Real-world patient characteristics and treatment patterns in US patients with advanced non-small cell lung cancer.

BACKGROUND: Patients from non-small cell lung cancer (NSCLC) controlled clinical trials do not always reflect real-world heterogeneous patient populations. We designed a study to describe the real-world patient characteristics and treatment patterns of first-line treatment in patients in the US with NSCLC. METHODS: This was an observational, retrospective cohort study based on electronic medical records of US adults with locally advanced or metastatic disease in the ConcertAI Patient360 NSCLC database who initiated first-line treatment with anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy between July 2016 and December 2020. The analysis used patient attributes, clinical characteristics, and treatments from each patient's medical records. RESULTS: A total of 2175 patients were eligible for analysis. The median age was 68 years, and 26.2% of the patients were ≥75 years old. At treatment initiation, 96.4% and 3.6% of the patients had Stage 4 and Stage 3 (B or C) NSCLC, respectively. The most common histology type was nonsquamous adenocarcinoma (66.4%), and 19.8% had Eastern Cooperative Oncology Group performance status ≥2. Immunosuppressive medications were being used by 17.7% of patients, and 11.0% were immunocompromised. Almost all patients had metastases: 64.6% had 1, 23.2% had 2, and 8.0% had ≥3 metastatic sites. Brain metastases were present in 22.9% of patients. Treatment evolution was observed with first-line standard of care shifting from single-agent immunotherapy in 2016 (90.2%) to combination immunotherapy and chemotherapy in 2020 (60.2%). CONCLUSION: Between 2016 and 2020, the first-line treatment paradigm for advanced NSCLC in the US shifted from anti-PD-1/PD-L1 monotherapy to combination chemoimmunotherapy, with increasing biomarker testing. Further research in heterogeneous patient populations to characterize treatment strategies is warranted.

C-reactive protein concentration and risk of selected obesity-related cancers in the Women's Health Initiative.

BACKGROUND: Obesity is a chronic inflammatory condition strongly associated with the risk of numerous cancers. We examined the association between circulating high-sensitivity C-reactive protein (hsCRP), a biomarker of inflammation and strong correlate of obesity, and the risk of three understudied obesity-related cancers in postmenopausal women: ovarian cancer, kidney cancer, and multiple myeloma. METHODS: Participants were 24,205 postmenopausal women who had measurements of baseline serum hsCRP (mg/L) in the Women's Health Initiative (WHI) CVD Biomarkers Cohort, a collection of four sub-studies within the WHI. Incident cancers were identified over 17.9 years of follow-up (n = 153 ovarian, n = 110 kidney, n = 137 multiple myeloma). hsCRP was categorized into study-specific quartiles. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of baseline hsCRP with the risk of these cancers. RESULTS: There was no clear association between baseline hsCRP concentration and the risk of ovarian cancer (quartile 4 vs. 1: HR 0.87, 95% CI 0.56-1.37), kidney cancer (HR 0.95, 95% CI 0.56-1.61), or multiple myeloma (HR 0.82, 95% CI 0.52-1.29). HRs for 1 mg/L increases in hsCRP also approximated the null value for each cancer. CONCLUSIONS: The results of this study suggest that elevated CRP is not a major risk factor for these obesity-related cancers (ovarian or kidney cancers, or multiple myeloma) among postmenopausal women. Given the importance of elucidating the mechanisms underlying the association of obesity with cancer risk, further analysis with expanded biomarkers and in larger or pooled prospective cohorts is warranted.

Lack of private health insurance is associated with higher mortality from cancer and other chronic diseases, poor diet quality, and inflammatory biomarkers in the United States.

