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1.
Arkh Patol ; 86(3): 5-11, 2024.
Article in Russian | MEDLINE | ID: mdl-38881000

ABSTRACT

BACKGROUND: Tumor infiltrating lymphocytes (TILs) are a promising inexpensive prognostic and predictive biomarker in breast cancer. High levels of TILs are associated with improved survival and higher probability to achieve pathological complete response in triple-negative breast cancer (TNBC). OBJECTIVE: To assess the level of TILs in TNBC samples and analyze the association between the level of TILs and the main pathological parameters, to identify their impact on long-term results. MATERIAL AND METHODS: The study included information on 140 patients with I-III stage TNBC and estrogen receptors <10%. Tumor tissue samples at baseline biopsies were evaluated the histological type, HER2 expression, estrogen expression levels, Ki-67 and TILs. The pathological response was evaluated according to the ypTNM, Miller-Payne, and RCB classifications. RESULTS: The average level of TILs in biopsy specimens before NACT was 29.3±23.1%. Low levels of TILs (<10%) were defined in 21% of cases, intermediate levels (≥10% to ≤40%) in 55% of cases, and high levels (>40%) in 24% of cases. Using the two-tiered system, low TILs (≤40%) were defined in 76% and high TILs (>40%) in 24% of cases. The level of TILs was correlated with histological grade (R=0.187; p=0.027) and estrogen receptor expression level (R=0.211; p=0.012). There were no significant differences depending on the level of TILs and other pathological parameters. Three-year event-free survival (EFS) in patients with high TILs levels was 95% versus 65% in the low TILs group (p=0.037). CONCLUSION: Stromal TILs are an important prognostic biomarker in TNBC. Using a cutoff of 40%, high TILs are significantly associated with longer EFS.


Subject(s)
Lymphocytes, Tumor-Infiltrating , Triple Negative Breast Neoplasms , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/pathology , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/metabolism , Female , Middle Aged , Adult , Aged , Prognosis , Receptors, Estrogen/metabolism , Biomarkers, Tumor/metabolism , Receptor, ErbB-2/metabolism , Disease-Free Survival
2.
Khirurgiia (Mosk) ; (7): 111-114, 2024.
Article in Russian | MEDLINE | ID: mdl-39008704

ABSTRACT

OBJECTIVE: To evaluate the possibility of using the method of sentinel lymph nodes (SLN) detection with indocyanine green (ICG) in patients with early breast cancer and its informativeness. MATERIAL AND METHODS: A «Determination of sentinel lymph nodes by fluorescence method intraoperatively with the use of indocyanine green¼ study, in which 168 patients are currently included, is being conducted in the clinic of the N.N. Petrov NMRC of Oncology from 2017 through the present. All patients who underwent biopsy of sentinel lymph nodes (BSLN) were primary with a T1-2N0M0 stage of process. RESULTS: The average number of axillary lymph nodes removed in BSLN was 3 (1-5). Accumulation of ICG was found in 147 (88%) patients, accumulation of labeled radiocolloid - in 137 (82%), in combination of ICG/radiocolloid - in 167 (99%) based on the results of imaging. CONCLUSION: The obtained results prove that the informativeness and relative simplicity of this method use allow its application in any hospital where breast cancer is surgically treated, as well as in the absence of radioisotopic equipment.


Subject(s)
Breast Neoplasms , Indocyanine Green , Sentinel Lymph Node Biopsy , Humans , Breast Neoplasms/surgery , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Female , Indocyanine Green/administration & dosage , Middle Aged , Sentinel Lymph Node Biopsy/methods , Sentinel Lymph Node/pathology , Sentinel Lymph Node/surgery , Neoplasm Staging , Lymphatic Metastasis , Aged , Axilla , Adult , Lymph Node Excision/methods
3.
Article in Russian | MEDLINE | ID: mdl-37141520

