Assessment of cardiopulmonary exercise capacity in early stage of patients with breast cancer undergoing neoadjuvant chemotherapy and related factors

doi:10.3969/j.issn.1674-8115.2021.12.014

Abstract

Abstract: Objective

·To assess the cardiopulmonary exercise capacity in patients with breast cancer after neoadjuvant chemotherapy in the early stage and explore possible factors leading to the reduced functional tolerance in those patients.

Methods

·Fifty-two consecutive patients suffering from breast cancer and receiving neoadjuvant chemotherapy were included and completed cardiopulmonary exercise testing (CPET), laboratory tests, electrocardiograph and echocardiography after 1 cycle of chemotherapy in the Department of Cardiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from September, 2020 to May, 2021. Fifty-two healthy age-, gender- and body mass index (BMI)-matched volunteers were enrolled and received CPET as the control group. The general conditions, hematological biomarkers, electrocardiogram and echocardiography of the subjects in the two groups were collected and recorded.

Results

·Compared to the control group, the group of patients receiving neoadjuvant chemotherapy had reduced peak VO₂ [(18.22±3.48) mL/(min·kg) vs (22.80±3.13) mL/(min·kg), P=0.000], anaerobic threshold [(12.09±2.35) mL/(min·kg) vs (14.93±2.60) mL/(min·kg), P=0.000] and oxygen pulse [(7.67±1.45) mL/beat vs (8.87±1.29) mL/beat), P=0.000]. On multivariable regression analysis, BMI was independently associated with peak VO₂ (β=-0.528,P=0.047) of patients in the early stage of neoadjuvant chemotherapy.

Conclusion

·Decreased cardiopulmonary function could be detected in the early stage of neoadjuvant chemotherapy on patients with breast cancer via CPET. High BMI can be an independent predictor of the reduced peak VO₂. Maintaining BMI at normal level by losing weight may help to improve patients' cardiopulmonary function and long-term cardiovascular prognosis.

Key words: breast cancer, neoadjuvant chemotherapy, cardiopulmonary exercise testing (CPET), peak VO₂, body mass index (BMI)

CLC Number:

R541.9

Ye-zi CHAI, Jun MA, Wen-long JIANG, Qi-ming LIU, Qi-fan LU, Zheng-yu TAO, Meng JIANG, Jun PU. Assessment of cardiopulmonary exercise capacity in early stage of patients with breast cancer undergoing neoadjuvant chemotherapy and related factors[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(12): 1643-1648.

Figures/Tables 4

TrendMD

References 19

1	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer J Clin, 2021, 71(3): 209-249.
2	Cobleigh M, Yardley DA, Brufsky AM, et al. Baseline characteristics, treatment patterns, and outcomes in patients with HER2-positive metastatic breast cancer by hormone receptor status from SystHERs[J]. Clin Cancer Res, 2020, 26(5): 1105-1113.
3	Florescu DR, Nistor DE. Therapy-induced cardiotoxicity in breast cancer patients: a well-known yet unresolved problem[J]. Discoveries (Craiova), 2019, 7(1): e89.
4	Riihimäki M, Thomsen H, Brandt A, et al. Death causes in breast cancer patients[J]. Ann Oncol, 2012, 23(3): 604-610.
5	Hall ME. Body mass index and heart failure mortality: more is less?[J]. JACC: Heart Fail, 2018, 6(3): 243-245.
6	Recalde M, Davila-Batista V, Díaz Y, et al. Body mass index and waist circumference in relation to the risk of 26 types of cancer: a prospective cohort study of 3.5 million adults in Spain[J]. BMC Med, 2021, 19(1): 10.
7	Belardinelli R, Lacalaprice F, Carle F, et al. Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing[J]. Eur Heart J, 2003, 24(14): 1304-1313.
8	Kavanagh T, Mertens DJ, Hamm LF, et al. Prediction of long-term prognosis in 12 169 men referred for cardiac rehabilitation[J]. Circulation, 2002, 106(6): 666-671.
9	Sato T, Yoshihisa A, Kanno Y, et al. Cardiopulmonary exercise testing as prognostic indicators: comparisons among heart failure patients with reduced, mid-range and preserved ejection fraction[J]. Eur J Prev Cardiol, 2017, 24(18): 1979-1987.
10	Palau P, Domínguez E, Núñez E, et al. Peak exercise oxygen uptake predicts recurrent admissions in heart failure with preserved ejection fraction[J]. Rev Esp Cardiol (Engl Ed), 2018, 71(4): 250-256.
11	Fedele P, Orlando L, Schiavone P, et al. BMI variation increases recurrence risk in women with early-stage breast cancer[J]. Future Oncol, 2014, 10(15): 2459-2468.
12	Warren LEG, Ligibel JA, Chen YH, et al. Body mass index and locoregional recurrence in women with early-stage breast cancer[J]. Ann Surg Oncol, 2016, 23(12): 3870-3879.
13	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.
14	Chan DSM, Vieira AR, 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.
15	Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline[J]. J Clin Oncol, 2012, 30(13): 1553-1561.
16	Kamimura K, Matsumoto Y, Zhou Q, et al. Myelosuppression by chemotherapy in obese patients with gynecological cancers[J]. Cancer Chemother Pharmacol, 2016, 78(3): 633-641.
17	Kushlinskii NE, Gershtein ES, Nikolaev AA, et al. Insulin-like growth factors (IGF), IGF-binding proteins (IGFBP), and vascular endothelial growth factor (VEGF) in blood serum of patients with colorectal cancer[J]. Bull Exp Biol Med, 2014, 156(5): 684-688.
18	Yu H, Mistry J, Nicar MJ, et al. Insulin-like growth factors (IGF-I, free IGF-I, and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation[J]. J Clin Lab Anal, 1999, 13(4): 166-172.
19	Horwich TB, Fonarow GC, Clark AL. Obesity and the obesity paradox in heart failure[J]. Prog Cardiovasc Dis, 2018, 61(2): 151-156.