OBJECTIVE: The lack of health insurance reduces access to care and often results in poorer health outcomes. The present study simultaneously assessed the effects of health insurance on cancer and chronic disease mortality, as well as the inter-relationships with diet, obesity, smoking, and inflammatory biomarkers. We hypothesized that public/no insurance versus private insurance would result in increased cancer/chronic disease mortality due to the increased prevalence of inflammation-related lifestyle factors in the underinsured population. METHODS: Data from the Third National Health and Nutrition Examination Survey participants (NHANES III;1988-1994) were prospectively examined to assess the effects of public/no insurance versus private insurance and inflammation-related lifestyle factors on mortality risk from cancer, all causes, cardiovascular disease (CVD) and diabetes. Cox proportional hazards regression was performed to assess these relationships. RESULTS: Multivariate regression analyses revealed substantially greater risks of mortality ranging from 35% to 245% for public/no insurance versus private insurance for cancer (HR=1.35; 95% CI=1.09,1.66), all causes (HR=1.54; 95% CI=1.39,1.70), CVD (HR=1.62; 95% CI=1.38,1.90) and diabetes (HR=2.45; 95% CI=1.45,4.14). Elevated CRP, smoking, reduced diet quality and higher BMI were more prevalent in those with public insurance, and were also associated with increased risks of cancer/chronic disease mortality. DISCUSSION: Insurance status was strongly associated with cancer/chronic disease mortality after adjusting for lifestyle factors. The results suggest that inadequate health insurance coverage results in a substantially greater need for preventive strategies that focus on tobacco control, obesity, and improved dietary quality. These efforts should be incorporated into comprehensive insurance coverage programs for all Americans.

Real-world treatment patterns and outcomes of patients with metastatic nonsquamous non-small cell lung cancer after progression on standard-of-care therapy in the United States.

OBJECTIVES: Data to guide treatment selection in metastatic nonsquamous (mNSq) non-small cell lung cancer (NSCLC) after progression on current standard-of-care (SoC) treatment are limited. We investigated patterns of treatment and clinical outcomes following one or more disease progressions on SoC. MATERIALS AND METHODS: Electronic medical records in the ConcertAI Patient360 NSCLC database were analyzed for US adults with mNSq NSCLC who initiated treatment between 2016 and 2021. Analyses were conducted separately for patients who had ≥1 prior lines of therapy and progression(s) without (Cohort 1) or with (Cohort 2) evidence of targetable genetic alterations (EGFR, ALK, or ROS1). Outcomes included real-world progression-free survival (rwPFS) and overall survival (rwOS). RESULTS: Cohorts 1 and 2 included 281 and 109 patients, respectively. In Cohort 1, subsequent treatment was most often with docetaxel monotherapy (18.5%) or docetaxel + ramucirumab (32.4%). Most patients in Cohort 2 received platinum-based doublet chemotherapy with (22.9%) or without (34.9%) immunotherapy. Median rwPFS and rwOS were 2.9 and 7.2 months, respectively, in Cohort 1, and 3.2 and 10.4 months in Cohort 2. Neither the addition of ramucirumab to docetaxel in Cohort 1 nor the addition of immunotherapy to chemotherapy in Cohort 2 was associated with a marked improvement in additional survival. CONCLUSION: Patients with progressive mNSq NSCLC most commonly received later-line docetaxel for cancer without driver mutations, or platinum-based chemotherapy (following one or more lines of tyrosine kinase inhibitor therapy) for cancer with driver mutations, consistent with guideline recommendations. Median survival was poor regardless of subsequent treatment, highlighting the need for more effective options.

Real-world insights into patients with advanced NSCLC and MET alterations.