ABSTRACT

The concept of the personalized rehabilitation is based on the principle of applying physical and rehabilitative medicine techniques depending on the factors that mostly influence on rehabilitation efficacy in a particular patient - determinant of effectiveness. Current achievements in the diagnosis and treatment of breast cancer (BC) significantly increased overall patients' life expectancy, updating rehabilitative treatment stage, which is often unmet. OBJECTIVE: To perform the comprehensive analysis of the efficacy of personalized rehabilitation programs in patients with BC. MATERIAL AND METHODS: The combined comparative multi-centre randomised trial of rehabilitation program efficacy in patients with breast cancer was done. The study included 219 patients aged from 30 to 45 years (median 39.4 year), who were divided into 2 groups. The rehabilitation by programs, that included current personalized rehabilitative techniques (RT) with proved efficiency, based on scientometrical analysis of evidential research was performed in the first group patients. In the second group aftercare was done according to the standard programs. The comprehensive evaluation of treatment efficacy was conducted in several stages: 1) performance analysis of rehabilitative programs; 2) verification of the effectiveness' determinant of rehabilitation; 3) factor analysis to assess the mechanisms of therapeutic effects in experimental groups; 4) comparative analysis of alternative strategies for selecting rehabilitation programs. RESULTS: The use of rehabilitative programs, based on recommended RT, changes the rehabilitation structure, significantly increasing its efficacy by 17%. Furthermore, the percentage of high-efficiency usage of this type programs increases by 17% compared with standard programs. The main determinants, affecting the efficacy of rehabilitation programs, based on selected RT, are anamnestic data, parameters of exercise tolerance and physical activity and ultrasound parameters of upper limb blood flow. The therapeutic effects of personalized rehabilitation programs are realized by correction of clinical rates, increasing exercise tolerance and physical activity, as well as psychophysiological parameters. CONCLUSION: The use of the evaluation system of anamnestic, clinical, functional and psychophysiological features of patient (the effectiveness' determinant) in realization of personalized rehabilitation programs for women with BC, allows to predict and manage the efficacy of RT applying.


Subject(s)
Breast Neoplasms , Humans , Female , Adult , Middle Aged , Exercise , Treatment Outcome , Quality of Life
4.
Ann Oncol ; 33(5): 534-543, 2022 05.
Article in English | MEDLINE | ID: mdl-35182721

ABSTRACT

BACKGROUND: High-risk triple-negative breast cancers (TNBCs) are characterized by poor prognosis, rapid progression to metastatic stage and onset of resistance to chemotherapy, thus representing an area in need of new therapeutic approaches. Programmed death-ligand 1 (PD-L1) expression is an adaptive mechanism of tumour resistance to tumour-infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, available data support the concept that blockade of PD-L1/programmed cell death protein 1 checkpoint may improve efficacy of classical chemotherapy. PATIENTS AND METHODS: Two hundred and eighty patients with TNBC were enrolled in this multicentre study (NCT002620280) and randomized to neoadjuvant carboplatin area under the curve 2 and nab-paclitaxel 125 mg/m2 intravenously (i.v.) on days 1 and 8, without (n = 142) or with (n = 138) atezolizumab 1200 mg i.v. on day 1. Both regimens were given q3 weeks for eight cycles before surgery followed by four cycles of an adjuvant anthracycline regimen. The primary aim of the study was to compare event-free survival (EFS), and an important secondary aim was the rate of pathological complete response (pCR defined as the absence of invasive cells in breast and lymph nodes). The primary population for all efficacy endpoints is the intention-to-treat (ITT) population. RESULTS: The ITT analysis revealed that pCR rate after treatment with atezolizumab (48.6%) did not reach statistical significance compared to no atezolizumab [44.4%: odds ratio (OR) 1.18; 95% confidence interval 0.74-1.89; P = 0.48]. Treatment-related adverse events were similar with either regimen except for a significantly higher overall incidence of serious adverse events and liver transaminase abnormalities with atezolizumab. CONCLUSIONS: The addition of atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pCR in women with TNBC. In multivariate analysis, the presence of PD-L1 expression was the most significant factor influencing the rate of pCR (OR 2.08). Continuing follow-up for the EFS is ongoing, and molecular studies are under way.


