A Pilot Study of Interpersonal Psychotherapy for Depressed Women with Breast Cancer.

This study sought to examine the feasibility and preliminary efficacy of interpersonal psychotherapy (IPT) in the treatment of major depressive disorder (MDD) among women with breast cancer. Seven women with breast cancer and MDD received 12 sessions of IPT. Outcome measures included changes in depression severity, as measured by the Hamilton Rating Depression Scale (HAM-D), and global functioning, as measured by the Global Assessment Scale (GAF). Mixed linear models were used to examine whether change in depressive symptoms mediated change in global functioning. The HAM-D decreased from 21.3 (SD 8.1) to 11.1 (9.6) (p 0.02), whereas the GAF improved from 56.7 (5.5) to 70.3 (15.6) (p 0.049). A mixed regression model indicated that change in HAM-D scores predicted change in GAF scores (p 0.03). These results suggest that IPT is a promising treatment for depression in women with breast cancer. Randomized controlled trials are warranted to confirm the results of this study.

Portrayal of complementary and alternative medicine for cancer by top online news sites.

BACKGROUND: Medical research news provided through the World Wide Web is easily accessible to the general public. Thus, it is necessary to understand how research findings released from online news sources are portrayed. METHODS: The sample includes articles (n=205) published between January 1, 2010 and June 18, 2010 in top online news sites with competitive traffic rankings in the United States as determined by Alexa.com. Google Reader was used to find health-related news articles corresponding to the relevant news sources. Data analysis was performed using SPSS with two-tailed significance values of the χ(2) statistic. RESULTS: A content analysis (n=205 stories) revealed that the majority of complementary and alternative medicine (CAM) modalities for cancer discussed in top online news sources are classified as nutritional therapeutics, and the cancer topic that appeared most frequently was that of prevention. General oncology was the most frequently cited cancer type that was discussed with regard to CAM. Medical journals were the most frequently cited source in CAM/cancer news articles. The majority of news stories on CAM/cancer were neutral in tone, and the relationship between tone and evidence type reported was statistically significant. Observational studies rather than randomized controlled trials were the predominant form of evidence provided for research findings. CONCLUSIONS: Overall, the quality of how online news sources report research findings on complementary and alternative medicine therapies for cancer is fairly high. However, certain top online media sources are more reliable and informative than others when it comes to reporting about CAM remedies for cancer.

Does absolute neutrophil count predict high tumor grade in African-American men with prostate cancer?

BACKGROUND: African-Americans (AA) are at risk for benign ethnic neutropenia (BEN), which has been implicated as a potential source of disparity in cancer outcomes among AAs. Since AAs with prostate cancer (PCa) are more likely to have aggressive pathological features, this investigation sought to determine if absolute neutrophil count (ANC) is associated with adverse pathologic findings at radical prostatectomy (RP) within a cohort of AA men. METHODS: A single-institution, retrospective review was conducted of all AA patients undergoing RP who had a pre-operative CBC with differential and known RP pathology. Neutropenia was defined as ANC ≤1.5 × 10(9) /L (1.5). Clinical and pathologic variables were characterized for the study cohort, and Cox regression and Kaplan-Meier analyses performed to evaluate the association between ANC and adverse pathology. RESULTS: A total of 336 patients were included, and 18 patients (5.4%) had ANC ≤1.5. Mean age was 59.8 ± 7.5 years; mean follow-up time 47.4 ± 43.3 months. Neutropenic patients had significantly higher clinical stages and pathologic Gleason scores (P < 0.05). On multivariable analysis, ANC ≤1.5 was significantly predictive of high tumor grade (HR 1.22, CI 1.01-1.48). CONCLUSIONS: Neutropenia in AAs predicts high tumor grade at prostatectomy. Further studies are necessary to further characterize the importance of these findings with regard to the pathogenesis of PCa, particularly as it relates to the AA population.

FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an incurable disease where most patients succumb within the first year of diagnosis. Both standard chemotherapy regimens and mAbs directed against ATLL tumor markers do not alter this aggressive clinical course. Therapeutic development would be facilitated by the discovery of genes and pathways that drive or initiate ATLL, but so far amenable drug targets have not been forthcoming. Because the IL-2 signaling pathway plays a prominent role in ATLL pathogenesis, mutational analysis of pathway components should yield interesting results. In this study, we focused on JAK3, the nonreceptor tyrosine kinase that signals from the IL-2R, where activating mutations have been found in diverse neoplasms. We screened 36 ATLL patients and 24 ethnically matched controls and found 4 patients with mutations in JAK3. These somatic, missense mutations occurred in the N-terminal FERM (founding members: band 4.1, ezrin, radixin, and moesin) domain and induced gain of function in JAK3. Importantly, we show that these mutant JAK3s are inhibited with a specific kinase inhibitor already in human clinical testing. Our findings underscore the importance of this pathway in ATLL development and offer a therapeutic handle for this incurable cancer.

Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer.

PURPOSE: Noncompliance with adjuvant hormonal therapy among women with breast cancer is common. Little is known about the impact of financial factors, such as co-payments, on noncompliance. PATIENTS AND METHODS: We conducted a retrospective cohort study by using the pharmacy and medical claims database at Medco Health Solutions. Women older than age 50 years who were taking aromatase inhibitors (AIs) for resected breast cancer with two or more mail-order prescriptions, from January 1, 2007, to December 31, 2008, were identified. Patients who were eligible for Medicare were analyzed separately. Nonpersistence was defined as a prescription supply gap of more than 45 days without subsequent refill. Nonadherence was defined as a medication possession ratio less than 80% of eligible days. RESULTS: Of 8110 women younger than age 65 years, 1721 (21.1%) were nonpersistent and 863 (10.6%) were nonadherent. Among 14,050 women age 65 years or older, 3476 (24.7%) were nonpersistent and 1248 (8.9%) were nonadherent. In a multivariate analysis, nonpersistence (ever/never) in both age groups was associated with older age, having a non-oncologist write the prescription, and having a higher number of other prescriptions. Compared with a co-payment of less than $30, a co-payment of $30 to $89.99 for a 90-day prescription was associated with less persistence in women age 65 years or older (odds ratio [OR], 0.69; 95% CI, 0.62 to 0.75) but not among women younger than age 65, although a co-payment of more than $90 was associated with less persistence both in women younger than age 65 (OR, 0.82; 95% CI, 0.72 to 0.94) and those age 65 years or older (OR, 0.72; 95% CI, 0.65 to 0.80). Similar results were seen with nonadherence. CONCLUSION: We found that higher prescription co-payments were associated with both nonpersistence and nonadherence to AIs. This relationship was stronger in older women. Because noncompliance is associated with worse outcomes, future policy efforts should be directed toward interventions that would help patients with financial difficulties obtain life-saving medications.

Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers.

UNLABELLED: Comparative effectiveness research has become an integral part of health care planning in most developed countries. In a simulated cohort of women, aged 30-65, who tested positive for BRCA1 or BRCA2 mutations, we compared outcomes of mammography with and without MRI, prophylactic oophorectomy with and without mastectomy, mastectomy alone, and chemoprevention. METHODS: Using Treeage 9.02 software, we developed Markov models with 25,000 Monte Carlo simulations and conducted probabilistic sensitivity analysis. We based mutation penetrance rates, breast and ovarian cancer incidence, and mortality rates, and costs in terms of 2009 dollars, on published studies and data from the Surveillance, Epidemiology, and End RESULTS (SEER) Program and the Centers for Medicare and Medicaid Services. We used preference ratings obtained from mutation carriers and controls to adjust survival for quality of life (QALYs). RESULTS: For BRCA1 mutation carriers, prophylactic oophorectomy at $1,741 per QALY, was more cost effective than both surgeries and dominated all other interventions. For BRCA2 carriers, prophylactic oophorectomy, at $4,587 per QALY, was more cost effective than both surgeries. Without quality adjustment, both mastectomy and BSO surgeries dominated all other interventions. In all simulations, preventive surgeries or chemoprevention dominated or were more cost effective than screening because screening modalities were costly. CONCLUSION: Our analysis suggested that among BRCA1/2 mutation carriers, prophylactic surgery would dominate or be cost effective compared to chemoprevention and screening. Annual screening with MRI and mammography was the most effective strategy because it was associated with the longest quality-adjusted survival, but it was also very expensive.

