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.

Effectiveness of a Health Talk Education Program on Human Papillomavirus (HPV) Knowledge, Attitudes, and Intentions to Vaccinate Children Among Mothers of Secondary School Boys in Thua Thien Hue Province, Vietnam.

BACKGROUND: The incidence of cancer related to human papillomavirus (HPV) that affects males is rising throughout the world. Currently, Vietnamese boys are typically not vaccinated against HPV while girls are. There are only a few studies pertaining to HPV vaccination among boys in Asian countries where parents play the most important role in deciding on such vaccination. We present here the first study to assess the effectiveness of a health talk education program on HPV knowledge, attitudes and intention to vaccinate children among mothers of secondary school students in the Thua Thien Hue province, Vietnam. METHODS: This was a quasi-experimental study. Two secondary schools in the Thua Thien Hue province, Vietnam were selected by purposive sampling. A total of 288 mothers of male students of two secondary schools were selected to participate, n=144 as controls and n=144 for the intervention arm for every school. Mothers of male students were invited to answer interview questions. The questionnaires covered social demographics, health history, HPV knowledge and HPV vaccination perception and intention. The study ran from September 2019 to January 2020. RESULTS: In total, 279 mothers finished the questionnaires. At the baseline, HPV knowledge in both groups was at the same level (p>0.05). One month after receiving the HPV health talk education, mothers of male students had much higher HPV knowledge than those who did not receive such HPV health talk education. The intervention group also had a much higher HPV vaccination intention than the control group (p<0.05). CONCLUSION: Health education was shown in this study to be an effective method to increase HPV knowledge and vaccination intention among mothers of boys in Vietnam.

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.

A Lifestyle Intervention via Email in Minority Breast Cancer Survivors: Randomized Parallel-Group Feasibility Study.

BACKGROUND: Our data have indicated that minority breast cancer survivors are receptive to participating in lifestyle interventions delivered via email or the Web, yet few Web-based studies exist in this population. OBJECTIVE: The aim of this study was to examine the feasibility and preliminary results of an email-delivered diet and activity intervention program, "A Lifestyle Intervention Via Email (ALIVE)," delivered to a sample of racial and ethnic minority breast cancer survivors. METHODS: Survivors (mean age: 52 years, 83% [59/71] African American) were recruited and randomized to receive either the ALIVE program's 3-month physical activity track or its 3-month dietary track. The fully automated system provided tools for self-monitoring and goal setting, tailored content, and automated phone calls. Descriptive statistics and mixed-effects models were computed to examine the outcomes of the study. RESULTS: Upon completion, 44 of 71 survivors completed the study. Our "intention-to-treat" analysis revealed that participants in the physical activity track made greater improvements in moderate to vigorous activity than those in the dietary track (+97 vs. +49 min/week, P<.001). Similarly, reductions in total sedentary time among those in the physical activity track (-304 vs. -59 min/week, P<.001) was nearly 5 times greater than that for participants in the dietary track. Our completers case analysis indicated that participants in the dietary track made improvements in the intake of fiber (+4.4 g/day), fruits and vegetables (+1.0 cup equivalents/day), and reductions in saturated fat (-2.3 g/day) and trans fat (-0.3 g/day) (all P<.05). However, these improvements in dietary intake were not significantly different from the changes observed by participants in the physical activity track (all P>.05). Process evaluation data indicated that most survivors would recommend ALIVE to other cancer survivors (97%), were satisfied with ALIVE (82%), and felt that ALIVE was effective (73%). However, survivors expressed concerns about the functionality of the interactive emails. CONCLUSIONS: ALIVE appears to be feasible for racial and ethnic minority cancer survivors and showed promising results for larger implementation. Although survivors favored the educational content, a mobile phone app and interactive emails that work on multiple email domains may help to boost adherence rates and to improve satisfaction with the Web-based platform. TRIAL REGISTRATION: ClinicalTrials.gov NCT02722850; https://clinicaltrials.gov/ct2/show/NCT02722850 (Archived by WebCite at http://www.webcitation.org/6tHN9VsPh).

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.

Addressing cancer health disparities using a global biopsychosocial approach.

The Center for Research on Minority Health has translated the biopsychosocial framework to address global cancer health disparities through the integration of biological (eg, endogenous steroids, genetic susceptibility, and pesticide levels) and behavioral (eg, dietary interventions) determinants, along with community-based research (eg, comprehensive involvement of community advisory boards) and educational approaches (eg, kindergarten through postgraduate training). Evidence of successful implementation of this framework includes health disparities training for >2000 individuals ranging from elementary to the postgraduate level, and conducting transdisciplinary projects that incorporate traditional and nontraditional health professionals to examine associations between biological and nonbiological determinants of health. Examples and recommendations for implementation of the biopsychosocial approach as it applies to cancer health disparities research are described.

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.