Lovell A. Jones

A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study

The Womens Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

p53 Mutations and expression in ovarian cancers : Correlation with overall survival

The p53 gene is altered in approximately 50% of all human malignancies. p53 overexpression, identified by immunohistochemistry, and p53 mutations, identified by single-strand conformational polymorphism (SSCP) and DNA sequencing, have been described in ovarian cancers. p53 overexpression has been correlated with poor outcome for women with ovarian cancer in some studies. With only limited data, the assumption has been made that p53 overexpression corresponds to p53 mutations. The purpose of this investigation was to assess p53 alterations in ovarian cancer to determine if p53 overexpression corresponds with mutations in the p53 gene, and to assess whether either predicts clinical outcome in ovarian carcinoma. Frozen ovarian carcinoma tumor specimens from 105 patients were analyzed by immunohistochemical staining for p53 expression. SSCP was used to screen for mutations and DNA sequencing was used to confirm the specific mutation in exons 2 to 11, encompassing the entire p53 open reading frame. Those ovarian carcinomas identified as wild-type p53 by SSCP were subjected to automated DNA sequence analysis of the entire open reading frame. Relative to DNA sequence analysis, the sensitivity of SSCP was 85% and the specificity was 98%. Immunohistochemical staining demonstrated that 72 of the 105 (69%) cases had positive immunostaining. SSCP and DNA sequencing identified and confirmed mutations in 60 of the 105 carcinomas (57%). Although there was a statistically significant association between p53 immunostaining and p53 mutations (p = 0.0002), false-negative and -positive results were identified. Tumor grade (p = 0.03), stage (p = 0.08), and overall survival (p = 0.15) were moderately associated with positive p53 immunostaining. Patients with p53 mutations and overexpression had shorter overall patient survival (p = 0.02). The findings demonstrated that, individually, p53 mutations and p53 overexpression were each related to shorter patient survival, but the strongest predictor of outcome was a combination of both mutations and overexpression. Comparisons of overall survival for women with mutations in loop 2, loop 3, and the loop-sheet-helix domains together showed a statistically significant difference in survival compared to survival of women whose ovarian cancers had other mutations (p = 0.046).

The role of patient navigators in eliminating health disparities

Despite many important efforts to increase equity in the US health care system, not all Americans have equal access to health care—or similar health outcomes. With the goal of lowering costs and increasing accessibility to health care, the nations new health care reform legislation includes certain provisions that expand health insurance coverage to uninsured and underinsured populations, promote medical homes, and support coordination of care. These provisions may help narrow existing health care disparities. Many of the most vulnerable patients, however, may continue to have difficulty accessing and navigating the complex US health care delivery system. This article explores the unique role that patient navigation can play in improving health outcomes for racial and ethnic minorities, as well as other underserved populations, in the context of a changing healthcare environment. Patient navigators can not only facilitate improved health care access and quality for underserved populations through advocacy and care coordination, but they can also address deep‐rooted issues related to distrust in providers and the health system that often lead to avoidance of health problems and non‐compliance with treatment recommendations. By addressing many of the disparities associated with language and cultural differences and barriers, patient navigators can foster trust and empowerment within the communities they serve. Specific patient navigator activities are discussed, and metrics to evaluate program efforts are presented. Cancer 2011;117(15 suppl):3541–50.

Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer

Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Womens Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):614–20)

Associations among physical activity, body mass index, and health-related quality of life by race/ethnicity in a diverse sample of breast cancer survivors

Health‐related quality of life (HRQOL), body mass index (BMI), and physical activity (PA) levels have all been associated with prognosis following breast cancer and may explain partially the higher mortality for breast cancer in certain racial/ethnic subgroups. In this study, associations between PA, BMI, and HRQOL by race were examined in a sample of breast cancer survivors.

Plasma Carotenoids and Recurrence-Free Survival in Women With a History of Breast Cancer

PURPOSE Previous studies suggest that diet may affect recurrence or survival rates in women who have been diagnosed with breast cancer. The purpose of this study was to examine the relationship between plasma carotenoid concentration, as a biomarker of vegetable and fruit intake, and risk for a new breast cancer event in a cohort of women with a history of early-stage breast cancer. METHODS Participants were 1,551 women previously treated for breast cancer who were randomly assigned to the control arm of a diet intervention trial between March 1995 and November 2000. Outcome events were probed during semiannual interviews and verified by medical record review. During the period under study, 205 women had a recurrence or new primary breast cancer. Plasma carotenoid concentrations were measured in baseline blood samples. Hazard ratios (HR) and 95% CIs by quartiles of plasma carotenoids were computed, controlling for tumor stage, grade, and hormone receptor status; chemotherapy and tamoxifen therapy; clinical site; age at diagnosis; body mass index; and plasma cholesterol concentration. RESULTS Women in the highest quartile of plasma total carotenoid concentration had significantly reduced risk for a new breast cancer event (HR, 0.57; 95% CI, 0.37 to 0.89), controlled for covariates influencing breast cancer prognosis. CONCLUSION Plasma carotenoids are a biologic marker of intake of vegetables and fruit, so this observation supports findings from previous studies that have linked increased vegetable and fruit intake with greater likelihood of recurrence-free survival in women who have been diagnosed with early-stage breast cancer.