Prophylactic pancreatectomy for intraductal papillary mucinous neoplasm does not negatively impact quality of life: a preliminary study.

BACKGROUND: Uncertainties remain over whether prophylactic surgery or surveillance is the better management option for intraductal papillary mucinous neoplasm of the pancreas. The aim of this preliminary study was to determine if differences in anxiety and quality of life exist between patients who have surgery or undergo surveillance. METHODS: Recruited patients were given the Hospital Anxiety and Depression Scale, a general survey that evaluates anxiety, and the Functional Assessment of Cancer Therapy-Pancreas, a disease-specific survey that assesses quality of life. Questionnaires were scored by standardized algorithms and compared using Student's t test or Wilcoxon rank-sum test. RESULTS: Sixteen patients had surgery and 16 patients were undergoing surveillance. Mean age was 66.8 ± 19.9 years. Responses from both groups were remarkably similar. Surgery patients scored higher on the anxiety questionnaire than surveillance patients, although not statistically significant (p = 0.09). Surgery patients scored lower on the functional well-being domain of the quality-of-life instrument (p = 0.03), though there were no differences in overall quality of life. CONCLUSION: Prophylactic surgery does not reduce quality of life, and a protocol of surveillance does not appear to generate undue anxiety in this select patient group. Further investigation with more patients is required to validate these findings.

Breast cancer-related preferences among women with and without BRCA mutations.

Preference ratings are used to quantify quality of life in analyses used for health care policy making. Subjects indicated how many years of their life expectancy they would trade to avoid BRCA mutations, breast/ovarian cancer, and five preventive measures including prophylactic surgery, annual mammograms, and annual magnetic resonance imaging (MRI). Among 243 respondents, both the 83 women with mutations and the 160 controls rated mammography highest (most favorably), MRI next highest, having a child with a mutation lowest, and ovarian cancer next lowest. Controls rated prophylactic surgery higher than cancer (P < 0.01), but women with mutations did not. In logistic regression, controls were twice as willing as women with mutations to trade time except for screening modalities; younger, lower-income, and non-white women were more willing to trade time than older, higher-income, and white women. Our findings support the use of average-risk individuals' time trade-off preference ratings for health care policy development.

Pancreatic proteolytic enzyme therapy compared with gemcitabine-based chemotherapy for the treatment of pancreatic cancer.

PURPOSE Conventional medicine has had little to offer patients with inoperable pancreatic adenocarcinoma; thus, many patients seek alternative treatments. The National Cancer Institute, in 1998, sponsored a randomized, phase III, controlled trial of proteolytic enzyme therapy versus chemotherapy. Because most eligible patients refused random assignment, the trial was changed in 2001 to a controlled, observational study. METHODS All patients were seen by one of the investigators at Columbia University, and patients who received enzyme therapy were seen by the participating alternative practitioner. Of 55 patients who had inoperable pancreatic cancer, 23 elected gemcitabine-based chemotherapy, and 32 elected enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. Primary and secondary outcomes were overall survival and quality of life, respectively. Results At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group (median survival, 14 months) and enzyme treatment groups (median survival, 4.3 months) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 (P < .001). At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P < .01). CONCLUSION Among patients who have pancreatic cancer, those who chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better quality of life than those who chose proteolytic enzyme treatment.

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.

Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma.

