Public health oncology: a framework for progress in low- and middle-income countries.

BACKGROUND: The problems of cancer are increasing in low- and middle-income countries (LMCs), which now have significant majorities of the global case and mortality burdens. The professional oncology community is being increasingly called upon to define pragmatic and realistic approaches to these problems. PATIENTS AND METHODS: Focusing on mortality and case burden outcomes defines public health oncology or population-affecting cancer medicine. We use this focus to consider practical approaches. RESULTS: The greatest cancer burdens are in Asia. A public health oncology perspective mandates: first, addressing the major and social challenges of cancer medicine for populations: human rights, health systems, corruption, and our limited knowledge base for value-conscious interventions. Second, adoption of evolving concepts and models for sustainable development in LMCs. Third, clear and realistic statements of action and inaction affecting populations, grounded in our best cancer science, and attention to these. Finally, framing the goals and challenges for population-affecting cancer medicine requires a change in paradigm from historical top-down models of technology transfer, to one which is community-grounded and local-evidence based. CONCLUSION: Public health oncology perspectives define clear focus for much needed research on country-specific practical approaches to cancer control.

Improving outcomes from breast cancer in a low-income country: lessons from bangladesh.

Women in low- and middle-income countries (LMICs) have yet to benefit from recent advances in breast cancer diagnosis and treatment now experienced in high-income countries. Their unique sociocultural and health system circumstances warrant a different approach to breast cancer management than that applied to women in high-income countries. Here, we present experience from the last five years working in rural Bangladesh. Case and consecutive series data, focus group and individual interviews, and clinical care experience provide the basis for this paper. These data illustrate a complex web of sociocultural, economic, and health system conditions which affect womens' choices to seek and accept care and successful treatment. We conclude that health system, human rights, and governance issues underlie high mortality from this relatively rare disease in Bangladesh.

Family history, BRCA mutations and breast cancer in Vietnamese women.

The purpose of this report is to estimate the proportions of familial and hereditary breast cancers among unselected cases of breast cancer in Vietnam. Two hundred and ninety-two unselected cases of incident breast cancer were recruited from the National Cancer Hospital, Hanoi, the largest cancer centre in Vietnam. Family histories were collected for 292 cases and a DNA sample was obtained for 259 cases. DNA samples were screened for mutations in the large exons of BRCA1 and BRCA2 using the protein truncation test and by allele-specific testing for 17 founder mutations which have been reported in other Asian populations. Complete gene sequencing was performed on two cases of familial breast cancer. Seven of 292 cases reported a relative with breast cancer and one patient reported a relative with ovarian cancer. A pathogenic BRCA mutation was detected in 2 of 259 cases; one BRCA1 carrier was diagnosed at age 51 and one BRCA2 carrier was diagnosed at age 42. Neither case reported a relative with breast or ovarian cancer. A family history of breast cancer is very uncommon among Vietnamese breast cancer patients. The frequency of pathogenic BRCA mutations in Vietnamese breast cancer patients is among the lowest reported worldwide.

The effects of tamoxifen on the vaginal epithelium in postmenopausal women.

Although increased vaginal discharge occurs with treatment, clinicians often presume the effects of tamoxifen on the vaginal epithelium are antiestrogenic. We studied 16 postmenopausal women before they began tamoxifen treatment, at 6 months, and then at annual intervals for up to 6 years. Vaginal scrapings for cytology smears and maturation values (MV) for these were performed. MV scores increased by a mean of 32% and these were predictably related to baseline values, with greater increases seen when there were lower scores before treatment. Only one woman with an MV of 0 before treatment had no significant changes with 3 years' treatment. The effects of tamoxifen on the vaginal epithelium are influenced by the baseline hormonal milieu and are maturational in the majority of postmenopausal women.

Serum homocysteine levels in postmenopausal breast cancer patients treated with tamoxifen.

