Is plasma caveolin-1 level a prognostic biomarker in metastatic pancreatic cancer?

BACKGROUND/AIMS: To evaluate the prognostic significance of plasma caveolin (CAV)-1 and its association with survival and treatment response rates in metastatic pancreatic cancer (MPC). PATIENTS AND METHODS: Plasma samples were prospectively collected from 41 patients with newly diagnosed MPC. Moreover, plasma samples were collected from 48 patients with chronic pancreatitis and 41 healthy individuals (control groups) for assessing Cav-1 levels. Plasma Cav-1 levels were evaluated at baseline and after three cycles of chemotherapy in the patients with MPC. RESULTS: The median Cav-1 level was 13.8 ng/mL for the patients with MPC and 12.2 ng/mL for healthy individuals (P = 0.009). The Cav-1 cut-off level was calculated as 11.6 ng/mL by using the receiver operating characteristic curve. The median overall survival and progression-free survival rates were 5 and 2.4 months, respectively, for participants with a high basal plasma Cav-1 level; the corresponding values were 10.5 and 9.4 months for participants with a low plasma Cav-1 level (P = 0.011 and P= 0.003, respectively). Of the 41 patients with MPC, 23 completed at least three cycles of chemotherapy. The median Cav-1 level was 13 ng/mL for post-treatment MPC (r2: 0.917; P= 0.001). High basal plasma caveolin-1 level have continued to remain at high levels even after chemotherapy, showing a trend toward worse response rates (P = 0.086). CONCLUSION: High basal plasma Cav-1 levels seem to be associated with poor survival and tend to yield worse therapeutic outcomes in patients with MPC. This study is the first to evaluate the prognostic significance of plasma Cav-1 levels as a prognostic factor in patients with MPC. However, larger prospective clinical trials are warranted.

Comparative study of receptor discordance between primary and corresponding metastatic lesions in breast cancer.

PURPOSE: It is well-known that tumor phenotype may change during the progression of breast cancer (BC). The purpose in this study was to compare the discordance in estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary and recurrent/metastatic lesions (RML) and also to evaluate the prognostic significance of change in tumor phenotype on survival in patients with metastatic BC. METHODS: The medical records of 6638 patients with BC from two breast centers treated between 1992 and 2015 were retrospectively analyzed. Of the 6638 patients, 549 cases in whom recurrence was histologically proven by biopsy or by surgical resection were enrolled into this study. RESULTS: Our presentation 13.5% of the patients had metastatic disease. Biopsy on recurrence was obtained from distant metastasis sites in 250 (63.6%) patients or from locoregional soft tissues/lymph-nodes in 143 (36.4%). Receptor discordance in ER, PgR and HER2 expressions between primary and RML were 27.2% (p=0.32), 38.6% (p<0.001) and 14.4% (p=0.007), respectively. Subsequent gain of ER and PgR showed significantly higher overall survival (OS) and post-recurrence survival (PRS) compared to the corresponding concordant-negative patients (119 vs 57 months, p=0.001 and 56 vs 31 months, p=0.03 for ER, 148 vs 58 months, p=0.003 and 64 vs 31 months, p=0.01 for PgR, respectively), hormone receptor (HR) loss was associated with worse OS. Similarly, HER2-loss cases experienced poorer PRS and OS outcomes, compared with those having stable HER2 expression (median 26 vs 60 months, p=0.009 for PRS and median 60 vs 111 months, p=0.06 for OS, respectively). CONCLUSION: This study confirmed the receptor discordance in ER/PgR and HER2 receptor expressions between primary and RML in patients with metastatic BC. As the loss of receptor expression is the most responsible factor for the discordance, treatments of recurrent/metastatic tumors should be individualized on the basis of molecular and genomic properties.

Clinicopathological features of patients with breast cancer aged 70 years or over.

