Is the percentage of hormone receptor positivity in HR+ HER2-metastatic breast cancer patients receiving CDK 4/6 inhibitor with endocrine therapy predictive and prognostic?

PurposeThere is no clear information in the literature about the relationship between the efficacy of CDK 4/6i combined with ET and HR positivity. However, we know that the longest overall survival was in the ER-strong positive/PR intermediate or strong positive groups. Therefore, we aimed to investigate CDK4/6i treatments that create positivity in HR.MethodsPatients with the diagnosis of HR+/HER2- MBC who were treated with CDK 4/6i and HR >10% were retrospectively evaluated. To analyze the role of HR positivity, ER was moderately positive (10-49%) and ER was strongly positive (50-100%); PR was grouped as moderately positive (10-49%) and PR strongly positive (50-100%).ResultsMedian follow-up of 150 patients included in the study was 15.2 months (95% CI, 2.1-40.9 months). The highest response in the whole group was obtained in the ER-strong positive/PR moderate or strong positive group, and the ER moderate positive/PR moderate or strong group. This was followed by the ER strong positive/PR negative group, and then the ER moderate positive/PR negative group. Although these advantages were not statistically significant, they were numerically higher (ORR: 83.8% vs. 83.3% vs. 77.4% vs. 62.5%, p=0.488, respectively). The highest survival in the whole group was achieved in the ER strong positive/PR moderate or strongly positive group, followed by the ER moderately positive/PR moderate or strongly positive group, the ER strongly positive/PR negative group followed by the ER moderate positive/PR negative group, respectively(p=0.410). However, these advantages were not statistically significant.ConclusionAs a result, HR+/HER2- MBC patients receiving CDK 4/6i combined with ET suggest that the percentage of HR positivity may have a predictive and prognostic role

A severe case of levothyroxine intoxication successfully treated in intensive care unit

Levothyroxine intoxication is a rare clinical entity which is usually asymptomatic. However, severe symptoms such as respiratory failure, malignant hyperthermia, seizures, arrhythmia, and coma have been reported. In this case report, a patient who ingested high dose (15 mg) levothyroxine for suicide and admitted to intensive care unit was presented. There was a decrease in Glasgow coma score in the follow-up. The patient was intubated due to acute respiratory failure. Gastric lavage, activated charcoal, methylprednisolone, cholestyramine and therapeuthic plasma exchange were administered. Despite ingestion of high dose of levothyroxine, thyrotoxicosis symptoms resolved with appropriate treatment and the patient was discharged from the intensive care unit

Natural products to enhance anti-tumor effects of trastuzumab and paclitaxel on the SKBR3, which is human breast cancer cell line.

e13051 Background: Neoadjuvant chemotherapy (ChT) with targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)- positive breast cancer (BC). In this context, Trastuzumab (Tz) and ChT significantly improved the pathological complete response (pCR) rate. Tz and Paclitaxel (PTX) combination therapy is also one of the neoadjuvant treatments used in HER2+BC, and despite the effectiveness of this treatment, there is a critical need for innovative approaches and further research that will improve the neoadjuvant response rate. Addressing this, the NaturaProDB tool presents a novel avenue for predicting in silico natural non-toxic compounds with potential anti-cancer properties. Our study aims to investigate synergistic effect of natural products proposed by this database on theurapeutic action of Tz and PTX on BC. Methods: The NaturaProDB database was searched using the ‘Target Cancer’ option in order to identify those natural products with anti-BC potential and the corresponding experimentally verified target genes. Using this database, Biochanin A (BCA) and Delphinidin (Dp) were selected as natural compounds because they both commonly inhibit the MAPK signaling pathway. We used the HER2+ SKBR3 cell line to determine IC20, IC30 and IC50 doses for BCA, Dp, Tz, and PTX through MTT assay. Notably, all experiments were done after 72 hrs treatment of all compounds. Further, various combinations within different concentrations of natural products and Tz and PTX were tested to define additive anti-proliferative effects on SKBR3 cell line. Results: We first defined two natural products with drug-like properties, BCA and Dp, which have anti-proliferative effect on BC. Treatment of SKBR3 with increasing concentrations of BCA and Dp caused dose-dependent proliferation inhibition and IC50 dose of compounds were defined as 42,70uM and 40,70uM, respectively. In addition, IC20 dose of Tz was 2,8µM, while IC30 dose of PTX was 2,3nM.Then, we showed that combinations of increasing doses of Dp (from 30µM to 90 µM) with IC20 Tz caused significant dose-dependent cell death compared to the control group (p&lt;0.0001). And the combinations of increasing doses of BCA (from 45µM to 360 µM) with IC20 Tz led similar significant results (p&lt;0.0001). Conclusions: Herein, it is shown that combining natural compounds (Dp, BCA) with conventional treatments (PTX,Tz) predicted for the SKBR3 cell line can enhance the inhibitory effect on cell proliferation. This study is one of the rare first cell line studies in which the synergistic effect of BCA and Dp, which are natural compounds selected using the NaturaProDB database, were combined with ChT and Tz to show their synergistic effect, and these findings indicate that synergistic combination treatments acting through different pathways (MAPK signaling pathway) can be used in the treatment of HER2+ and TN BC. It opens avenues for further research. </jats:p

The effect of low HER2 expression on treatment outcomes in metastatic hormone receptor positive breast cancer patients treated with a combination of a CDK4/6 inhibitor and endocrine therapy: A multicentric retrospective study

Background: CDK4/6 inhibitors combined with endocrine therapy have significantly improved treatment outcomes for metastatic hormone receptor-positive (HR+) breast cancer patients. However, the impact of low HER2 expression on treatment response and progression-free survival (PFS) remains unclear. Methods: This multicenter retrospective study included 204 HR+ breast cancer patients treated with a combination of CDK4/6 inhibitor and endocrine therapy. HER2-zero disease was detected in 138 (68%) and HER2-low disease in 66 (32%) patients. Treatment-related characteristics and clinical outcomes were analyzed, with a median follow-up of 22 months. Results: The objective response rate (ORR) was 72.7% in the HER2 low group and 66.6% in the HER2 zero group (p = 0.54). Median PFS was not significantly different between the HER2-low and HER2 zero groups (19 months vs.18 months, p = 0.89), although there was a trend toward longer PFS in the HER2-low group for first-line treatment (24 months progression-free survival rate 63% vs 49%). In recurrent disease, the median PFS was 25 months in the HER2-low group and 12 months in the HER2-zero group (p = 0.08), while in de novo metastatic disease, the median PFS was 18 months in the HER2-low group and 27 months in the HER2-zero group (p = 0.16). The order of CDK4/6 inhibitor use and the presence of visceral metastasis were identified as independent variables affecting PFS. Conclusion: Low HER2 expression did not significantly impact treatment response or PFS in HR+ breast cancer patients treated with a CDK4/6 inhibitor and endocrine therapy. Because of the conflicting results in the literature, further prospective studies are needed to evaluate the clinical significance of HER2 expression in HR+ breast cancer

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study)

Introduction Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. Materials and methods This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group >= 40% and low-positive group = 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the >= 60% group. Conclusion Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs

Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia