Sobha Kurian

A population-based study comparing HRQoL among breast, prostate, and colorectal cancer survivors to propensity score matched controls, by cancer type, and gender

Objectives were to compare health‐related quality of life (HRQoL) between breast cancer survivors, prostate cancer survivors (PCS), and colorectal cancer survivors (CCS) to matched controls, stratified by short and long‐term survivors, by cancer type, and gender.

Initial clinical test of a breast-PET scanner

Introduction: The goal of this initial clinical study was to test a new positron emission/tomography imager and biopsy system (PEM/PET) in a small group of selected subjects to assess its clinical imaging capabilities. Specifically, the main task of this study is to determine whether the new system can successfully be used to produce images of known breast cancer and compare them to those acquired by standard techniques.

Complete response after high-dose chemotherapy and autologous hemopoietic stem cell transplatation in metastatic breast cancer results in survival benefit.

Abstract:  Metastatic breast cancer is an incurable disease even with high‐dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT). Even though phase III studies have not shown a survival advantage for this group as a whole, it is possible that a small subset of patients may benefit from HDC/ASCT with careful patient selection. A total of 198 patients from three different institutions were treated with HDC/ASCT. After complete staging, patients with central nervous system or bone marrow involvement were excluded. The HDC regimen consisted of: Carboplatin 600 mg/m2 IV infusion over 48 hours, Thiotepa 300 mg/m2 IV infusion over 2 hours, and Cytoxan 60 mg/kg IV infusion given over 2 hours ×3 days. The median age at the time of transplant was 46 (24–62) years and median follow‐up was 20 months. Hormone receptor status was known in 148 patients, of whom 84 had estrogen receptor (ER) and/or progestrone receptor (PgR)‐positive tumors. Eighty patients had no evidence of disease at the time of HDC/ASCT (CR1). At the completion of HDC and ASCT, complete responses (CR) were seen in an additional 57 patients (CR2). Using Kaplan–Meier analysis, the median relapse‐free survival (RFS) for the entire group was 15 months and overall survival (OS) was 27 months. The patients in CR1 had a median RFS and OS of 20.7 and 50.6 months, respectively. This was very similar to the RFS and OS in patients achieving CR2 after HDC/ASCT (p < 0.001; median: 19 and 40 months, respectively). In contrast, the patients with persistent residual disease had an RFS and OS of 7 and 12 months (p < 0.001). These data show that patients achieving a CR after HDC/ASCT have a better relapse‐free and OS, when compared to patients with persistent residual disease after HDC/ASCT. This study suggests that a subset of patients with residual metastatic breast cancer after standard chemotherapy can achieve CR with HDC and ASCT which may result in better long‐term outcome.

Overcoming endocrine resistance in breast cancer: role of the PI3K and the mTOR pathways

Overcoming endocrine resistance is a 21st century hurdle in the treatment of hormone receptor-positive breast cancers. Estrogen plays a role in the growth of 70% of breast cancers. There are many strategies evolved to overcome estrogen resistance. Established strategies include using drugs such as tamoxifen, a selective estrogen receptor modulator to selectively block estrogen receptors and aromatase inhibitors to decrease the synthesis of estrogen. However, endocrine resistance is commonly encountered in treating patients with standard single-therapy regimens. Recently, the role of the PI3K and the mTOR pathways has been targeted to overcome resistance. The mTOR pathway is a complex pathway regulating cell metabolism, growth and apoptosis. Novel agents such as mTOR inhibitors, PI3K inhibitors and Akt inhibitors are transitioning from bench-top research to clinical application with promising results. This article reviews the common mechanisms of endocrine resistance, and combination therapies that utilize the mTOR/PI3K pathways to overcome resistance.

Esthesioneuroblastoma in Maffucci's syndrome

Maffucci’s syndrome consists of multiple cutaneous hemangiomas, dyschondroplasia, and enchondromas with potential for malignant change. We report a case of a 33-year-old man with Maffucci’s syndrome who presented with a several month history of nasal congestion, facial pain, and diminished vision in his left eye. Radiological studies showed a large soft tissue mass centered in the sinonasal area, extending bilaterally into maxillary sinuses and orbits with compression of left optic nerve. Biopsy of the mass showed esthesioneuroblastoma (olfactory neuroblastoma). Chemotherapy resulted in initial improvement, but the tumor recurred and did not respond to further treatment, resulting in his death. Sarcomatous tumors are reported in Maffucci’s syndrome, but this is a rare case of a neuroendocrine tumor in a patient with Maffucci’s syndrome.

