Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer.

To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells (PGCCs) in ovarian and breast cancer cell lines, high-grade serous cancer (HGSC)-derived organoids, and patient-derived xenografts (PDXs). Time-lapse tracking of ovarian cancer cells revealed that PGCCs primarily developed from endoreplication after exposure to sublethal concentrations of olaparib. PGCCs exhibited features of senescent cells but, after olaparib withdrawal, can escape senescence via restitutional multipolar endomitosis and other noncanonical modes of cell division to generate mitotically competent resistant daughter cells. The contraceptive drug mifepristone blocked PGCC formation and daughter cell formation. Mifepristone/olaparib combination therapy substantially reduced tumor growth in PDX models without previous olaparib exposure, while mifepristone alone decreased tumor growth in PDX models with acquired olaparib resistance. Thus, targeting PGCCs may represent a promising approach to potentiate the therapeutic response to PARPi and overcome PARPi-induced resistance.

Molecular Profiles of Serum-Derived Extracellular Vesicles in High-Grade Serous Ovarian Cancer.

Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated the findings with therapeutic outcomes in patients with HGSC. Using EV-DNA whole-genome sequencing and EV-RNA sequencing, we identified distinct somatic EV-DNA alterations in cancer-hallmark genes and in ovarian cancer genes, as well as significantly altered oncogenic pathways between the R0 group and NACT groups. We also found significantly altered EV-RNA transcriptomic variations and enriched pathways between the groups. Taken together, our data suggest that the molecular characteristics of EVs could enable prediction of patients with HGSC who could undergo R0 surgery or respond to chemotherapy.

Molecular Analysis of Clinically Defined Subsets of High-Grade Serous Ovarian Cancer.

The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC), which is the most lethal gynecologic malignancy, is not well understood. Here, we perform comprehensive multi-platform omics analyses, including integrated analysis, and immune monitoring on primary and metastatic sites from highly clinically annotated HGSC samples based on a laparoscopic triage algorithm from patients who underwent complete gross resection (R0) or received neoadjuvant chemotherapy (NACT) with excellent or poor response. We identify significant distinct molecular abnormalities and cellular changes and immune cell repertoire alterations between the groups, including a higher rate of NF1 copy number loss, and reduced chromothripsis-like patterns, higher levels of strong-binding neoantigens, and a higher number of infiltrated T cells in the R0 versus the NACT groups.

A Pilot Study Evaluating Organochlorine and Organophosphate Pesticide Exposure in Children and Adolescents of Mexican Descent Residing in Hidalgo County, Texas.

Children and adolescents of Mexican descent residing in Hidalgo County (TX) were evaluated for exposure to organochlorine (OC) and organophosphate (OP) pesticides. A convenience sample of 60 participants enrolled in our pilot study. The lipid-adjusted serum concentrations of nine OC metabolites and creatinine-adjusted urinary concentrations of six OP metabolites were measured and compared with data from the Centers for Disease Control and Prevention's Fourth Report on Human Exposure to Environmental Chemicals. Descriptive statistics were used to summarize the concentration levels for each metabolite. Study participants were aged 5-18 years. For most of the OC and OP metabolites, our findings showed that participants had concentration levels within the distributional range of the national data. However, notable outlying levels (greater than the 95th percentile in the Fourth Report) were identified for the following OC metabolites: gamma-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethene, and p,p'-dichlorodiphenyltrichloroethane. Among the children aged 5-11 years, one child had an outlying value for the OP metabolite: dimethylphosphate. Our findings on the levels of OC and OP pesticide exposure enhances the credibility of national estimates, and can serve as baselines for children and adolescents of Mexican descent residing in Lower Rio Grande Valley. Furthermore, our study contributes to the lacunae of knowledge regarding environmental exposures and presses further investigation of outlying OC and OP exposure levels.

Cost-Effectiveness Analysis of a Capitated Patient Navigation Program for Medicare Beneficiaries with Lung Cancer.

