Barbara A. Parker

Adjuvant chemotherapy in older women with early-stage breast cancer.

BACKGROUND Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older. METHODS We randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival. RESULTS When the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P=0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%). CONCLUSIONS Standard adjuvant chemotherapy is superior to capecitabine in patients with early-stage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.)

Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity

PURPOSE Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. PATIENTS AND METHODS A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. RESULTS In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor-positive cancers. CONCLUSION A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.

Abuse during pregnancy: associations with maternal health and infant birth weight.

A stratified, prospective cohort analysis was completed on 1,203 African American, Hispanic, and white women. All women were assessed for abuse at the first prenatal visit and twice more during pregnancy. They were also assessed for risk factors of low birth weight using Institute of Medicine correlates. Prevalence of physical or sexual abuse during pregnancy was 16% (1 of 6). Abused women were twice as likely to begin prenatal care during the third trimester, with abuse preceding late entry. Abuse was recurrent, with 60% of the women reporting repeated episodes. More severe abuse was significantly correlated with lower infant birth weights for all three ethnic groups. Abuse during pregnancy was a significant risk for low birth weight as well as maternal low weight gain, infections, anemia, smoking, and use of alcohol and drugs. When compared to women who were not abused, women abused during pregnancy delivered infants averaging 133 g less. Abused white women delivered infants with the greatest reduction in birth weight.

Relation between food intake and visual analogue scale ratings of appetite and other sensations in healthy older and young subjects

Objective: Visual analogue scales are widely used in appetite research, yet the validity of these scales to evaluate appetite and mood has not been assessed in older subjects. The aim of this study was to determine the relations between food intake and visual analogue scale (VAS) ratings of appetite and nonappetite sensations in healthy older and young subjects.Design: Retrospective combined analysis of four single-blind, randomised, controlled appetite studies.Setting: All studies were conducted in the University of Adelaide, Department of Medicine, Adelaide, Australia.Subjects: A total of 45 healthy young men (n=24) and women (n=21) aged 18–35 y and 45 healthy older men (n=24) and women (n=21) aged 65–85 y were recruited by advertisement.Interventions: Oral, intraduodenal or intravenous administration of treatments which suppressed food intake were compared to control. Up to 90 min after treatment, a test meal was offered and subjects ate freely for between 30 and 60 min. Perceptions were assessed by 100-mm visual analogue scales administered at regular intervals.Results: Food intake at the test meal was positively related to perceptions of hunger, drowsiness, and calmness at both baseline and premeal (r>0.16, P<0.05), and inversely related to premeal ratings of fullness (r> 0.2, P<0.05) in both older and young subjects. Food intake was related to VAS ratings at least as strongly, if not more so, in older as in young subjects.Conclusions: These observations (i) confirm that food intake is related to perceptions of hunger and fullness as assessed by VAS in healthy older and young subjects, and (ii) suggest that sensations, not obviously associated with appetite, including ‘drowsiness’ and ‘calmness’, are also associated with food intake.

Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To update the 2009 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and Cochrane Collaboration Library. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. Guideline recommendations were revised based on an Update Committees review of the literature. RESULTS Nineteen articles met the selection criteria. Six chemoprevention agents were identified: tamoxifen, raloxifene, arzoxifene, lasofoxifene, exemestane, and anastrozole. RECOMMENDATIONS In women at increased risk of BC age ≥ 35 years, tamoxifen (20 mg per day for 5 years) should be discussed as an option to reduce the risk of estrogen receptor (ER) -positive BC. In postmenopausal women, raloxifene (60 mg per day for 5 years) and exemestane (25 mg per day for 5 years) should also be discussed as options for BC risk reduction. Those at increased BC risk are defined as individuals with a 5-year projected absolute risk of BC ≥ 1.66% (based on the National Cancer Institute BC Risk Assessment Tool or an equivalent measure) or women diagnosed with lobular carcinoma in situ. Use of other selective ER modulators or other aromatase inhibitors to lower BC risk is not recommended outside of a clinical trial. Health care providers are encouraged to discuss the option of chemoprevention among women at increased BC risk. The discussion should include the specific risks and benefits associated with each chemopreventive agent.

