Clinical Outcomes and Healthcare Resource Utilization for Patients With Lower-Risk Myelodysplastic Syndromes Treated With Erythropoiesis-Stimulating Agents.

INTRODUCTION: Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States. PATIENTS AND METHODS: This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019. The primary analysis assessed patient demographic and clinical characteristics, treatment patterns, clinical outcomes (hematologic response, transfusion requirements, disease progression), and HCRU (medical encounters, laboratory tests, and medication use). Subgroup analyses of patients repeatedly treated with ESA therapy evaluated selected clinical outcomes and primary ESA failure by SF3B1 mutational status, per recently updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines©). RESULTS: A total of 142 patients were included with a median follow-up time of 17 months (interquartile range [IQR], 7-33). Median age at ESA initiation was 79 years (IQR, 73-85). Patients were predominantly male (54%), overweight or obese (32% and 23%, respectively), of White race (96%) and non-Hispanic ethnicity (89%). Overall, 57% patients were initially treated with darbepoetin alfa and 43% with epoetin alfa. Clinical outcomes were poor, and there was a significant burden on both the health system and individual patients treated with ESA therapies. Hematologic improvement- erythroid was only seen in 26% of 142 patients treated with ESAs, and 65% of 82 retreated patients experienced primary ESA failure. CONCLUSION: Our results indicate that primary ESA failure is largely unrecognized and that many patients should be considered for alternative treatments.

Cervical cancer screening compliance among active duty service members in the US military.

Previous research suggests active duty service members (ADSM) experience higher rates of human papilloma virus infection and cervical dysplasia, which puts them at greater risk for cervical cancer. The current study examined crude rates and correlates of cervical cancer screening compliance in 2003-2015 among screening-eligible ADSM in the Millennium Cohort Study (MCS). Data were drawn from the MCS, Defense Manpower Data Center, and Military Health System Data Repository. Screening eligibility and compliance were calculated each year and initial analyses examined crude rates of compliance. Generalized estimating equations were calculated to determine whether sociodemographic, military, and mental/behavioral health covariates were associated with cervical cancer screening compliance. A majority of participants were 21-29 years old (79.4%), non-Hispanic White (60.6%), and enlisted (82.2%). Crude rates of cervical cancer screening compliance increased from 2003 (61.2%) to 2010 (83.1%), and then declined from 2010 to 2015 (59.8%). Older ADSM and those who had a history of deployment had lower odds of screening compliance. ADSM in the Air Force and those in healthcare occupations had higher odds of screening compliance. Study findings suggest that cervical cancer screening compliance is declining among ADSM. Interventions to improve screening should target groups with lower screening compliance.

Factors Associated with Human Papillomavirus Vaccine Initiation and Compliance Among U.S. Military Service Members.

INTRODUCTION: The primary objective of the current study was to assess factors associated with Human Papillomavirus (HPV) vaccine initiation and compliance in a cohort of active duty US military service members (SM). MATERIALS AND METHODS: We included active-duty participants aged 18-26 years from the Millennium Cohort Study, a longitudinal cohort study of over 200,000 military SMs. The eligible study population included 22,387 female SMs and 31,705 male SMs. Vaccination was assessed over the period 2006-2017. Logistic regression was used to estimate the odds of vaccine initiation and compliance (3 doses within a 1-year period) in relation to demographic, military, health, and behavioral characteristics. RESULTS: Among female SMs, 37.8% initiated the vaccine and 40.2% of initiators completed the series within a year. Among male SMs, 3.9% initiated the vaccine and 22.1% of initiators completed the series within a year. Differences by sociodemographic factors, deployment status, branch of service, occupation, and smoking status-but not by selected mental health conditions-were observed. CONCLUSION: HPV vaccination uptake is subpar across all military service branches. Certain subgroups of SMs could be targeted to increase overall HPV vaccine coverage in the US military population.

The Millennium Cohort Study: The first 20 years of research dedicated to understanding the long-term health of US Service Members and Veterans.

PURPOSE: The Millennium Cohort Study, the US Department of Defense's largest and longest running study, was conceived in 1999 to investigate the effects of military service on service member health and well-being by prospectively following active duty, Reserve, and National Guard personnel from all branches during and following military service. In commemoration of the Study's 20th anniversary, this paper provides a summary of its methods, key findings, and future directions. METHODS: Recruitment and enrollment of the first 5 panels occurred between 2001 and 2021. After completing a baseline survey, participants are requested to complete follow-up surveys every 3-5 years. RESULTS: Study research projects are categorized into 3 core portfolio areas (psychological health, physical health, and health-related behaviors) and several cross-cutting areas and have culminated in more than 120 publications to date. For example, some key Study findings include that specific military service-related factors (e.g., experiencing combat, serving in certain occupational subgroups) were associated with adverse health-related outcomes and that unhealthy behaviors and mental health issues may increase following the transition from military service to veteran status. CONCLUSIONS: The Study will continue to foster stakeholder relationships such that research findings inform and guide policy initiatives and health promotion efforts.