Adjuvant treatment of breast cancer with tamoxifen may be associated with reduced risk of cardiovascular disease. Serum homocysteine level has been suggested to be a risk factor for cardiovascular disease influenced by estrogenic hormones. We evaluated a subset of postmenopausal women who had participated in a longitudinal, double-blind, randomized, placebo-controlled toxicity study of tamoxifen 10 mg orally, twice daily. Twenty-seven treated subjects and 37 placebo subjects had measurements of serum homocysteine levels made on previously frozen samples obtained at baseline and after 12 months. After treatment with tamoxifen, we found lower levels of serum homocysteine of borderline statistical significance.

Perceived benefits of and barriers to participation in a phase I/II colon cancer chemoprevention trial.

METHOD: A questionnaire was administered to 42 subjects completing a one-year cancer chemoprevention trial (response rate = 69%, n = 29). The questionnaire assessed subjects' 1) previous study participation, 2) perceived benefits/barriers of participation, 3) likelihood of participating in future trials, 4) willingness to pay out-of-pocket expenses for trial participation, and 5) interest in post-trial continuation of the drug. RESULTS: The most highly rated benefits of trial participation were the possibility of reducing one's chance of getting cancer and the possibility of preventing others from getting cancer in the future. Barriers considered to be the most troublesome were billing problems and having colonoscopies done. Only 29% would have joined the trial had they been required to pay for trial-related costs. CONCLUSION: Results of this study may be used to educate potential participants about the benefits of/barriers to trial participation. Additionally, by learning from the experiences of trial participants, investigators can improve the execution of clinical trials, increasing participant satisfaction.

Symptoms associated with oophorectomy and tamoxifen treatment for breast cancer in premenopausal Vietnamese women.

There are very few data about the efficacy and toxicity of adjuvant systemic therapies for breast cancer in non-western populations. In 1993 in Vietnam we began a randomized controlled clinical trial on premenopausal women with operable breast cancer comparing adjuvant surgical oophorectomy plus tamoxifen with observation and this same combined hormonal treatment on recurrence. We evaluated the symptoms reported at regular follow-up visits by the first 482 premenopausal women entered in this clinical trial and treated with surgical oophorectomy plus tamoxifen or observation. Hot flash frequency and intensity, vaginal discharge, and genital pruritus were the only symptoms to occur more frequently in oophorectomy and tamoxifen-treated subjects. Seventy-seven percent of oophorectomy/tamoxifen subjects reported grade 1 or more and 44% grade 2 or more hot flash frequency symptoms in the first 12 months, versus 9% and 1% of observation subjects, respectively. Twenty percent of oophorectomy/tamoxifen subjects had grade 2 or greater intensity of hot flashes some time in the first 12 months versus 0% in observation subjects. Through three years, vasomotor symptoms were reported more frequently in oophorectomy/tamoxifen-treated women (in 23% vs. 3% at three years, mostly grade 1 toxicities). While noted and persistent vasomotor symptoms were found with oophorectomy plus tamoxifen in this population of Vietnamese women, these were of lower grades and tolerable. This adjuvant treatment may be widely accepted if it is demonstrated to be effective in this population.

A randomized, placebo-controlled trial of low-dose alpha-difluoromethylornithine in individuals at risk for colorectal cancer.

DFMO is an irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in mammalian polyamine biosynthesis. The goal of this study was to determine the effects of DFMO 0.5 g/m2/day as a single oral dose on polyamine and ODC levels in rectal, rectosigmoidal, and cecal colonic mucosae of individuals at risk for colon cancer because of a personal history of adenomatous polyps of the colon or a family history of colon cancer in at least one first-degree relative. A second goal was to determine toxicity of this treatment given over 1 year. Forty-five randomized subjects had a flexible sigmoidoscopy with no preparation and a colonoscopy after lavage preparation at baseline, a sigmoidoscopy with no preparation after 3 months, and both procedures (as at baseline) after 12 months, with mucosal biopsies taken from the rectosigmoid area (sigmoidoscopy) or rectal and cecal areas (colonoscopy) for evaluations of ODC and polyamine levels. Significantly decreased levels of putrescine and spermidine were found in rectosigmoid colonic mucosae of DFMO-treated (n = 24) compared with placebo (n = 21) subjects at 3 months (P = 0.03 and 0.04) and 12 months (P = 0.005, P = 0.004). Similar trends, none reaching statistical significance, were found for individual polyamine levels in rectal and cecal mucosae. No significant differences in ODC levels were detected marginally. There was evidence of global suppression of ODC and polyamine levels in the treatment group (P = 0.035). Three DFMO recipients (12.5%) developed clinically noticeable and audiologically demonstrated hearing loss, which was reversible and attributed to DFMO after 3 months (two subjects) and 12 months (one subject). The tissue polyamine changes demonstrated in this study are consistent with findings in other studies in colon and other tissues. The ototoxicity findings here suggest that investigation of other DFMO schedules, such as ones with a drug "holiday," will be a necessary step before Phase III chemoprevention studies can be pursued.

Trait anxiety, symptom perceptions, and illness-related responses among women with breast cancer in remission during a tamoxifen clinical trial.

Postmenopausal women with breast cancer in remission (N = 140) who were participating in a randomized clinical trial of tamoxifen chemoprevention therapy completed measures of trait anxiety, symptoms, cancer worry, and breast self-examinations (BSEs) during the first 6 months of the trial. Trait anxiety was associated with heightened sensitivity to tamoxifen-induced symptoms (but not with tendencies to report increases in symptoms unrelated to tamoxifen use), greater tendencies to attribute symptoms to tamoxifen use, and greater cancer worry. Tamoxifen use increased BSE rates among high-anxiety participants. For low-anxiety participants, tamoxifen use increased cancer worry but not BSE rates. Trait anxiety appears to be associated with vigilant activation of illness-related representations that trigger attentiveness to sensations, worry, and protective coping in response to somatic cues.

alpha-difluoromethylornithine ototoxicity. Chemoprevention clinical trial results.

OBJECTIVES: To determine the effects of low-dose oral eflornithine hydrochloride (difluoromethylornithine [DFMO]) administration on hearing and to identify factors that influence those effects. DESIGN: Combined data from 2 studies: a prospective, randomized phase 1 clinical trial of eflornithine (n = 26 subjects) and a prospective, randomized, placebo-controlled phase 2 clinical trial of eflornithine (n = 40 subjects). SETTING: Ambulatory academic tertiary care referral center. PARTICIPANTS: Sixty-six volunteer subjects who had previously treated bladder, prostate, or colon cancer with no current evidence of neoplastic disease, or who were healthy individuals at increased risk for colon cancer, all without need of hearing amplification. INTERVENTIONS: Subjects were randomized to receive oral eflornithine at daily doses between 0.5 and 3 g per square meter of body surface area (g/m2) for 6 to 12 months (phase 1 study) or randomized to receive placebo or eflornithine, 0.5 g/m2 for 12 months (phase 2 study). OUTCOME MEASURES: Auditory thresholds were measured before, during, and after eflornithine administration. Auditory thresholds and threshold shifts were evaluated with regard to eflornithine dose, serologic variables, and demographic factors. RESULTS: Predictable shifts in auditory thresholds occurred following administration of eflornithine. As the daily dose of eflornithine increased, the magnitude and incidence of threshold shift increased, and the time until onset of threshold shift decreased. Threshold changes were greater in the lower frequencies than in the higher frequencies. Subjects' sex, age, and renal function had no effect on eflornithine-associated threshold shifts. Threshold shifts were reversible after eflornithine treatment was discontinued. CONCLUSIONS: Administration of eflornithine is associated with a predictable shift in auditory thresholds. The magnitude and incidence of threshold shift correlate with the daily eflornithine dose.

Health promotion and screening services reported by older adult patients of urban primary care physicians.

