| ObjectiveThe preoperative systemic treatment is an important medical model for patients with locally or regionally advanced breast cancer, which can improve respectability by downstaging the primary tumor and increase the rate of tumor resection and breast-conserving surgery, discontinue ineffective treatment and switch to another regimen to maximize the degree of response by efficacy evaluation, and instruct the adjuvant therapy by the early evaluation of the effectiveness of the chosen therapy. At the same time, a great of biological information on breast cancer can be obtained by the neoadjuvant chemotherapy which is a good platform for efficacy evaluation and prognosis prediction which are not ideal enough because of only partial thinking about biological information on cancer and a main research direction of finding or screening the therapeutic benefit groups. But Neo-Bioscroe system almost covers all biological information on the neoadjuvant chemotherapy of breast cancer and quantifies the prognostic information by the score of each prognostic indicator. Therefore, this research is aimed at providing a feasible model for predicting the therapeutic effect and prognosis by exploring the role of Neo-Bioscroe in predicting disease-free survival in Chinese breast cancer patients.MethodsWe analyzed the medical data of locally or regionally advanced breast cancer patients who accepted the neoadjuvant chemotherapy by the basic regimen of anthracycline combined with paclitaxel in the Affiliated Hospital of Academy of Military Medical Sciences of the PLA from January 1, 2005 to December 31, 2015. And we followed up the disease-free survival time of patients in the group whose clinical and pathological stages are based on the 7th edition of American Joint Committee on Cancer, clinical evaluation is based on the response evaluation criteria in solid tumors 1.1, and clinical treatments are based on the guidelines of National Comprehensive Cancer Network.SPSS 22.0 software was used for statistical analysis, and we describe data by using frequency and percentage, use Kaplan-Meier curve to the survival related univariate analysis, compare the survival difference by Log-rank test, analyze the survival by Cox risk regression model, estimate the best score of Neo-Bioscore by ROC curve, test by both sides, and think that it is a significant finding with P <0.05.ResultsA total of 429 patients were enrolled in this study,with a median age of 47 (26?73)years,with a median follow-up time of 42 (1 ?133) months. There was a total of 376 patients who were followed up and 53 patients who were lost to follow-up, and the lost rate was 12.4%.1. The correlation of Neo-Bioscore and DFS was analyzed. The Neo-Bioscore of 429 patients who received neoadjuvant chemotherapy was calculated by the Neo-Bioscore system. We analyzed the correlation of Neo-Bioscore and DFS and found that Neo-Bioscore was closely related with DFS (P <0.001). With the increase of Neo-Bioscore, the percentage of disease recurrence in 5 years showed an upward trend,and the rate of disease-free survival in 5 years showed a downward trend.2. The boundary value of Neo-Bioscore in prediction of the DFS of patients with neoadjuvant chemotherapy was determined. With the Neo-Bioscore 0 score of 429 patients in group as reference, we analyzed the correlation of Neo-Bioscore and DFS by the Cox regression model and found that the 5 years' disease-free survival rate of Neo-Bioscore? 3 score groups was >80%, while the 5 years' disease-free survival rate of Neo-Bioscore > 3 score groups was <70%, and the demarcation of the cumulative disease-free survival rate curves over time of Neo-Bioscore? 3 and >3 score groupswas obvious. The ROC curve was draw in patients whether the disease recurrence,and the area under curve (AUC) was 0.747 (95% ? 0.819 CI=0.675,P <0.001). While the best cut-off score was 2.5, the highest correct diagnosis index was 0.377 (sensitivity 0.809, specificity 0.432). Based on the conclusion of Cox regression analysis and ROC curve, we finally identified Neo-Bioscore 3 score as a predictor of disease recurrence risk which was in low risk group when Neo-Bioscore < 3 score or in high risk group when Neo-Bioscore >3 score. By further analysis, we found Neo-Bioscore 3 score as the boundary value was better correlation with DFS (HR =5.093 vs. HR =2.044).3. Compare the proportion distribution of endocrine therapy of postmenopausal and HR positive breast cancer patients with prognostic prediction in different risk groups. There were 195 postmenopausal and HR positive patients in our study, which were divided respectively into two groups by the traditional recurrence risk or Neo-Bioscore 3 score as the boundary value, and the consistent