Association of Combat Experiences With Suicide Attempts Among Active-Duty US Service Members.

Importance: There is uncertainty about the role that military deployment experiences play in suicide-related outcomes. Most previous research has defined combat experiences broadly, and a limited number of cross-sectional studies have examined the association between specific combat exposure (eg, killing) and suicide-related outcomes. Objective: To prospectively examine combat exposures associated with suicide attempts among active-duty US service members while accounting for demographic, military-specific, and mental health factors. Design, Setting, and Participants: This cohort study analyzed data from the Millennium Cohort Study, an ongoing prospective longitudinal study of US service members from all military branches. Participants were enrolled in 4 phases from July 1, 2001, to April 4, 2013, and completed a self-administered survey at enrollment and every 3 to 5 years thereafter. The population for the present study was restricted to active-duty service members from the first 4 enrollment phases who deployed in support of the wars in Iraq and Afghanistan. Questionnaire data were linked with medical encounter data through September 30, 2015. Data analyses were conducted from January 10, 2017, to December 14, 2020. Exposures: Combat exposure was examined in 3 ways (any combat experience, overall combat severity, and 13 individual combat experiences) using a 13-item self-reported combat measure. Main Outcomes and Measures: Suicide attempts were identified from military electronic hospitalization and ambulatory medical encounter data using the International Classification of Diseases, Ninth Revision codes. Results: Among 57 841 participants, 44 062 were men (76.2%) and 42 095 were non-Hispanic White individuals (72.8%), and the mean (SD) age was 26.9 (5.3) years. During a mean (SD) follow-up period of 5.6 (4.0) years, 235 participants had a suicide attempt (0.4%). Combat exposure, defined broadly, was not associated with suicide attempts in Cox proportional hazards time-to-event regression models after adjustments for demographic and military-specific factors; high combat severity and certain individual combat experiences were associated with an increased risk for suicide attempts. However, these associations were mostly accounted for by mental disorders, especially posttraumatic stress disorder. After adjustment for mental disorders, combat experiences with significant association with suicide attempts included being attacked or ambushed (hazard ratio [HR], 1.55; 95% CI, 1.16-2.06), seeing dead bodies or human remains (HR, 1.34; 95% CI, 1.01-1.78), and being directly responsible for the death of a noncombatant (HR, 1.81; 95% CI, 1.04-3.16). Conclusions and Relevance: This study suggests that deployed service members who experience high levels of combat or are exposed to certain types of combat experiences (involving unexpected events or those that challenge moral or ethical norms) may be at an increased risk of a suicide attempt, either directly or mediated through a mental disorder.

A Population-Based Study of Morbidity After Pancreatic Cancer Diagnosis.

BACKGROUND: Pancreatic cancer is an aggressive disease characterized by early and relentless tumor spread, thus leading healthcare providers to consider it a "distant disease." However, local pancreatic tumor progression can lead to substantial morbidity. This study defines the long-term morbidity from local and nonlocal disease progression in a large population-based cohort. METHODS: A total of 21,500 Medicare beneficiaries diagnosed with pancreatic cancer in 2000 through 2011 were identified. Hospitalizations were attributed to complications of either local disease (eg, biliary disorder, upper gastrointestinal ulcer/bleed, pain, pancreas-related, radiation toxicity) or nonlocal/distant disease (eg, thromboembolic events, cytopenia, dehydration, nausea/vomiting/motility problem, malnutrition and cachexia, ascites, pathologic fracture, and chemotherapy-related toxicity). Competing risk analyses were used to identify predictors of hospitalization. RESULTS: Of the total cohort, 9,347 patients (43.5%) were hospitalized for a local complication and 13,101 patients (60.9%) for a nonlocal complication. After adjusting for the competing risk of death, the 12-month cumulative incidence of hospitalization from local complications was highest in patients with unresectable disease (53.1%), followed by resectable (39.5%) and metastatic disease (33.7%) at diagnosis. For nonlocal complications, the 12-month cumulative incidence was highest in patients with metastatic disease (57.0%), followed by unresectable (56.8%) and resectable disease (42.8%) at diagnosis. Multivariable analysis demonstrated several predictors of hospitalization for local and nonlocal complications, including age, race/ethnicity, location of residence, disease stage, tumor size, and diagnosis year. Radiation and chemotherapy had minimal impact on the risk of hospitalization. CONCLUSIONS: Despite the widely known predilection of nonlocal/distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and frequent hospitalization.

