Publications by authors named "Melissa Klein Cabral"

4 Publications

  • Page 1 of 1

Knowledge and attitudes about microsatellite instability testing among high-risk individuals diagnosed with colorectal cancer.

Cancer Epidemiol Biomarkers Prev 2007 Oct;16(10):2110-7

Division of Population and Medical Science, Fox Chase Cancer Center, 333 Cottman Avenue, P1100 Philadelphia, PA 19111, USA.

For individuals meeting Bethesda criteria for hereditary nonpolyposis colorectal cancer syndrome, the microsatellite instability (MSI) test is recommended as a screening evaluation before proceeding to genetic testing. The MSI test is new to the medical setting, but will be increasingly used to screen patients at high risk for hereditary nonpolyposis colorectal cancer. The main goals of this study were to examine knowledge about and exposure to the MSI test among individuals considering the test, to evaluate perceived benefits and barriers to undergoing the MSI test, and to identify the demographic, medical, and psychosocial correlates of the perceived benefits and barriers to undergoing the test. One hundred and twenty-five patients completed a survey after being offered the test, but prior to making the decision whether to pursue MSI testing. Results indicated low levels of knowledge about and previous exposure to the MSI test. Participants held positive attitudes about the potential benefits of the test and perceived few barriers to undergoing the test. Motivations were similar to those cited by individuals considering other genetic tests. Participants with nonmetastatic disease, with lower perceived risk for cancer recurrence, and who reported more self-efficacy endorsed more benefits from the test. Higher levels of cancer-specific psychological distress were associated with more perceived barriers to having the test. These findings suggest that individuals considering the MSI test know very little about it but hold positive attitudes about the test's utility. More distressed patients, patients who perceive themselves at higher risk for cancer recurrence, and patients with metastatic disease might be less motivated to have the MSI test.
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http://dx.doi.org/10.1158/1055-9965.EPI-07-0412DOI Listing
October 2007

Ethnic disparities in adjuvant chemotherapy for breast cancer are not caused by excess toxicity in black patients.

Clin Breast Cancer 2005 Aug;6(3):260-6; discussion 267-9

Department of Oncology-Hematology, Memorial-Sloan Kettering Cancer Center, USA.

Background: Black patients with breast cancer may be at greater risk for chemotherapy-related hematologic toxicity than white patients because of lower baseline blood cell counts. We hypothesize that these baseline differences could lead to excess hematologic toxicity and greater modification of chemotherapy dosing in black patients and that this may contribute to the poorer survival observed in black patients with breast cancer compared with white patients with breast cancer.

Patients And Methods: We performed a retrospective cohort study of black and white patients with breast cancer treated with adjuvant chemotherapy at an academic medical center over an 18-month period. Clinical chart review and pharmacy records were used to collect data on the following: modification of chemotherapy dose or administration; hematologic toxicity; blood cell counts before, during, and after therapy; occurrence of febrile neutropenia; use of prophylactic antibiotics; and use of granulocyte colony-stimulating factor in order to determine whether ethnicity was an independent predictor of these outcomes.

Results: Among 23 black patients and 98 white patients with breast cancer treated with adjuvant chemotherapy, modification of chemotherapy administration occurred in 56 patients (46%). Modification was more common among black patients (65.2% vs. 41.8%; relative risk [RR], 1.56; P = 0.04). Black patients were more likely to receive reduced cumulative doses of adjuvant chemotherapy (RR, 2.49; P = 0.03).

Conclusion: Our findings suggest that hematologic tolerability of adjuvant chemotherapy is similar in black and white patients. Strategies aimed at improving psychosocial barriers to adjuvant therapy and at reducing surgical complications in black patients may improve overall breast cancer outcomes in this group.
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http://dx.doi.org/10.3816/CBC.2005.n.029DOI Listing
August 2005

Drug-metabolizing enzyme polymorphisms predict clinical outcome in a node-positive breast cancer cohort.

J Clin Oncol 2005 Aug;23(24):5552-9

Department of Biostatistics and Epidemiology, Abramson Cancer Center, PA, USA.

Purpose: Adjuvant chemotherapy cures only a subset of women with nonmetastatic breast cancer. Genotypes in drug-metabolizing enzymes, including functional polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST), may predict treatment-related outcomes.

Patients And Methods: We examined CYP3A4*1B, CYP3A5*3, and deletions in GST mu (GSTM1) and theta (GSTT1), as well as a priori-defined combinations of polymorphisms in these genes. Using a cohort of 90 node-positive breast cancer patients who received anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem-cell rescue, we estimated the effect of genotype and other known prognostic factors on disease-free survival (DFS) and overall survival (OS).