Subject(s)
Neoadjuvant Therapy , Triple Negative Breast Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/genetics , B7-H1 Antigen/therapeutic use , Carboplatin , Female , Humans , Neoadjuvant Therapy/adverse effects , Paclitaxel , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics
5.
Ann Oncol ; 32(8): 994-1004, 2021 08.
Article in English | MEDLINE | ID: mdl-34219000

ABSTRACT

BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. CONCLUSION: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.


Subject(s)
Triple Negative Breast Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Paclitaxel/therapeutic use , Progression-Free Survival , Triple Negative Breast Neoplasms/drug therapy
6.
Adv Gerontol ; 33(1): 65-73, 2020.
Article in Russian | MEDLINE | ID: mdl-32362086

ABSTRACT

Modern approaches to the organization of diagnosis and treatment of elderly and senile patients with malignant tumors allow to maintain the necessary level of health, improve the quality of life and increase life expectancy. Assessment of geriatric status in Oncology allows: to predict complications during the complex treatment, including drug treatment; to modify treatment to reduce the risk factors of adverse outcomes; to select patients for specialized treatment using standard schemes. So, timely assessment of geriatric syndromes and their correction can expand the indications for specialized treatment of elderly and senile patients.


Subject(s)
Geriatric Assessment , Medical Oncology , Neoplasms/therapy , Aged , Humans , Quality of Life
7.
Ann Oncol ; 28(8): 1700-1712, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28838210

ABSTRACT

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.


Subject(s)
Breast Neoplasms/therapy , Adjuvants, Immunologic/therapeutic use , Antineoplastic Agents/therapeutic use , Austria , Breast Neoplasms/pathology , Combined Modality Therapy , Early Diagnosis , Female , Humans , Neoadjuvant Therapy , Radiotherapy , Surgical Procedures, Operative
8.
Ann Oncol ; 27(6): 1041-1047, 2016 06.
Article in English | MEDLINE | ID: mdl-26940688

ABSTRACT

BACKGROUND: The optimal regimen for adjuvant breast cancer chemotherapy is undefined. We compared sequential to concurrent combination of doxorubicin and cyclophosphamide with docetaxel chemotherapy in women with node-positive non-metastatic breast cancer. We report the final, 10-year analysis of disease-free survival (DFS), overall survival (OS), and long-term safety. PATIENTS AND METHODS: A total of 3298 women with HER2 nonamplified breast cancer were randomized to doxorubicin and cyclophosphamide every 3 weeks for four cycles followed by docetaxel (AC → T) every 3 weeks for four cycles or docetaxel, doxorubicin, and cyclophosphamide (TAC) every 3 weeks for six cycles. The patients received standard radiotherapy and endocrine therapy and were followed up for 10 years with annual clinical evaluation and mammography. RESULTS: The 10-year DFS rates were 66.5% in the AC → T arm and 66.3% in the TAC arm (P = 0.749). OS was 79.9% in the AC → T arm and 78.9% in the TAC arm (P = 0.506). TAC was associated with higher rates of febrile neutropenia, although G-CSF primary prophylaxis greatly reduced this risk. AC → T was associated with a higher rate of myalgia, hand-foot syndrome, fluid retention, and sensory neuropathy. CONCLUSION: This 10-year analysis of the BCIRG-005 trial confirmed that the efficacy of TAC was not superior to AC → T in women with node-positive early breast cancer. The toxicity profiles differ between arms and were consistent with previous reports. The TAC regimen with G-CSF support provides shorter adjuvant treatment duration with less toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00312208.