Effect of Palliative Care on Aggressiveness of End-of-Life Care Among Patients With Advanced Cancer.

PURPOSE: Palliative care's role in oncology has expanded, but its effect on aggressiveness of care at the end of life has not been characterized at the population level. METHODS: This matched retrospective cohort study examined the effect of an encounter with palliative care on health-care use at the end of life among 6,580 Medicare beneficiaries with advanced prostate, breast, lung, or colorectal cancer. We compared health-care use before and after palliative care consultation to a matched nonpalliative care cohort. RESULTS: The palliative care cohort had higher rates of health-care use in the 30 days before palliative care consultation compared with the nonpalliative cohort, with higher rates of hospitalization (risk ratio [RR], 3.33; 95% CI, 2.87 to 3.85), invasive procedures (RR, 1.75; 95% CI, 1.62 to 1.88), and chemotherapy administration (RR, 1.61; 95% CI, 1.45 to 1.78). The opposite pattern emerged in the interval from palliative care consultation through death, where the palliative care cohort had lower rates of hospitalization (RR, 0.53; 95% CI, 0.44-0.65), invasive procedures (RR, 0.52; 95% CI, 0.45 to 0.59), and chemotherapy administration (RR, 0.46; 95% CI, 0.39 to 0.53). Patients with earlier palliative care consultation in their disease course had larger absolute reductions in health-care use compared with those with palliative care consultation closer to the end of life. CONCLUSION: This population-based study found that palliative care substantially decreased health-care use among Medicare beneficiaries with advanced cancer. Given the increasing number of elderly patients with advanced cancer, this study emphasizes the importance of early integration of palliative care alongside standard oncologic care.

Unplanned 30-day hospital readmission as a quality measure in gynecologic oncology.

OBJECTIVES: Thirty-day readmission is used as a quality measure for patient care and Medicare-based hospital reimbursement. The primary study objective was to describe the 30-day readmission rate to an academic gynecologic oncology service. Secondary objectives were to identify risk factors and costs related to readmission. METHODS: This was a retrospective, concurrent cohort study of all surgical admissions to an academic, high volume gynecologic oncology service during a two-year period (2013-2014). Data were collected on patient demographics, medical comorbidities, psychosocial risk factors, and results from a hospital discharge screening survey. Mixed logistic regression was used to identify factors associated with 30-day readmission and costs of readmission were assessed. RESULTS: During the two-year study period, 1605 women underwent an index surgical admission. Among this population, a total of 177 readmissions (11.0%) in 135 unique patients occurred. In a surgical subpopulation with >1 night stay, a readmission rate of 20.9% was observed. The mean interval to readmission was 11.8days (SD 10.7) and mean length of readmission stay was 5.1days (SD 5.0). Factors associated with readmission included radical surgery for ovarian cancer (OR 2.87) or cervical cancer (OR 4.33), creation of an ostomy (OR 11.44), a Charlson score of ≥5 (OR 2.15), a language barrier (OR 3.36), a median household income in the lowest quartile (OR 6.49), and a positive discharge screen (OR 2.85). The mean cost per readmission was $25,416 (SD $26,736), with the highest costs associated with gastrointestinal complications at $32,432 (SD $32,148). The total readmission-related costs during the study period were $4,523,959. CONCLUSIONS: Readmissions to a high volume gynecologic oncology service were costly and related to radical surgery for ovarian and cervical cancer as well as to medical, socioeconomic and psychosocial patient variables. These data may inform interventional studies aimed at decreasing unplanned readmissions in gynecologic oncology surgical populations.

Disparities in Surgical Care Among Women With Endometrial Cancer.

