Victor R. Grann

Randomized Trial of Black Cohosh for the Treatment of Hot Flashes Among Women With a History of Breast Cancer

PURPOSE Most breast cancer survivors experience hot flashes; many use complementary or alternative remedies for these symptoms. We undertook a randomized clinical trial of black cohosh, a widely used herbal remedy for menopausal symptoms, among breast cancer patients. PATIENTS AND METHODS Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use. At enrollment, patients completed a questionnaire about demographic factors and menopausal symptoms. Before starting to take the pills and at 30 and 60 days, they completed a 4-day hot flash diary. At the final visit, they completed another menopausal symptom questionnaire. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in a subset of patients at the first and final visits. RESULTS Of 85 patients (59 on tamoxifen, 26 not on tamoxifen) enrolled in the study, 42 were assigned to treatment and 43 were assigned to placebo; 69 completed all three hot flash diaries. Both treatment and placebo groups reported declines in number and intensity of hot flashes; the differences between the groups were not statistically significant. Both groups also reported improvements in menopausal symptoms that were, for the most part, not significantly different. Changes in blood levels of FSH and LH also did not differ in the two groups. CONCLUSION Black cohosh was not significantly more efficacious than placebo against most menopausal symptoms, including number and intensity of hot flashes. Our study illustrates the feasibility and value of standard clinical trial methodology in assessing the efficacy and safety of herbal agents.

Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study

PURPOSE Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged > or = 65 years with long-term follow-up. PATIENTS AND METHODS In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women > or = 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. RESULTS Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. CONCLUSION When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

Racial Disparities in Treatment and Survival Among Women With Early-Stage Breast Cancer

PURPOSE Black women with breast cancer are known to have poorer survival than white women. Suboptimal treatment may compromise the survival benefits of adjuvant chemotherapy. We analyzed the association of race and survival with duration of treatment and number of treatment cycles among women receiving chemotherapy for early-stage breast cancer. PATIENTS AND METHODS Patients were women in the Henry Ford Health System tumor registry who were diagnosed with stage I/II breast cancer between January 1, 1996, and December 31, 2001, who received adjuvant chemotherapy. We calculated an observed/expected ratio of treatment duration and of completed chemotherapy cycles for each patient. Using Cox proportional hazards models, we analyzed the association of early treatment termination and treatment duration with all-cause mortality, controlling for age, race, stage, hormone receptor status, grade, comorbidity score, and doxorubicin use. RESULTS Of 472 eligible patients, 28% (31% black, 23% white; P = .03) received fewer cycles of treatment than expected. Black race, receipt of < or = 75% of the expected number of cycles, increasing age, hormone receptor negativity, and a comorbidity score of more than 1 were associated with poorer survival. Among the 344 patients receiving the expected number of cycles, 60% experienced delays. These delays did not reduce survival. CONCLUSION This study is the first to find that a substantial fraction of women with early-stage breast cancer terminated their chemotherapy prematurely and that early termination was associated with both black race and poorer survival. A better understanding of the determinants of suboptimal treatment may lead to interventions that can reduce racial disparities and improve breast cancer outcomes for all women.

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-Hodgkins 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.

Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1- positive or BRCA2-positive patients

PURPOSE Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. METHODS A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature. RESULTS For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs. CONCLUSION Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.

Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma.

The objective of this study was to assess hormone receptor status as an independent predictor of survival in a population‐based cohort of women with breast carcinoma who were followed for up to 11 years.

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

Use of Adjuvant Chemotherapy and Radiation Therapy for Rectal Cancer Among the Elderly: A Population-Based Study

30, a co-payment of

Effect of Prevention Strategies on Survival and Quality-Adjusted Survival of Women With BRCA1/2 Mutations: An Updated Decision Analysis

30 to

Variations in the Use of Chemotherapy for Elderly Patients With Advanced Ovarian Cancer: A Population-Based Study

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