OBJECTIVE: To assess the cost-effectiveness of implementing a patient navigation (PN) program with capitated payment for Medicare beneficiaries diagnosed with lung cancer. DATA SOURCES/STUDY SETTING: Cost-effectiveness analysis. STUDY DESIGN: A Markov model to capture the disease progression of lung cancer and characterize clinical benefits of PN services as timeliness of treatment and care coordination. Taking a payer's perspective, we estimated the lifetime costs, life years (LYs), and quality-adjusted life years (QALYs) and addressed uncertainties in one-way and probabilistic sensitivity analyses. DATA COLLECTION/EXTRACTION METHODS: Model inputs were extracted from the literature, supplemented with data from a Centers for Medicare and Medicaid Services demonstration project. PRINCIPAL FINDINGS: Compared to usual care, PN services incurred higher costs but also yielded better outcomes. The incremental cost and effectiveness was $9,145 and 0.47 QALYs, respectively, resulting in an incremental cost-effectiveness ratio of $19,312/QALY. One-way sensitivity analysis indicated that findings were most sensitive to a parameter capturing PN survival benefit for local-stage patients. CE-acceptability curve showed the probability that the PN program was cost-effective was 0.80 and 0.91 at a societal willingness-to-pay of $50,000 and $100,000/QALY, respectively. CONCLUSION: Instituting a capitated PN program is cost-effective for lung cancer patients in Medicare. Future research should evaluate whether the same conclusion holds in other cancers.

Circle of Sisters: raising awareness of Native American women to breast cancer.

The Circle of Sisters is a breast cancer education initiative that incorporates free mammography for American Indian women. In two separate but similar initiative-sponsored one-day events, 37 American Indian women underwent screening mammography and experienced a full day of culturally tailored educational activities. Women observed a cooking demonstration, participated in moderate exercise activity, strung beads to learn about the dimensions of breast tumors, and listened to an American Indian breast cancer survivor recount her story of diagnosis and treatment. Significant shifts in opinion included an increase in the understanding that a woman's chances of being diagnosed with breast cancer increase with age (p=.015) and with never bearing children (p <.001) and that breast cancer can be detected early (p=.043). The percentage of those expressing an intention to get a mammogram every year grew from 81.1% to 94.6%.

A randomized parallel-group dietary study for stages II-IV ovarian cancer survivors.

OBJECTIVE: Few studies have examined the dietary habits of ovarian cancer survivors. Therefore, we conducted a study to assess the feasibility and impact of two dietary interventions for ovarian cancer survivors. METHODS: In this randomized, parallel-group study, 51 women (mean age, 53 years) diagnosed with stages II-IV ovarian cancer were recruited and randomly assigned to a low fat, high fiber (LFHF) diet or a modified National Cancer Institute diet supplemented with a soy-based beverage and encapsulated fruit and vegetable juice concentrates (FVJCs). Changes in clinical measures, serum carotenoid and tocopherol levels, dietary intake, anthropometry, and health-related quality of life (HRQOL) were assessed with paired t-tests. RESULTS: The recruitment rate was 25%, and the retention rate was 75% at 6 months. At baseline, 28% and 45% of women met guidelines for intake of fiber and of fruits and vegetables, respectively. After 6 months, total serum carotenoid levels and α- and ß-carotene concentrations were significantly increased in both groups (P<0.01); however, ß-carotene concentrations were increased more in the FVJC group. Serum ß-cryptoxanthin levels, fiber intake (+5.2g/day), and daily servings of juice (+0.9 servings/day) and vegetables (+1.3 servings/day) were all significantly increased in the LFHF group (all P<0.05). Serum levels of albumin, lutein and zeaxanthin, retinol, and retinyl palmitate were significantly increased in the FVJC group (all P<0.05). No changes in cancer antigen-125, anthropometry, or HRQOL were observed. CONCLUSION: Overall, this study supports the feasibility of designing dietary interventions for stages II-IV ovarian cancer survivors and provides preliminary evidence that a low fat high fiber diet and a diet supplemented with encapsulated FVJC may increase phytonutrients in ovarian cancer survivors.

Was race a factor in the outcomes of the Women's Health Eating and Living Study?