OBJECTIVE: To analyze contemporary U.S. use of minimally invasive surgery for the treatment of endometrial cancer and associated inpatient complications and costs. METHODS: In this retrospective cohort study, the National Inpatient Sample database was analyzed in patients with nonmetastatic endometrial cancer who underwent hysterectomy during 2012-2013. Hierarchical multiple logistic regression and propensity score matching were used to compare complications among patients treated with open compared with minimally invasive hysterectomy surgery. Cost of care was also compared using generalized linear modeling. RESULTS: We identified 9,799 patients; 52.4% underwent open and 47.6% minimally invasive hysterectomy. Many patients (43.4%) were treated at low-volume hospitals (less than 10 endometrial cancer cases annually). Patients were less likely to undergo open surgery in high-volume compared with low-volume hospitals (51.8% compared with 58.1%, respectively; adjusted odds ratio [OR] 0.35, 95% confidence interval [CI] 0.13-0.94) and more likely to undergo open surgery in rural compared with urban teaching hospitals (75.6% compared with 51.1%, respectively; adjusted OR 14.34, 95% CI 9.66-21.27), government compared with nonprofit hospitals (61.3% compared with 51.1%, respectively; adjusted OR 1.66, 95% CI 1.15-2.39), and in patients of black (67.9%; OR 1.46, 95% CI 1.30-1.65) and "other" race (60.5%; adjusted OR 2.39, 95% CI 1.99-2.87) compared with white race (49.2%, referent). Open surgery was associated with increased perioperative complications (adjusted OR 2.80, 95% CI 2.48-3.17) and a $1,243 increase in cost per case compared with minimally invasive approaches (P<.001). Using minimally invasive surgery for 80% of study patients may have averted 2,733 complications and saved approximately $19 million. CONCLUSION: Most U.S. women with endometrial cancer continue to be treated with open hysterectomy surgery despite increased complication rates and financial costs associated with this approach. A disparity in endometrial cancer surgical care exists that is affected by patient race and hospital geography and cancer volumes.

Geographic Disparity in the Use of Hypofractionated Radiation Therapy Among Elderly Women Undergoing Breast Conservation for Invasive Breast Cancer.

PURPOSE: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States. METHODS AND MATERIALS: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors of hypofractionated RT. RESULTS: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements. CONCLUSIONS: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery.

Patterns of Palliative Care Consultation Among Elderly Patients With Cancer.

BACKGROUND: The role of palliative care has expanded over the past several decades, although the oncology-specific regional evolution of this specialty has not been characterized at the population-based level. METHODS: This study defined the patterns of palliative care delivery using a retrospective cohort of patients with advanced cancer within the SEER-Medicare linked database. We identified 83,022 patients with metastatic breast, prostate, lung, and colorectal cancers. We studied trends between 2000 through 2009, and determined patient-level and regional-level predictors of palliative care delivery. RESULTS: Palliative care consultation rates increased from 3.0% in 2000 to 12.9% in 2009, with most consultations occurring in the last 4 weeks of life (77%) in the inpatient hospital setting. The rates of palliative care delivery were highest in the West (7.6%) and lowest in the South (3.2%). The likelihood of palliative care consultation increased with decreasing numbers of regional acute care hospital beds per capita. The use of palliative care consultation increased with increasing numbers of regional physicians. The use of palliative care decreased with increasing regional Medicare expenditure with a $1,387 difference per beneficiary between the first and fourth quartiles of palliative care use. CONCLUSIONS: Geographic location influences a patient's options for palliative care in the United States. Although the overall rates of palliative care are increasing, future effort should focus on improving palliative care services in regions with the least access.

Modern Radiation Therapy and Cardiac Outcomes in Breast Cancer.

PURPOSE: Adjuvant radiation therapy, which has proven benefit against breast cancer, has historically been associated with an increased incidence of ischemic heart disease. Modern techniques have reduced this risk, but a detailed evaluation has not recently been conducted. The present study evaluated the effect of current radiation practices on ischemia-related cardiac events and procedures in a population-based study of older women with nonmetastatic breast cancer. METHODS AND MATERIALS: A total of 29,102 patients diagnosed from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Medicare claims were used to identify the radiation therapy and cardiac outcomes. Competing risk models were used to assess the effect of radiation on these outcomes. RESULTS: Patients with left-sided breast cancer had a small increase in their risk of percutaneous coronary intervention (PCI) after radiation therapy-the 10-year cumulative incidence for these patients was 5.5% (95% confidence interval [CI] 4.9%-6.2%) and 4.5% (95% CI 4.0%-5.0%) for right-sided patients. This risk was limited to women with previous cardiac disease. For patients who underwent PCI, those with left-sided breast cancer had a significantly increased risk of cardiac mortality with a subdistribution hazard ratio of 2.02 (95% CI 1.23-3.34). No other outcome, including cardiac mortality for the entire cohort, showed a significant relationship with tumor laterality. CONCLUSIONS: For women with a history of cardiac disease, those with left-sided breast cancer who underwent radiation therapy had increased rates of PCI and a survival decrement if treated with PCI. The results of the present study could help cardiologists and radiation oncologists better stratify patients who need more aggressive cardioprotective techniques.

Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer.

Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression.

The impact of radiotherapy costs on clinical outcomes in breast cancer.

