Garik Dashyan - Academia.edu (original) (raw)
Papers by Garik Dashyan
The Breast, 2011
Goals: The primary endpoint of our study was the evaluation of the impact of the canonical biomar... more Goals: The primary endpoint of our study was the evaluation of the impact of the canonical biomarkers expression and prognostic factors such as ER, PR and HER2/neu on OS, DFS and RFS based on data from N.N. Petrov Research. Methods: The total of 679 pts (selected from N.N. Petrov Research Institute Cancer Register holding information on 5060 BC pts) enrolled into the study. Cohort 1 consisted of 600 pts with primary early BC (p)T1N0M0, Cohort 2 included 79 patients with advanced BC which had been downstaged to (p)T1N0M0 by means of neoadjuvant chemotherapy. Neoadjuvant chemotherapy was AT×4. Pts with HER2/neu-positive primary (p)T1N0 BC did not receive adjuvant trastuzumab. Pts with HER2/neupositive and ER-negative disease received adjuvant FAC×6. Pts with ERpositive tumors received adjuvant tamoxifen for 5 years. The mean follow up was approximately 6.5 years. The primary endpoints were DFS and OS evaluated in correlation with the reliable standard biomarker expression (ER, PR, HER2/neu and G). Cohort 2 was added for comparison of tumors that had been downstaged with n/a chemo to (p)T1N0M0 and primary (p)T1N0M0. Results: For primary (p)T1N0M0 DFS rate was 84% whereas for advanced BC (c)T2−4N0−1M0 downstaged to (p)T1N0M0 by means of n/a chemotherapy DFS was 78% (p = 0.005). The 5-years DFS rate of ER-positive patients was 73% whereas DFS of ER-negative patients was 67% (p < 0.05). For HER2-positive tumors (p)T1N0M0 OS rate was 67%, whereas for HER2-negative patients it was 86% (p < 0.05). DFS rates of patients in accordance with the G-grade was estimated. DFS was 98%, 80% and 76% for patients with G1, G2 and G3 respectively. The difference in DFS rate between G2 and G3 was not significant, whereas the difference in DFS rate between G1 and G2/3 was statistically significant (p = 0.05). Conclusion: Downstaging to (p)T1N0M0 by means of neoadjuvant chemo (AT×4) does not lead to achieving of survival rates similar to those in patients with primary (p)T1N0M0.The prognosis for early (p)T1N0M0 HER2-positive tumors, and for hormone-receptor-negative tumors is notably worse.
European Journal of Cancer, 2012
Cancer, 2007
BACKGROUND. Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chem... more BACKGROUND. Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients. The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive tumors. This randomized, controlled, phase 2 study evaluated the efficacy of neoadjuvant chemotherapy compared with endocrine treatment with aromatase inhibitors in postmenopausal women with ER-positive and/or PgR-positive breast cancer. METHODS. Eligible patients were randomly assigned to receive neoadjuvant anastrozole 1 mg/day (n 5 61) or exemestane 25 mg/day (n 5 60) for 3 months or doxorubicin 60 mg/m 2 with paclitaxel 200 mg/m 2 (four 3-week cycles). Study end points included overall objective response determined by palpation, mammography, and ultrasound, and the number of patients who qualified for breastconserving surgery and radiotherapy. RESULTS. Clinical objective response was 64% in the endocrine therapy and chemotherapy treatment groups. Median time to clinical response was 57 and 51 days with aromatase inhibitors and chemotherapy, respectively (P > .05). Rates of pathological complete response (3% vs 6%) and disease progression (9% vs 9%) did not differ significantly in the endocrine therapy or chemotherapy group, respectively (P > .05). Rates of breast-conserving surgery were slightly higher in the endocrine group (33% vs 24%; P 5 .058). The most frequent toxicities from chemotherapy were alopecia (79%), grade 3/4 neutropenia (33%), and grade 2 neuropathy (30%). Endocrine treatment was well tolerated. No deaths occurred during the preoperative treatment. CONCLUSIONS. Preoperative neoadjuvant endocrine therapy with aromatase inhibitors was well tolerated and resulted in rates similar to chemotherapy in overall objective response and breast-conserving surgery in postmenopausal women with ER-positive and/or PgR-positive tumors.
