| Objective:Breast cancer is the most common malignant tumor in women worldwide,which seriously threatens women’s health and life.According to different pathological types of breast cancer patients,surgery,chemotherapy,radiotherapy,endocrine therapy and targeted therapy can be selected,greatly improving the survival and prognosis of patients.In recent years,with the improvement of the economic level,the number of obese people worldwide has shown a rapid growth trend.Obesity is strongly associated with poor prognosis in breast cancer patients.Preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy are important treatment methods for breast cancer patients,studies have found that,about 50-96%of breast cancer patients will gain weight during treatment period.At present,there are relatively few studies on the effect of weight change during neoadjuvant chemotherapy and adjuvant chemotherapy on the prognosis of breast cancer patients at home and abroad,and there are some controversies.The objectives of this study were（1）to clarify BMI change during chemotherapy in breast cancer patients;（2）to evaluate the relationship between the change in BMI during neoadjuvant chemotherapy and pCR;and（3）to analyze the correlation between BMI change during neoadjuvant chemotherapy and adjuvant chemotherapy and the prognosis of breast cancer,in order to provide reference opinions and suggestions for clinicians to make clinical decisions and perform weight intervention for patients.Methods:Retrospective collection of data related to female patients first diagnosed with breast cancer and receiving neoadjuvant chemotherapy or adjuvant chemotherapy at the Department of Breast Surgery,Second Hospital of Shandong University from January 2014 to August 2019.All patients received a complete cycle of chemotherapy,and there were no other types of malignant tumors,no distant metastases,and no serious cardiovascular and cerebrovascular diseases at the first diagnosis.By collecting the weight and height of the patient before each cycle of neoadjuvant chemotherapy or adjuvant chemotherapy,calculating the body mass index（BMI）of the last chemotherapy cycle and the first chemotherapy cycle,and the difference between the two to obtain the BMI change value during chemotherapy,and patients were divided into three groups based on the value of BMI change:the decreased BMI group（BMI decrease greater than 0.5 kg/m2）,the stable BMI group（BMI change within±0.5 kg/m2）,and the increased BMI group（BMI increase greater than 0.5 kg/m2）.At the same time,clinical pathological data and treatment methods of patients were collected.The recurrence,metastasis and survival status of patients were obtained through telephone follow-up,outpatient follow-up,and medical history.SPSS 26.0 software was used for statistical analysis,the main basic characteristics of the different BMI change groups were tested using the χ2 test and Kruskal-Wallis H rank sum test.Factors affecting pathological complete response（pCR）among neoadjuvant chemotherapy patients were analyzed using the univariate logistic regression analysis,and variables with statistical significance in the univariate analysis were included in the multivariate logistic regression analysis.Kaplan-Meier method and Log-rank test were used for survival analysis,and Cox proportional hazard regression model was used for multivariate analysis and subgroup analysis,both multivariate and subgroup analyses adjusted for first visit BMI as baseline BMI.p<0.05 was considered statistically significant.Results:1.Basic clinicopathological characteristics of patientsA total of 678 female patients were included,including 209 patients undergoing neoadjuvant chemotherapy,469 patients undergoing adjuvant chemotherapy,there were 58 patients（8.6%）in the decreased BMI group,394 patients（58.1%）in the stable BMI group,and 226 patients（33.3%）in the increased BMI group.Statistically significant differences existed between the different BMI change groups in terms of first visit BMI（p<0.001）,presence of diabetes（p<0.001）,ER status（p=0.048）,and lymph node status（p=0.001）.2.Relationship between the change in BMI during neoadjuvant chemotherapy and pCRAmong 209 patients of neoadjuvant chemotherapy,a total of 42 patients（20.1%）obtained pCR.The pCR rate was higher in the increased BMI group（21.0%）than in the decreased BMI group（19.0%）and the stable BMI group（19.6%）,but the difference between the three groups was not statistically significant（p=0.966）,and the change in BMI was not associated with the pCR rate in patients undergoing neoadjuvant chemotherapy.Univariate analysis showed that age at first visit（p=0.027）,ER status（p=0.024）,PR status（p=0.004）,and clinical TNM stage（p=0.016）were associated with the pCR rate of neoadj uvant chemotherapy patients.The results of multivariate analysis showed that clinical TNM stage II and III were independent predictors of pCR rates in patients on neoadjuvant chemotherapy（both p<0.05）,with clinical TNM stage Ⅱ（OR=0.229,95%CI:0.067-0.780,p=0.018）and III（OR=0.211,95%CI:0.054-0.819,p=0.025）patients had lower pCR rates.3.Survival analysisA total of 678 patients were followed up,and median follow-up time 36 months,69 patients developed recurrence or metastasis,and 17 patients died.3.1 Survival analysis of all patients3.1.1 3-year disease-free survival analysis of all patientsAmong all patients,6 patients in the decreased BMI group had recurrence or metastasis,37 patients in the stable BMI group,26 patients in the increased BMI group,the 3-year disease-free survival rates of the decreased BMI group,the stable BMI group,and the increased BMI group were 80.0%,87.6%,and 72.6%,respectively,there was statistically significant difference in the three survival curves（χ2=10.988,p=0.004）,patients in the increased BMI group had the worst 3-year disease-free survival rate.The multivariate Cox proportional hazards regression model showed that change in BMI during chemotherapy was an independent prognostic influence on 3-year disease-free