The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

Case report: Drug-induced vitiligo during treatment with BRAF/MEK inhibitors in a patient with metastatic conjunctival melanoma.

INTRODUCTION: Autoimmune side effects can be detected during the use of BRAF/MEK inhibitor. Although its frequency, mechanism and importance are not known exactly, there are cases reported in the literature. CASE REPORT: We report a case of drug-induced vitiligo in a patient with metastatic conjunctival malignant melanoma who was treated with BRAF/MEK inhibition therapy. MANAGEMENT AND OUTCOME: In the case, vitiligo was controlled with topical treatments. Follow-up process of the patient has been continuing with no progression on month 12 of the current treatment. DISCUSSION: Although ICI-related autoimmune side effects and vitiligo have been described more frequently, vitiligo may also occur secondary to BRAK/MEK inhibition. This case also points out that cutaneous toxicity is manageable with no delay in treatment thanks to collaboration of dermatologists and oncologists.

Neuroendocrine Differentiated Breast Cancer Cases: A Retrospective Analysis and Literature Review.

Objectives: Neuroendocrine breast carcinoma (NEBC) is a rare subgroup of breast cancer, which makes up 2-5% of all invasive breast cancers. The aim of this retrospective analysis is to present and analyze our own data of primary NEBCs. Methods: We retrospectively analyzed clinical, pathological, and radiological characteristics of 36 patients diagnosed with neuroendocrine differentiated breast cancer between 2008 and 2019 compared to that of 925 patients with invasive ductal carcinoma (IDC/NOS) along with a literature review. Results: In this study, 36 patients with neuroendocrine differentiated breast carcinoma and 961 patients with (IDC/NOS), as the comparison group, were identified between 2008 and 2019. In NEBC patients, seven were premenopausal and 29 postmenopausal. Patients whose ultrasound (USG), magnetic resonance, and mammographic (MMG) images available in our hospital, high-density masses were detected in the MMG with irregular (77%), microlobulated (80%) and spiculated margins (63%), unaccompanied by asymmetry and structural distortion. Calcifications were less common than invasive breast cancer, present only in four patients (17%). When NEBC were compared to ductal carcinomas (n=925), NEBC were more often human epidermal growth factor receptor 2 negative (p=0.039), estrogen receptor positive (p=0.05), progesterone receptor positive (0.03), and the NEBC patients were older (p=0.02). Age, grade, metastatic status, lymph node number, and molecular type were identified as prognostic factors that significantly affect survival in both groups (p<0.05). Conclusion: NEBC is a subtype that is both histopathologically and radiologically distinct from other breast cancer subtypes, and neuroendocrine differentiation may be an important predictive marker in the future.

Preliminary study of serum Galectin-1 in breast cancer carcinogenesis [Izmir Oncology Group (IZOG) study].

PURPOSE: Galectin-1 is a lectin involved in the carcinogenesis of many cancers. In the present study, we aimed to investigate the importance of galectin-1 in breast cancer carcinogenesis and its relationship with tumor development. METHODS: Patients who were diagnosed with new breast cancer and a healthy volunteer population were included in the study. Preoperative and postoperative (1 month following visit at the medical oncology outpatient clinic) serum samples were collected from breast cancer patients and the healthy volunteer control group. RESULTS: There was no statistically significant difference between patients' age, height, weight and body mass index (BMI) (p>0.05). The mean galectin-1 value of the preoperative group was 2.16±0.69 ng/ml, in the postoperative group; 1.75±0.31 ng/ml, and the healthy control group 1.64±0.40 ng/ml. A comparison of mean galectin-1 values between the groups showed that the highest galectin-1 level was found in the preoperative patients. When the mean serum galectin-1 levels of preoperative and postoperative patients were compared, a statistically significant difference was found between the two groups (p<0.001). Furthermore, a comparison of the control group and preoperative patients also revealed a statistically significant difference between the groups (p<0.001). When the control group and postoperative patients were compared, no statistically significant difference was found between them (p=0.16). CONCLUSION: Serum galectin-1 levels were higher in breast cancer patients than in the healthy control group. In addition, postoperative galectin-1 levels of breast cancer patients tended to decrease. This suggests that serum galectin-1 levels are important in breast carcinogenesis and positively correlated with the presence of tumors.

Prognostic role of De Ritis and basal neutrophil to lymphocyte ratio in patients with advanced stage pancreatic cancer [Izmir Oncology Group (IZOG) Study].

PURPOSE: We aimed to investigate the prognostic significance of neutrophil/lymphocyte ratio (NLR), an indirect indicator for the immune response and AST/ALT ratio (De Ritis), liver enzymes that are commonly used in various clinical fields, in patients with advanced-stage pancreatic cancer. METHODS: NLR and De Ritis of the patients with diagnosis of locally advanced and metastatic pancreatic cancer between the 2010-2017 were evaluated retrospectively. All patients were divided into two groups as high and low according to NLR and De Ritis cut-off values which were 2.4 and 0.75, respectively. RESULTS: A total of 191 patients were evaluated. The mean overall survival (OS) in patients with NLR<2.4 at the time of diagnosis was 10±0.8 months, while it was 4±0.49 months in patients with NLR>2.4 (p<0.0001). The mean OS of the patients with a De Ritis <0.75 was 8±1.2 months, whereas the survival of those with De Ritis >0.75 was 6±0.74 months (p=0.024). The mean progression free survival (PFS) in patients with NLR<2.4 and De Ritis <0.75 at diagnosis were 5±0.76 months and 6±0.87 months respectively, whilst it was 3±0.37 months in patients with NLR>2.4 (p=0.017) and 4±0.3 months in patients with De Ritis >0.75 (p=0.14). CONCLUSIONS: The NLR and De Ritis are associated with prognosis in many cancers and have been found to be associated with survival outcome in advanced-stage pancreatic cancer patients.