rate of the two groups was as high as 84.6%.Different groups were compared by the distribution proportion of initial adjuvant endocrine regimen, and we found that the proportional distribution of initial adjuvant endocrine regimen was similar in Neo-Bioscore > 3 score group and high-risk group of traditional recurrence risk, and Neo-Bioscore < 3 score group was like middle and low-risk groups of the traditional recurrence risk. DFS was analyzed in patients with consistent prognosis of the two groups, and the results showed that the two groups were significant difference in DFS (P =0.018). DFS was analyzed in patients with Neo-Bioscore < 3 score and high-risk of the traditional recurrence risk group, or non-high-risk of the two recurrence risk groups, and the two groups were not significant difference in DFS (P =0.076). Because there were 5 patients with Neo-Bioscore > 3 score and non-high-risk of the traditional recurrence risk group, they were not significant difference with non-high-risk of the two recurrence risk groups in DFS (P=0.266). Therefore, the above analysis showed that the groups of Neo-Bioscore 3 score as the boundary value were at least equivalent to the traditional recurrence risk groups in guiding the selection of endocrine regimens for HR-positive breast cancer patients who had not been menopause after neoadjuvant chemotherapy.4. The 429 patients in our study were grouped respectively by whether pCR or Neo-Bioscore 3 score as the boundary value, and the survival of the patients in each group was analyzed by DFS. And the two grouping methods could predict the DFS (P=0.023 vs. P <0.001). Further subgroup analysis, we grouped separately 238 HR positive HER2 negative patients, 97 HER2 positive patients and 94 HR negative HER2 negative patients with the above two methods, and the survival of the patients in each subgroup was analyzed by DFS. And only the groups by Neo-Bioscore 3 score as the boundary value in each subgroup could predict the DFS (P <0.05). These showed that the groups of Neo-Bioscore 3 score as the boundary value were better than the groups whether pCR in prediction of the DFS for breast cancer patients with neoadjuvant chemotherapy.5. There were 5 patients who received pCR and Neo-Bioscore > 3 score, including 1 HER2 positive patient and 5 HR negative HER2 negative patients. And there were 328 patients, including 222 HR positive HER2 negative patients, 47 HER2 positive patients and 59 HR negative HER2 negative patients, who received non-pCR and were grouped by Neo-Bioscore 3 score as the boundary value. Through the survival analysis of DFS,we found that there were statistically different whether in all non-pCR patients (P<0.001), or in the same molecular pathologic subgroup of HR negative HER2 negative,HER2 positive and HR negative HER2 negative (P <0.001? P <0.001 and P =0.017).Therefore, the Neo-Bioscore not only assessed the prognosis of many non-pCR patients,but also identified subgroups of patients who received pCR but still had a high risk of recurrence, which cloud provide guidance for individualized adjuvant therapy.Conclusion1. The Neo-Bioscore of locally or regionally advanced breast cancer patients with neoadjuvant chemotherapy was closely related to their DFS, which could be used to predict the patients' DFS.2. The patients were in low risk group when Neo-Bioscore < 3 and in high risk group when Neo-Bioscore >3, which had a better correlation with the patient's long-term prognosis.3. The groups of Neo-Bioscore 3 as the boundary value were equivalent to the traditional recurrence risk groups in guiding the selection of endocrine regimens for HR-positive breast cancer patients who had not been menopause after neoadjuvant chemotherapy.4. The groups of Neo-Bioscore 3 as the boundary value were better than the groups whether pCR in prediction of the DFS.5. The Neo-Bioscore not only assessed the prognosis of non-pCR patients,but also identified subgroups of patients who received pCR but still had a high risk of recurrence,which cloud provide guidance for individualized adjuvant therapy.6. The Neo-Bioscore system was clinical easy to get, simple calculation and repeatability and so on, which could help clinicians determine which patients needed intensive treatment or could avoid unnecessary overtreatment by quantitative prognostic information, and it could not only facilitate the communication between doctors and patients, but also help screen patients in clinical studies. Maybe, the Neo-Bioscore system could be used as a potential replacement endpoint for the evaluation of neoadjuvant therapy efficacy, facilitating the development of new drugs and the optimization of individualized treatments. |
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