Clinical and Pathological Characteristics of Patients with High-Risk Breast Cancer Based on BRCA Mutation Profiles: A Retrospective Study.

OBJECTIVE: This study aimed to determine the differences in clinicopathological features of Turkish patients with high-risk breast cancer based on the mutation status of two breast cancer susceptibility genes (BRCA1/2) . MATERIALS AND METHODS: This study enrolled patients with invasive breast cancer who have been evaluated for BRCA1/2 mutations due to the presence of high-risk factors admitted to two tertiary referral centers in Turkey. Clinical and histopathological features were analyzed in BRCA1 mutation carriers, BRCA2 mutation carriers, and non-carriers. RESULTS: A total of 302 patients with a mean age of 44.2±9.9 (22-82) years were included. BRCA1/2 mutation was found in 75 (24%) patients, of whom 41 (13.6%) were BRCA1 mutation carriers and 37 (12.3%) were BRCA2 mutation carriers. Moreover, 104 (34.4%) and 4 (1.3%) patients had family history of breast and ovarian carcinoma, respectively. The rates of triple negativity (56.1%), histologic grade 3 (65.9%), and lymphovascular invasion (78%) were significantly higher in BRCA1 mutation carriers than in non-carriers and BRCA2 mutation carriers. Furthermore, 87% of triple-negative BRCA1 mutation carriers had histologic grade 3 tumors compared with 38.9% in non-triple-negative BRCA1 mutation carriers, and the difference was significant. CONCLUSION: Findings of this study showed that BRCA1-related breast cancers represent a distinct group with unique pathological features, which are usually associated with a poor prognosis.

The conversion of RAS status in metastatic colorectal cancer patients after first-line biological agent treatment.

AIM: The aim was to investigate the RAS discordance between initial and recurrent metastasectomy specimens in metastatic colorectal cancer (mCRC) patients treated with chemotherapy (CT) plus biological agents in a first-line setting. METHODS: Patients who had been treated with CT plus bevacizumab or cetuximab or panitumumab followed by R0 resection for potentially resectable colorectal cancer liver metastases were scanned. Among these, patients who developed resectable new metastases after a disease-free interval longer than 6 months were included in the study. We compared the RAS mutation status between the first biopsy and the second metastasectomy specimen. RESULTS: A total of 82 mCRC patients treated with CT plus biological agents in a first-line setting were included in the study. The first biopsy assessment showed wild-type RAS tumours in 39 (47.6%) patients and mutant RAS tumours in 43 (52.4%) patients. The mean time for new operable liver metastasis after R0 resection was 15.5 months. In the second metastasectomy specimens, the numbers of wild-type and mutant RAS tumours were 30 (36.6%) and 52 (63.4%), respectively. The comparison with the first biopsy specimens showed RAS status conversions in 17 (20.7%) patients. Univariate comparison between patients with and without RAS status conversion revealed that grade, pathological T stage, wild-type RAS tumour and longer biological agent use time in the first-line treatment were significant factors for RAS conversion. CONCLUSION: Our results suggest that re-biopsy is needed for an optimal second-line treatment decision in mCRC patients regardless of backbone biological agent, especially in patients with wild-type RAS mCRC.

Does the Waiting Period for Genetic Tests Affect the Prognosis in Chemotherapy-Treated de novo Metastatic Non-Small Cell Lung Cancer Patients without a Driver Mutation?

INTRODUCTION: The length of the necessary waiting period to test driver mutations may generate anxiety in patients and clinicians. For this reason, an investigation was conducted to determine whether the duration between diagnosis and the start of first-line chemotherapy (DDC) in non-small cell lung cancer (NSCLC) patients without driver mutations has an impact on prognosis. METHODS: The study included 303 de novo metastatic NSCLC patients without a driver mutation and patients were divided into 2 groups according to DDC: ≤30 days (group A) or >30 days (group B). The determinant factors for progression-free survival (PFS) and overall survival (OS) were examined by Cox regression analysis. RESULTS: The mean DDC was calculated as 38.2 ± 54.5 days. The number of patients in group A and B were 183 and 120, respectively. The median PFS in groups A and B was 5.0 and 6.0 months (p = 0.268) and the median OS was 10.0 and 11 months, respectively (p = 0.341). Univariate and multivariate analyses revealed that DDC was not a factor associated with PFS and OS. CONCLUSION: Our results show that a higher DDC was not associated with a worse prognosis in metastatic NSCLC patients without driver mutations. In this context, it is safer for patients and their physicians to wait for test results before starting chemotherapy.

The Clinical Importance of Androgen Receptor Status in Response to Neoadjuvant Chemotherapy in Turkish Patients with Local and Locally Advanced Breast Cancer.

PURPOSE: To investigate whether androgen receptor (AR) status affects neoadjuvant chemotherapy (NACT) in stage II and III Turkish breast cancer patients. METHODS: The histological response for breast and axilla was assessed according to the Miller-Payne grading system. In light microscopy, nuclear staining in tumor cells was evaluated, and nuclear staining above 1% was accepted as positive for AR expression. The patients were divided into 3 groups according to the intensity of AR staining: low, moderate, and high. RESULTS: In total, 71 women with breast cancer were included in the study. In univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) status were tested to determine which of these factors were associated with >90% responsiveness. AR negativity was found to be the only statistically significant factor. In multivariate analysis, AR positivity at each intensity was found to be the single important factor affecting decreasing pathologic response in patients receiving NACT for breast cancer. CONCLUSION: Our results show that AR positivity is associated with poor response to NACT in Turkish breast cancer patients and that AR positivity is independent of stage, hormone receptor status, HER-2 status, and disease stage.

