Symptom response analysis of a randomized controlled trial of reflexology for symptom management among women with advanced breast cancer.

PURPOSE: To examine symptom responses resulting from a home-based reflexology intervention delivered by a friend/family caregivers to women with advanced breast cancer undergoing chemotherapy, targeted, and/or hormonal therapy. METHODS: Patient-caregiver dyads (N = 256) were randomized to 4 weekly reflexology sessions or attention control. Caregivers in the intervention group were trained by a reflexology practitioner in a 30-min protocol. During the 4 weeks, both groups completed telephone symptom assessments using the M. D. Anderson Symptom Inventory. Those who completed at least one weekly call were included in this secondary analysis (N = 209). Each symptom was categorized as mild, moderate, or severe using established interference-based cut-points. Symptom response meant an improvement by at least one category or remaining mild. Symptom responses were treated as multiple events within patients and analyzed using generalized estimating equations technique. RESULTS: Reflexology was more successful than attention control in producing responses for pain (OR = 1.84, 95% CI (1.05, 3.23), p = 0.03), with no significant differences for other symptoms. In the reflexology group, greater probability of response across all symptoms was associated with lower number of comorbid condition and lower depressive symptomatology at baseline. Compared to odds of responses on pain (chosen as a referent symptom), greater odds of symptom response were found for disturbed sleep and difficulty remembering with older aged participants. CONCLUSIONS: Home-based caregiver-delivered reflexology was helpful in decreasing patient-reported pain. Age, comorbid conditions, and depression are potentially important tailoring factors for future research and can be used to identify patients who may benefit from reflexology. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01582971.

Using gene expression data to direct breast cancer therapy: evidence from a preclinical trial.

The heterogeneity both within and between breast cancers presents a significant clinical challenge for both diagnosis and therapy. This heterogeneity is present at all levels of analysis in breast cancer, ranging from genomic to metabolomic. A function of this heterogeneity is that numerous signaling networks are activated, and while treatment of one arm may be initially effective, this allows the tumor to be poised to evolve a resistance mechanism. Here we review the classification of breast cancers and discuss therapy of hormone positive, HER2 positive, and triple negative breast cancers. Model systems for breast cancer are examined allowing for a preclinical trial using a personalized medicine approach to be tested. This preclinical trial was based solely on cell signaling pathway activation and effectively and specifically blocked tumor growth in a preclinical model system.

A Randomized Clinical Trial of Caregiver-Delivered Reflexology for Symptom Management During Breast Cancer Treatment.

PURPOSE: The objective of this study was to determine the effects of a home-based reflexology intervention delivered by a friend/family caregiver compared with attention control on health-related quality of life of women with advanced breast cancer undergoing chemotherapy, targeted and/or hormonal therapy. METHODS: Patient-caregiver dyads (N = 256) were randomized to four weekly reflexology sessions or attention control. Caregivers in the intervention group were trained in a 30-minute protocol. During the four weeks, both groups had telephone symptom assessments, and intervention group had fidelity assessments. The intervention effects were assessed using linear mixed-effects models at weeks 5 and 11 for symptom severity and interference with daily activities, functioning, social support, quality of patient-caregiver relationship, and satisfaction with life. RESULTS: Significant reductions in average symptom severity (P = 0.02) and interference (P < 0.01) over 11 weeks were found in the reflexology group compared with control, with no group differences in functioning, social support, quality of relationship, or satisfaction with life at weeks 5 and 11. Stronger quality of relationship was associated with lower symptom interference in the entire sample (P = 0.02), but controlling for it did not diminish the effect of intervention on symptoms. Significant reductions in symptom severity in the reflexology group compared with attention control were seen during weeks 2-5 but were reduced at Week 11. DISCUSSION: Efficacy findings of caregiver-delivered reflexology with respect to symptom reduction open a new evidence-based avenue for home-based symptom management.

The Dilemma of Breast Cancer Treatment and Existing Collagen Vascular Disease: A Case of Scleroderma and Review of the Literature.

Collagen vascular diseases present a treatment dilemma for patients with breast cancer. Due to the potential for severe, acute, and late complications of radiation therapy, a history of collagen vascular disease (CVD) is a relative contraindication to breast-conserving treatment. We present a case of early stage breast cancer in a patient with severe scleroderma treated with breast-conserving surgery without radiation and a brief review of the published literature regarding the therapeutic approach to the patient with CVD and breast cancer.

Endothelin-1 enriched tumor phenotype predicts breast cancer recurrence.