Subject(s)
Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Drug-Related Side Effects and Adverse Reactions/physiopathology , Taxoids/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Chemotherapy, Adjuvant/adverse effects , Cyclophosphamide/adverse effects , Disease-Free Survival , Docetaxel , Doxorubicin/adverse effects , Drug-Related Side Effects and Adverse Reactions/classification , Female , Granulocyte Colony-Stimulating Factor/genetics , Humans , Lymphatic Metastasis , Middle Aged , Receptor, ErbB-2/genetics , Taxoids/adverse effects
9.
Vopr Onkol ; 62(2): 208-13, 2016.
Article in Russian | MEDLINE | ID: mdl-30452195

ABSTRACT

This manuscript includes an update on the latest developments in the biology of breast cancer as well as the most recent advances in prevention and multidisciplinary management of this disease: surgery after neoadjuvant chemotherapy and anti-HER2 therapy of HER2 positive breast cancer, neoadjuvant and adjuvant endocrine treatment of ER+ (Luminal A) breast cancer. Our task (as in the St. Gallen and ESMO consensus recommendations) is to assist physicians to improve both therapy impact in patients and their results.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Receptors, Estrogen , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Female , Humans , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism
10.
Vopr Onkol ; 62(3): 552-9, 2016.
Article in Russian | MEDLINE | ID: mdl-30463117

ABSTRACT

Phylloides tumors (PT) are a rare and the least studied pathology of the breast. Data on physical examination and imaging methods of diagnostics in most cases do not allow accurate diagnosing at the preoperative stage as there are no clear characteristics that allow differentiating benign from malignant variants of PT or other benign breast diseases. Surgery is the main treatment of PT. Chemotherapy and radiation therapy of malignant variants of PT in the adjuvant setting do not significantly improve survival rates. In recurrent or metastatic forms of PT these methods can be effective in some cases. Currently there are identified molecular signaling pathways that play an important role in the pathogenesis of PT. Thus there are prerequisites for the study of the effectiveness of targeted therapies for this pathology.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Phyllodes Tumor/diagnosis , Phyllodes Tumor/therapy , Breast Neoplasms/pathology , Female , Humans , Neoplasm Recurrence, Local/pathology , Phyllodes Tumor/pathology
11.
Vopr Onkol ; 62(1): 31-4, 2016.
Article in Russian | MEDLINE | ID: mdl-30444329

ABSTRACT

Whole-genome expression analysis methods significantly clarified contemporary breast cancer classification. Besides today clinical practice lacks the use of expression methods due to complexity of conduction, analysis and lack of clinical application. Further studies of breast cancer expression characteristics and clinical trials with stratification based of phonotypical features may improve the results of existing anticancer agents. Creation of limited clinically applicable test system, which incorporates all the specific breast cancer subtypes is currently needed.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Breast Neoplasms/classification , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans
12.
Khirurgiia (Mosk) ; (5): 26-30, 2016.
Article in Russian | MEDLINE | ID: mdl-27271716

ABSTRACT

AIM: To study the results of intraperitoneal chemoperfusion combined with cytoreductive procedure in patients with peritoneal pseudomyxoma. MATERIAL AND METHODS: For the period 2006--2015 seven patients with peritoneal pseudomyxoma underwent aggressive treatment using hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure at the Department of General Oncology of N.N. Petrov Research Institute of Oncology. RESULTS: Two patients had postoperative complications. One of them died after 12 days postoperatively. Features of postoperative complications were predominantly determined by volume of cytoreduction. Advanced tumoral process caused death in 2 patients additionally. Other patients are still alive during 4--28 months after surgery. CONCLUSION: Hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure is advisable for peritoneal pseudomyxoma to improve survival. Optimal cytoreduction should be developed in researches with large number of patients to decrease incidence of complications.


