| Background:Breast cancer is the most common malignancy and the leading cause of cancer death in women.Neoadjuvant therapy(NAT)refers to the systemic treatment conducted before local treatment for breast cancer patients without distant metastasis.As an important part of comprehensive treatment of breast cancer,NAT is of great significance for patients with locally advanced breast cancer,especially for those with inoperable breast cancer.Effective and standardized NAT schemes can increase the rate of breast-conserving and surgical resection.Patients with a pathologic complete response(p CR)have shown significant improvements in prognosis.Therefore,precise and effective NAT regimens and timely and accurate evaluation methods of response to NAT are crucial for the follow-up treatment decision-making and prognosis management of breast cancer patients.Histologic grade,lymph node status,tumor size and biomarkers estrogen receptor(ER),progesterone receptor(PR),human epidermal growth factor receptor type 2(HER2)and Ki67are not only important for clinical staging and grading of breast cancer and predicting prognosis,but also the basis for formulating individualized NAT scheme.Different prognostic factors of breast cancer are targeted with different NAT strategies.Analyzing the imaging characteristics of the above prognostic factors can provide certain imaging reference for guiding clinical treatment and prognosis evaluation and a research foundation for finding an effective imaging method for evaluating the response to NAT.Pathological technique is the―gold standard‖for evaluating the responce to NAT in breast cancer patients.However,it is an invasive examination and can not be used to evaluate the responce to NAT in every treatment cycle,resulting in some patients who are not sensitive to the initial NAT regimen can not change the NAT regimen or undergo other treatments,which is not conducive to the prognosis of patients.Conventional ultrasound and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)are currently commonly used as imaging methods for assessing the responce to NAT in clinical,with the advantages of non-invasiveness and reproducibility.However,it is difficult for conventional ultrasound to distinguish the fibrous scar formed after NAT from the residual cancer burden.And conventional ultrasound is poor in detecting low-velocity microvessels within tumors.DCE-MRI is currently the preferred evaluation method,but some studies suggest that DCE-MRI is prone to overestimate or underestimate the size of residual lesions after NAT.Moreover,the clinical application of DCE-MRI is limited due to that it is not suitable for patients with metal implants and renal insufficiency and its long examination time leading to intolerance in some patients.Contrast enhanced ultrasound(CEUS)is a new imaging technique,which can make up for the disadvantages of conventional ultrasound and DCE-MRI.The contrast agent used by CEUS is a pure blood pool contrast agent,which can clearly show the microvessels in and around the tumor and real-time and dynamically display the internal microcirculation perfusion of tumors and the extent of infiltration to the periphery.CEUS can not only accurately observe the changes of tumor shape and size,but also effectively evaluate the blood perfusion characteristics of residual lesions after NAT.Therefore,this study intends to analyze the correlation between the CEUS qualitative characteristics and quantitative parameters and histologic grade,lymph node status,tumor size,ER,PR,HER2,Ki67,so as to provide more information for the development of clinical NAT regimens and the evaluation of the prognosis of breast cancer patients;explore the value of CEUS quantitative analysis in the early evaluation of response to NAT,and to provide a reliable imaging method for evaluation of response to NAT;compare the efficacy of CEUS and DCE-MRI in the evaluation of response to NAT,and to analyze the value of CEUS and DCE-MRI in the evaluation response to NAT,to provide reference for clinical selection of NAT evaluation methods.Objective:(1)To analyze the correlation between the CEUS qualitative characteristics and quantitative parameters and prognostic factors of breast cancer,and provide more information for the development of clinical NAT regimens and the evaluation of the prognosis of breast cancer patients.(2)To explore the value of CEUS quantitative analysis in the early evaluation of response to NAT,and provide a reliable imaging method for evaluation of response to NAT.(3)To compare the efficacy of CEUS and MRI in the evaluation of response to NAT,and to analyze the value of CEUS and DCE-MRI in the evaluation response to NAT,and provide reference for clinical selection of NAT evaluation methods.Methods:This research is divided into the following there parts:(1)Relationship between CEUS characteristics and prognostic factor of breast cancer:The clinical data of 89 patients with breast cancer who diagnosed and treated in Southwest Hospital,Army Medical University from May 2021 to August 2022 were retrospectively analyzed.The CEUS qualitative characteristics and quantitative parameters of89 patients were analyzed.The correlation between the qualitative characteristics and quantitative parameters of CEUS and prognostic factors of breast cancer,including histologic grade,lymph node status,tumor diameter,ER,PR,HER2 and Ki67 were explored.(2)Quantitative CEUS evaluation of the effect of in eraly stage of NAT in patients with breast caner:Between September 2022 and March 2022,Patients with breast cancer scheduled for NAT in Southwest Hospital,Army Medical University were enrolled in this study.Participants were required to undergo conventional ultrasound and CEUS before starting NAT and after the first cycle of NAT.The CEUS dynamic video was analyzed quantitatively.The CEUS quantitative parameters before and after NAT were compared to analyze the value of CEUS quantitative parameters in early prediction of the response to NAT.