PURPOSE: The risk of breast cancer (BC) increases in parallel with increasing age. Despite the increased disease burden in elderly patients, there is still a great uncertainty regarding "how to manage" BC in aging-population. The purpose of this study was to investigate the clinicopathological features and treatment approaches of patients with BC aged 70 years or over. METHODS: The medical records of 4413 patients with BC followed between 1994-2015 were retrospectively analyzed. Of the 4413 patients, 238 with stage I to III disease aged 70 years or over at BC diagnosis were enrolled into this study. Patients were divided into 2 groups according to the age as group 1 (70-79 years, N=192) and group 2 (80 or over, N=46). Clinicopathological features of patients including tumor histology, grade, estrogen (ER) and progesterone receptor (PgR) status, human epidermal growth factor receptor 2 (HER2) status, tumor size, lymph node involvement (LNI), lymphovascular invasion (LVI), perineural invasion (PNI), clinical stage, type of surgery, treatments and comorbid diseases were evaluated. RESULTS: The median age was 74 for group 1 (range 70-79) and 82 for group 2 (range 80-92). Excluding tumor size and grade, no statictically significant difference was found between the two groups according to histopathological characteristics. Patients in group 2 had more commonly larger T stage (T4), and less frequently presented with grade I tumor (p=0.014 and p=0.044, respectively). Modified radical mastectomy and adjuvant chemotherapy were more commonly performed in group 1 (p=0.001 and p=0.001, respectively). In contrast, neoadjuvant treatment was more frequently applied in group 2 (p=0.003). There was no difference in disease-free survival (DFS) between the groups (p=0.012), however, median overall survival (OS) was significantly higher in group 1 (p=0.03). CONCLUSION: Excluding the tumor grade and tumor size, both groups had similar histopathological features. However, patients aged between 70-79 years were likely to receive more agressive treatments for BC, indicating that treatment choice in patients over the age of 80 years was likely to be based on age-related factors rather than tumor characteristics.

Invasive Pleomorphic Lobular Histology Is an Adverse Prognostic Factor on Survival in Patients with Breast Cancer.

Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and different subtype of classical invasive lobular carcinoma (ILC). This special variant is characterized by significant cytological atypia and pleomorphism which differs from the cytological uniformity of ILC. IPLC has been shown to have some poor prognostic factors such as axillary node metastasis and higher histological grade which may lead to poor clinical courses including a short relapse time, increased risk of recurrence and a decreased survival. The aim of this study is to investigate the clinicopathological characteristics and prognosis of IPLC in comparison with ILC and also to evaluate if IPLC is a different clinical entity compared to ILC. A total number of 4418 breast cancer patients treated between 1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients diagnosed with pure IPLC. In this present study, clinicopathological characteristics, disease free survival (DFS) and overall survival (OS) of patients with ILC and IPLC were compared. This study design is one of the rare face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased rate of higher histologic grade, extracapsular extension, lymphovascular invasion and lower percentage of hormone positivity than those of patients with ILC. During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence, 5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC group. Patients with IPLC had a worse DFS and OS duration than patients with ILC (P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a special breast cancer subtype. This study suggests that IPLC is a distinct clinical entity with an advanced stage and more aggressive clinical course. Patients with IPLC reveal poorer prognostic factors such as higher histological grade, relative lower percentages of hormone positivity, and increased rate of recurrences resulting in poor clinical outcomes and worse survival. Nowadays, it is observed that current treatment methods for IPLC do not seem as successful as in ILC and failed to be effective. Thence, individual therapies including more aggressive surgery and adjuvant or neoadjuvant chemotherapy even in the earlier stages of breast cancer should be performed for this distinct variant.

The association between body mass index and immunohistochemical subtypes in breast cancer.

