Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers

PLOS ONE, Dec 2019

Purpose Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC) to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results. Patients and Methods Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB), residual disease in breast and nodes (RDBN), tumor response ratio, Sataloff’s classification, and Miller—Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival. Results In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN) had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan—Meier curves. Conclusion Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR+/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC.

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Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers

September Comparison of Pathologic Response Evaluation Systems after Anthracycline with/ without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers Hee Jin Lee 0 1 2 In Ah Park 0 1 2 In Hye Song 0 1 2 Sung-Bae Kim 0 1 2 Kyung Hae Jung 0 1 2 Jin- Hee Ahn 0 1 2 Sei-Hyun Ahn 0 1 2 Hak Hee Kim 0 1 2 Gyungyub Gong 0 1 2 0 1 Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea , 2 Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea , 3 Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea , 4 Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea 1 Funding: This study was supported by a grant (2015-0169) from the Asan Institute for Life Sciences , Seoul , Korea 2 Editor: William B. Coleman, University of North Carolina School of Medicine, UNITED STATES - Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC) to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results. Patients and Methods Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB), residual disease in breast and nodes (RDBN), tumor response ratio, Sataloff’s classification, and Miller—Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival. In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN) had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan—Meier curves. Competing Interests: The authors have declared that no competing interests exist. Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR +/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC. Neoadjuvant chemotherapy (NAC) is often used to treat three categories of patient: those with locally advanced breast cancer; those with operable breast cancer who are not candidates for breast-conserving surgery; and those with proven lymph node metastases [1, 2]. NAC induces a spectrum of morphologic changes in tumors and lymph nodes, including the complete disappearance of invasive cancer cells (pathologic complete response [pCR]), partial tumor regression, no response, or progressive tumor growth during treatment [3–5]. The pCR rate varies according to the molecular subtype of breast cancer and the therapeutic regimen [6, 7], and correlates well with prolonged survival [7, 8]. However, the majority of post-NAC breast cancer cases show residual tumor in the tumor bed. Several pathologic response evaluation systems for residual cancer have been proposed. These evaluation systems can be roughly divided into two categories: absolute assessment of the residual tumor and relative assessment of the treatment response (comparing the cellularity or tumor size of post-NAC specimens with those of pre-NAC specimens or images)[9–14]. Parameters such as ypTNM stage, residual disease in breast and nodes (RDBN), and residual cancer burden (RCB) evaluate only residual tumor in the breast parenchyma and lymph nodes [6, 13, 15]. Conversely, Miller—Payne grading and Sataloff’s classification compare the size and cellularity of the pre- and post-NAC tumor [9, 10]. The recently developed tumor response ratio (TRR) compares tumor size on pre-NAC images and post-NAC microscopic tumor size [14]. Each evaluation system predicts survival outcome for breast cancer patients. Recent studies compared several of these classification systems and found that they yielded different predictive values.[16, 17] However, no standardized and/or superior pathologic response evaluation system exists at the present time. Breast cancers can be classified using immunohistochemistry-based approaches, the results of which correlate well with the molecular subtypes determined by micro (...truncated)


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Hee Jin Lee, In Ah Park, In Hye Song, Sung-Bae Kim, Kyung Hae Jung, Jin-Hee Ahn, Sei-Hyun Ahn, Hak Hee Kim, Gyungyub Gong. Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers, PLOS ONE, 2015, Volume 10, Issue 9, DOI: 10.1371/journal.pone.0137885