American Journal of Clinical Oncology, 1992
Problems in oncology, 2017
The aim of the study was to evaluate a 3-year distant treatment outcomes of patients with early b... more The aim of the study was to evaluate a 3-year distant treatment outcomes of patients with early breast cancer who had undergone sentinel lymph node biopsy. Methods. A total of 681 patients with early cT1-2N0M0 breast cancer treated in the N.N. Petrov research institute of oncology form 2012 till 2016 were retrospectively enrolled in the study. Radioisotopes were used to identify sentinel nodes. In case a macrometastatic lesion was found (>2mm) ALND was performed. Subsequent adequate systemic treatment and radiotherapy were administered in accordance with the pTNM status, biologic subtype and age. Results. A 3-year overall survival equaled 99.3% (SE 0.4%), recurrence-free survival was 99.2% (SE 0.4%). Survival of patients without nodal involvement reached 100%, whereas for patients with metastatic nodes it was 97.4% (SE 1.8%). The threshold for the number of the affected nodes significantly influencing survival equaled 1 (р=0,0187). Overall survival of patients with 0 to 1 positiv...
Problems in oncology
There are presented the immediate and long-term results of neoadjuvant endocrine therapy versus c... more There are presented the immediate and long-term results of neoadjuvant endocrine therapy versus chemotherapy in ER+ breast cancer and chemotherapy (carboplatin + taxane) at triple-negative tumor subtype. We marked a tendency of improving a 10-year disease-free survival at luminal A subtype in patients who received endocrine therapy compared with chemotherapy (72.8% vs. 53.9%; p=0.062). Only 5.9% of patients with ER+ /HER2+ co-expression, who received target therapy, reached complete regression (pCR). There was a greater frequency of pCR, among patients with triple-negative breast cancer who received neoadjuvant chemotherapy with paclitaxel + carboplatin.
Problems in oncology
Purpose: To analyze the results of treatment and the quality of medical care for breast cancer pa... more Purpose: To analyze the results of treatment and the quality of medical care for breast cancer patients with breast reconstruction using thoracodorsal flap (TDF). Material and methods: The study was conducted on the basis of the N.N. Petrov National Medical Research Center of Oncology at the Department of Breast Tumors for the period 2016-2017. When using the reconstruction of the breast with the help of TDF the feature was the complete intersection of the muscle in the anterior-axillary line before closing the defect of the breast tissue but with the preservation of the thoracodorsal vascular sheaf. Surgical treatment was provided to 67 patients with breast cancer including after neoadjuvant therapy. Results: One-time reconstruction was performed in 16 (23.8%) patients under the organ-preserving surgery, mastectomy in two (2.9%) patients and mastectomy with implant placement in 27 (40.2%) patients. Delayed reconstruction of the breast: TDF in combination with the implant - 20 (29.8...
Problems in oncology
Purpose: To create a unified system of accelerated clinical trials of new drugs and regimens for ... more Purpose: To create a unified system of accelerated clinical trials of new drugs and regimens for breast cancer (BC). Materials and methods: The study included 1214 patients with BC of different stages (cT1N1, cT2N1-2, cT2-3N0-2, cT2-3N0-1, cT4N0M0). According to trepan biopsy data and immunohistochemical examination (IHC) expression of ER, PR, HER2, and Ki67 was determined. The expression TUBBßIII, TOP2a, analyzes on the BRCA1/2 mutation was studied. The clinical response to neoadjuvant treatment was determined using the physical method, ultrasonography-elas-tography, mammography, contrast magnetic resonance imaging (MRI) and single-photon emission computer mammotography (SPECT-CT). Results: The correlation index of complete responses (cCR) and total pathomorphological responses (pCR) according to MRI was 0.80, according to ultrasound - 0.61, mammography - 0.60, palpation - 0.57. The low level of amplification of the TUBßIII mRNA gene with a high level of amplification of the TOP2-a...