The predictive role of metabolic tumor volume on no response to neoadjuvant chemotherapy in patients with breast cancer.

INTRODUCTION: To evaluate the predictive significance of pretreatment metabolic tumor volume on pathologic response in patients who received neoadjuvant chemotherapy for breast cancer. METHODS: Seventy patients who received neoadjuvant chemotherapy between 2013 and 2017 years were enrolled in the study. Pathologic responses and 18-fluorodeoxyglucose positron emission tomography/computed tomography metabolic dates of patients were obtained from archive files. RESULTS: Forty-six (65.7%) patients were in stage II and 24 (34.3%) patients were in stage III; 25 (35.7%) patients were human epidermal growth factor receptor 2 positive, 46 (65.7%) patients were estrogen receptor-positive, 26 (37.1%) patients were progesterone receptor-positive. According to the Miller-Payne grading system, 24 (34.3%) patients constituted 100% pathological response; patients with 91-99% pathological response were 12 (17.1%), the number of patients with non-pathologic response was 6 (8.6%). Median metabolic tumor volume was 7.3 cm3 (7.1 ± 3.5), 8.8 (11.4 ± 9.4), 7.7 (8.3 ± 4.6) and 22 cm3 (19.8 ± 11.0) in patients with stages IIA, IIB, IIIA, and IIIB, respectively (p = 0.032). In Miller-Payne grading, the median metabolic tumor volume value was higher in patients with no pathologic response group than 100% response group (p = 0.003). The cut-off metabolic tumor volume value determining no pathologic response was calculated as higher than 13.62 cm3 (sensitivity 83.3% and specificity 82.8%). CONCLUSIONS: Our study results suggest that higher pretreatment metabolic tumor volume values are predictive on no pathologic response in patients treated with neoadjuvant chemotherapy for breast cancer.

The effects of diabetes and fasting plasma glucose on treatment of breast cancer with neoadjuvant chemotherapy.

PURPOSE: To determine the effects of diabetes and fasting plasma glucose (FPG) level on the pathologic response in patients with breast cancer who received neoadjuvant chemotherapy. METHODS: One hundred and thirty-five patients files who received neoadjuvant chemotherapy between 2013 and 2017 years, were scanned. Pathologic responses, diabetes, and FPG dates of patients were reached from archive files. Patients were grouped as diabetic and nondiabetic. RESULTS: Patients with higher than 90% pathologically response according to Miller-Payne grading system, constituted 11 (44%) and 61 (55.5%) of patients; patients with equally or lower than 90% pathologically response were 14 (56%) and 49 (44.5%) and the number of patients with nonpathologic response 5 (20%) and 2 (1.8%) in diabetic and nondiabetic group, respectively. This difference between diabetic and nondiabetic groups was statistically significant (P = 0.005). In Miller-Payne groups, the median FPG levels were 135 mg/dl (165.6 ± 86.5), 96 mg/dl (110.0 ± 30.6), 97 mg/dl (101.9 ± 23.9), 91.5 mg/dl (102.5 ± 44.3) and 93.5 mg/dl (112.0 ± 61.2) respectively 0%, 1%-30%, 31%-90%, 91%-99%, and 100%. Patients with lower 91% pathologic response had statistically significant higher FPG levels compared with patients with higher patholocig response (P = 0.008). The cut-of FPG value to determine nonpathologic response was calculated 105 mg/dl (sensitivity 85.7% specificity 74.2%). The FPG, diabetes, lymph node positivity, and disease stage were statistically significant in the multivariate analysis for affecting non-pathologic response (P = 0.013, P = 0.016, P = 0.036, and P = 0.035 respectively). CONCLUSION: Diabetes and high FPG level may be predictive to the non-response of neoadjuvant chemotherapy in patients with breast cancer.

Single Gallstone Associated with High Fasting Insulin Level.

Gallstone (GS) formation is a multifactorial process and one of the associated factors is hyperinsulinemia. The aim of this cross-sectional study was to determine the association between size and count of gallstones, and insulin levels and resistance. The study group composed of 84 patients who have ultrasonographically confirmed gallstone(s). Insulin level of all participants were measured and insulin resistance was calculated with the homeostasis model assessment of insulin resistance (HOMA-IR) index. All p-values < 0.05 were considered statistically significant. There were 28 patients with single stone and 56 with multiple stones. Mean insulin level was 12.54 ±11.66 ml/U (median 9.91 ml/U, IQR 6.33) and 56.3% of patients had insulin resistance. Mean stone size was 7.82 ±7.52 mm (median 6 mm and IQR 11.75). There was a non-significant association and correlation between insulin level and size of GS (p=0.129; r =0.16). There was significant difference between single stone group and multiple stones group, according to the insulin level.