Subject(s)
Cytoreduction Surgical Procedures/methods , Peritoneal Neoplasms , Pseudomyxoma Peritonei , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Combined Modality Therapy , Female , Humans , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Male , Middle Aged , Neoplasm Staging , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/mortality , Pseudomyxoma Peritonei/pathology , Pseudomyxoma Peritonei/surgery , Retrospective Studies , Russia , Survival Analysis , Treatment Outcome
13.
Ann Oncol ; 26(2): 320-5, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25403587

ABSTRACT

BACKGROUND: HannaH (NCT00950300) was a phase III, randomized, international, open-label study that compared pharmacokinetics (PK), efficacy, and safety of two different trastuzumab formulations [subcutaneous (s.c.) and intravenous (i.v.)] in HER2-positive, operable, locally advanced, or inflammatory breast cancer in the neoadjuvant/adjuvant setting. The co-primary end points, to show noninferiority of s.c. versus i.v. trastuzumab in terms of serum concentration (Ctrough) and pathologic complete response (pCR) were met; safety profiles were comparable at 12 months' median follow-up. Secondary end points included safety and tolerability, PK profile, immunogenicity, and event-free survival (EFS). We now report updated safety and efficacy data after a median follow-up of 20 months. PATIENTS AND METHODS: Patients (N = 596) were treated with eight cycles of neoadjuvant chemotherapy, administered concurrently with 3-weekly s.c. trastuzumab (fixed dose of 600 mg) or the standard weight-based i.v. method. Following surgery, patients continued trastuzumab treatment to complete 1 year of therapy. Updated analyses of PK, efficacy, safety, and immunogenicity data were carried out. RESULTS: s.c. trastuzumab was generally well tolerated and the incidence of adverse events (AEs), including grade 3 or 4 AEs, between treatment groups was comparable. A slightly higher incidence of serious AEs (SAEs), mainly due to infections, was reported with s.c. treatment {64 [21.5%; 95% confidence interval (CI) 17.0%-26.7%] versus 42 (14.1%; 95% CI 10.4%-18.6%) in the i.v. group}; however, the differences were small and often based on rare events, with no observable pattern across reported events. An early analysis of EFS showed rates of 95% in both groups 1 year postrandomization. Exploratory analyses did not reveal an association between toxicity and body weight or exposure. CONCLUSIONS: Overall, the safety profile of s.c. trastuzumab was consistent with the previously published data from HannaH and the known safety profile of i.v. trastuzumab. EFS rates were comparable between the i.v. and s.c. groups. CLINICAL TRIAL NUMBER: NCT00950300.


Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Trastuzumab/administration & dosage , Adult , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Breast Neoplasms/genetics , Female , Humans , Infusions, Intravenous , Injections, Subcutaneous , Middle Aged , Receptor, ErbB-2/biosynthesis , Receptor, ErbB-2/genetics , Trastuzumab/adverse effects
14.
Ann Oncol ; 26(9): 1948-1953, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26122726

ABSTRACT

BACKGROUND: Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen(®), in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC). PATIENTS AND METHODS: A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomized 1:1:1:1 into four arms. Two arms received only one product (nonalternating), biosimilar or reference, and two arms (alternating) received alternating treatments during each cycle (biosimilar then reference or vice versa). The primary end point was duration of severe neutropenia (DSN) during cycle 1. RESULTS: The baseline characteristics were balanced between the four treatment arms. Noninferiority of biosimilar versus the reference was demonstrated: DSN (days) in cycle 1 was 1.17 ± 1.11 (biosimilar, N = 101) and 1.20 ± 1.02 (reference, N = 103), 97.5% confidence interval lower boundary for the difference was -0.26 days (above the predefined limit of -1 day). No clinically meaningful differences were observed regarding any other efficacy parameter: incidence of febrile neutropenia (FN); hospitalization due to FN; incidence of infections; depth and time of absolute neutrophil count (ANC) nadir and time to ANC recovery during cycle 1 and across all cycles. The pattern and frequency of adverse events were similar across all treatments. CONCLUSION: This study demonstrates that biosimilar and the reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially benefiting public health by increasing access to filgrastim treatment. STUDY NUMBER: NCT01519700.