Problems in oncology
Purpose: To assess the influence of systemic and radiation therapy on complications in oncoplasti... more Purpose: To assess the influence of systemic and radiation therapy on complications in oncoplastic surgery. Material and methods: The scientific work was carried out on the basis of the Department of Breast Tumors of the N.N. Petrov National Medical Research Center of Oncology. Between January 2016 and December 2017 710 patients with morphologically confirmed BC who had undergone oncoplastic and reconstructive-plastic surgery were included in the study. The average age of the patients was 41.6 years. Patients with early breast cancer (283 patients) and locally advanced breast cancer (427 patients) were included in the study groups. Neoadjuvant treatment was performed in 239 patients, adjuvant in 132 patients. Results: Postoperative complications were observed in 45 patients (6.3 %, N = 710) and were as follows: endoprosthesis protrusion (12 patients, 1.6 %), endoprosthesis rotation (2 patients, 0.28 %), marginal necrosis of the flap (3 patients, 0.42 %), defect of the endoprosthesis...
Problems in oncology
Materials and methods. The effect of melatonin (MLT) and metformin (MTF) on the efficacy of neoad... more Materials and methods. The effect of melatonin (MLT) and metformin (MTF) on the efficacy of neoadjuvant hormone therapy with toremifene was investigated in 54 patients with estrogen receptor-positive, locally advanced breast cancer (ER + BC). The average age of women was 67 years. The patients had no diabetes mellitus. The first group of patients (n = 19) received toremifene 120 mg per day, the second group (n = 16) - toremifene in combination with MLT 3 mg orally every night, the third group (n = 19) - toremifene in combination with MTF 850 mg twice daily. Randomization was performed - 1: 1: 1. The duration of therapy in all study groups was 4 months. After the end of treatment, all patients were undergone surgery. Further adjuvant treatment depended on the results of the postoperative pathomorphological conclusion. The primary endpoint was a decrease in the Ki-67% level (a surrogate marker for the effectiveness of hormone therapy), the secondary endpoints were the objective respon...
Problems in oncology
Neoadjuvant systemic treatment of patients with breast cancer (BC) may include neoadjuvant chemot... more Neoadjuvant systemic treatment of patients with breast cancer (BC) may include neoadjuvant chemotherapy (NHT), neoadjuvant hormone therapy (NGT), neoadjuvant targeted therapy. The type of systemic therapy is determined by the level of expression of estrogen/progesterone receptors, HER2, i.e. immunohistochemical characteristic of the disease. In this article, we evaluated the predictive value of the profile of plasma exosomal microRNA, assessing the immediate efficacy of NHT, which included taxanes. Obtained results revealed a correlation between the level of concentration of several miRNA molecules in circulating exosomes and the effect of NHT. Furthermore, the index calculated as the ratio of miR-34a and miR-451 concentrations, allowеd to predict the effect of taxanecontaining NHT. The results confirm the assumption on the predictive significance of exosomal miRNA. Further research is needed to confirm the validity of a new method of prediction of the NHT efficacy in breast cancer.
Journal of Clinical Oncology
e12097 Background: Innovative advances in neoadjuvant systemic and targeted breast cancer therapy... more e12097 Background: Innovative advances in neoadjuvant systemic and targeted breast cancer therapy implicate surgical treatment in specific patient groups can be avoided. The core biopsy of the tumor bed and some diagnostic approaches (breast ultrasound, mammography, SPECT/CT) allow for precise evaluation of the treatment efficacy. Methods: This research started in our department in 2018, we picked two groups of 15 patients each treated for locally advanced TNBC or grade cT1-4N1-3M0 HER2-positive breast cancer: HER2+/ER+ or HER2+/ER- breast cancer. The TNBC group received 6 cycles of NACT of paclitaxel combined with doxorubicin and carboplatin AUC5. The HER2+ group received 4 cycles of АС polychemotherapy followed by 4 cycles of monochemotherapy with the docetaxel and 3-weekly trastuzumab. The HER2+ group is receiving adjuvant trastuzumab for up to one year, where ER-positive patients are also given hormone therapy with tamoxifen or aromatase inhibitors. The response to neoadjuvant t...