Results: Patients who carried homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer DFS (P = .021) and a four-fold poorer OS (P = .031) compared with individuals who did not carry any CYP3A4*1B or CYP3A5*3 variants but had deletions in both GSTT1 and GSTM1 (denoted high-drug genotype group). After adjustment for other significant prognostic factors, the low-drug genotype group retained a significantly poorer DFS (hazard ratio [HR] = 4.9; 95% CI, 1.7 to 14.6; P = .004) and OS (HR = 4.8; 95% CI, 1.8 to 12.9; P = .002) compared with the high- and intermediate-drug combined genotype group. In the multivariate model, having low-drug genotype group status had a greater impact on clinical outcome than estrogen receptor status.

Conclusion: Combined genotypes at CYP3A4, CYP3A5, GSTM1, and GSTT1 influence the probability of treatment failure after high-dose adjuvant chemotherapy for node-positive breast cancer.
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http://dx.doi.org/10.1200/JCO.2005.06.208DOI Listing
August 2005

Interleukin-6 -174G-->C polymorphism is associated with improved outcome in high-risk breast cancer.

Cancer Res 2003 Nov;63(22):8051-6

Department of Medicine (Heme/Onc), Rowan Breast Center of the Abramson Cancer Center, University of Pennsylvania, 14 Penn Tower, 3400 Spruce Street, Philadelphia, PA 19104, USA.

Axillary lymph node involvement in breast cancer is a marker of recurrence risk. Despite aggressive adjuvant therapy, recurrence in patients with four or more involved lymph nodes approaches 50% at 5 years from diagnosis. Markers that can distinguish those likely to relapse from those likely to be cured are needed to tailor therapy and provide accurate prognostic information to patients. Although most work in this area has focused on tumor characteristics, we hypothesized that the host environment might also play a role in determining risk of relapse. We hypothesized that host inflammatory response, mediated in part by production of interleukin-6 (IL-6), might play a role in the elimination of microscopic residual tumor. Polymorphisms in the IL-6 promoter region appear to modulate serum levels of the cytokine via regulation of gene transcription. A single nucleotide polymorphism involving substitution of cytosine for guanine at position -174 has been associated with reduced transcription and improved outcome in a variety of nonmalignant diseases, including coronary artery disease and several autoimmune conditions. Tumor necrosis factor (TNF) alpha is a proinflammatory cytokine that also plays a role in regulating IL-6 transcription. We hypothesized that polymorphisms in IL-6 (-174 G>C) or TNF-alpha (G-238 or G-308) might be associated with prognosis in a subset of patients with high-risk breast cancer. Genotyping was performed on DNA from stored stem cells in 80 breast cancer patients diagnosed with at least four positive axillary lymph nodes at diagnosis who underwent anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem cell rescue. Cox proportional hazards models were used to estimate the effect of genotype and other known prognostic factors on disease-free and overall survival (DFS and OS, respectively). The presence of at least one C allele in the IL-6 promoter at position -174 was significantly associated with both DFS and OS compared with G/G homozygotes. After adjustment for estrogen receptor (ER) status, number of involved lymph nodes, and tumor size, those patients carrying the G/G genotype had a 2.1-fold increase in the rate of failure and a 2.6-fold increase in the rate of death compared with carriers of any C allele at a mean follow-up of 55 months. ER status modulated the effect of IL-6 polymorphism: both DFS and OS were most favorable in patients who were carriers of any C-allele (G/C or C/C) and had ER-positive tumors. The presence of either G/G genotype or an ER-negative tumor increased the hazard of failure [hazard ratio (HR), 2.6 and 3.2, respectively] and death (HR, 2.0 and 2.2, respectively). The combination of both G/G genotype and ER-negative tumor resulted in an additional increase in the hazard of failure (HR, 5.4; four-group comparison, P = 0.003) and death (HR, 6.2; four-group comparison, P = 0.001). TNF-alpha -308 and -238 polymorphisms were not associated with variation in DFS or OS in this cohort. The IL-6-174 promoter polymorphism is associated with clinical outcome in this cohort of node-positive breast cancer patients who received high-dose adjuvant therapy. IL-6 genotype modulated the effect of ER status on outcome. These results support the hypothesis that IL-6 may play an important role in the control of micrometastatic disease in breast cancer. Additional studies are needed to confirm these results and elucidate the mechanisms responsible for these differences.
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November 2003