Purpose To evaluate cMET and phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival outcomes. Experimental Design We measured protein levels of cMET and p-cMET in 257 breast cancers using reverse phase protein array. Regression tree method and Martingale residual plots were applied to find best cutoff point for high and low levels. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall (OS) survival. Cox proportional hazards models were fit to determine associations of cMET/p-cMET with outcomes after adjustment for other characteristics. Results Median age was 51years. There were 140 (54.5%) hormone receptor (HR)-positive, 53 (20.6%) HER2-positive and 64 (24.9%) triple-negative tumors. Using selected cutoffs, 181 (70.4%) and 123 (47.9%) cancers had high levels of cMET and p-cMET, respectively. There were no significant differences in mean expression of cMET (P<0.128) and p-cMET (P<0.088) by breast cancer subtype. Dichotomized cMET and p-cMET level was a significant prognostic factor for RFS (HR:2.44,95%CI:1.34-4.44,P=0.003 and HR:1.64,95%CI:1.04-2.60,P=0.033) and OS (HR:3.18,95%CI:1.43-7.11,P=0.003 and HR:1.92,95% CI:1.08-3.44,P=0.025). Within breast cancer subtypes, high cMET levels were associated with worse RFS (P=0.014) and OS (P=0.006) in HR-positive tumors, and high p-cMET levels were associated with worse RFS (P=0.019) and OS (P=0.014) in HER2-positive breast cancers. In multivariable analysis patients with high cMET had a significantly higher risk of recurrence (HR:2.06; 95%CI:1.08-3.94,P=0.028) and death (HR:2.81; 95%CI:1.19-6.64,P=0.019). High p-cMET level was associated with higher risk of recurrence (HR:1.79,95%CI 1.08-2.95.77,P=0.020). Conclusions High levels of cMET and p-cMET were seen in all breast cancer subtypes and correlated with poor prognosis.
Purpose To evaluate the impact of low ER/PR expression and effect of endocrine therapy on survival outcomes in HER2-negative tumors with ER/PR < 10%, previously labeled as triple negative. Methods In a retrospective review, 1257 patients were categorized according their ER/PR percentages into three groups, ER/PR <1% (Group A), ER/PR 1–5% (Group B) and ER/PR 6–10% (Group C). Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics. Results Group A, B and C had 897 (71.4%), 241 (19.2%) and 119 (9.4%) patients respectively. After a median follow up of 40 months there was no significant difference in 3-year recurrence free survival (RFS): 64%, 67% and 77% (P = 0.34) or overall survival (OS): 79%, 81% and 88% (P = 0.33) for groups A, B and C respectively. ER/PR expression was not an independent predictor for RFS (HR=1.10, 95% CI: 0.86–1.39, P=0.46 for group B and HR=0.96, 95% CI: 0.66–1.38, P=0.81 for group C, compared to group A), or OS (HR=1.11, 95% CI: 0.84–1.46, P=0.46 for group B and HR=0.94, 95% CI: 0.63–1.42, P=0.78 for group C, compared to group A). Endocrine therapy had no impact on survival outcomes (RFS: P=0.10; OS: P=0.45) among groups. Conclusions In this cohort, a low ER/PR level (1–5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6–10% is seen. Benefit of endocrine therapy in these patients is unclear.
Small bowel adenocarcinoma (SBA) is a rare cancer that has been treated similarly to colorectal cancer (CRC) in the advanced setting. Incidence has been increasing as detection efforts have been improving for these challenging-to-diagnose tumors, but patients frequently experience prolonged nonspecific symptoms due to delayed diagnosis. As a result of such delays and likely due to variant biology, patient outcomes for SBA are inferior to those for CRC at all stages of diagnosis. Recent molecular studies highlight the genomic differences underpinning these tumors and suggest new future pathways for treatment, distinct from CRC.
Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin–stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients’ treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.
Malignant small bowel obstruction (MSBO) that does not resolve with conservative measures frequently leaves few treatment options other than palliative care. This single‐institution retrospective study assesses the outcomes of a more aggressive approach—concurrent systemic chemotherapy and total parenteral nutrition (TPN)—in the treatment of MSBO. The MD Anderson pharmacy database was queried to identify patients who received concurrent systemic chemotherapy and TPN between 2005 and 2013. Only patients with MSBO secondary to peritoneal carcinomatosis requiring TPN for ≥8 days were included. Survival and multivariate analyses were performed using the Kaplan–Meier method and Cox proportional hazard models. The study included 82 patients. MSBO resolution was observed in 10 patients. Radiographic assessments showed a response to chemotherapy in 19 patients; 6 of these patients experienced MSBO resolution. Patients spent an average of 38% of their remaining lives hospitalized, and 28% of patients required admission to the intensive care unit. In multivariate modeling, radiographic response to chemotherapy correlated with MSBO resolution (odds ratio [OR] 6.81; 95% confidence interval [CI], 1.68–27.85, P = 0.007). Median overall survival (OS) was 3.1 months, and the 1‐year OS rate was 12.6%. Radiographic response to chemotherapy (HR 0.30; 95% CI, 0.16–0.56, P < 0.001), and initiation of new chemotherapy during TPN (HR 0.55; 95% CI, 0.33–0.94, P = 0.026) independently predicted for longer OS. Concurrent treatment with systemic chemotherapy and TPN for persistent MSBO results in low efficacy and a high morbidity and mortality, and thus should not represent a standard approach.
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