PURPOSE: Anthracycline-based chemotherapy, which improves survival for patients with non-Hodgkin's lymphoma, is often withheld from elderly patients because of its cardiotoxicity. We studied the cardiac effects of doxorubicin in a population-based sample of older patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Among patients age > or = 65 years diagnosed with DLBCL from 1991 to 2002 in the Surveillance, Epidemiology, and End Results-Medicare database, we developed logistic regression models of the associations of doxorubicin with demographic, clinical, and cardiac variables. We then developed Cox proportional hazards models of the association between doxorubicin and subsequent congestive heart failure (CHF), taking predictors of CHF into account. RESULTS: Of 9,438 patients with DLBCL, 3,164 (42%) received doxorubicin-based chemotherapy. Any doxorubicin use was associated with a 29% increase in risk of CHF (95% CI, 1.02 to 1.62); CHF risk increased with number of doxorubicin claims, increasing age, prior heart disease, comorbidities, diabetes, and hypertension; hypertension intensified the effect of doxorubicin on risk of CHF (hazard ratio = 1.8; P < .01). In the 8 years after diagnosis, the adjusted CHF-free survival rate was 74% in doxorubicin-treated patients versus 79% in patients not treated with doxorubicin. CONCLUSION: Among patients receiving chemotherapy for DLBCL, those with prior heart disease were less likely than others to be treated with doxorubicin, and those who received doxorubicin were more likely than others to develop CHF. Various cardiac risk factors increased CHF risk, but only hypertension was synergistic with doxorubicin. Doxorubicin has dramatically improved survival of DLBCL patients; nonetheless, some subgroups may benefit from efforts to reduce doxorubicin-related CHF risk.

Comparing genetic ancestry and self-described race in african americans born in the United States and in Africa.

Genetic association studies can be used to identify factors that may contribute to disparities in disease evident across different racial and ethnic populations. However, such studies may not account for potential confounding if study populations are genetically heterogeneous. Racial and ethnic classifications have been used as proxies for genetic relatedness. We investigated genetic admixture and developed a questionnaire to explore variables used in constructing racial identity in two cohorts: 50 African Americans and 40 Nigerians. Genetic ancestry was determined by genotyping 107 ancestry informative markers. Ancestry estimates calculated with maximum likelihood estimation were compared with population stratification detected with principal components analysis. Ancestry was approximately 95% west African, 4% European, and 1% Native American in the Nigerian cohort and 83% west African, 15% European, and 2% Native American in the African American cohort. Therefore, self-identification as African American agreed well with inferred west African ancestry. However, the cohorts differed significantly in mean percentage west African and European ancestries (P < 0.0001) and in the variance for individual ancestry (P < or = 0.01). Among African Americans, no set of questionnaire items effectively estimated degree of west African ancestry, and self-report of a high degree of African ancestry in a three-generation family tree did not accurately predict degree of African ancestry. Our findings suggest that self-reported race and ancestry can predict ancestral clusters but do not reveal the extent of admixture. Genetic classifications of ancestry may provide a more objective and accurate method of defining homogenous populations for the investigation of specific population-disease associations.

Neutropenia in 6 ethnic groups from the Caribbean and the U.S.

BACKGROUND: Low white blood cell counts (WBC) or absolute neutrophil counts (ANC) may delay or prevent the completion of appropriate chemotherapy, especially among women receiving adjuvant therapy for breast and colon cancer, and affect cancer survival. Because race/ethnicity is also associated with survival, the authors compared WBC and ANC in healthy American-born women of African descent and European descent, and women from Barbados/Trinidad-Tobago, the Dominican Republic, Haiti, and Jamaica. METHODS: Blood samples from 261 healthy women ages 20 to 70 years were tested for WBC with differential, cytokine and growth factor levels, and ancestry informative and neutrophil elastase polymorphisms. The authors analyzed the association between neutropenia and serum WBC growth factor levels, cytokine levels, and neutrophil elastase c199a polymorphism. RESULTS: The median WBC and ANC differed among the 6 groups (P < .01 for WBC and P < .0001 for ANC). Dominicans were found to have higher median WBC and ANC than all other groups (P < .03). Neutropenia (ANC < 1500 cu/mm) was observed among 2.7% to 12.5% of the groups of predominantly African descent; no other groups were found to have neutropenia (P < .05). Granulocyte-colony-stimulating factor was found to be lower in white women, but tumor necrosis factor-alpha and C-reactive protein were not found to be correlated with ethnicity. Women of African origin were more likely to have polymorphisms of African ancestry (P < .001) and c199a alleles (P < .0001), which were also associated with low ANC levels. CONCLUSIONS: In the current study, the authors observed a strong association between neutropenia and African descent among asymptomatic women from the U.S. and the Caribbean. Among women of African descent who develop a malignancy, this association may contribute to racial disparities in treatment and outcomes.