Journal of Clinical Oncology
The Breast, 2011
Goals: The primary endpoint of our study was the evaluation of the impact of the canonical biomar... more Goals: The primary endpoint of our study was the evaluation of the impact of the canonical biomarkers expression and prognostic factors such as ER, PR and HER2/neu on OS, DFS and RFS based on data from N.N. Petrov Research. Methods: The total of 679 pts (selected from N.N. Petrov Research Institute Cancer Register holding information on 5060 BC pts) enrolled into the study. Cohort 1 consisted of 600 pts with primary early BC (p)T1N0M0, Cohort 2 included 79 patients with advanced BC which had been downstaged to (p)T1N0M0 by means of neoadjuvant chemotherapy. Neoadjuvant chemotherapy was AT×4. Pts with HER2/neu-positive primary (p)T1N0 BC did not receive adjuvant trastuzumab. Pts with HER2/neupositive and ER-negative disease received adjuvant FAC×6. Pts with ERpositive tumors received adjuvant tamoxifen for 5 years. The mean follow up was approximately 6.5 years. The primary endpoints were DFS and OS evaluated in correlation with the reliable standard biomarker expression (ER, PR, HER2/neu and G). Cohort 2 was added for comparison of tumors that had been downstaged with n/a chemo to (p)T1N0M0 and primary (p)T1N0M0. Results: For primary (p)T1N0M0 DFS rate was 84% whereas for advanced BC (c)T2−4N0−1M0 downstaged to (p)T1N0M0 by means of n/a chemotherapy DFS was 78% (p = 0.005). The 5-years DFS rate of ER-positive patients was 73% whereas DFS of ER-negative patients was 67% (p < 0.05). For HER2-positive tumors (p)T1N0M0 OS rate was 67%, whereas for HER2-negative patients it was 86% (p < 0.05). DFS rates of patients in accordance with the G-grade was estimated. DFS was 98%, 80% and 76% for patients with G1, G2 and G3 respectively. The difference in DFS rate between G2 and G3 was not significant, whereas the difference in DFS rate between G1 and G2/3 was statistically significant (p = 0.05). Conclusion: Downstaging to (p)T1N0M0 by means of neoadjuvant chemo (AT×4) does not lead to achieving of survival rates similar to those in patients with primary (p)T1N0M0.The prognosis for early (p)T1N0M0 HER2-positive tumors, and for hormone-receptor-negative tumors is notably worse.
European Journal of Cancer, 2012
Cancer, 2007
BACKGROUND. Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chem... more BACKGROUND. Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients. The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive tumors. This randomized, controlled, phase 2 study evaluated the efficacy of neoadjuvant chemotherapy compared with endocrine treatment with aromatase inhibitors in postmenopausal women with ER-positive and/or PgR-positive breast cancer. METHODS. Eligible patients were randomly assigned to receive neoadjuvant anastrozole 1 mg/day (n 5 61) or exemestane 25 mg/day (n 5 60) for 3 months or doxorubicin 60 mg/m 2 with paclitaxel 200 mg/m 2 (four 3-week cycles). Study end points included overall objective response determined by palpation, mammography, and ultrasound, and the number of patients who qualified for breastconserving surgery and radiotherapy. RESULTS. Clinical objective response was 64% in the endocrine therapy and chemotherapy treatment groups. Median time to clinical response was 57 and 51 days with aromatase inhibitors and chemotherapy, respectively (P > .05). Rates of pathological complete response (3% vs 6%) and disease progression (9% vs 9%) did not differ significantly in the endocrine therapy or chemotherapy group, respectively (P > .05). Rates of breast-conserving surgery were slightly higher in the endocrine group (33% vs 24%; P 5 .058). The most frequent toxicities from chemotherapy were alopecia (79%), grade 3/4 neutropenia (33%), and grade 2 neuropathy (30%). Endocrine treatment was well tolerated. No deaths occurred during the preoperative treatment. CONCLUSIONS. Preoperative neoadjuvant endocrine therapy with aromatase inhibitors was well tolerated and resulted in rates similar to chemotherapy in overall objective response and breast-conserving surgery in postmenopausal women with ER-positive and/or PgR-positive tumors.
