性及心脏亚结构剂量评估的重要性研究[J]. 中国癌症杂志, 2022, 32(5): 427-435.
[14]	许炳琦, 张国强. 乳腺癌新辅助治疗二次活检诊断病理学应答研究进展及临床意义[J]. 中国癌症杂志, 2022, 32(4): 335-342.
[15]	中国抗癌协会乳腺癌专业委员会单位. 中国乳腺癌筛查与早期诊断指南[J]. 中国癌症杂志, 2022, 32(4): 363-372.