Introduction. Breast cancer recurrence can develop years after primary treatment. Crosstalk between breast cancer cells and their stromal microenvironment may influence tumor progression. Our primary study aim was to determine whether endothelin-1 (ET-1) expression in tumor and stroma predicts breast cancer relapse. The secondary aim was to determine ET-1/endothelin receptor A (ETAR) role on signaling pathways and apoptosis in breast cancer. Experimental Design. Patients with histologically documented stages I-III invasive breast cancer were included in the study. ET-1 expression by immunohistochemistry (IHC) in tumor cells and stroma was analyzed. Association between ET-1 expression and clinical outcome was assessed using multivariate Cox proportional hazard model. Kaplan-Meier curves were used to estimate disease-free survival (DFS). In addition, the effect of ET-1/ETAR on signaling pathways and apoptosis was evaluated in MCF-7 and MDA-MB-231 breast cancer cells. Results. With a median followup of 7 years, ET-1 non-enriched tumor phenotype had a significant association with favorable disease-free survival (HR = 0.16; 95% CI 0.03-0.77; P value <0.02). ER negativity, advanced stage of disease and ET-1-enriched tumor phenotype were all associated with a higher risk for recurrence. Experimental study demonstrated that ET-1 stimulation promoted Akt activation in MCF-7 and MDA-MB-231 cells. Furthermore, silencing of ETAR induced apoptosis in both hormone receptor negative and hormone receptor positive breast cancer cells. Conclusions. We found ET-1 expression in tumor and stroma to be an independent prognostic marker for breast cancer recurrence. Prospective studies are warranted to examine whether ET-1 expression in tumor/stroma could assist in stratifying patients with hormone receptor positive breast cancer for adjuvant therapy.

Concordance between patient reports of cancer-related symptoms and medical records documentation.

CONTEXT: Two sources of symptom data, patient report and medical records documentation, have been used in studies focusing on chronic conditions. The concordance of patient-reported cancer-related symptoms and clinician reports as documented in the medical records needs to be evaluated. OBJECTIVES: To compare patient reports with medical record documentation of 12 disease- and treatment-related symptoms for women with advanced breast cancer undergoing chemotherapy or hormonal therapy for cancer control. METHODS: Women (n=384) were recruited from 13 oncology clinics in the midwestern U.S. They completed telephone interviews at intake, five, and 11 weeks, where they reported the presence of 12 symptoms using a checklist. Medical records were abstracted when women completed the study. The concordance between patient reports and medical record documentation was assessed using percent agreement, kappa statistics, and McNemar's tests. Administration of medication for symptoms and patient characteristics were investigated in relation to the agreement of the two sources of data. RESULTS: Poor to slight agreement was found, and disagreement was significant for all 12 symptoms. The concordance between symptom presence in the medical record and administration of medication for the management of those symptoms was moderate. Patient characteristics were not associated with agreement, except for age. The agreement was higher for older women for the symptom of mouth sores. CONCLUSION: Medical records may not provide adequate documentation of symptoms, and collection of patient-reported symptom data from women with advanced breast cancer is critical to quality clinical management.

Recruitment and early retention of women with advanced breast cancer in a complementary and alternative medicine trial.

More than 80% of women with breast cancer are now reported to be using complementary and alternative medicine (CAM) therapies during conventional treatment. A randomized clinical trial (RCT) of reflexology with late stage breast cancer patients serves as the data source for this article. The purposes were to investigate: (i) reasons for refusal to participate in a RCT of reflexology; (ii) the differences between those who completed the baseline interview and those who dropped out before baseline; and (iii) the utility of the Palliative Prognostic Score (PPS) as a prognostic screening tool in minimizing early attrition (before baseline) from the trial. Eligible women (N = 400) approached at 12 cancer centers in the Midwest had advanced breast cancer, were on chemotherapy or hormonal therapy, and had a PPS of 11 or less. Comparisons of those who dropped out early (N = 33) to those who stayed in the trial (N = 240) were carried out using Wilcoxon rank, t-, chi-squared and Fisher's exact tests. The reasons of being "too sick" or "overwhelmed" were given by less than 12% of the women who refused to participate. There was a higher early dropout rate among black women compared to other (primarily white) women (P = .01). Cancer recurrence and metastasis, age, and the PPS were not predictive of early retention of women. Specialized techniques may be needed to ensure black women remain in the trial once consented. Women with advanced disease were likely to enter and remain in the trial despite deterioration in health.

Lymphomatoid granulomatosis masquerading as interstitial pneumonia in a 66-year-old man: a case report and review of literature.