Subject(s)
Biosimilar Pharmaceuticals/therapeutic use , Filgrastim/analogs & derivatives , Filgrastim/therapeutic use , Neutropenia/prevention & control , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Double-Blind Method , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Middle Aged , Neoadjuvant Therapy , Neutropenia/drug therapy , Young Adult
15.
Ann Oncol ; 26(12): 2429-36, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26387142

ABSTRACT

BACKGROUND: To investigate in the NeoSphere trial the contribution of the immune system to pathologic complete response in the breast (pCRB) after neoadjuvant docetaxel with trastuzumab (TH), pertuzumab (TP), or both (THP), or monoclonal antibodies alone (HP). PATIENTS AND METHODS: Immune gene mRNA expression (n = 350, 83.8%), lymphocyte infiltration (TIL, n = 243, 58.3%), and PDL1 by immunohistochemistry (n = 305, 73.1%) were correlated with pCRB. We studied five selected genes (IFNG, PD1, PDL1, PDL2, CTLA4) and six immune metagenes corresponding to plasma cells (IGG), T cells (CD8A), antigen-presenting cells (MHC2), and to MHC1 genes (MHC1), STAT1 co-expressed genes (STAT1), and interferon-inducible genes (IF-I). Gene expression data from the NOAH trial were used for validation. RESULTS: TIL as continuous variable and PDL1 protein expression were not significantly associated with pCRB. Expression of immune genes/metagenes had different association with pCRB after THP than after other therapies. With THP, higher expression of PD1 and STAT1, or any among PDL1, CTLA4, MHC1, and IF-I were linked with lower pCRB. In the combined TH/TP/HP treatment group, in multivariate analysis, higher expression of PD1, MHC2, and STAT1 were linked with pCRB, and higher PDL1, MHC1, or IF-I to lower pCRB. In the NOAH, a similar association of higher STAT1 with higher pCRB, and higher MHC1 and IF-I with lower pCRB was found for trastuzumab/chemotherapy but not for chemotherapy treatment only. CONCLUSIONS: The immune system modulates response to therapies containing trastuzumab and pertuzumab. Greatest benefit from THP is observed for low expression of some immune markers (i.e. MHC1, CTLA4). The involvement of PDL1 in resistance supports testing combinations of HER2-directed antibodies and immune-checkpoint inhibitors.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Neoadjuvant Therapy/methods , Receptor, ErbB-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Female , Humans , Immunity, Cellular/drug effects , Immunity, Cellular/immunology , Middle Aged , Receptor, ErbB-2/antagonists & inhibitors , Trastuzumab/administration & dosage , Treatment Outcome , Young Adult
16.
Vopr Onkol ; 61(2): 162-8, 2015.
Article in Russian | MEDLINE | ID: mdl-26087591

ABSTRACT

Neoadjuvant systemic treatment (NST) remains important approach for the assessment of biological and clinical effects of new methods of treatments in clinical trials. Recent trials failed to support that pathological complete response (pCR) after NST is an early surrogate end point of treatment efficacy. This may limit the use of NST in operable breast cancer in clinical routine. Pathological complete response (pCR) is a relatively "late" end point, and therefore new early predictors of treatment efficacy are needed in order to timely change for futile therapy. After NST an accurate management of post-treatment residual disease is mandatory. Sentinel lymph-node (SLN) surgery is an acceptable option to spare axillary dissection in case of SLN negative disease. No data support the modulation of the extent of loco-regional radiation therapy on the basis of the response attained after NST.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Lymph Node Excision/methods , Lymph Nodes/surgery , Neoadjuvant Therapy/methods , Axilla , Breast Neoplasms/pathology , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Mastectomy, Segmental , Sentinel Lymph Node Biopsy , Treatment Outcome
17.
Vopr Onkol ; 61(2): 169-73, 2015.
Article in Russian | MEDLINE | ID: mdl-26087592

ABSTRACT

Cancer stem cells (CSCs) possess self-renewal and heterogeneous cancer cell lines formation. Numerous data confirm the existence of a model in which CSCs have an important role in cancer initiation, progression and clinical outcome. Analysis of CSCs role in metastasis, in contrast, remains mainly conceptual and hypothetical. Recent data are summarized in this review which support the CSCs theory as a source of breast cancer metastatic lesions with noting the key role of the microenvironment.