(3)Application of CEUS and DCE-MRI in evaluation of response to NAT:Between September 2022 and March 2022,Patients with breast cancer scheduled for NAT in Southwest Hospital,Army Medical University were enrolled in this study.Participants were required to undergo conventional ultrasound,CEUS and DCE-MRI before starting NAT and before surgery after the completion of all cycles of NAT.The efficacy of CEUS and DCE-MRI in the evaluation of response to NAT was compared,and the value of CEUS and DCE-MRI in the evaluation response to NAT was analyzed.Results:1.Relationship between CEUS characteristics and prognostic factor of breast cancer(1)Relationship between CEUS qualitative characteristics and prognostic factor of breast cancer:HER2-positive tumors were more likely to show fast enhancement than HER2-negative tumors(χ~2=4.633,P=0.031).Compared with tumors with low expression of Ki67,tumors with high expression of Ki67 tended to show hyperenhancement perfusion patterns(χ~2=4.355,P=0.037),and the size of lesions was usually larger after enhancement(χ~2=4.355,P=0.037).Perfusion defect was more often observed in tumors with histologic grade III,rather than tumors with histologic gradeⅠ/Ⅱ(χ~2=4.395,P=0.036).Lesions with diameter≥20mmwere more likely to show fast enhancement pattern than lesions with diameter<20mm(χ~2=6.036,P=0.014).(2)Relationship between CEUS quantitative parameters and prognostic factor of breast cancer:The WIS(Wash in slope),PI(Peak intensity),Wi AUC(Wash-in area under curve)of ER-negative tumors were significantly larger than those of ER-positive tumors(Z=-2.472,P=0.013;Z=-2.870,P=0.004;Z=-2.140,P=0.032).The WIS,PI,Wi AUC of PR-negative tumors were significantly larger than those in PR-positive tumors(Z=-2.965,P=0.003;Z=-3.361,P=0.001;Z=-2.672,P=0.008).The WIS,PI and Wi AUC of tumors with high expression of Ki67 were significantly larger than those of tumors with low expression of Ki67(Z=-2.172,P=0.030;Z=-2.713,P=0.007;Z=-2.620,P=0.009).In addition,the Wi AUC of HER2-positive tumors was significantly larger than that of HER2-negative tumors(Z=-2.161,P=0.031).(3)Binary Logistic regression analysis:The qualitative characteristics and quantitative parameters of CEUS with statistical significance were analyzed by binary Logistic regression with prognostic factors as dependent variables.The results suggested that PI was an independent predictor of ER status(P=0.037),and the enhancement degree and Wi AUC were independent predictors of Ki67(P=0.041,P=0.019).2.Quantitative CEUS evaluation of the effect of in eraly stage of NAT in patients with breast caner(1)Changes of quantitative parameters of CEUS and MD before and after NAT:After two cycles of NAT,the PI,Wi AUC and MD were significantly lower than those before NAT(Z=-2.341,P=0.019;Z=-2.246,P=0.025;Z=-3.724,P=0.000).(2)Comparison of quantitative parameters of CEUS and MD between minor responders and good responders after NAT:After two cycles of NAT,compared with the minor responders,the WIS and PI of good responders were lower,with a statistically significant difference(Z=-2.310,P=0.021;t=2.539,P=0.022;t=2.443,P=0.027).There was a significant difference in△WIS and△PI between minor responders and good responders(Z=-2.577,P=0.010;Z=-2.488,P=0.013;t=-4.203,P=0.001).(3)Efficacy of CEUS quantitative parameters in early prediction of response to NAT:The efficacy of△WIS and PI in early prediction of response to NAT were equivalent,the AUC was 0.863,with a sensitivity of 90.00%,and a specificity of 75.00%.The AUC of the WIS is 0.825,with a sensitivity and specificity of 90.00%and 75.00%,respectively.The AUC,sensitivity,and specificity of△PI were 0.850,80.00%,and 87.50%,respectively.3.Application of CEUS and DCE-MRI in evaluation of response to NAT(1)The efficacy of conventional ultrasound,CEUS,and DCE-MRI in in evaluation of response to NAT:The sensitivity,specificity,positive predictive value,and negative predictive value of conventional ultrasound in evaluating the response to NAT were 81.82%,37.50%,64.29%,and 60.00%,respectively.For CEUS,the sensitivity was 100.00%,the specificity was 50.00%,the positive predictive value was 73.33%,and the negative predictive value was100.00%.And for DCE-MRI,the sensitivity,specificity,positive predictive value,and negative predictive value were 90.91%,62.50%,76.92%,and 83.33%,respectively.(2)The consistency between the results of conventional ultrasound,CEUS and DCE-MRI evaluation and the results of the post-operative pathological evaluation:The Kappa value of conventional ultrasound was 0.204(P=0.603),that of CEUS was 0.537(P=0.018),and that of DCE-MRI was 0.553(P=0.041).This suggested that CEUS and DCE-MRI have a good efficiency in evaluating the response to NAT based on histopathological examinations.Conclusions:1.The CEUS qualitative characteristics and quantitative parameters have a certain correlation with the prognostic factors of breast cancer patients.CEUS can be used as a non-invasive method to provide more imaging information for the development of clinical NAT regimens and the evaluation of the prognosis of breast cancer patients.2.CEUS quantitative parameters can quantitatively reflect the changes of blood flow perfusion of tumors in early stage of NAT,and have certain potential value in early evaluation and prediction of response to NAT.3.CEUS and MRI have comparable efficacy in evaluation of response to NAT,and display a good consistency with pathological evaluation results. |
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