Judith S. Jacobson

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.

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.

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

PURPOSE Combined adjuvant fluorouracil (5-FU)-based chemotherapy with radiation is now the standard of care for locally advanced rectal cancer in the United States. We investigated the use of these treatments for stages II and III rectal cancer among the elderly and the effectiveness of these treatments on a population-based scale. PATIENTS AND METHODS The linked Surveillance, Epidemiology, and End-Results-Medicare database was used to identify 1,807 Medicare beneficiaries > or = 65 years of age with stage II or III rectal cancer who underwent surgical resection between 1992 and 1996. We excluded members of a health maintenance organization in the 12 months before or 4 months after their diagnosis and those who died within 4 months of diagnosis. We used multivariate analysis to identify factors associated with combined 5-FU and radiation therapy, and propensity score methodology to determine survival benefit for those treated. RESULTS We found that 37% of patients received both adjuvant 5-FU and radiation therapy, 11% 5-FU alone, and 14% radiation alone. Decreasing age, increasing lymph node positivity, comorbid conditions, and nonblack race were associated with increased probability of treatment with 5-FU and radiation. Combined chemotherapy/radiation therapy was associated with improved survival for stage III (relative risk, 0.71; 95% confidence interval, 0.56 to 0.90), but not for stage II rectal cancer (relative risk, 0.89; 95% confidence interval, 0.70 to 1.14). CONCLUSION The association of combined treatment with improved survival in node-positive disease was similar to that observed in other studies. In the absence of data from well-designed randomized controlled trials, our observational data support efforts on the part of clinicians to make appropriate referrals and provide combined treatment for elderly patients with stage III rectal cancer.

Use of Unconventional Therapies by Children With Cancer at an Urban Medical Center

Purpose The aim of this study was to determine the prevalence, modalities, and determinants of use of unconventional therapies among children with cancer receiving conventional treatment at an urban academic medical center in the United States. Patients and Methods We interviewed the parents of patients and/or patients who were receiving or had received conventional therapy for treatment of childhood cancer. Of 78 patients/parents asked, 75 consented to the interview, which included demographic factors, life events, and use of unconventional therapies. All participants also consented to the abstraction of chart data for this study. Results Overall, 84% of respondents reported the use of one or more unconventional therapies. The most commonly used modalities were changes in diet, nutritional and herbal agents, and mind/body treatments. Most users had tried more than one unconventional modality. No difference in use was seen by cancer diagnosis, race/ethnicity, socio-economic status, or educational attainment of the respondent. Of the therapies used, 50% were not reported to the physicians. Of patients reporting use of an unconventional approach, 85% were concurrently enrolled on clinical trials for primary treatment of their cancer. Conclusions The use of unconventional therapies is highly prevalent among children with cancer and is not associated with demographic or clinical factors or participation in clinical trials. The possibility that an unconventional treatment may interact with a protocol treatment underscores the need for more information about the use of such therapies among all patients.

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

PURPOSE This study updates findings regarding the effects of prophylactic surgery, chemoprevention, and surveillance on the survival and quality-adjusted survival of women who test positive for BRCA1/2 mutations. MATERIALS AND METHODS Markov modeling of outcomes was performed in a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations. The model incorporated breast and ovarian cancer incidence rates from the literature and mortality rates from the Surveillance, Epidemiology, and End Results Program. Quality adjustment of survival estimates were obtained from a survey of women aged 33 to 50 years. Sensitivity analyses were performed of varied assumptions regarding timing and effects of preventive measures on cancer incidence and adverse effects. RESULTS A 30-year-old woman could prolong her survival beyond that associated with surveillance alone by use of preventive measures: 1.8 years with tamoxifen, 2.6 years with prophylactic oophorectomy, 4.6 years with both tamoxifen and prophylactic oophorectomy, 3.5 years with prophylactic mastectomy, and 4.9 years with both surgeries. She could prolong her quality-adjusted survival by 2.8 years with tamoxifen, 4.4 years with prophylactic oophorectomy, 6.3 years with tamoxifen and oophorectomy, and 2.6 years with mastectomy, or with both surgeries. The benefits of all of these strategies would decrease if they were initiated at later ages. CONCLUSION Women who test positive for BRCA1/2 mutations may derive greater survival and quality adjusted survival benefits than previously reported from chemoprevention, prophylactic surgery, or a combination. Observational studies and clinical trials are needed to verify the results of this analysis of the long-term benefits of preventive strategies among BRCA1/2-positive women.