The role of inflammation in adjuvant chemotherapy-induced sarcopenia (Izmir Oncology Group (IZOG) study).

INTRODUCTION: Although the chemotherapy-induced sarcopenia has some explanatory presence in clinical practice, the mechanisms underlying this phenomenon have not been clearly distinguished in patients with cancer. Therefore, we aimed with this study to investigate the role of inflammation by examining the inflammatory markers in the physiopathology of adjuvant chemotherapy-induced sarcopenia in patients with gastrointestinal tract cancer. MATERIAL AND METHOD: To detect the presence of sarcopenia, patients' body composition measurements were assessed using the BIA, and their muscular strength was assessed with a handgrip dynamometer in both pre- and post-adjuvant chemotherapy. At the same time, we examined the baseline and post-adjuvant chemotherapy anthropometric measurements and inflammatory markers in serum (Hs-CRP, IL8, and TNF-α). Patients were divided in three groups. Group 1 consisted of patients who presented post-treatment sarcopenia although they did not have it prior to the treatment, group 2 included the patients who had no pre- or post-treatment sarcopenia, and group 3 was comprised of patients who presented pre-treatment sarcopenia. Each group included 30 patients. RESULTS: A total of 90 patients were included in the study. Fifty-one of them were female patients. Median age was 60.5 (range 27-83). The patients consisted of cases with colorectal and gastric cancers. In group 1, Wilcoxon signed-rank test revealed a significant difference between scores of IL-8 (pg/mL), TNF-α (pg/mL) and Hs-CRP (mg/dL) given for the post-chemotherapy compared with the pre-chemotherapy ((Z 3.61, p < 0.001), (Z 3.254, p = 0.001), (Z 3.319, p = 0.001)). The post-chemotherapy median scores of IL-8 (pg/mL), TNF-α (pg/mL), and Hs-CRP were 76.31, 7.34, and 1.55, respectively, which remained on the levels of 12.25, 1.6, and 0.51 for the pre-chemotherapy. For group 2, a Wilcoxon signed-rank test indicated no significant difference between scores of the same markers given for the post-chemotherapy compared with the pre-chemotherapy. In all patients (including groups 1, 2, and 3), a comparison of the patients with pre-treatment sarcopenia (n = 30) and non-sarcopenic patients (n = 60) in terms of baseline IL-8, TNF-α, and Hs-CRP mean levels, IL-8 and Hs-CRP were found to be statistically different (146.02 (SD 311.96) vs. 47.24 (SD 66.3) (p = 0.009), 3.91 (SD 4.26) vs. 0.75 (SD 1.08) (p < 0.001), respectively). CONCLUSIONS: The present prospective observational study suggested an association of chemotherapy-induced sarcopenia with inflammatory markers Hs-CRP, IL8, and TNF-α. Inflammation may play a role in chemotherapy-induced sarcopenia in newly diagnosed non-metastatic patients.

Chemotherapy-induced sarcopenia in newly diagnosed cancer patients: Izmir Oncology Group (IZOG) study.

BACKGROUND: Sarcopenia is associated with physical disability, increased post-operative complications, poorer tolerance to chemotherapy, and reduced survival outcome. However, little is known about the changes in body composition during chemotherapy treatment. We aimed to determine whether adjuvant or palliative chemotherapy causes the development of sarcopenia in newly diagnosed cancer patients and to reveal the relationship of sarcopenia with the duration of chemotherapy. METHODS: The study included newly diagnosed cancer patients who underwent curative surgery for primary tumor and also cancer patients who were metastatic at diagnosis. Body composition and handgrip strength were assessed by bio-electric impedance analysis (BIA) and handgrip dynamometer tools, respectively. Measurement tests were performed prior to chemotherapy, in the third and sixth months of chemotherapy. RESULTS: The median age of a total of 276 patients was 57.5 years (range 18-83), and majority of them (55.8%) were women. Among the pre-chemotherapy factors that could be associated with sarcopenia, male gender ≥ 65 years of age, body mass index (BMI) < 25, and nutritional risk screening 2002 score < 3 were found to be positively associated with sarcopenia (p < 0.001, p = 0.036, p < 0.001, and p < 0.001, respectively). In the multivariate analysis, male gender (p < 0.001) and BMI < 25 (p = 0.047) were found to be significant. Of 276 patients, 14.5% were sarcopenic prior to chemotherapy. After chemotherapy, 21.4% of them were sarcopenic at the end of the third month and 23.9% were sarcopenic at the end of the sixth month. CONCLUSION: The incidence of sarcopenia was found to be increased with chemotherapy itself and its duration in both non-metastatic and metastatic cancer patients which has to be evaluated in detail in disease-specific prospective and randomized studies.