Systemic treatment of AIDS-related kaposi's sarcoma: Results of a randomized trial

PURPOSE Patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposis sarcoma generally respond well to cytotoxic chemotherapy. However, due to the associated myelosuppression, these patients are at risk for developing complicating infections that may affect survival. We therefore conducted a multi-center randomized clinical trial comparing single-agent against combination chemotherapy in advanced AIDS-related Kaposis sarcoma. Low-dose chemotherapy was employed to evaluate its role in combination therapy for this disease and the toxicities associated with the lower intensity. PATIENTS AND METHODS Sixty-one patients with extensive mucocutaneous Kaposis sarcoma or visceral involvement were randomized for treatment with low-dose Adriamycin (doxorubicin, 20 mg/m2) alone (31 cases) or in combination with bleomycin and vincristine (ABV) (30 cases). Patients were randomized within strata based on prognostic features associated with shorter survival in prior studies. Both treatment arms were evenly matched at study entry. RESULTS Complete and partial tumor remissions were significantly higher with ABV (88%) than with Adriamycin alone (48%) (p = 0.004). The median survival was 9 months in both groups. Study entry criteria significantly associated with shorter survival included CD4 lymphocyte counts less than 100/mm3, hemoglobin level less than 10 g/dL, a history of constitutional symptoms, and a prior history of opportunistic infection(s). Toxicities were similar in both arms, and the regimens were well tolerated. Neutropenia (granulocyte count less than 1,000/mm3) occurred in 34% of patients receiving Adriamycin alone and in 52% of patients receiving ABV and was progressive in successive courses of chemotherapy in both treatment arms. The development of AIDS-defined opportunistic infections was relatively infrequent during therapy (14%). CONCLUSIONS Low-dose ABV is an effective chemotherapy regimen for the treatment of extensive Kaposis sarcoma. ABV chemotherapy is associated with significantly higher responses than Adriamycin alone and with acceptable toxicity.

Tamoxifen Metabolite Concentrations, CYP2D6 Genotype, and Breast Cancer Outcomes

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4‐hydroxytamoxifen (4OH‐tamoxifen), and N‐desmethyltamoxifen (ND‐tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)‐positive breast cancer who were participating in the Womens Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4‐hydroxytamoxifen, and ND‐tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55–1.00)). The predictors of this higher‐risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold.

Physical and emotional abuse in pregnancy: a comparison of adult and teenage women.

A sample of 691 African American, Hispanic, and white pregnant teenage and adult women were interviewed in the prenatal setting. On their first prenatal visit, 182 (26%) women reported physical or sexual abuse within the past year. There were significant differences between the teens and adults, with a higher percentage of teens (31.6%) reporting abuse during the prior year than adults (23.6%). The rate of abuse during pregnancy was 21.7% for teens and 15.9% for adult of women. Adult women scored significantly higher than teens on two measures of mental abuse. Mental abuse was significantly correlated with physical abuse for all subjects.

Identifying and helping battered pregnant women.

Because battering during pregnancy is a frequent occurrence, nurses must routinely assess women for injury during prenatal visits

Randomized Trial of a Fitbit-Based Physical Activity Intervention for Women

INTRODUCTION Direct-to-consumer mHealth devices are a potential asset to behavioral research but rarely tested as intervention tools. This trial examined the accelerometer-based Fitbit tracker and website as a low-touch physical activity intervention. The purpose of this study is to evaluate, within an RCT, the feasibility and preliminary efficacy of integrating the Fitbit tracker and website into a physical activity intervention for postmenopausal women. METHODS Fifty-one inactive, postmenopausal women with BMI ≥25.0 were randomized to a 16-week web-based self-monitoring intervention (n=25) or comparison group (n=26). The Web-Based Tracking Group received a Fitbit, instructional session, and follow-up call at 4 weeks. The comparison group received a standard pedometer. All were asked to perform 150 minutes/week of moderate to vigorous physical activity (MVPA). Physical activity outcomes were measured by the ActiGraph GT3X+ accelerometer. RESULTS Data were collected and analyzed in 2013-2014. Participants were aged 60 (SD=7) years with BMI of 29.2 (3.5) kg/m(2). Relative to baseline, the Web-Based Tracking Group increased MVPA by 62 (108) minutes/week (p<0.01); 10-minute MVPA bouts by 38 (83) minutes/week (p=0.008); and steps by 789 (1,979) (p=0.01), compared to non-significant increases in the Pedometer Group (between-group p=0.11, 0.28, and 0.30, respectively). The Web-Based Tracking Group wore the tracker on 95% of intervention days; 96% reported liking the website and 100% liked the tracker. CONCLUSIONS The Fitbit was well accepted in this sample of women and associated with increased physical activity at 16 weeks. Leveraging direct-to-consumer mHealth technologies aligned with behavior change theories can strengthen physical activity interventions.