Weight change associated with third-generation adjuvant chemotherapy in breast cancer patients.

BACKGROUND Studies have shown that breast cancer treatment can cause an increase in weight. Weight gain during chemotherapy is usually significant and may be associated with poor survival. However, the role of third- generation chemotherapy regimens and weight gain is not well reviewed. METHODS We retrospectively analyzed the mean percentage weight change during the first year after breast cancer diagnosis in 246 patients at West Virginia University during September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise comparisons were used to assess the influence of age, histology, stage, ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities received on the percentage weight change. Kaplan-Meier method with log-rank test was used to evaluate recurrence-free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free patients were censored at last follow-up. RESULTS Mean weight gain was 0.39% (SD, 0.40) of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal status was the only factor associated with significant weight gain (+1.67% vs -0.10% for postmenopausal patients; P = .02). Stages ≥ III was associated with significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II; P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs 0.91; P = .19). There was no significant change in weight relative to other factors. CONCLUSIONS Our study in patients receiving third-generation adjuvant chemotherapy regimens did not show any significant change in percentage weight with chemotherapy. Premenopausal status was the only significant factor associated with weight gain. As expected, stage III or higher disease was associated with significant weight loss and lower RFS.

Breast Cancer Pathology, Receptor Status, and Patterns of Metastasis in a Rural Appalachian Population

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n = 42) or visceral sites (n = 53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P = 0.042). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P = 0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P = 0.033). Triple-negative tumors that metastasized to visceral sites were larger (P = 0.007). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

CA 27-29 in Patients with Breast Cancer with Pulmonary Fibrosis

Cancer antigen (CA) 27-29, which is expressed on most carcinoma cells, is a soluble form of glycoprotein MUC1. It is overexpressed in tumors involving glandular epithelial cells, such as breast tumors. Measurement of CA 27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in patients with breast cancer. Although serial determination of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. False-positive results might be observed in certain patients with no evidence of malignant disease, such as benign breast disease, ovarian cysts, and liver disease. Herein, we report a series of 4 patients with breast cancer (2 patients with interstitial lung fibrosis and 2 patients with nonspecific fibrotic lung changes) who have persistent elevation in CA 27.29 (normal, <38 U/mL).

Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia:: a case report and review of the literature

A 69-year-old woman developed microgranular acute promyelocytic leukemia (APL-M3) 10 months after receiving adjuvant cyclophosphamide, doxorubicin, and paclitaxel for breast cancer. Replicate bone marrow aspirate karyotypes contained a translocation between the long arms of chromosomes 15 and 17, but not at breakpoints typical for APL. Fluorescence in situ hybridization paints and RARalpha/PML cosmid probes verified that the breakpoints on chromosomes 15 and 17 were proximal to both the PML and RARalpha genes; t(15;17)(q13;12). Although the patient received induction chemotherapy and a several month trial of all-trans retinoic acid (ATRA), there was no clinical improvement or hematological remission. We suspect that this patient developed postchemotherapy secondary APL with an atypical t(15;17), which rendered her leukemic cells unresponsive to ATRA therapy.

Predominance of Brain and Lung Metastases in Triple-Negative Breast Cancer Patients.

Background: Patients with triple-negative breast cancer have an increased likelihood of recurrence compared to other types of breast cancer, however, little is known about their pattern of metastatic spread. Our object was to evaluate the metastatic patterns of women diagnosed with triple-negative breast cancer compared to other subtypes. Methods: We studied a cohort of 572 white patients diagnosed with invasive breast cancer at West Virginia University Hospital between 1999 and 2004. Hospital registry, charts, and pathology records provided clinical data including tumor receptor status and biopsy-proven metastatic spread to bone, brain, liver and lung. Breast cancers that were negative for estrogen, progesterone, and HER2neu, otherwise known as triple-negative were compared with HER2neu-postive and HER2neu-negative (endocrine receptor positive) disease. Body mass index was calculated and a value of ≥30 considered indicative of obesity. Specimens of primary carcinoma were available for analysis of Ki67 mitotic index and expression of p53. Results: 134/572 (23.4%) had triple-negative breast cancer, while the frequencies were 108/572 (18.9%) and 330/572 (57.7%) in HER2neu-positive and HER2neu-negative (endocrine receptor positive) groups. Women with triple-negative disease were more likely to have brain-metastasizing breast cancer; 10.5% versus 4.6% for HER2neu-positive and 3.3% for HER2neu-negative (P Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6159.