Combining Endocrine Therapy with Trastuzumab Emtansine Improves Progression-Free Survival and Overall Survival in HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer.

Background and Objectives: Patients with human epidermal growth factor receptor 2 (HER2) -positive, hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) usually undergo trastuzumab emtansine (T-DM1) therapy in subsequent lines. Combining endocrine therapy (ET) with T-DM1 can improve treatment outcomes in this subtype. Therefore, this study aimed to investigate the benefits of using T-DM1 with ET in HER2-positive and HR-positive MBC. This study was the first to investigate the benefits of combining ET with T-DM1. Material and Methods: This study analyzed the medical records of patients with HER2-positive and HR-positive MBC who were treated with T-DM1 from June 2010 to December 2021. The patients were divided into groups based on whether they received concomitant ET with T-DM1. The primary endpoint was to determine the progression-free survival (PFS), while the secondary endpoints were overall survival (OS), objective response rate, and safety of the treatment. Results: Our analysis examined 88 patients, of whom 32 (36.4%) were treated with T-DM1 in combination with ET. The combination therapy showed a significant improvement in median PFS (15.4 vs. 6.4 months; p = 0.00004) and median OS (35.0 vs. 23.1 months; p = 0.026) compared to T-DM1 alone. The ORR was also higher in the combination group (65.6% vs. 29.3%; p = 0.026). Patients treated with pertuzumab priorly had reduced median PFS on T-DM1 compared to those who were not treated with pertuzumab (11.7 vs. 5.4 months, respectively; p < 0.01). T-DM1 demonstrated better median PFS in HER2 3+ patients compared to HER2 2+ patients, with an amplification ratio of >2.0 (10.8 vs 5.8 months, respectively; p = 0.049). The safety profiles were consistent with previous T-DM1 studies. Conclusions: The combination of T-DM1 with ET can significantly improve PFS and OS in patients with HER2-positive and HR-positive MBC. Our study suggests that prior pertuzumab treatment plus trastuzumab treatment might decrease T-DM1 efficacy.

The effect of parity, breastfeeding history, and duration on clinical and pathological characteristics of breast cancer patients.

Background/aim: The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer. Materials and methods: A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child. Results: The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed. Conclusion: Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.

Pretreatment platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as a predictor of pathological complete response to neoadjuvant chemotherapy in patients with breast cancer: single center experience from Turkey.

The aim of this study was to investigate the predictive value of PLR and NLR as an indicator of pathological complete response (pCR) in patients with breast cancer after NACT. One hundred thirty-nine patients with early or LABC and candidates to NACT were retrospectively analyzed. The prognostic significance of PLR and NLR was analyzed. In addition, predictive indicators of pCR to NACT were also evaluated. pCR was obtained in 48.9% of patients. Significant difference was detected between pCR and PLR, tumor grade, clinical lymph node status and molecular subgroup. The higher rate of pCR was significantly achieved for patients with PLR low ( < 181.7) compared with those with PLR high (>181.7) (68.6% vs. 33.4%; P < 0.001). PLR, tumor grade and pCR to NACT for disease-free survival (DFS), and PLR, NLR, tumor grade and pCR to NACT for overall survival were detected to be prognostic factors by univariate analysis. On the other hand, a logistic regression analysis indicated that PLR and NLR were found to be an independent factors for predicting pCR to NACT ( P < 0.001; OR, 0.07; 95% CI, 0.02-0.25 and P = 0.016; OR, 4.66; 95% CI, 1.33-16.2, respectively), as were molecular subtypes ( P = 0.001; OR, 0.23; 95% CI, 0.09-0.56). Our results showed that PLR low and NLR low before NACT are readily feasible and simple and also inexpensive biomarkers predicting pCR to NACT for patients with LABC.

Rechallenge of Trastuzumab-based Therapy in HER2-Positive Breast Cancer Patients who Progressed Under TDM-1.

Data on rechallenges of HER2 targetted agents in breast cancer patients is limited. The goal of the study was to evaluate the effectiveness of trastuzumab-based therapy in patients who progressed under trastuzumab emtansine (TDM-1). The study was designed as a retrospective observational study. Survival plots were performed with the Kaplan-Meier method. Fifteen patients were involved in the study. The average age was 45 (range, 30-66). De novo metastatic patient number was six (40%), and the average number of metastatic sites was 2 (range, 1-4) at diagnosis. Fourteen patients (92.3%) had undergone breast surgery (lumpectomy or mastectomy). All patients previously had been treated with trastuzumab-based chemotherapy and TDM-1. Also, nine (60%) patients had received endocrine therapy, and nine (60%) patients had palliative radiotherapy. After progression under TDM-1, patients received trastuzumab with chemotherapy (73.3%) or alone (26.7%). The overall response ratio was 66.7%. Median progression-free survival was 9.4 months (95% CI, 3.4-15.3). The median OS duration was 24.2 (95% CI, 13.5-34.9) months. Toxicity in all grades was observed in ten (66.7%) patients, and grade 3-4 toxicity (anemia and neutropenia) in two patients (13.3%). This study showed that rechallenge trastuzumab-based therapy was effective and good-tolerated in heavily pretreated patients who had progressed under TDM-1.

