Pilot Study Of Diffusion-Weighted MRI In Predicting The Efficacy Of Neoadjuvant Chemotherapy Of Breast Cancer

Background:Neoadjuvant chemotherapy has been widely used in the treatment of locally advanced breast cancer as well as early breast cancer.But to date,there isn't any reliable method which can provide early assessment of therapeutic response of the tumor to neoadjuvant chemotherapy.Diffusion weighted imaging(DWI), evaluating intrinsic tissue structure through measuring the diffusion of water moleculor,has been studied mainly in brain tumors,metastatic liver lesions and rectal carcinomas.The role of diffusion-weighted magnetic resonance imaging in assessing the response of breast cancer to neoadjuvant chemotherapy awaits further study.Objective:To approach the apparent diffusion coefficient(ADC) obtained on DWI in predicting the response of breast cancer to neoadjuvant chemotherapy.Methods:53 locally advanced breast cancer patients participated in this prospective study on neoadjuvant chemotherapy.All patients were confirmed as invasive breast cancer through core needle biopsy and were treated with neoadjuvant paclitaxel plus carboplatin for 4 cycles.DWI and ADC value were examined before chemotherapy(the first time point),after the first cycle of chemotherapy(the second time point) and before surgery(the third time point).We assessed the relationship between the percentage changes in ADC value at the third time points and clinical or pathological characteristics of the patients as well as the reduction of tumor.The relationship between the size reduction of breast cancer and the changes in ADC value after the first cycle of neoadjuvant chemotherapy was also evaluated.Logistic regression was conducted to examine the independent factors associated with clinical complete response(CR) and pathologic complete response(pCR),and receiver operating characteristic curve(ROC curve) was drawn to determine the cutoff value of the diagnostic test of the percentage changes of the ADC value at the second time point in predicting CR and pCR.According to the ADC value at the first and second time points,patients were categorized as high responders if their ADC at the second time point were higher by 2 times the standard deviation than the mean pre-chemotherapy ADC,and otherwise the patients were considered as low responsers. The diagnostic value of this categorizing system in predicting CR and pCR was examined.Results:According to the results of physical examination,clinical complete response was documented in 13 patients(24.5%);36 patients(67.9%) obtained partial response; stable disease was observed in 4 patients(7.5%);no patient had progressive disease. 11 patients(20.8%) have achieved pCR after neoadjuvant chemotherapy.There was a strong positive correlation between the percentage changes in ADC value at the third time points and the degree of the tumor reduction,and no significant correlations between the changes in ADC value and the clinical or pathological characteristics of the patients were observed.A significant increase in ADC value was observed at the second time point compared with the first time point(1.104±0.117×10^-3mm²/s, 1.220±0.158×10^-3mm²/s,P＜0.001),while the decrease of the longest diameter of the tumors measured by physical examination,ultrasound or MRI or the tumor volumn measured by MRI were not(P＞0.05).Logistic regression revealed that percentage changes of ADC value at the second time pointwere significantly associated with CR(P=0.022) and pCR(P=0.022).The AUC value of the ROC curve were 0.721(95%CI:0.512～0.931,P=0.017) and 0.775(95%CI:0.598～0.952, P=0.005) in the two diagnostic tests for CR and pCR,and the sensitivity and specificity were 76.9%,63.6%and 77.5%,90.5%,respectively.10 patients(18.9%) were considered as high responders and 43 patients(81.1%) low responders according to categorizing system described above.7 patients(70%) of the high responders have achieved clinical CR and pCR after neoadjuvant chemotherapy while for the low responders there were only 6 patients(14.0%) and 4 patients(9.3%) proven to have CR and pCR.The difference have both reached statistical significance(P=0.001,P＜0.001).Logistic regression confirmed that the categorizing system was independently predictive of CR(P=0.008) and pCR(P=0.012).Taking this categorizing system as a dignostic test,the sensitivity,specificity,positive predictive value and negative predictive value were 53.8%,92.5%,70.0%and 86.0%for CR and 63.6%,92.9%,70.0%and 90.7%for pCR,respectively.Conclusions:The ADC value obtained on DWI before and after neoadjuvant chemotherapy of breast cancer could assess the efficacy of chemotherapy.The change of ADC value after the first cycle of neoadjuvant chemotherapy occured prior to the morphologic changes of the tumor and at this time ADC value could to some extent predict the efficacy of neoadjuvant chemotherapy.