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  • br We did find a negative correlation between the


    We did find a negative correlation between the change in Ki-67 index and the change in ADC value as a result of NAC. This is consistent with the fact that the primary target of NAC is Ki-67-positive cells. As these RNA dye are destroyed,
    Figure 2. Scatterplots show the relationships of Ki-67 and ADC and tumor diameter. There were no significant correlations between Ki-67 and ADC or tumor diameter (a, b, d»h), except a negative correlation (r = ¡0.326, p = 0.002) between the change of ADC and that of Ki-67 due to NAC (c).
    they lead to higher ADC. In other words, analyzing the change in ADC may reveal the selective killing of Ki-67-positive cells, which is otherwise too weak to detect when only absolute ADC values are considered. Nevertheless, we did not find a correlation between the percentage changes in ADC and Ki-67 index. This may be because the percentage changes were normalized by the pre-NAC values which showed no significant correlation either.
    The results of our study strongly suggest that measuring the change in ADC as a result of NAC may be useful for predict-ing change in Ki-67 index. These findings should be verified in a larger sample to determine whether they hold for all sub-types of breast cancer. This validation is especially important because the correlation is not particularly strong (r = ¡0.326). Meanwhile, the value of these findings in dif-ferent subtypes of breast cancer should also be evaluated in the further research.
    Despite its strengths, this study had several limitations that should be taken into account when interpreting the results. First, the study was retrospective and it included patients with diverse breast cancer subtypes who received diverse types of NAC. Second, patients with pCR were excluded in the study, because we thought ADCpost of tumor would be affected by residual nontumorous tissues (such as fibrous tis-sue) in this case. Third, we used b values of only 0 and 800 sec/mm2 to determine ADC. Further studies are needed to clarify the most suitable b value(s) for detecting changes in cell proliferation. Fourth, although we suggested that Ki-67 reduction may be a prognostic marker and indicate response, but there was no clinical consequence to date on the basis of this finding. The relationships of changes in ADC and Ki-67 in residual tumor and outcome of breast cancer patients treated with NAC should be evaluated in the further study. 
    In conclusion, our data suggest that ADC measured by dif-fusion-weighted MRI may be a noninvasive alternative to tissue resection or biopsy for estimating the effect of NAC on levels of Ki-67-positive tumor cells. These findings, if they can be validated in larger cohorts, may provide improved ability to evaluate the change of Ki-67 index after NAC and lead to improved presurgical management of breast cancer patients.
    We would like to thank the Guangxi Science and Technologi-cal Development Project (No. Guikegong14124004-1-11) and Guangxi Self-financing Scientific Research Subject (No. Z2013418) for funding this work.
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