BACKGROUND: The objective of this study was to determine whether women who were participating in the Women's Healthy Eating and Living (WHEL) Study exhibited similar dietary changes, second breast cancer events, and overall survival regardless of race/ethnicity. METHODS: For this secondary analysis, the authors used data from 3013 women who were self-identified as Asian American, African American, Hispanic, or white and who were assigned randomly to a dietary intervention or a comparison group. Changes in dietary intake over time by race/ethnicity and intervention status were examined using linear mixed-effects models. Cox proportional hazards models were used to examine the effects of the intervention on the occurrence of second breast cancer events and overall survival. Statistical tests were 2-sided. RESULTS: African Americans and Hispanics consumed significantly more calories from fat (+3.2%) and less fruit (-0.7 servings daily) than Asians and whites at baseline (all P < .01). Overall, intervention participants significantly improved their dietary pattern from baseline to the end of Year 1, reducing calories from fat by 4.9% and increasing intake of fiber (+6.6 grams daily), fruit (+1.1 servings daily), and vegetables (+1.6 servings daily; all P < .05). Despite improvements in the overall dietary pattern of these survivors, the intervention did not significantly influence second breast cancer events or overall survival. CONCLUSIONS: Overall, all racial groups significantly improved their dietary pattern over time, but the maintenance of these behaviors were lower among African-American women. More research and larger minority samples are needed to determine the specific factors that improve breast cancer-specific outcomes in diverse populations of survivors.

Young Asian Americans' knowledge and perceptions of cervical cancer and the human papillomavirus.

Cervical cancer is a major health disparity among Asian Americans, with cervical cancer rates of Vietnamese women being significantly higher than for the general US female population and low screening rates reported for Asian American females. Focus groups and interviews were conducted with young Vietnamese, Filipino, and Korean adults (ages 18-29) to collect information on knowledge, perceptions and sources of information regarding cervical cancer, Pap tests and the human papillomavirus. 16 Korean, 18 Vietnamese, and 18 Filipino (50% female) adults participated in the study. Many participants had never heard of HPV, cervical cancer and Pap testing. Cervical cancer screening rates were low for Korean and Vietnamese females and were influenced by moral beliefs and lack of awareness. Culturally relevant education materials that consider specific Asian ethnicity and language are needed to increase awareness of cervical cancer, Pap testing, and HPV among Asian American young adults.

Medical comorbidities predict mortality in women with a history of early stage breast cancer.

This analysis was conducted to determine whether comorbid medical conditions predict additional breast cancer events and all-cause mortality in women with a history of early stage breast cancer. Women (n = 2,542) participating in a randomized diet trial completed a self-administered questionnaire regarding whether they were currently being treated for a wide variety of diseases (cardiovascular, diabetes, gallbladder, gastrointestinal, arthritis, and osteoporosis) and conditions (high blood pressure, elevated cholesterol level). Height and weight were measured at baseline. Participants were followed for a median of 7.3 years (range 0.8-15.0). Cox regression analysis was performed to assess whether comorbidities predicted disease-free and overall survival; hazard ratio (HR) was the measure of association. Overall, there were 406 additional breast cancer events and 242 deaths. Participants with diabetes had over twofold the risk of additional breast cancer events (HR 2.1, 95% CI: 1.3, 3.4) and mortality (HR 2.5, 95% CI: 1.4, 4.4). The presence of multiple comorbidities did not statistically significantly predict additional breast cancer events. However, compared to no comorbidities, participants with 3 or more comorbidities had a HR of 2.1, 95% CI: 1.3, 3.3 for mortality. In conclusion, type 2 diabetes is associated with poor breast cancer prognosis. Given that 85% of deaths were caused by breast cancer, these findings suggest that multiple comorbidities may reduce the likelihood of surviving additional breast cancer events.

Time-varying effects of prognostic factors associated with disease-free survival in breast cancer.

Early detection and effective treatments have dramatically improved breast cancer survivorship, yet the risk of relapse persists even 15 years after the initial diagnosis. It is important to identify prognostic factors for late breast cancer events. The authors investigated time-varying effects of tumor characteristics on breast-cancer-free survival using data on 3,088 breast cancer survivors from 4 US states who participated in a randomized dietary intervention trial in 1995-2006, with maximum follow-up through 15 years (median, 9 years). A piecewise constant penalized spline approach incorporating time-varying coefficients was adopted, allowing for deviations from the proportional hazards assumption. This method is more flexible than standard approaches, provides direct estimates of hazard ratios across time intervals, and is computationally tractable. Having a stage II or III tumor was associated with a 3-fold higher hazard of breast cancer than having a stage I tumor during the first 2.5 years after diagnosis; this hazard ratio decreased to 2.1 after 7.7 years, but higher tumor stage remained a significant risk factor. Similar diminishing effects were found for poorly differentiated tumors. Interestingly, having a positive estrogen receptor status was protective up to 4 years after diagnosis but detrimental after 7.7 years (hazard ratio = 1.5). These results emphasize the importance of careful statistical modeling allowing for possibly time-dependent effects in long-term survivorship studies.

