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Biomedical subjects

William B Farrar

Publications and source records attributed to William B Farrar.

9 recordsLinked to original sources
PubMed2007

Pilot study of rosiglitazone therapy in women with breast cancer: effects of short-term therapy on tumor tissue and serum markers.

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARgamma is associated with antiproliferative effects on human breast cancer cells in preclinical studies. The purpose of this study was to test the hypothesis that PPARgamma ligand therapy might inhibit tumor growth and progression in human breast cancer. EXPERIMENTAL DESIGN: We conducted a pilot trial of short-term (2-6 weeks) treatment with the thiazolidinedione rosiglitazone in 38 women with early-stage (T(is)-T(2), N(0-1), M(0)) breast cancer, administered between the time of diagnostic biopsy and definitive surgery. RESULTS: Short-term treatment with rosiglitazone (8 mg/d) did not elicit significant effects on breast tumor cell proliferation using Ki67 expression as a measure of cell proliferation and surrogate marker of tumor growth and progression. In pretreatment tumors notable for nuclear expression of PPARgamma by immunohistochemistry, down-regulation of nuclear PPARgamma expression occurred following rosiglitazone administration (P = 0.005). No PPARG mutations were identified, and the incidence of P12A and H446H polymorphisms did not differ relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in increased serum adiponectin (P < 0.001), decreased insulin levels (P = 0.005), and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated without serious adverse events. CONCLUSION: Our data indicate that short-term rosiglitazone therapy in early-stage breast cancer patients leads to local and systemic effects on PPARgamma signaling that may be relevant to breast cancer.

Adult↗
PubMed2006

Prospective randomized clinical trial comparing intradermal, intraparenchymal, and subareolar injection routes for sentinel lymph node mapping and biopsy in breast cancer.

BACKGROUND: Multiple injection routes, including intradermal (ID), intraparenchymal (IP), and subareolar (SA), are used for 99mTc-sulfur colloid administration for sentinel lymph node (SLN) mapping and biopsy in breast cancer. The aim of this study was to compare localization by ID, IP, and SA injection routes based on preoperative lymphoscintigraphy and intraoperative identification. METHODS: Four hundred prospectively randomized breast cancers underwent SLN mapping and biopsy. RESULTS: Preoperative lymphoscintigraphy demonstrated localization to the axilla in 126/133 (95%) ID, 82/132 (62%) IP, and 96/133 (72%) SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.081 IP vs. SA), with a mean duration of preoperative lymphoscintigraphy of 139 +/- 18 minutes. Mean time to first localization when localization was demonstrated on preoperative lymphoscintigraphy was 8 +/- 14 minutes for ID, 53 +/- 49 for IP, and 22 +/- 29 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.003 IP vs. SA). Intraoperative identification of a SLN at the time of SLN biopsy was successful in 133/133 (100%) ID, 121/134 (90%) IP, and 126/133 (95%) SA (P < 0.001 ID vs IP; P = 0.014 ID vs. SA; P = 0.168 IP vs. SA), with a mean time from injection of 99mTc-sulfur colloid to start of SLN biopsy of 288 +/- 71 minutes. Mean intraoperative time to harvest the first SLN was 9 +/- 4 minutes for ID, 13 +/- 6 for IP, and 12 +/- 6 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.410 IP vs. SA). CONCLUSIONS: The ID injection route demonstrated a significantly greater frequency of localization, decreased time to first localization on preoperative lymphoscintigraphy, and decreased time to harvest the first SLN. This represents the first prospective randomized clinical trial to confirm superiority of the ID route for administration of 99mTc-sulfur colloid during SLN mapping and biopsy in breast cancer.

Breast Neoplasms↗
PubMed2005

Psychological responses to cancer recurrence.

BACKGROUND: There is a dearth of knowledge regarding the psychological responses to a diagnosis of cancer recurrence. METHODS: An ongoing randomized clinical trial provided the context for prospective study. Women with Stage II/III breast carcinoma (N = 227) were initially assessed after their diagnosis/surgery and before adjuvant therapy and then reassessed every 6 months. Eight years into the trial, 30 patients had recurred (R) and were assessed shortly after receiving their second diagnosis. Their data were compared with a sample of trial patients who had no evidence of disease (disease free [DF]; n = 90). The groups were matched on study arm, disease stage, estrogen receptor status, menopausal status, and time since initial diagnosis. RESULTS: As hypothesized, patients' cancer-specific stress at recurrence in the R group was higher (P < 0.05) than stress levels for the DF group at the equivalent point in time. Importantly, the R group reported stress for their recurrent diagnosis equivalent to that reported for their initial diagnosis. Identical results were found for measures of health status and symptomatology. In contrast, analyses for emotional distress and social functioning showed no pattern of disruption for the R group at cancer recurrence and levels equivalent to that of the DF group. CONCLUSIONS: To the authors' knowledge, this was the first controlled, prospective psychological analysis of patients' responses to cancer recurrence. The findings were consistent with a learning theory conceptualization of the cancer stressor. Patients' stress was "compartmentalized" and did not, at least in the early weeks, result in diffuse emotional distress and quality of life disruption, underscoring the resilience of patients when confronted with cancer recurrence.