Indicator	Control group （n=52）	Chemotherapy group （n=52）	P value
Female/n（%）	52 （100.0）	52 （100.0）	1.000
Age/year	51 （43，60）	49 （41，58）	0.385
BMI/（kg·m^-2）	22.61±2.87	23.04±2.35	0.411
Clinical feature
Hypertension/n（%）	5 （9.6）	8 （15.4）	0.374
Hyperlipidemia/n（%）	4 （7.7）	6 （11.5）	0.506
Diabetes/n（%）	‒	3 （5.8）	‒
Smoking/n（%）	‒	‒	‒
Family history of cancer/n（%）	‒	3 （5.8）	‒
Laboratory examination
NT-proBNP/（pg·mL^-1）	22.04 （12.93，32.34）	23.98 （11.04， 40.56）	0.902
BNP/（pg·mL^-1）	23.00 （16.00，35.00）	17.00 （13.00， 27.00）	0.098
ST2/（ng·mL^-1）	19.55±5.35	21.98±7.60	0.103
Indicators of Echocardiography
LAD/mm	34.27±4.14	33.58±4.43	0.387
LVEDD/mm	44.06±3.58	44.65±3.19	0.601
LVESD/mm	28.55±2.68	28.68±2.38	0.501
IVST/mm	8.24±1.35	8.08±1.36	0.388
LVPWT/mm	7.85±0.83	7.70±1.08	0.240
LVEF/%	64.61±3.39	64.02±3.77	0.734

Indicator	Control group （n=52）	Chemotherapy group （n=52）	P value
Female/n（%）	52 （100.0）	52 （100.0）	1.000
Age/year	51 （43，60）	49 （41，58）	0.385
BMI/（kg·m^-2）	22.61±2.87	23.04±2.35	0.411
Clinical feature
Hypertension/n（%）	5 （9.6）	8 （15.4）	0.374
Hyperlipidemia/n（%）	4 （7.7）	6 （11.5）	0.506
Diabetes/n（%）	‒	3 （5.8）	‒
Smoking/n（%）	‒	‒	‒
Family history of cancer/n（%）	‒	3 （5.8）	‒
Laboratory examination
NT-proBNP/（pg·mL^-1）	22.04 （12.93，32.34）	23.98 （11.04， 40.56）	0.902
BNP/（pg·mL^-1）	23.00 （16.00，35.00）	17.00 （13.00， 27.00）	0.098
ST2/（ng·mL^-1）	19.55±5.35	21.98±7.60	0.103
Indicators of Echocardiography
LAD/mm	34.27±4.14	33.58±4.43	0.387
LVEDD/mm	44.06±3.58	44.65±3.19	0.601
LVESD/mm	28.55±2.68	28.68±2.38	0.501
IVST/mm	8.24±1.35	8.08±1.36	0.388
LVPWT/mm	7.85±0.83	7.70±1.08	0.240
LVEF/%	64.61±3.39	64.02±3.77	0.734