Neutropenia in 6 ethnic groups from the Caribbean and the U.S.

BACKGROUND: Low white blood cell counts (WBC) or absolute neutrophil counts (ANC) may delay or prevent the completion of appropriate chemotherapy, especially among women receiving adjuvant therapy for breast and colon cancer, and affect cancer survival. Because race/ethnicity is also associated with survival, the authors compared WBC and ANC in healthy American-born women of African descent and European descent, and women from Barbados/Trinidad-Tobago, the Dominican Republic, Haiti, and Jamaica. METHODS: Blood samples from 261 healthy women ages 20 to 70 years were tested for WBC with differential, cytokine and growth factor levels, and ancestry informative and neutrophil elastase polymorphisms. The authors analyzed the association between neutropenia and serum WBC growth factor levels, cytokine levels, and neutrophil elastase c199a polymorphism. RESULTS: The median WBC and ANC differed among the 6 groups (P < .01 for WBC and P < .0001 for ANC). Dominicans were found to have higher median WBC and ANC than all other groups (P < .03). Neutropenia (ANC < 1500 cu/mm) was observed among 2.7% to 12.5% of the groups of predominantly African descent; no other groups were found to have neutropenia (P < .05). Granulocyte-colony-stimulating factor was found to be lower in white women, but tumor necrosis factor-alpha and C-reactive protein were not found to be correlated with ethnicity. Women of African origin were more likely to have polymorphisms of African ancestry (P < .001) and c199a alleles (P < .0001), which were also associated with low ANC levels. CONCLUSIONS: In the current study, the authors observed a strong association between neutropenia and African descent among asymptomatic women from the U.S. and the Caribbean. Among women of African descent who develop a malignancy, this association may contribute to racial disparities in treatment and outcomes.

Surgeon characteristics and receipt of adjuvant radiotherapy in women with breast cancer.

BACKGROUND: Adjuvant radiotherapy following breast conservation surgery (BCS) is considered to be an indicator of quality of care for the majority of women with breast cancer, but many women do not receive adjuvant radiotherapy. We investigated the association of surgeon-related factors with receipt of adjuvant radiotherapy after BCS. METHODS: We used the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database to identify women aged 65 years or older with stage I/II breast cancer who were diagnosed between 1991 and 2002 and underwent BCS. We collected demographic and clinical data from SEER and treatment information from Medicare claims data. The American Medical Association Masterfile was used to obtain information on surgeons' characteristics, including sex, medical school location (United States or elsewhere), and type of degree (MD or Doctorate in Osteopathic Medicine [DO]). The associations of patient (age, race, rural vs urban residence, comorbidities, marital status), tumor (hormone receptor status, grade, stage), and surgeon-related factors with receipt of adjuvant radiotherapy were analyzed using Generalized Estimating Equations to control for clustering. All statistical tests were two-sided. RESULTS: Of 29,760 women in our sample, 22,207 (75%) received radiotherapy. Patients who received adjuvant radiotherapy were younger, had fewer comorbidities, and were more likely to be white, married, from an urban area, and diagnosed in a later year compared with those who did not. They were also more likely to have a surgeon who was female (79% vs 73%), had an MD degree (75% vs 68%), or was US trained (75% vs 70%). The multivariable analysis confirmed the association of radiotherapy with having a surgeon who was female (odds ratio [OR] = 1.13; 95% confidence interval [CI] = 1.06 to 1.27), had an MD degree (OR = 1.55; 95% CI = 1.24 to 1.91), was US trained (OR = 1.12; 95% CI = 1.01 to 1.25), or had more than 15 patients (OR = 1.18; 95% CI = 1.10 to 1.28). CONCLUSIONS: Surgeon characteristics were associated with patients' receipt of adjuvant radiotherapy after BCS after controlling for patient and tumor characteristics, although the individual effect sizes were small for surgeon sex, location of training, and type of medical degree. More research is warranted to confirm the associations to determine whether they reflect surgeon behavior, patient response, or physician-patient interactions.