Adaptation, Psychological↗
PubMed2005

Breast cancer.

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Antineoplastic Agents↗
PubMed2005

Thyroid carcinoma.

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Biomarkers, Tumor↗
PubMed2004

Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial.

PURPOSE: This randomized clinical trial tests the hypothesis that a psychological intervention can reduce emotional distress, improve health behaviors and dose-intensity, and enhance immune responses. PATIENTS AND METHODS: We studied 227 women who were surgically treated for regional breast cancer. Before adjuvant therapy, women completed interviews and questionnaires assessing emotional distress, social adjustment, and health behaviors. A 60-mL blood sample was drawn for immune assays. Patients were randomly assigned to either the intervention group or assessment only group. The intervention was conducted in small patient groups, with one session per week for 4 months. The sessions included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care. Reassessment occurred after completion of the intervention. RESULTS: As predicted, patients receiving the intervention showed significant lowering of anxiety, improvements in perceived social support, improved dietary habits, and reduction in smoking (all P <.05). Analyses of adjuvant chemotherapy dose-intensity revealed significantly more variability (ie, more dispersion in the dose-intensity values) for the assessment arm (P <.05). Immune responses for the intervention patients paralleled their psychological and behavioral improvements. T-cell proliferation in response to phytohemagglutinin and concanavalin A remained stable or increased for the Intervention patients, whereas both responses declined for Assessment patients; this effect was replicated across three concentrations for each assay (all P <.01). CONCLUSION: These data show a convergence of significant psychological, health behavior, and biologic effects after a psychological intervention for cancer patients.

Adaptation, Psychological↗
PubMed2003

Patterns of recurrence after sentinel lymph node biopsy for breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is gaining acceptance as an alternative to axillary lymph node dissection. The purpose of this study was to determine the frequency and pattern of disease recurrence after SLNB. METHODS: Two-hundred twenty-two consecutive patients undergoing SLNB from April 6, 1998, to October 27, 1999, and who were >or=24 months out from their procedure were identified from a prospectively maintained database. Retrospective chart review and data analysis were performed to identify variables predictive of recurrence. RESULTS: The median patient follow-up was 32 months (range, 24-43 months). A total of 159 patients (72%) were sentinel lymph node (SLN) negative and had no further axillary treatment. Five of these patients (3.1%) developed a recurrence (one local and four distant), with no isolated regional (axillary) recurrences. Sixty-three patients (28%) were SLN positive and underwent a subsequent axillary lymph node dissection. Six of these patients (9.5%) developed a recurrence (three local, one regional, and two distant). Pathologic tumor size (P <.001), lymphovascular invasion (P =.018), and a positive SLN (P =.048) were all statistically significantly associated with disease recurrence. CONCLUSIONS: With a minimum follow-up of 24 months, patients with a negative SLN and no subsequent axillary treatment demonstrate a low frequency of disease recurrence. This supports the use of SLNB as the sole axillary staging procedure in SLN-negative patients.

Adult↗
PubMed2002

Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019.

PURPOSE: There are no published survival data after chemoradiotherapy (chemoRT) in pathologically documented stage IIIB non-small-cell lung cancer. Studies of radiotherapy (RT) alone or chemotherapy followed by RT yield 5-year survivals less than 10%. The Southwest Oncology Group (SWOG) employed the same concurrent chemoRT induction regimen used in its predecessor trimodality trial to determine the efficacy, safety, and long-term outcome of replacing postinduction surgery with additional chemoRT. PATIENTS AND METHODS: Eligible patients for SWOG-9019 had pathologic documentation of T4N0/1, T4N2, or N3 stage IIIB non-small-cell lung cancer. They had pulmonary function adequate to withstand combined-modality therapy, identical to the requirements of the previous trial with postchemoRT surgery. Induction therapy was two cycles of cisplatin plus etoposide (PE) concurrent with once-daily thoracic RT (45 Gy). In the absence of progressive disease, RT was completed to 61 Gy, with two additional cycles of cisplatin plus etoposide. RESULTS: Fifty eligible patients were accrued with tumor-node (TN) substage confirmed on central review: 18, T4N0/1; 12, T4N2; and 20, N3. Grade 4 neutropenia was the most common toxicity (32%). Grade 3/4 esophagitis occurred in 12% and 8%. Median follow-up was 52 months, and overall median survival was 15 months (10 to 22, 95% confidence interval). Three- and 5-year survivals were 17% and 15% (5-year T4N0/1, 17%; T4N2, 13%; and N3, 15%). CONCLUSION: Feasibility and long-term survival support the application of these results as a standard against which mature outcomes of chemoRT trials with new chemotherapy agents can be compared. These results also justify use of the SWOG-9019 approach as a control arm in ongoing phase III trials.

Adult↗