Lymphomatoid granulomatosis (LG) is a rare, Epstein-Barr virus (EBV)-associated systemic angiodestructive lymphoproliferative disorder that may progress to a diffuse large B cell lymphoma. Pulmonary involvement may mimic other more common lung pathologies including pneumonias. Therapeutic standards have not been established for LG, but rituximab, interferon-alpha2b (INF-alpha2b), and chemotherapy have shown to improve symptoms and long term prognosis.We report a case of rapid respiratory deterioration in a 66-year-old man with clinical presentation, chest radiography, pulmonary function testing and high resolution computed tomography (HRCT) findings consistent with idiopathic interstitial pneumonia, but very poor response to antibiotics and low dose steroids. Lung biopsy showed histopathology consistent with LG that was confirmed by a positive in situ hybridization for Epstein - Barr virus encoded RNA (EBER). The patient was treated with rituximab and combination chemotherapy and showed significant initial clinical improvement with gradual resolution of abnormal findings on imaging. However, the patient developed pancytopenia as a complication of chemotherapy and died secondary to septic shock and renal failure that were refractory to medical management. Autopsy showed diffuse alveolar damage but no evidence of any residual LG within the lungs.This case demonstrates that an open lung biopsy or video-assisted thoracoscopic surgical (VATS) biopsy is often necessary to rule out the presence of LG in order to determine the appropriate therapeutic strategy early in the course of illness to improve prognosis.

Managing symptoms among patients with breast cancer during chemotherapy: results of a two-arm behavioral trial.

PURPOSE: In this study, we compare symptom response and times to response among patients with breast cancer who were assigned to either a cognitive behavioral Nurse-Administered Symptom Management intervention or an Automated Telephone Symptom Management (ATSM) intervention. PATIENTS AND METHODS: Patients with breast cancer were identified from a larger trial. Baseline equivalence existed between arms, and there was no differential attrition by arm. Anchor-based definition of response using mild, moderate, and severe categories of symptom severity were used. Responses and times to response for 15 symptoms were investigated in relation to trial arm, comorbid conditions, treatment protocols, and metastatic versus localized disease. RESULTS: The ATSM arm was more effective among patents with metastatic disease. Compared with patients receiving combination chemotherapy protocols, those treated with single agents had greater response and shorter time to response. CONCLUSION: An educational information intervention delivered via an automated voice response system that assesses symptoms and refers patients to a Symptom Management Guide is more effective than a complex cognitive behavioral approach in terms of producing greater symptom responses in shorter time intervals among patients with metastatic disease.

Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27.

PURPOSE: National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 was designed to determine whether four cycles of doxorubicin and cyclophosphamide (AC) administered preoperatively improved breast cancer disease-free survival (DFS) and overall survival (OS) compared with AC administered postoperatively. Protocol B-27 was designed to determine the effect of adding docetaxel (T) to preoperative AC on tumor response rates, DFS, and OS. PATIENTS AND METHODS: Analyses were limited to eligible patients. In B-18, 751 patients were assigned to receive preoperative AC, and 742 patients were assigned to receive postoperative AC. In B-27, 784 patients were assigned to receive preoperative AC followed by surgery, 783 patients were assigned to AC followed by T and surgery, and 777 patients were assigned to AC followed by surgery and then T. RESULTS: Results from B-18 show no statistically significant differences in DFS and OS between the two groups. However, there were trends in favor of preoperative chemotherapy for DFS and OS in women less than 50 years old (hazard ratio [HR] = 0.85, P = .09 for DFS; HR = 0.81, P = .06 for OS). DFS conditional on being event free for 5 years also demonstrated a strong trend in favor of the preoperative group (HR = 0.81, P = .053). Protocol B-27 results demonstrated that the addition of T to AC did not significantly impact DFS or OS. Preoperative T added to AC significantly increased the proportion of patients having pathologic complete responses (pCRs) compared with preoperative AC alone (26% v 13%, respectively; P < .0001). In both studies, patients who achieved a pCR continue to have significantly superior DFS and OS outcomes compared with patients who did not. CONCLUSION: B-18 and B-27 demonstrate that preoperative therapy is equivalent to adjuvant therapy. B-27 also showed that the addition of preoperative taxanes to AC improves response.

Thrombotic microangiopathy syndrome as an AIDS-defining illness: the experience of J. Stroger Hospital of Cook County.

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are severe life-threatening disseminated thrombotic microangiopathies (TMA). Although many cases are idiopathic, TMA can occur in association with pregnancy, malignancy, autoimmune diseases, and HIV infection. We retrospectively analyzed the cases of 17 patients with TMA coexistent with HIV infection admitted to our institution. Median T-cell count at presentation was 28 cells/mm3 Patients presented with severe thrombocytopenia (median platelet count 19 x 10(9)/L) and high lactate dehydrogenase levels (median 1,057 U/L). The majority of patients (82%) presented with renal dysfunction. Forty-one percent of patients had fever and 29% had neurological signs at presentation, which were associated with inferior outcome. Despite plasma exchange, inpatient mortality for the first TMA episode was 47%. Some patients relapsed following an initial TMA episode. However, there were responders with remissions lasting 5 years. We conclude that TMA, coexistent with an HIV-associated low CD4 count, is a treatable condition. Considering TMA as an AIDS-defining illness may help clinicians recognize this syndrome earlier, leading to prompter treatment and improved survival rates.