Efficacy of Lapatinib Plus Capecitabine After TDM-1 in HER2-Positive Metastatic Breast Cancer Patients.

Different targeted therapy options exist for treating HER2-positive metastatic breast cancer patients. This study evaluated the efficacy and tolerability of the lapatinib plus capecitabine combination after TDM-1 in HER2-positive metastatic breast cancer patients. We retrospectively evaluated the HER2-positive metastatic breast cancer patients' data. The patients who progressed after trastuzumab-based chemotherapy and TDM-1 were included in the study. We used the Kaplan-Meier for survival analysis. Eighteen patients were involved in the study. The average age was 48 (range 31-65). De novo metastatic patient's number was 5 (27.8%). The most common metastatic sites were liver (50%), lung (44.4%), and brain (44.4%), respectively. All patients were previously treated with trastuzumab + chemotherapy and TDM-1. Also, seven (38.9%) patients received hormonotherapy and twelve (66.7%) patients received palliative radiotherapy. The complete response ratio was 5.6%, partial response 11.8%, and stable response 29.4%. Median progression-free survival was found as 5.5 (95% CI, 3.2-7.7) months. The hematological and non-hematological toxicity ratio was 41.2% and 52.9%, respectively. Grade 3-4 toxicity (diarrhea, anemia, and mucositis) was observed in four (22.2%) patients. The median OS duration was 8.2 months (95% CI, 4.3-12.0). Treatment options are limited in heavily pretreated HER2-positive breast cancer patients. Despite a small number of patients, this study showed that the lapatinib plus capecitabine combination was effective and well-tolerated in heavily pretreated HER2-positive breast cancer patients after TDM-1.

Therapeutic efficacy of high-dose chemotherapy with autologous stem-cell transplantation in 44 relapsed or refractory germ-cell tumor patients: A retrospective cohort study.

Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory germ-cell tumors. Therefore, selecting the best patient group for this treatment is critical. This study aimed to determine the factors that affect survival in our relapsed/refractory GCT cohort who received HDCT and autologous stem-cell transplantation. Between September 2010 and 2020, we included in the study 44 relapsed/refractory male patients with GCT treated with HDCT plus autologous stem-cell transplantation. The patients' demographic features, clinical characteristics, and treatment outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with survival. The median age of all cohorts was 28 years. Thirty-six patients had nonseminomatous tumors, and 8 patients had seminomatous tumors. The most common primary tumor sites were the gonads (75%), followed by the mediastinum (15.9%) and the retroperitoneum (9.1%). After HDCT, 11 patients had a complete response, 12 patients had a partial response, and 17 patients had a progressive disease, respectively. About 23 patients (52.3%) experienced at least 1 treatment-related grade 3 to 4 nonhematological toxicity. About 4 patients (10%) died due to HDCT-related toxicity. The total group's median progression-free survival (PFS) was 7 months, and the median overall survival (OS) was 14.9 months. Primary tumor site (hazard ratio [HR]: 1.84; P = .028), type of HDCT regimen (HR: 0.35; P = .010), and best response to HDCT (HR: 11.0; P < .0001) were independent prognostic risk factors for PFS. The only independent prognostic risk factor associated with OS was the best response to HDCT (HR: 6.62; P = .001). The results of the study promise the best response to HDCT as a primary measure for predicting survival in relapsed/refractory GCT. In contrast, primary mediastinal GCT is not a good candidate for HDCT. Furthermore, a carboplatin-etoposide regimen in combination with cyclophosphamide and paclitaxel may improve PFS.

Prognostic implications of response to neoadjuvant chemotherapy in breast cancer subtypes.

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

Comparison of the efficacy of sunitinib and pazopanib in patients with advanced non-clear renal cell carcinoma.