American Journal of Clinical Oncology, 1992
Problems in oncology, 2017
The aim of the study was to evaluate a 3-year distant treatment outcomes of patients with early b... more The aim of the study was to evaluate a 3-year distant treatment outcomes of patients with early breast cancer who had undergone sentinel lymph node biopsy. Methods. A total of 681 patients with early cT1-2N0M0 breast cancer treated in the N.N. Petrov research institute of oncology form 2012 till 2016 were retrospectively enrolled in the study. Radioisotopes were used to identify sentinel nodes. In case a macrometastatic lesion was found (>2mm) ALND was performed. Subsequent adequate systemic treatment and radiotherapy were administered in accordance with the pTNM status, biologic subtype and age. Results. A 3-year overall survival equaled 99.3% (SE 0.4%), recurrence-free survival was 99.2% (SE 0.4%). Survival of patients without nodal involvement reached 100%, whereas for patients with metastatic nodes it was 97.4% (SE 1.8%). The threshold for the number of the affected nodes significantly influencing survival equaled 1 (р=0,0187). Overall survival of patients with 0 to 1 positiv...
Problems in oncology
There are presented the immediate and long-term results of neoadjuvant endocrine therapy versus c... more There are presented the immediate and long-term results of neoadjuvant endocrine therapy versus chemotherapy in ER+ breast cancer and chemotherapy (carboplatin + taxane) at triple-negative tumor subtype. We marked a tendency of improving a 10-year disease-free survival at luminal A subtype in patients who received endocrine therapy compared with chemotherapy (72.8% vs. 53.9%; p=0.062). Only 5.9% of patients with ER+ /HER2+ co-expression, who received target therapy, reached complete regression (pCR). There was a greater frequency of pCR, among patients with triple-negative breast cancer who received neoadjuvant chemotherapy with paclitaxel + carboplatin.
Problems in oncology
Purpose: To analyze the results of treatment and the quality of medical care for breast cancer pa... more Purpose: To analyze the results of treatment and the quality of medical care for breast cancer patients with breast reconstruction using thoracodorsal flap (TDF). Material and methods: The study was conducted on the basis of the N.N. Petrov National Medical Research Center of Oncology at the Department of Breast Tumors for the period 2016-2017. When using the reconstruction of the breast with the help of TDF the feature was the complete intersection of the muscle in the anterior-axillary line before closing the defect of the breast tissue but with the preservation of the thoracodorsal vascular sheaf. Surgical treatment was provided to 67 patients with breast cancer including after neoadjuvant therapy. Results: One-time reconstruction was performed in 16 (23.8%) patients under the organ-preserving surgery, mastectomy in two (2.9%) patients and mastectomy with implant placement in 27 (40.2%) patients. Delayed reconstruction of the breast: TDF in combination with the implant - 20 (29.8...
Problems in oncology
Purpose: To create a unified system of accelerated clinical trials of new drugs and regimens for ... more Purpose: To create a unified system of accelerated clinical trials of new drugs and regimens for breast cancer (BC). Materials and methods: The study included 1214 patients with BC of different stages (cT1N1, cT2N1-2, cT2-3N0-2, cT2-3N0-1, cT4N0M0). According to trepan biopsy data and immunohistochemical examination (IHC) expression of ER, PR, HER2, and Ki67 was determined. The expression TUBBßIII, TOP2a, analyzes on the BRCA1/2 mutation was studied. The clinical response to neoadjuvant treatment was determined using the physical method, ultrasonography-elas-tography, mammography, contrast magnetic resonance imaging (MRI) and single-photon emission computer mammotography (SPECT-CT). Results: The correlation index of complete responses (cCR) and total pathomorphological responses (pCR) according to MRI was 0.80, according to ultrasound - 0.61, mammography - 0.60, palpation - 0.57. The low level of amplification of the TUBßIII mRNA gene with a high level of amplification of the TOP2-a...
