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      Histopathologic changes following neoadjuvant chemotherapy in various malignancies

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          Abstract

          Background:

          Various histopathological changes have been observed following neoadjuvant chemotherapy in individual tumors in the literature.

          Aims and Objectives:

          To observe histopathologic changes seen after neoadjuvant chemotherapy in breast malignancies, squamous cell carcinomas, adenocarcinomas, and Wilms′ tumor using breast cancer predominantly as the model.

          Materials and Methods:

          The present prospective study was carried out on 60 patients including 40 patients with carcinoma breast and 20 patients with other malignancies who received neoadjuvant chemotherapy.

          Results:

          Post neoadjuvant chemotherapy, mastectomy specimens revealed nuclear enlargement, nuclear shrinkage, necrosis, vacuolation of nucleus, vacuolation of cytoplasm, dyscohesion, and shrinkage of tumor cells with nuclear changes of nonviability like karyorrhexis, karyolysis, and pyknosis. Stromal reactions manifested as fibrosis, elastosis, collagenization, hyalinization, microcalcification, and neovascularization. Areas of necrosis included both vascular and avascular pattern. The stroma also revealed fibrinoid necrosis and mucinous change. Hyalinization of the blood vessel wall was a common finding. The most common inflammatory host response observed in the present study was lymphocytic; others included mixed inflammation, plasmacytic, prominent histiocytic, and giant cell types. Giant cell reaction was significantly correlated to all types of tumor responses ( P < 0.05). Similar changes were also observed in other malignancies. A detailed review of the literature has also been done and presented.

          Conclusion:

          The tumor grade decreases and differentiation improves, in addition to the retrogressive changes and increase in stromal component, as a result of chemotherapy in carcinoma breast as well as in other malignancies.

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          Most cited references16

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          Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy.

          Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel therapy and if they correlate with response to treatment. Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients. Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the tumor cell apoptotic response to the first dose of paclitaxel. These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment.
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            Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome

            The aim of this study was to provide a better insight into breast cancer response to chemotherapy. Chemotherapy improves outcome in breast cancer patients. The effect of cytotoxic treatment cannot be predicted for individual patients. Therefore, the identification of tumour characteristics associated with tumour response and outcome is of great clinical interest. We studied 97 patients, who received anthracycline-based neoadjuvant chemotherapy. Tumour samples were taken prior to and after chemotherapy. We quantified the response to chemotherapy clinically and pathologically and determined histological and molecular tumour characteristics. We assessed changes in the expression of Bcl-2, ER, P53 HER2 and Ki-67. Association with response and outcome was tested for all parameters. The experimental results showed 15 clinical (17%) and three (3%) pathological complete remissions. There were 18 (20%) clinical vs 29 (33%) pathological nonresponders. The expression of most markers was similar before and after chemotherapy. Only Ki-67 was significantly decreased after chemotherapy. Factors correlated with response were: large tumour size, ER negativity, high Ki-67 count and positive P53 status. Tumour response and marker expression did not predict disease-free or overall survival. In conclusion, clinical and pathological response assessments are poorly associated. Proliferation decreases significantly after chemotherapy. ER negativity and a high proliferation index are associated with better response. HER2 status does not predict response, and outcome is not related to tumour response.
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              Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer

              Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2–4 N0–1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (P 75% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P=0.004).
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                Author and article information

                Journal
                Int J Appl Basic Med Res
                Int J Appl Basic Med Res
                IJABMR
                International Journal of Applied and Basic Medical Research
                Medknow Publications & Media Pvt Ltd (India )
                2229-516X
                2248-9606
                Jul-Dec 2012
                : 2
                : 2
                : 111-116
                Affiliations
                [1]Department of Pathology, PGIMS, Rohtak, India
                [1 ]Department of Radiology, PGIMS, Rohtak, India
                Author notes
                Address for correspondence: Dr. Divya Sethi, Department of Pathology, PGIMS, Rohtak, India. E-mail: dr.divyasethi@ 123456gmail.com
                Article
                IJABMR-2-111
                10.4103/2229-516X.106353
                3678690
                23776823
                b26d0162-9af6-46d5-8cf7-50853848dee2
                Copyright: © International Journal of Applied and Basic Medical Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Original Article

                breast carcinoma,changes following chemotherapy,neoadjuvant chemotherapy

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