Non-clear cell renal cell carcinoma (non-ccRCC) is a highly heterogeneous disease group, accounting for approximately 25% of all RCC cases. Due to its rarity and especially heterogeneity, phase III trial data is limited and treatment options generally follow those of clear cell RCC. In the literature, there exists a number of studies with sunitinib, cabozantinib, and everolimus, but data on the efficacy of pazopanib are limited. Our aim in this study was to compare the efficacy of pazopanib and sunitinib, in a multicenter retrospective cohort of non-ccRCC patients. Our study included patients diagnosed with non-ccRCC who received pazopanib or sunitinib treatment as first-line therapy from 22 tertiary hospitals. We compared the progression-free survival (PFS), overall survival (OS), and response rates of pazopanib and sunitinib treatments. Additionally, we investigated prognostic factors in non-ccRCC. PFS and response rates of sunitinib and pazopanib were found to be similar, while a numerical difference was observed in OS. Being 65 years and older, being in the intermediate or poor risk group according to the International Metastatic Renal Cell Carcinoma Database Consortium, having liver metastases, presence of a sarcomatoid component, and having de novo metastatic disease were found to be significantly associated with shorter PFS. Pazopanib treatment appears to have similar efficacy in the treatment of non-ccRCC compared to sunitinib. Though randomized controlled trials are lacking and will probably be never be available, we suggest that pazopanib could be a preferred agent like sunitinib and cabozantinib.

Pazopanib and sunitinib treatments show similar progression free survival, overall survival and objective response rate.IMDC risk group, liver metastasis, sarcomatoid component and de novo metastatic disease were determined as prognostic factors.

Predictors of response in EGFR-mutant metastatic non-small cell lung cancer patients treated with tyrosine kinase inhibitors.

BACKGROUND: The goal of the study was to evaluate the efficacy of tyrosine kinase inhibitors in patients with epidermal growth factor receptor (EGFR)-mutant metastatic non-small cell cancer and to determine the factors that predict objective response. MATERIALS AND METHODS: In the study, data from metastatic non-small cell lung cancer patients with EGFR mutations treated with tyrosine kinase inhibitors were retrospectively reviewed. Factors predicting objective response were evaluated with logistic regression analysis. RESULTS: The study evaluated the data of 105 patients. The most common EGFR mutations detected in patients were exon 19 (56.2%) and exon 21 (23.8%). The median progression-free survival (PFS) associated with EGFR tyrosine kinase inhibitors was 20.1 (95% confidence interval [CI], 13.4-26.7) months. The median overall survival (OS) in the post-metastasis period was found to be 30.8 (95% CI, 20.2-41.4) months. Five- and seven-year OS was determined as 28.7% and 22.9%, respectively. Factors predicting the objective response were analyzed. Presence of drug-related toxicity (P = 0.02), histopathologic type (P = 0.01), metastasis burden (P = 0.03), and EGFR mutation type (P = 0.04) were found to be statistically significant in multivariate analysis. CONCLUSIONS: In our study, we found that EGFR tyrosine kinase inhibitors are effective and safe. Better response to EGFR inhibitors was observed in the presence of drug-induced toxicity, adenocarcinoma histology, low metastasis burden, and exon 19 mutation.

Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study.

Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.

Eating patterns of Turkish adolescents: a cross-sectional survey.

BACKGROUND: Adolescence is a crucial period for development of dietary behaviors that continue into adulthood and influence the risk of chronic diseases later in life. The aim of this study was to determine the eating patterns of adolescents' and their compliance with the Food Guide Pyramid. METHODS: 625 students, aged between 11-15 years, from an elementary school in Istanbul, Turkey were enrolled in this cross-sectional survey. A questionnaire of eating patterns (QEP) was administered to all participants. QEP is consisted of questions assessing the knowledge and behaviors on healthy eating, factors affecting food choice, physical activity status and demographical variables. Height and weight of all participants were measured. Physical activity status was determined by questioning about participation in regular sport activities, how much time spent watching TV, playing computer games or doing homework. RESULTS: The mean age of the participants was 12.15 ± 1.15 and 50.5% were female. According to body mass index (BMI) percentiles, 8.3% (52) were obese and 10.2% were overweight. 51% had breakfast every day and only 1.9% met all the recommendations of the Food Guide Pyramid. Among the participants, 31% have fast food at least once every day and 60.8% skip meals. When participants were asked to rate the factors effecting their food choice according to a 10 point Likert scale, the highest mean scores (high impact on food choice) were for the factors; family, health, body perception, teachers and friends; 7.5 ± 3.1, 7.4 ± 3.1, 6.1 ± 3.2, 4.8 ± 3.3 and 4.2 ± 3.0 respectively. Total mean time spent on all passive activities (TV, computer, reading homework etc) per day was 9.8 ± 4.7 hours. CONCLUSIONS: In this study we have demonstrated that, adolescents do not have healthy eating patterns. Educational interventions should be planned to decrease the health risks attributable to their eating behaviors.