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

PURPOSE Since 1986, the recommended therapy for patients with ovarian cancer has included surgery and chemotherapy with a platinum compound (cisplatin or carboplatin). The purpose of this study is to assess the use of chemotherapy in elderly patients with advanced ovarian cancer. METHODS The Surveillance, Epidemiology, and End Results-Medicare database represents approximately 14% of the United States population and provides clinical and demographic information on cancer patients covered by Medicare, along with health care-utilization data from Medicare claims files. We analyzed the association of demographic and clinical factors with treatment among patients diagnosed from 1992 to 1996 with stage III or IV ovarian cancer, who survived > or = 120 days beyond diagnosis, and were > or = 65 years of age (N = 1,775). RESULTS Approximately 83% of elderly patients received some form of chemotherapy within 4 months of diagnosis. In a multiple logistic regression model with patients aged 65 to 69 years as the reference, the odds ratios of receiving chemotherapy were 0.96 (95% confidence interval [CI], 0.63 to 1.46) for ages 70 to 74, 0.65 (95% CI, 0.43 to 1.00) for 75 to 79, 0.24 (95% CI, 0.15 to 0.37) for 80 to 84, and 0.12 (95% CI, 0.07 to 0.19) for 85+. Hispanic patients were less likely to receive chemotherapy than non-Hispanic white patients. Since 1992, paclitaxel has gradually replaced cyclophosphamide as the drug most commonly used with platinum. CONCLUSION Despite its proven efficacy in treating ovarian cancer, chemotherapy seems to be used less among patients over age 65, especially those who are nonwhite and/or in the oldest age groups. Further research is needed to elucidate to what degree this represents appropriate clinical judgment and to what degree other factors, such as patient choice, play a role.

Duration of Adjuvant Chemotherapy for Colon Cancer and Survival Among the Elderly

PURPOSE In randomized trials, patients with stage III colon cancer who received 6 months of fluorouracil (FU)-based adjuvant chemotherapy had better survival than patients who did not. However, little is known about the predictors of, or the survival associated with, duration of chemotherapy in the community. PATIENTS AND METHODS The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify individuals > or = 65 years of age diagnosed with stage III colon cancer between 1995 and 1999. We used logistic and Cox proportional hazards regression models to analyze factors associated with early discontinuation of FU-based chemotherapy among these elderly colon cancer patients. RESULTS Among 1,722 patients who received 1 to 7 months of FU-based chemotherapy, older age, being unmarried, and having comorbid conditions were associated with receiving less than 5 months of treatment. Among the 1,579 patients who survived > or = 8 months, the 1,091 (69.1%) who received 5 to 7 months of treatment had lower overall (hazard ratio [HR], 0.59; 95%, CI 0.49 to 0.71) and colon cancer-specific (HR, 0.53; 95% CI, 0.43 to 0.66) mortality than the 488 (30.9%) who received 1 to 4 months of treatment. CONCLUSION More than 30% of elderly patients who initiated FU-based chemotherapy for stage III colon cancer and survived for at least 8 months discontinued treatment early. Mortality rates among such patients were nearly twice as high as among patients who completed 5 to 7 months of treatment. If the association we observed between duration of treatment and survival is confirmed, additional investigation is warranted to determine whether dose-intensity, cumulative dose, or other factors related to receipt of full adjuvant treatment are responsible.