Indicator	Control group （n=52）	Chemotherapy group （n=52）	P value
Peak VO₂/（mL·min^-1·kg^-1）	22.80±3.13	18.22±3.48	0.000
Peak MET	6.51±0.89	5.20±1.00	0.000
AT/（mL·min^-1·kg^-1）	14.93±2.60	12.09±2.35	0.000
VE/VCO₂ slope	27.35±3.08	27.13±3.28	0.728
ΔVO₂/ΔWR/（mL·min^-1·W^-1）	10.16±1.37	9.50±1.39	0.017
O₂P/（mL·beat^-1）	8.87±1.29	7.67±1.45	0.000
Resting SBP/mmHg	118.93±17.69	116.08±16.27	0.550
Resting DBP/mmHg	68.59±10.92	71.76±10.16	0.285
Peak SBP/mmHg	158.27±24.61	150.95±25.22	0.155
Peak DBP/mmHg	72.58±14.19	73.27±17.04	0.828
Resting HR/（beat·min^-1）	68.35±8.76	68.51±11.15	0.945
Peak HR/（beat·min^-1）	147.79±15.33	143.31±17.43	0.167

Indicator	Control group （n=52）	Chemotherapy group （n=52）	P value
Peak VO₂/（mL·min^-1·kg^-1）	22.80±3.13	18.22±3.48	0.000
Peak MET	6.51±0.89	5.20±1.00	0.000
AT/（mL·min^-1·kg^-1）	14.93±2.60	12.09±2.35	0.000
VE/VCO₂ slope	27.35±3.08	27.13±3.28	0.728
ΔVO₂/ΔWR/（mL·min^-1·W^-1）	10.16±1.37	9.50±1.39	0.017
O₂P/（mL·beat^-1）	8.87±1.29	7.67±1.45	0.000
Resting SBP/mmHg	118.93±17.69	116.08±16.27	0.550
Resting DBP/mmHg	68.59±10.92	71.76±10.16	0.285
Peak SBP/mmHg	158.27±24.61	150.95±25.22	0.155
Peak DBP/mmHg	72.58±14.19	73.27±17.04	0.828
Resting HR/（beat·min^-1）	68.35±8.76	68.51±11.15	0.945
Peak HR/（beat·min^-1）	147.79±15.33	143.31±17.43	0.167

Indicator	Normal BMI subgroup （n=39）	Overweight and obesity subgroup （n=13）	P value
Indicators of CPET
Peak VO₂/（mL·min^-1·kg^-1）	18.84±3.62	16.38±2.22	0.006
Peak MET	5.39±1.04	4.65±0.63	0.004
AT/（mL·min^-1·kg^-1）	12.44±2.51	11.05±1.38	0.017
VE/VCO₂ slope	27.07±3.52	27.33±2.54	0.806
ΔVO₂/ΔWR/（mL·min^-1·W^-1）	9.39±1.02	9.82±2.15	0.502
O₂P/（mL·beat^-1）	7.52±1.55	8.10±1.02	0.219
Resting SBP/mmHg	117.37±17.79	112.00±10.26	0.493
Resting DBP/mmHg	72.58±11.10	69.17±6.40	0.485
Peak SBP/mmHg	148.94±25.31	155.77±25.32	0.419
Peak DBP/mmHg	74.71±17.27	69.85±16.64	0.394
Resting HR/（beat·min^-1）	67.66±10.08	69.64±11.18	0.318
Peak HR/（beat·min^-1）	144.15±16.79	140.77±19.72	0.550
Indicators of echocardiography
LAD/mm	32.77±4.23	36.50±4.14	0.033
IVST/mm	7.93±1.33	8.63±1.41	0.206
LVPWT/mm	7.55±1.02	8.25±1.17	0.105
LVEF/%	63.90±3.04	64.38±5.56	0.691
Laboratory examination
BNP/（pg·mL^-1）	21.44±14.38	23.83±12.68	0.607
NT-pro BNP/（pg·mL^-1）	27.17±19.76	29.97±24.51	0.686