BACKGROUND: Body mass index (BMI) is defined as a poor prognostic factor in patients with breast cancer (BC). However, there are controversial results regarding the various effects of BMI on BC, hence the exact pathophysiology of the relation between obesity and BC is still under debate, and remains unclear. This paper aims to investigate the association between BMI at presentation and BC subtypes defined according to the immunohistochemical classification in both premenopausal and postmenopausal patients with BC. PATIENTS AND METHODS: This study is a retrospective and explorative analysis of the 3767 female BC patients from a single center. All patients' BMI at the time of initial diagnosis and tumor demographics were recorded. BMI was stratified into 3 groups as normal-weighted (BMI <25 kg/m2), over-weighted (BMI = 25-29.9 kg/m2), and obese (BMI ≥30 kg/m2). Immunohistochemical classification of the tumors was categorized into 4 groups as follows; luminal-like, HER2/luminal-like, HER2-like, and triple-negative according to the ER/PR and HER2 status. Distribution of Immunohistochemical subtypes, tumor characteristics, and overall survival (OS) analysis were evaluated according to the BMI groups in both premenopausal and postmenopausal patients. RESULTS: Median BMI of premenopausal and postmenopausal patients was 25.5 (kg/m2) and 28.8 (kg/m2), respectively (P < 0.001). In parallel with the increasing age, patients were more obese at diagnosis in both premenopausal (P < 0.001) and postmenopausal period (P < 0.001). Triple-negative subtype was significantly more frequent in premenopausal patients with BMI ≥30 kg/m2 compared to BMI <30 kg/m2 (P = 0.007). Additionally, premenopausal patients with BMI ≥30 kg/m2 had less common luminal-like subtype (P = 0.033) and more frequently presented with higher tumor stage (P = 0.012) and tumor grade (P = 0.004) compared to patients with BMI <25 kg/m2. On the other hand, premenopausal patients with BMI <25 kg/m2 had significantly more ER-positive tumors (P < 0.001) and lower stages of disease (P = 0.01) compared to their counterparts with BMI ≥25 kg/m2. Premenopausal obese patients with triple-negative (P = 0.001) and luminal-like subtype (P = 0.002) had significantly shorter OS duration compared to overweight counterparts. HER2/luminal-like subtype was found to be significantly greater in postmenopausal overweight patients (P = 0.005). However, BMI had no any other significant effect on survival and immunohistochemical subtypes in postmenopausal patients. Multivariate analysis revealed that triple-negative subtype, grade III tumor, BMI ≥30 kg/m2, T3-4 (P < 0.001), nodal involvement, metastatic disease, and lymphovascular involvement were significantly associated with poorer OS. CONCLUSION: Our data indicated that BMI was an independent factor in patients with BC, with an association indicating a decreased incidence for luminal-like subtype and increased incidence for triple-negative subtype among premenopausal patients. However, this significance was not found in postmenopausal patients. Accordingly, a plausible etiological heterogeneity in BC might play a role among immunohistochemical subtypes in every life stage of women.

Left laterality is an independent prognostic factor for metastasis in N3 stage breast cancer.

PURPOSE: Development of metastasis in patients with breast cancer (BC) is the most important negative prognostic factor and this process mainly begins with lymphatic involvement. Therefore, axillary, subclavicular, internal mammary or supraclavicular nodal involvement is a crucial step before metastasis. Anatomical differences between the right and left lymphatic drainages of the breasts may significantly affect the rate, site and time to development of distant metastasis. The purpose of this study was to investigate if laterality is an independent prognostic factor for metastasis in N3 breast cancer patients. METHODS: From a total of 4215 BC patients diagnosed between 1994 and 2015 in our center, 305 non-metastatic women with pathological N3 (pN3) nodal status at presentation were enrolled in this study. Patients were divided into two groups: left and right BC. Analysis of overall survival (OS) and time to first metastasis (TTM) was performed according to Kaplan-Meier method with log-rank test. RESULTS: The median number of lymph node involvement and lymph node ratio (number of positive lymph nodes / total number of excised lymph nodes) between the two groups was equal (14 and 0,66 respectively). Recurrence was observed in 123 patients [53 (35%) right vs 70 (44%) left group]. Patients with left BC had significantly higher rate of axial bone metastases compared with the right BC group (55.7 vs 35.8%, p<0.02, respectively). TTM was significantly shorter in the left BC group [49.1 months (95% CI 36.5-61.8) vs 103.6 months (95% CI 47.0-160); p7equals;0.03, respectively]. Median OS did not differ between the groups, however, there was a trend towards lower OS in patients with left BC (p=0.68). CONCLUSION: Left laterality in patients with pN3 non-metastatic BC is an independent prognostic factor associated with shorter TTM, increased risk of distant metastases and axial bone involvement compared with right laterality.