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    Original Investigation
    Changes in Apparent Diffusion Coefficient as Surrogate Marker for Changes in Ki-67 Index Due to Neoadjuvant Chemotherapy in Patients with Invasive Breast Cancer
    Abbreviations
    ADC
    apparent Z-VAD-FMK
    coefficient
    NAC
    neoadjuvant chemotherapy
    pCR
    pathological complete
    response
    IHC
    Immunohistochemistry
    ER
    Estrogen receptor
    HER2
    Human epidermal growth fac-
    tor receptor type 2 
    Rationale and Objectives: To evaluate possible correlation between changes in apparent diffusion coefficient (ADC) and Ki-67 index as a result of neoadjuvant chemotherapy (NAC) in patients with inva-sive breast cancer.
    Methods and Materials: Between February 2016 and October 2017, 87 patients with breast cancer underwent diffusion-weighted magnetic resonance imaging (b = 0 and 800 sec/mm2) before and after NAC. ADC and tumor diameter before and after NAC were compared to the Ki-67 index determined from biopsy or surgical specimens.
    Conclusion: Comparison of pre- and post-NAC ADC can be used to estimate the change in Ki-67 index in patients with invasive breast cancer.
    Key Words: Breast cancer; Neoadjuvant chemotherapy; Ki-67 index; Diffusion weighted imaging; Apparent diffusion coefficient.
    © 2019 Published by Elsevier Inc. on behalf of The Association of University Radiologists.
    INTRODUCTION
    Breast cancer is the most commonly diagnosed cancer among women, accounting for 30% of all cancers and 14% of cancer-related deaths worldwide (1).
    Chemotherapy can significantly improve survival of breast cancer patients, and neoadjuvant chemotherapy (NAC) is
    © 2019 Published by Elsevier Inc. on behalf of The Association of University Radiologists.
    routinely used for patients with operable as well as locally advanced breast cancer (2,3). The purpose of NAC is to shrink tumors, increase operability rates and treat distant metastases in order to improve overall survival (4 6). How-ever, NAC leads to pathological complete response (pCR), a powerful surrogate marker for long-term oncological out-comes (7,8), in only 10% 30% of patients (9 11). This highlights the need to identify alternative surrogate markers for survival that can be used to manage patients who fail to experience pCR.
    One candidate marker is Ki-67, a nuclear protein expressed during all phases of the cell cycle except G0 (12). A well-established marker of tumor proliferation (13), Ki-67 can independently predict prognosis of patients with operable breast cancer (14,15), and a reduction in its levels due to NAC has been associated with favorable outcomes (16 18).
    ARTICLE IN PRESS
    The available evidence suggests that comparing the Ki-67 index before and after NAC should allow assessment of tumor response to chemotherapy and design of further man-agement strategies for breast cancer patients. However, obtaining tumor tissue for detecting Ki-67 is not always feasi-ble. Thus, a less invasive and more convenient surrogate for the Ki-67 index is needed.