survival in breast cancer patients（p=0.005）and that patients with elevated BMI during chemotherapy had a higher risk of recurrent metastasis at 3 years compared to patients in the stable BMI group（HR=2.755,95%CI:1.504-5.047,p=0.001）.Subgroup analysis showed that compared to the BMI stable group,patients with elevated BMI during chemotherapy had a higher risk of 3-year recurrence and metastasis in the ER-positive（p=0.014）,PR-negative（p=0.024）,HER2-negative（p=0.017）,tumor>2 cm（p=0.013）,and lymph node positive（p=0.037）subgroups,the 3-year risk of recurrence and metastasis was higher in patients with reduced BMI during chemotherapy in the postmenopausal（p=0.006）and HER2-positive（p=0.020）subgroups.3.1.2 3-year overall survival analysis of all patientsAmong all 17 patients who died,there were 2 patients in the decreased BMI group,8 patients in the stable BMI group,7 patients in the increased BMI group,and the 3year overall survival rates of the decreased BMI group,the stable BMI group,and the increased BMI group were 95.5%、98.8%、94.5%,the difference of the three survival curves was not statistically significant（x2=4.899,p=0.086）.The multivariate Cox proportional hazards regression model showed that elevated BMI during chemotherapy was an independent prognostic influence on 3-year overall survival in breast cancer patients（HR=8.470,95%CI:1.226-58.507,p=0.030）and that patients with elevated BMI during chemotherapy had a higher risk of death at 3 years compared to patients in the stable BMI group.Subgroup analysis showed that in the tumor>2 cm（p=0.042）subgroups,patients with elevated BMI during chemotherapy had a higher risk of death at 3 years compared to the BMI stable group.3.2 Survival analysis of patients with neoadjuvant chemotherapy3.2.1 3-year disease-free survival analysis of patients with neoadjuvant chemotherapyThere were 37 patients in the neoadjuvant chemotherapy group with recurrence or metastasis,4 patients in the decreased BMI group,18 patients in the stable BMI group,and 15 patients in the increased BMI group,the 3-year disease-free survival rates of the decreased BMI group,the stable BMI group,and the increased BMI group were 66.7%,77.8%,and 62.5%,respectively,the difference of the three survival curves was not statistically significant（x2=2.735,p=0.255）.The multivariate Cox proportional hazards regression model showed that change in BMI during neoadjuvant chemotherapy was not an independent prognostic influence on 3-year disease-free survival in breast cancer patients（p=0.300）.Subgroup analysis showed that compared to the BMI stable group,patients with elevated BMI during neoadjuvant chemotherapy had a higher risk of 3-year recurrence and metastasis in the postmenopausal（p=0.039）,PR-negative（p=0.005）and HER2-negative（p=0.010）subgroups,patients with reduced BMI during neoadjuvant chemotherapy had a higher risk of 3-year recurrence and metastasis in the postmenopausal（p=0.036）subgroups.3.2.2 3-year overall survival analysis of patients with neoadjuvant chemotherapyA total of 14 patients died in the neoadjuvant chemotherapy group,1 patients in the decreased BMI group,7 patients in the stable BMI group,6 patients in the increased BMI group,and the 3-year overall survival rates of the decreased BMI group,the stable BMI group,and the increased BMI group were 100.0%、97.2%、88.9%,the difference of the three survival curves was not statistically significant（χ2=3.309,p=0.191）.There were too few patients who died in the different BMI change groups of neoadjuvant chemotherapy patients for univariate and multivariate analysis.3.3 Survival analysis of patients with adjuvant chemotherapy3.3.1 3-year disease-free survival analysis of patients with adjuvant chemotherapyThere were 32 patients in the adjuvant chemotherapy group with recurrence or metastasis,2 patients in the decreased BMI group,19 patients in the stable BMI group,and 11 patients in the increased BMI group,the 3-year disease-free survival rates of the decreased BMI group,the stable BMI group,and the increased BMI group were 87.5%、91.6%,and 78.8%,respectively,there was statistically significant difference in the three survival curves（x2=6.754,p=0.034）.The multivariate Cox proportional hazards regression model showed that change in BMI during adjuvant chemotherapy was an independent prognostic influence on 3-year disease-free survival in breast cancer patients（p=0.011）and that patients with elevated BMI during adjuvant chemotherapy had a higher risk of recurrent metastasis at 3 years compared to patients in the stable BMI group（HR=4.192,95%CI:1.645-10.681,p=0.003）.Subgroup analysis showed that in the ER-positive（p=0.032）,PR-negative（p=0.016）,tumor>2 cm（p=0.033）,and lymph node negative（p=0.037）subgroups,patients with elevated BMI during adjuvant chemotherapy had a higher risk of 3-year recurrence and metastasis compared to the BMI stable group.3.3.2 3-year overall survival analysis of patients with adjuvant chemotherapyA total of 3 patients died in the adjuvant chemotherapy group,and 1 patient died in each of the decreased BMI,stable BMI,and increased BMI groups,the 3-year overall survival rates of the decreased BMI group,the stable BMI group,and the increased BMI group were 93.3%、99.4%、97.8%,there was no statistically significant difference in the three survival curves（χ2=4.358,p=0.113）.There were too few patients who died in the different BMI change groups of adjuvant chemotherapy patients for univariate and multivariate analysis.Conclusion:1.BMI increased in 33.3%of breast cancer patients and decreased in 8.6%of breast cancer patients during chemotherapy.2.BMI change during neoadjuvant chemotherapy were not associated with pCR in breast cancer patients.3.Elevated BMI during adjuvant chemotherapy was an independent prognostic influencer of 3-year disease-free survival in breast cancer patients,and breast cancer patients with elevated BMI during adjuvant chemotherapy had poorer 3-year diseasefree survival. |
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