Dietary change and reduced breast cancer events among women without hot flashes after treatment of early-stage breast cancer: subgroup analysis of the Women's Healthy Eating and Living Study.

BACKGROUND: A diet high in vegetables, fruit, and fiber and low in fat decreased additional risk of secondary breast cancer events in women without hot flashes (HF-) compared with that in women with hot flashes (HF+), possibly through lowered concentrations of circulating estrogens. OBJECTIVE: The objective was to investigate the intervention effect by baseline quartiles of dietary pattern among breast cancer survivors in the HF- subgroup of the Women's Healthy Eating and Living Study. DESIGN: A randomized controlled trial compared a putative cancer prevention diet with a diet of 5 servings of vegetables and fruit daily in early-stage breast cancer survivors. Participants did not experience hot flashes at baseline (n = 896). We confirmed cancer status for 96% of participants approximately 7.3 y after enrollment. RESULTS: The study intervention achieved a large between-group difference in dietary pattern that, at 4 y, was not significantly different across baseline quartiles of dietary pattern. The intervention group experienced fewer breast cancer events than did the comparison group for all of the baseline quartiles. This difference was significant only in upper baseline quartiles of intake of vegetables, fruit, and fiber and in the lowest quartile of fat. A significant trend for fewer breast cancer events was observed across quartiles of vegetable-fruit and fiber consumption. CONCLUSIONS: The secondary analysis showing the decreased risk in the HF- subgroup was not explained by amount of change in dietary pattern achieved. The difference was strongest in the quartile with the most putatively cancer-preventive dietary pattern at baseline.

Longitudinal biological exposure to carotenoids is associated with breast cancer-free survival in the Women's Healthy Eating and Living Study.

In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4, and 6 years and breast cancer-free survival in the Women's Healthy Eating and Living Study participants (N = 3,043), who had been diagnosed with early-stage breast cancer. The primary end point was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared with the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83) after adjustment. The interaction between the study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.

Dietary pattern influences breast cancer prognosis in women without hot flashes: the women's healthy eating and living trial.

PURPOSE: To determine whether a low-fat diet high in vegetables, fruit, and fiber differentially affects prognosis in breast cancer survivors with hot flashes (HF) or without HF after treatment. PATIENTS AND METHODS: A secondary analysis was conducted on 2,967 breast cancer survivors, age 18 to 70 years, who were randomly assigned between 1995 and 2000 in a multicenter, controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1, 2006. We compared the dietary intervention group with a group who received five-a-day dietary guidelines. RESULTS: Independent of HF status, a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day (54% higher; 10 v 6.5 servings/d, respectively), fiber (31% higher; 25.5 v 19.4 g/d, respectively), and percent energy from fat (14% lower; 26.9% v 31.3%, respectively). Adjusting for tumor characteristics and antiestrogen treatment, HF-negative women assigned to the intervention had 31% fewer events than HF-negative women assigned to the comparison group (hazard ratio [HR] = 0.69; 95% CI, 0.51 to 0.93; P = .02). The intervention did not affect prognosis in the women with baseline HFs. Furthermore, compared with HF-negative women assigned to the comparison group, HF-positive women had significantly fewer events in both the intervention (HR = 0.77; 95% CI, 0.59 to 1.00; P = .05) and comparison groups (HR = 0.65; 95% CI, 0.49 to 0.85; P = .002). CONCLUSION: A diet with higher vegetable, fruit, and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors. This suggestive finding needs confirmation in a trial in which it is the primary hypothesis.

Comparison of baseline dietary intake of Hispanic and matched non-Hispanic white breast cancer survivors enrolled in the Women's Healthy Eating and Living study.