OBJECTIVES: To describe characteristics, treatment and outcomes of non-small cell lung cancer (NSCLC) patients with MET alterations (MET exon 14 [METex14] skipping or MET amplification [METamp]) in real-world clinical care. METHODS: This non-interventional cohort study used real-world data extracted from electronic medical records from academic oncology sites in Israel, The Netherlands, Taiwan, and the USA. Patients had confirmed diagnosis of advanced (Stage IIIB-IV) NSCLC harboring MET alterations (date of diagnosis = index date) between 1 Jan 2010 and 30 Sept 2018. Medical history was assessed prior to and at the index date (baseline period), and outcomes from first date of treatment to death, loss to follow-up, or end of study period. RESULTS: A total of 117 patients were included (METex14 n = 70; METamp n = 47); testing methods were heterogeneous. Concomitant oncogenic mutations were more common in the METamp cohort than METex14. Patients in the METex14 cohort were older than those in METamp, and a larger proportion were never smokers. Anticancer first-line therapies received by patients (METex14; METamp) included chemotherapy only (44%; 41%), MET inhibitors (33%; 29%), immune checkpoint inhibitor (ICI) mono-(12%; 15%) and combination-therapy (8%; 3%). Second-line therapies included chemotherapy (35%; 30%) and MET inhibitors (30%; 39%). In the METex14 cohort, objective response rate (ORR) was generally low (first-line 28%; second-line 30%); no patients who received ICIs had a response. In the METamp cohort, ORR was 36% in first-line and 22% in second-line. Median (95% confidence interval) overall survival from start of first-line therapy was 12.0 months (6.8, 19.2) in the METex14 cohort and 22.0 months (9.8, 31.2) in METamp. CONCLUSIONS: Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, METex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations.

The Genomics of Young Lung Cancer: Comprehensive Tissue Genomic Analysis in Patients Under 40 With Lung Cancer.

INTRODUCTION: Lung adenocarcinomas in young patients (<40 y) are more likely to harbor targetable genomic alterations. This study aimed to determine whether the prevalence of targetable alterations is greater in young adults with lung carcinoma than in the overall lung cancer population. To reach this rare patient population, a web-based platform was used to recruit and enroll patients remotely. METHODS: In this prospective study, patients less than 40 years old at the time of primary lung cancer diagnosis with confirmed lung carcinoma were recruited from four global sites and remotely by means of a website. Genotyping data were collected, if available, or obtained by means of next-generation sequencing using the FoundationOne platform. The prevalence of targetable alterations was quantified across patients with advanced adenocarcinoma. RESULTS: Overall, 133 patients across five continents were included, 41% of whom enrolled online. The mean (SD) age at diagnosis was 34 (5.2) years; 79% had stage IV disease at diagnosis. Among patients with adenocarcinoma (n = 115), 112 entered the study with previous genomic testing results and 86 (77%) had targetable alterations in EGFR, ALK, ROS1, MET, ERBB2, or RET. Among those without targetable alterations, 14 received further testing and a targetable alteration was identified in eight (57%). CONCLUSIONS: This study revealed the feasibility of using a web-based platform to recruit young patients with lung cancer and revealed that 94 of 112 (84%) with adenocarcinoma at any stage had targetable genomic alterations. Among patients with stage IV adenocarcinoma, 85% had a targetable alteration, which is higher than historical expectations for the general population.

Exercise and dietary change after diagnosis and cancer-related symptoms in long-term survivors of breast cancer: CALGB 79804.

OBJECTIVE: Improving diet and exercise can reduce survivors' risk of cancer-related fatigue, poor physical functioning, and potential recurrence. A cancer diagnosis can represent a 'teachable moment', leading survivors to make positive changes in diet and exercise behaviors; however, little is known about how often this occurs or about factors that enhance or limit survivors' ability to make these changes. This cross-sectional descriptive study investigated both the prevalence and clustering of self-reported changes in diet and exercise and how these changes related to ongoing cancer-related symptoms, social support, and stressful life events among long-term breast cancer survivors. METHODS: Survivors (n=227, response rate=72%) of a prior Cancer and Leukemia Group B treatment trial, on average 12 years post-diagnosis, completed a mailed survey assessing health behavior changes since diagnosis and current symptoms, social support, and stressful life events. RESULTS: Over half of survivors reported making positive exercise or diet changes since diagnosis: over 25% reported making exercise and diet changes. Analyses of covariance models showed that survivors who reported increasing their exercise also reported lower fatigue. Trends were also found between increased fruit and vegetable intake and decreased fatigue and between increased exercise and increased social support. CONCLUSIONS: These results underscore the need for health promotion efforts among survivors. Exercise promotion is especially needed since more survivors attempted to change dietary behaviors than exercise on their own. Further, fatigue may limit survivors' ability to change their health behaviors; alternatively, survivors who increase their exercise may experience less fatigue.