BACKGROUND AND PURPOSE: In cost-effective healthcare systems, the cost of services should parallel patient complexity or quality of care. The purpose of this study was to determine whether the cost of radiotherapy correlates with patient-related outcomes among a large cohort of breast cancer patients treated with adjuvant breast radiation. MATERIALS AND METHODS: 23,127 women with non-metastatic breast cancer undergoing radiotherapy after breast conservation surgery were identified from the Surveillance, Epidemiology, and End Results database from 2000 to 2009. Medicare reimbursements were used as a proxy for cost of radiotherapy, and Medicare claims were examined to identify local toxicities, and breast cancer-related endpoints. The impact of cost on these outcomes was studied with multivariable Fine-Gray models to account for competing risks. RESULTS: The median cost (and interquartile range) of a course of breast radiation was $8100 ($6700-9700). Increased radiation costs were not associated with the occurrence of treatment-related toxicities (all p-values>0.05), ipsilateral breast recurrence (p=0.55), or breast cancer-related mortality (p=0.55). CONCLUSION: Higher costs for adjuvant radiation in breast cancer were not associated with a decreased risk of patient-related outcomes suggesting inefficiency in Medicare reimbursements. Future efforts should focus on prospective evaluation of alternative payment models for radiotherapy.

Variation in the Cost of Radiation Therapy Among Medicare Patients With Cancer.

PURPOSE: Radiation therapy represents a major source of health care expenditure for patients with cancer. Understanding the sources of variability in the cost of radiation therapy is critical to evaluating the efficiency of the current reimbursement system and could shape future policy reform. This study defines the magnitude and sources of variation in the cost of radiation therapy for a large cohort of Medicare beneficiaries. PATIENTS AND METHODS: We identified 55,288 patients within the SEER database diagnosed with breast, lung, or prostate cancer between 2004 and 2009. The cost of radiation therapy was estimated from Medicare reimbursements. Multivariable linear regression models were used to assess the influence of patient, tumor, and radiation therapy provider characteristics on variation in cost of radiation therapy. RESULTS: For breast, lung, and prostate cancers, the median cost (interquartile range) of a course of radiation therapy was $8,600 ($7,300 to $10,300), $9,000 ($7,500 to $11,100), and $18,000 ($11,300 to $25,500), respectively. For all three cancer subtypes, patient- or tumor-related factors accounted for < 3% of the variation in cost. Factors unrelated to the patient, including practice type, geography, and individual radiation therapy provider, accounted for a substantial proportion of the variation in cost, ranging from 44% with breast, 43% with lung, and 61% with prostate cancer. CONCLUSION: In this study, factors unrelated to the individual patient accounted for the majority of variation in the cost of radiation therapy, suggesting potential inefficiency in health care expenditure. Future research should determine whether this variability translates into improved patient outcomes for further evaluation of current reimbursement practices.

Dietary isoflavone intake is not statistically significantly associated with breast cancer risk in the Multiethnic Cohort.

Given the high intake levels of soya and low incidence rates of breast cancer in Asian countries, isoflavones, substances with an oestrogen-like structure occurring principally in soyabeans, are postulated to be cancer protective. In the present study, we examined the association of dietary isoflavone intake with breast cancer risk in 84,450 women (896 in situ and 3873 invasive cases) who were part of the Multiethnic Cohort (Japanese Americans, whites, Latinos, African Americans and Native Hawaiians) with a wide range of soya intake levels. The absolute levels of dietary isoflavone intake estimated from a baseline FFQ were categorised into quartiles, with the highest quartile being further subdivided to assess high dietary intake. The respective intake values for the quartiles (Q1, Q2, Q3, and lower and upper Q4) were 0-< 3·2, 3·2-< 6·7, 6·7-< 12·9, 12·9-< 20·3, and 20·3-178·7 mg/d. After a mean follow-up period of 13 years, hazard ratios (HR) and 95% CI were calculated using Cox regression models stratified by age and adjusted for known confounders. Linear trends were tested by modelling continuous variables of interest assigned the median value within the corresponding quartile. No statistically significant association was observed between dietary isoflavone intake and overall breast cancer risk (HR for upper Q4 v. Q1: 0·96 (95% CI 0·85, 1·08); P trend = 0·40). While the test for interaction was not significant (P=0·14), stratified analyses suggested possible ethnic/racial differences in risk estimates, indicating that higher isoflavone intakes may be protective in Latina, African American and Japanese American women. These results are in agreement with those of previous meta-analyses showing no protection of isoflavones at low intake levels, but suggesting inverse associations in populations consuming high amounts of soya.

Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.

BACKGROUND: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. METHODS: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. FINDINGS: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). INTERPRETATION: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. FUNDING: Carraresi Foundation and others.