Subject(s)
Breast Neoplasms/pathology , Neoplastic Stem Cells , Cell Line, Tumor , Disease Progression , Female , Humans , Neoplastic Stem Cells/pathology , Stromal Cells/pathology
18.
Vopr Onkol ; 61(3): 381-6, 2015.
Article in Russian | MEDLINE | ID: mdl-26242149

ABSTRACT

In the randomized phase 2 study there was evaluated the efficacy of neoadjuvant endocrine treatment (anastrozole, exemestane) in comparison with chemotherapy (doxorubicin plus paclitaxel). Preoperative endocrine therapy was well tolerated. There was a trend towards higher overall rates of objective response and breast conserving surgery (BCS) among patients with tumors expressing high levels of ER (luminal A) in endocrine therapy group compared with chemotherapy group (43% vs 24%; p = 0,054). In HER2-positive breast cancer patients the addition of trastuzumab to neoadjuvant chemotherapy improved the overall and pathological complete response. Trastuzumab made possible an increasing number of breast conserving surgery (23% vs 13%; p = 0,022). No patient treated with trastuzumab and with chemotherapy had a local recurrence after BCS.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Mastectomy, Segmental , Neoadjuvant Therapy/methods , Adult , Aged , Anastrozole , Androstadienes/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Breast Neoplasms/chemistry , Doxorubicin/administration & dosage , Everolimus , Female , Humans , Mastectomy, Segmental/statistics & numerical data , Middle Aged , Nitriles/administration & dosage , Paclitaxel/administration & dosage , Postmenopause , Receptor, ErbB-2/analysis , Receptors, Estrogen/analysis , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , TOR Serine-Threonine Kinases/antagonists & inhibitors , Trastuzumab , Treatment Outcome , Triazoles/administration & dosage
19.
Vopr Onkol ; 61(3): 460-6, 2015.
Article in Russian | MEDLINE | ID: mdl-26242162

ABSTRACT

The work is devoted to the methods of application of own adipose tissue as a plastic material and presents the summary of the currently known data on the use of transplantation of adipose tissue in order to correct various defects of the body in plastic and reconstructive surgery. There are analyzed theoretical basis for the use of adipose tissue, provided the methods of administration depending on the area of the use, the severity of the defect and its localization. Data on new methods of the use of adipose tissue and own observations are presented. As an example of the effective use there is provided a detailed analysis of the use of adipose tissue transplantation in breast cancer patients who have different area defects after reconstructive surgery.


Subject(s)
Adipose Tissue/transplantation , Breast Neoplasms/surgery , Mammaplasty/methods , Adult , Female , Humans , Microsurgery , Plastic Surgery Procedures/methods , Transplantation, Autologous , Treatment Outcome
20.
Vopr Onkol ; 61(4): 624-8, 2015.
Article in Russian | MEDLINE | ID: mdl-26571834

ABSTRACT

This study was performed in order to determine individual variability of axillary sentinel lymph nodes (SLN) localization in patient with breast cancer (BC). Individual topography of axillary SLN was determined in 182 patients with early BC. All women were candidates for conservative surgical treatment with postoperative radiotherapy. SPECT-CT visualization of SLN started 120-240 min after intratumoral injection of 74-150MBq of 99mTc-radiocolloids. Distribution of axillary SLN was allocated to following subregions: central (C), pectoral (P), apical (AP), lateral (L), subscapular (SSc). SLN visualization by SPECT-CT was successful in 153 cases (84%). AP nodes were detected in 7 patients (5%). SLN were localized on thoracic wall in 34 cases (22%), in the intrapectoral region--in 3 (2%) women. According to axillary levels they were detected on level I--in 149 (97%), level II--15 (10%), level III-- (7.5%) cases.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Adult , Aged , Axilla , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Contrast Media/administration & dosage , Female , Humans , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis/diagnosis , Middle Aged , Technetium/administration & dosage , Thoracic Cavity
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