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  • br ARTICLE IN PRESS br identified on the ADC

    2021-03-02


    ARTICLE IN PRESS
    identified on the ADC map by using contrast-enhanced MR imaging information as a reference. Regions of interest with-out overlap were randomly drawn within the solid portion on the largest section of lesion to extract data from several circles with diameters of 5 10 mm. Areas containing cysts, necrosis, liquefactions, or hemorrhage were excluded. Depend on the size of tumor, 3 5 regions of interests were obtained per lesion. Mean ADC was calculated over all the circles and taken as the value for the entire tumor. In this way, mean tumor ADC was determined before NAC (ADCpre) and afterwards (ADCpost). Change in ADC was cal-culated as DADC = ADCpost ¡ ADCpre, and the percentage change in ADC as DADC% = [ADCpost ¡ ADCpre]/ADCpre. Analogously, the change in tumor diameter was calculated as DD = Dpost ¡ Dpre, and the percentage change as DD% = [Dpost ¡ Dpre]/Dpre.
    Statistical Analysis
    Results were presented as mean § standard deviation. Differ-ences of ADC, Ki-67, and diameter of tumors between pre-and post-NAC were assessed for significance using the paired-samples t-test. Pearson correlation analyses were car-ried to explore the relationship between Ki-67pre and ADCpre, Ki-67pre and Dpre, Ki-67post and ADCpost, Ki-67post and Dpost, DKi-67 and DADC, DKi-67 and DD, DKi-67% and DADC%, and DKi-67% and DD%, respectively. All anal-yses were performed using SPSS 19.0 (IBM, Chicago, IL). Results associated with p < 0.05 were considered statistically significant.
    RESULTS
    The patients in our group were an average of 50.3 years old when initially diagnosed with breast cancer. Their demo-graphic and clinical characteristics are shown in Table 1.
    signi3
    TABLE 1. Characteristics of Patients
    Factor Number (%)
    Invasive ductal carcinoma 76 (87.4) Invasive lobular carcinoma 11 (12.6) Prechemotherapy clinical stage
    A, Adriamycin; C, cyclophosphamide; E, Epirubicin; ER, DNA dye receptor; F, 5-fluorouracil; HER2, human epidermal growth factor receptor 2; NAC, neoadjuvant chemotherapy; PD, progression of disease; PR, partial response; SD, stable disease; T, Taxotere.
    DISCUSSION
    Ki-67 can predict response to NAC (22 24); change in Ki-67 index as a result of NAC (16 18) can independently predict prognosis of patients with breast cancer. Change in Ki-67 index as a result of NAC may also predict early recur-rence of breast cancer (25). In the present study, we found that NAC significantly decreased the Ki-67 index, consistent with its prognostic role. In parallel, although tumor diameter also significantly decreased, but the change in diameter did not show significant correlation with change in Ki-67 index. This is consistent with the idea that Ki-67 index can serve as an independent parameter for evaluating tumor response to NAC.
    Since Ki-67 index cannot be easily determined in all patients with breast cancer, because of its invasive proce-dure, we wished to examine whether the ADC from diffu-sion-weighted MRI might serve as a noninvasive surrogate. The ADC reflects the diffusion of water mole-cules in the tissue, so it is sensitive to tissue characteristics that can inhibit this diffusion, including cell organization, cell density, microstructure, and microcirculation (26). Cells positive for Ki-67 may have a larger volume and ratio of nuclear to cytoplasmic volume than G0 cells negative for Ki-67. This means that group of cells positive for Ki-67 will feature narrower extra- and intercellular spaces,
    ARTICLE IN PRESS
    TABLE 2. Data of Tumor Pre- and Post-NAC
    Characteristics Pre-NAC Post-NAC t p
    **p < 0.01; ADC, apparent diffusion coefficient; D, diameter; NAC, neoadjuvant chemotherapy.
    Figure 1. A 53-year-old woman with invasive ductal carcinoma. a»c Before NAC (a) Transverse contrast-enhanced T1WI image showed a enhancing mass (arrow) in the right breast. (b) Corresponding ADC map shows the same lesion (arrow) with ADC value of 0.894 £ 10¡3mm2/s.
    TABLE 3. Correlation in Data of Tumor
    Characteristics r p
    Pre-NAC
    and post-NAC
    and post-NAC
    **p < 0.01; ADC, apparent diffusion coefficient; D, diameter; NAC, neoadjuvant chemotherapy. 
    decreasing ADC. This led to the hypothesis that ADC may be useful for estimating the Ki-67 index of tumors (27).
    Experimental studies to examine this possibility have given inconsistent results for patients with breast cancer. While some studies have reported significantly lower ADC in the presence of high Ki-67 expression (20,21), other studies have failed to find a correlation between ADC and Ki-67 (28,29). Similarly, we found no correlation between Ki-67 index and ADC before or after NAC in our patients with invasive breast cancer. This likely reflects the strong influence of myriad other factors on water molecule diffusion in breast tissue, including tissue structure, microperfusion, and diffusion het-erogeneity (30). Another factor to consider is that our study included a diverse patient population with various luminal and nonluminal subtypes of breast cancer (20).