BACKGROUND: Adult preventive services provided at intervals recommended by expert panel guidelines may reduce morbidity and mortality. As part of an intervention trial to increase primary preventive services in urban primary care practices, baseline data were collected on primary prevention and screening test rates in older adults and on patient characteristics associated with provision of these services. METHODS: A questionnaire on preventive services offered or provided over the past 2 years was completed by patients aged 52 to 77 years and another by their 42 participating physicians. Logistic regression was used to identify patient characteristics associated with increased provision of these services. RESULTS: Usable questionnaires were completed by 1457 (80.9%) patients. Patient age and sex were not associated with the provision of primary preventive and counseling services. The presence of two or more chronic diseases was predictive of primary preventive services (P < .02), but was not associated with an increase in screening tests or procedures. Age was positively associated with delivery of prostate-specific antigen blood tests (P < .001) and rectal examinations (P < .001) in men, but was negatively associated with mammography (P < .001) and Papanicolaou (Pap) tests (P = .02) in women. The negative trend in screening mammography was evident even for women aged 50 to 65 years despite the national consensus regarding the benefits of screening for this age group. Patients with health management organization insurance reported significantly more mammography (P = .002), cervical Pap tests (P = .050), sigmoidoscopies (P = .002), and fecal occult blood tests (P = .035). CONCLUSIONS: In our study patients, the provision of primary preventive and screening services was closer to consensus guidelines than is typically reported in the literature. The data suggest that future investigations and interventions to improve primary prevention and screening services in older adults who have access to primary care do not need to be directed at fundamental changes in the way preventive services are delivered, but rather should target procedures of proven benefit, such as mammography, where rates remain below recommended guidelines.

The delivery of preventive services in primary care practices according to chronic disease status.

OBJECTIVES: The current study examined the relationship between chronic disease status and the receipt of cancer preventive services over a 3-year period. METHODS: Adults (n = 4320) cared for by 167 nonacademic physicians in 42 primary care group practices were studied. Medical records were audited for each patient, as were patient responses to two questionnaires assessing health and sociodemographic characteristics. RESULTS: While the odds of having received counseling to obtain regular checkups were increased for men (1.56) and women (1.46) with hypertension, the odds were reduced (range = 0.32 to 0.81) for having received a sigmoidoscopy (women with diabetes or hypertension, men with hypertension or heart disease), fecal occult blood test (men with diabetes or heart disease, women with heart disease), mammogram or counseling about smoking (women with diabetes), clinical breast exam (women with heart disease), and Pap test (women with diabetes or heart disease). CONCLUSIONS: The presence of common chronic health problems in older adults is associated with lower levels of cancer screening services.

Breast cancer prevention strategies.

The ultimate goal of breast cancer prevention strategies is to reduce the incidence of this disease in populations. Greater understanding of recently identified associations of lactation, alcohol, exercise, and diet with breast cancer is necessary to bring these to bear favorably on the behavior of populations. As a hormonally related process, breast cancer incidence is associated with two major physiologic mechanisms: (1) extent of lobular maturation, which is profoundly influenced by the occurrence of a full-term pregnancy, and (2) hormonal exposure of the breast epithelium, which is influenced by a spectrum of lifestyle factors. Manipulation of these processes by technologically simple and practical means is a major goal of research. Modulation of preclinical growth of breast cancers by chemopreventive means poses significant challenges, due to the absence of target-organ specificity and frequent toxicity. With the emergence of well-supported models of breast cancer development, behavioral and social strategies are likely to be key to achieving the ultimate goal.

The simultaneous analysis of patient, physician and group practice influences on annual mammography performance.

The current study examined the relationship of several variables at the patient (n = 2780), physician (n = 166), and group practice (n = 45) levels for predicting receipt of annual mammography screening. Patient-level variables included constructs from the Triandis Model of Choice; physician-level variables included measures of barriers and receptivity to prevention, as well as demographic information. Hierarchical modeling demonstrated that variables at the patient and physician level reliably predict annual mammography screening, while frequency of screening did not vary across group practices after accounting for patient and physician variables. Patient-level predictors included social norms, perceived consequences and perceived barriers. The only physician-level predictor identified was annual mammography recommendation. These findings add to data which emphasize the importance of public education and social support in health maintenance activities.