OBJECTIVE: To assess the reported baseline dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study, a randomized plant-based dietary intervention clinical trial. DESIGN: Dietary data from 4 days repeated 24-hour recalls within 3 weeks included daily total intake of energy, protein, carbohydrates, cholesterol, total fat, monounsaturated fat, saturated fat, polyunsaturated fat, fruit/vegetable servings, carotenoids, alcohol, caffeine, and percentage of energy from protein, carbohydrates, alcohol, and fats. SUBJECTS: One hundred sixty-five Hispanic breast cancer survivors age-matched to 165 non-Hispanic white breast cancer survivors diagnosed with Stage I, II, or IIIA primary operable breast cancer. STATISTICAL ANALYSES: Two-sample t tests and Wilcoxon rank sum tests to compare dietary intake, and logistic and ordinal logistic regression analyses to examine the association between ethnicity, alcohol, and lycopene consumption, while controlling for place of birth, education, body mass index, and time since diagnosis. RESULTS: Hispanics were more likely to be foreign-born (P<0.001), less educated (P<0.0001) and to consume higher amounts of lycopene (P=0.029), while non-Hispanic whites were more likely to consume alcohol (P=0.001). However, no differences were observed in the average amounts of alcohol consumed or total percents of energy from alcohol. Both groups consumed more than five servings of fruits and vegetables daily. Being Hispanic remained a significant predictor of lower alcohol use (P=0.004) and higher lycopene consumption (P=0.005) after controlling for place of birth, education, body mass index, and time since diagnosis. CONCLUSIONS: There are more similarities than differences in the dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study. Further analysis is needed to determine if higher lycopene consumption shown among the Hispanic participants will translate to greater protection against breast cancer recurrence or increased survival.

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 (Women's 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.

Telephone counseling helps maintain long-term adherence to a high-vegetable dietary pattern.

Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women's Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole grain foods, with a 20% lower intake of energy from fat. At 4 y, the between-group differences were 65% for vegetables (including juice), 25% fruit, 30% fiber, 40% legumes, 30% whole grain foods, and 13% lower intake of energy from fat. The intervention effect on fat intake was similar for early vs. late enrollees. Plasma carotenoid concentrations on a random 28% sample validated self-reported vegetable and fruit intake, with a between-group difference of 66% at 1 y and over 40% at 4 y. This large change will allow testing of hypotheses on the role of dietary change in preventing additional breast cancer events.

Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial.

CONTEXT: Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival. OBJECTIVE: To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006. INTERVENTION: The intervention group (n = 1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n = 1551) was provided with print materials describing the "5-A-Day" dietary guidelines. MAIN OUTCOME MEASURES: Invasive breast cancer event (recurrence or new primary) or death from any cause. RESULTS: From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, -13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72-1.15; P = .43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment. CONCLUSION: Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003787.

Increase in cruciferous vegetable intake in women previously treated for breast cancer participating in a dietary intervention trial.

Consumption of cruciferous vegetables has been associated with reduced breast cancer risk mechanistically and in population-based studies, although evidence has been inconsistent. This inconsistency may be related to limitations in quantifying and qualifying cruciferous vegetable exposure using standard instruments for dietary assessment (for example, food-frequency questionnaires, FFQs) or due to low levels of intake demonstrated among U.S. population samples. Cruciferous vegetable intake data are presented from a longitudinal study of a high-vegetable dietary intervention to reduce breast cancer recurrence among breast cancer survivors (n=1,156; 536 intervention and 620 comparison group subjects). Intake was assessed using repeat administration of an FFQ and cross-sectional administration of a cruciferous vegetable-specific FFQ (CVFFQ). Mean intake in the intervention group assessed using the standard FFQ was 37.7 g/day at baseline and increased to 57.1 g/day at 12 mo (P=0.0001) and was sustained through 48 mo. Broccoli and cabbage were the most commonly consumed cruciferous vegetables, regardless of the instrument used to assess intake. Differences in intake by group assignment were shown for raw cruciferous vegetables (30.2 g/day vs. 24.6 g/day, assessed using the CVFFQ), suggesting increased exposure to biologically active, cancer-preventive food constituents. These data suggest that this study population will be the first U.S. population sample to provide ample quantity and variety in cruciferous intake to examine whether these vegetables are protective against breast cancer recurrence.