Problems in oncology
Purpose: To assess the influence of systemic and radiation therapy on complications in oncoplasti... more Purpose: To assess the influence of systemic and radiation therapy on complications in oncoplastic surgery. Material and methods: The scientific work was carried out on the basis of the Department of Breast Tumors of the N.N. Petrov National Medical Research Center of Oncology. Between January 2016 and December 2017 710 patients with morphologically confirmed BC who had undergone oncoplastic and reconstructive-plastic surgery were included in the study. The average age of the patients was 41.6 years. Patients with early breast cancer (283 patients) and locally advanced breast cancer (427 patients) were included in the study groups. Neoadjuvant treatment was performed in 239 patients, adjuvant in 132 patients. Results: Postoperative complications were observed in 45 patients (6.3 %, N = 710) and were as follows: endoprosthesis protrusion (12 patients, 1.6 %), endoprosthesis rotation (2 patients, 0.28 %), marginal necrosis of the flap (3 patients, 0.42 %), defect of the endoprosthesis...
Problems in oncology
Materials and methods. The effect of melatonin (MLT) and metformin (MTF) on the efficacy of neoad... more Materials and methods. The effect of melatonin (MLT) and metformin (MTF) on the efficacy of neoadjuvant hormone therapy with toremifene was investigated in 54 patients with estrogen receptor-positive, locally advanced breast cancer (ER + BC). The average age of women was 67 years. The patients had no diabetes mellitus. The first group of patients (n = 19) received toremifene 120 mg per day, the second group (n = 16) - toremifene in combination with MLT 3 mg orally every night, the third group (n = 19) - toremifene in combination with MTF 850 mg twice daily. Randomization was performed - 1: 1: 1. The duration of therapy in all study groups was 4 months. After the end of treatment, all patients were undergone surgery. Further adjuvant treatment depended on the results of the postoperative pathomorphological conclusion. The primary endpoint was a decrease in the Ki-67% level (a surrogate marker for the effectiveness of hormone therapy), the secondary endpoints were the objective respon...
Problems in oncology
Neoadjuvant systemic treatment of patients with breast cancer (BC) may include neoadjuvant chemot... more Neoadjuvant systemic treatment of patients with breast cancer (BC) may include neoadjuvant chemotherapy (NHT), neoadjuvant hormone therapy (NGT), neoadjuvant targeted therapy. The type of systemic therapy is determined by the level of expression of estrogen/progesterone receptors, HER2, i.e. immunohistochemical characteristic of the disease. In this article, we evaluated the predictive value of the profile of plasma exosomal microRNA, assessing the immediate efficacy of NHT, which included taxanes. Obtained results revealed a correlation between the level of concentration of several miRNA molecules in circulating exosomes and the effect of NHT. Furthermore, the index calculated as the ratio of miR-34a and miR-451 concentrations, allowеd to predict the effect of taxanecontaining NHT. The results confirm the assumption on the predictive significance of exosomal miRNA. Further research is needed to confirm the validity of a new method of prediction of the NHT efficacy in breast cancer.
Journal of Clinical Oncology
e12097 Background: Innovative advances in neoadjuvant systemic and targeted breast cancer therapy... more e12097 Background: Innovative advances in neoadjuvant systemic and targeted breast cancer therapy implicate surgical treatment in specific patient groups can be avoided. The core biopsy of the tumor bed and some diagnostic approaches (breast ultrasound, mammography, SPECT/CT) allow for precise evaluation of the treatment efficacy. Methods: This research started in our department in 2018, we picked two groups of 15 patients each treated for locally advanced TNBC or grade cT1-4N1-3M0 HER2-positive breast cancer: HER2+/ER+ or HER2+/ER- breast cancer. The TNBC group received 6 cycles of NACT of paclitaxel combined with doxorubicin and carboplatin AUC5. The HER2+ group received 4 cycles of АС polychemotherapy followed by 4 cycles of monochemotherapy with the docetaxel and 3-weekly trastuzumab. The HER2+ group is receiving adjuvant trastuzumab for up to one year, where ER-positive patients are also given hormone therapy with tamoxifen or aromatase inhibitors. The response to neoadjuvant t...
Journal of Clinical Oncology