Effects of a High-Fiber, Low-Fat Diet Intervention on Serum Concentrations of Reproductive Steroid Hormones in Women With a History of Breast Cancer

PURPOSE Diet intervention trials are testing whether postdiagnosis dietary modification can influence breast cancer recurrence and survival. One possible mechanism is an effect on reproductive steroid hormones. PARTICIPANTS AND METHODS Serum reproductive steroid hormones were measured at enrollment and 1 year in 291 women with a history of breast cancer who were enrolled onto a randomized, controlled diet intervention trial. Dietary goals for the intervention group were increased fiber, vegetable, and fruit intakes and reduced fat intake. Estradiol, bioavailable estradiol, estrone, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and sex hormone-binding globulin were measured. RESULTS The intervention (but not the comparison) group reported a significantly lower intake of energy from fat (21% v 28%), and higher intake of fiber (29 g/d v 22 g/d), at 1-year follow-up (P <.001). Significant weight loss did not occur in either group. A significant difference in the change in bioavailable estradiol concentration from baseline to 1 year in the intervention (-13 pmol/L) versus the comparison (+3 pmol/L) group was observed (P <.05). Change in fiber (but not fat) intake was significantly and independently related to change in serum bioavailable estradiol (P <.01) and total estradiol (P <.05) concentrations. CONCLUSION Results from this study indicate that a high-fiber, low-fat diet intervention is associated with reduced serum bioavailable estradiol concentration in women diagnosed with breast cancer, the majority of whom did not exhibit weight loss. Increased fiber intake was independently related to the reduction in serum estradiol concentration.

Obesity, non‐protein‐bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients

This study attempted to determine the relationship of nutritional status, menopausal status, presence of breast cancer, stage of disease, and tumor estrogen receptor levels to percent non‐protein‐bound estradiol (%NPBE) and percent distribution of estradiol on sex hormone‐binding globulin (SHBG) and albumin in breast cancer patients and control patients. Normal‐weight controls had significantly lower %NPBE compared with overweight controls and normal‐weight and overweight breast cancer patients. There was a significant shift in the percent distribution of estradiol from SHBG to albumin in breast cancer patients, independent of body weight. Elevated %NPBE and abnormal percent estradiol distribution on albumin persisted after mastectomy and were unrelated to menopausal status, presence and stage of disease, and tumor estrogen receptor levels. These results show that breast cancer patients have increased exposure to unbound circulating estradiol and an increased percentage of estradiol bound to albumin, which may influence the availability of estradiol, considering its low binding affinity to albumin. Because these abnormalities persist after mastectomy, the current results may be important in developing dietary intervention protocols that correct %NPBE and abnormal estradiol distribution on binding proteins.

Vitamin D and breast cancer recurrence in the Women's Healthy Eating and Living (WHEL) Study

BACKGROUND There is a paucity of research evaluating the relation between vitamin D and recurrence of breast cancer after treatment. OBJECTIVE This study was designed to evaluate the associations between circulating concentrations of 25-hydroxyvitamin D [25(OH)D] and dietary, supplemental, and total intake of vitamin D and recurrent or new breast cancer events within the Womens Healthy Eating and Living (WHEL) Study. DESIGN A prospective cohort study design (n = 3085) was used to evaluate the relation between dietary, supplemental, and total vitamin D intake and recurrent breast cancer, and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence. RESULTS No relation between 25(OH)D and breast cancer recurrence was observed. Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL, adjusted odds ratios (95% CI) for breast cancer recurrence were 1.14 (0.57, 2.31) for those with concentrations < 10 ng/mL, 1.00 (0.68-1.48) for concentrations ≥ 10 and < 20 ng/mL, and 1.05 (0.76, 1.47) for concentrations ≥ 20 and < 30 ng/mL. No significant associations were observed when analyses were stratified by pre- and postmenopausal status or for local, regional, or distant recurrence or death. Vitamin D intake was not related to breast cancer recurrence overall, although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence (P for trend = 0.02). CONCLUSION These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer. This trial is registered at clinicaltrials.gov for the WHEL Study as NCT00003787.

Between and Within: International Perspectives on Cancer and Health Disparities

The purpose of this article is to compare reasons for cancer health disparities in developing and developed countries. By 2010, approximately 60% of new cancer cases will occur in the developing world, higher than rates developed countries. However, disparities exist not only between countries but also within countries. Cancer epidemiology in developing countries is paradoxical: Increased incidence is partially due to increased development resulting in longer life expectancy and unhealthy lifestyle behaviors. Reduced mortality from infectious diseases results in relatively greater mortality from chronic diseases. However, infectious diseases are also risk factors for the leading causes of cancer mortality in these countries. While health disparities in developing versus developed countries are quantitatively worlds apart, they are qualitatively rather similar. They share common causes, such as environmental pollution, the need for social justice, large gaps between the rich and the poor, lack of access to cancer resources, and health services that are available to some but not to all. While industrialization and urbanization elevate a countrys economic base while contributing to cancer incidence and mortality. Strategies to reduce international cancer disparities include country- and regional-level interventions, utilizing nongovernmental organizations, and developing long-term inter-institutional partnerships. Although economic aid is undoubtedly necessary, it is not sufficient to control cancer in the developing world. To address these problems, it will be necessary to focus attention on what can be done locally-within countries, not only between countries.