Assessing the Impact of CALGB 9343 on Surgical Trends in Elderly-Women With Stage I ER+ Breast Cancer: A SEER-Based Analysis.

Purpose: Lumpectomy (L) and breast radiotherapy (RT) results in equivalent outcomes in comparison to mastectomy (M) for early-stage breast cancer (BC) based on randomized controlled trials (RCT). Since 2004, RCT support that L without RT yields equivalent survival and acceptable local-regional outcomes in women ≥70-years old with T1N0 hormone-sensitive (ER+) BC on endocrine therapy. Based on this, we hypothesized that M rates should decrease substantially after 2004 in this low-risk elderly population. Methods: We used the Surveillance Epidemiology and End Results registry data to conduct this study. We included women with T1N0 ER+ BC from 2000 to 2014. We compared M rates in women diagnosed from 2000 to 2004 vs. 2005-2012 using the Chi-Square test. Logistic regression analyses was performed to examine demographic/clinical factors associated with mastectomy. Results: 67,506 women met the study criteria. In elderly Stage I ER+ BC, the M rate decreased by 6.3%: 29.0% before 2004 to 22.7% after 2004 (p < 0.0001). M rates remained higher in elderly non-Hispanic black (NHB, 27.1%, p < 0.0001), non-Hispanic Asian-Pacific-Islander (NHAPI, 30.1%, p < 0.0001), and Hispanics (24.4%, p = 0.0004) vs. non-Hispanic White (NHW, 21.5%). Treatment in the modern cohort was associated with decreased odds of mastectomy (OR = 0.71, 95% CI 0.68-0.74, p < 0.0001) while NH-API race was associated with the highest increased odds of mastectomy (OR = 1.65, 95% 1.53-1.78, p < 0.0001). In the modern cohort specifically (2005-2014), Hispanic women (OR = 1.12, p = 0.014), NHB women (OR = 1.21, p < 0.0001), and NHAPI women (OR = 1.73, p < 0.0001) all had higher odds of undergoing mastectomy relative to NHW women after adjusting for all other patient and tumor related factors. Conclusions: In elderly patients with stage I, ER+ BC, M rates have decreased modestly since 2004. These trends are driven mostly be decreases in the M rate in NHW women, but M rates remain ~25% in Hispanic, NHB, and NHAPI women. Further research is needed to identify why M, which is associated with higher cost and morbidity than L alone, has not changed substantially in elderly, low-risk BC.

Applying a conceptual model for examining health-related quality of life in long-term breast cancer survivors: CALGB study 79804.

OBJECTIVES: The Survivor's Health and Reaction study used a quality-of-life model adapted for cancer survivors by Dow and colleagues to identify factors related to global health-related quality of life (HRQL) and to document the prevalence of problems and health-oriented behaviors in a follow-up study of breast cancer patients who participated in CALGB 8541. METHODS: A total of 245 survivors (78% of those invited) who were 9.4-16.5 years post-diagnosis completed surveys that inquired about current HRQL, economic, spiritual, physical and psychosocial concerns, and health-oriented behaviors (e.g. smoking, exercise, and supplement use). A regression model was developed to examine factors related to global HRQL across all domains. RESULTS: The regression model revealed that decreased energy levels (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.03, 1.07), having heart disease (OR=5.01, 95% CI: 1.39, 18.1), having two or more co-morbidities (OR=2.39, 95% CI: 1.10, 5.19), and lower social support (OR=1.03, 95% CI: 1.02, 1.05) were associated with lower global HRQL. Factors related to psychological, spiritual, and economic domains were not predictive of global HRQL. Regarding lifestyle changes, some women reported engaging in health-oriented behaviors since their cancer diagnosis, such as improving eating habits (54%), increasing exercise (32%), and reducing/quitting smoking (20%). The most prevalent problems reported by women at follow-up were menopausal symptoms (64%), such as hot flashes and vaginal dryness, osteoporosis (25%), and lymphedema (23%). CONCLUSION: Suggestions are provided to target interventions, such as provider-based strategies, in order to improve HRQL in long-term breast cancer survivors.

Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With Second-Line Therapies for Medicare Patients With Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: Real-world data on current treatment practices for non-small-cell lung cancer (NSCLC) are needed to understand the place in therapy and potential economic impact of newer therapies. PATIENTS AND METHODS: This retrospective cohort study identified patients ≥ 65 years old in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database with first-time diagnosis of stage IIIB/IV NSCLC from 2007-2011 who received second-line therapy after first-line platinum-based chemotherapy from 2007 through mid-2013. Second-line regimens, health care resource use, adverse events (AEs), and associated costs were analyzed descriptively. Overall survival was determined by Kaplan-Meier test. Costs were adjusted to 2013 US dollars. RESULTS: We identified 4033 patients with advanced NSCLC who received second-line therapy (47% of those who received first-line platinum-based chemotherapy). Mean (SD) age was 73 (5) years, 2246 (56%) were male; 1134 (28%) and 2899 (72%) had squamous and nonsquamous NSCLC, respectively. The 4 most common second-line regimens were pemetrexed (22%), docetaxel (12%), carboplatin/paclitaxel (11%), and gemcitabine (7%). Median overall survival from second-line therapy initiation was 7.3 months (95% confidence interval, 7.0-7.7). Dyspnea and anemia were the most common AEs of interest, affecting 29% and 26% of patients, respectively; atypical pneumonia was associated with the highest AE-related costs (mean, $5339). The mean total per-patient-per-month cost was $10,885; AE-related per-patient-per-month costs totaled $1036 (10%). Costs were highest for pemetrexed-treated patients. CONCLUSION: These real-world data illustrate the variety of second-line regimens, poor prognosis, and high cost of second-line chemotherapy for patients with advanced NSCLC treated before the approval of immunotherapies for these patients.

Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With First-line Therapies for Medicare Patients 65 Years and Older With Advanced Non-small-cell Lung Cancer: A Retrospective Study.

PURPOSE: This study sought to better understand real-world treatment patterns, overall and non-small-cell lung cancer (NSCLC)-specific survival, adverse event (AE) occurrence, and economic impact of first-line cancer therapies in Medicare patients. PATIENTS AND METHODS: This retrospective cohort study identified patients ≥ 65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database who received a first-time advanced (stage IV) NSCLC diagnosis from 2007 to 2011, and who received first-line platinum-based chemotherapy from 2007 through mid-2013. First-line regimens, healthcare resource use, occurrence of AEs, and associated costs (2013 US dollars) were analyzed. Median survival was determined using the Kaplan-Meier method. RESULTS: Surprisingly, only 46% of patients (n = 13,472) with stage IIIB/IV NSCLC received systemic therapy, and 5931 received platinum-based therapy. The mean age was 73 years, with 3354 (57%) males; 1489 (25%) had squamous and 4442 (75%) nonsquamous histology. The most common regimens were carboplatin doublets (70%), including carboplatin/paclitaxel (38%), carboplatin/pemetrexed (12%), carboplatin/gemcitabine (11%), and carboplatin/docetaxel (7%). The median overall survival from first-line therapy initiation was 7.2 months (95% confidence interval, 7.0-7.5 months). Dyspnea and anemia were the most common AEs of interest, whereas atypical pneumonia was associated with the greatest AE-related costs (mean, $5044). The mean total per-patient-per-month cost was $11,909, with AE-related costs comprising 9% of total costs. The highest costs and survival were observed for patients treated with carboplatin/pemetrexed and bevacizumab/carboplatin/paclitaxel. CONCLUSIONS: These real-world data illustrate the most common first-line regimens by histology, overall survival, AEs, and some of the high AE-related costs of therapy for advanced NSCLC, and provides extremely useful information for clinicians.

Ibuprofen and fatal lung cancer: A brief report of the prospective results from the Third National Health and Nutrition Examination Survey (NHANES III).

Chronic inflammation appears to increase the risk of lung cancer and, reciprocally, agents that reduce inflammation have been found to reduce this risk. However, few prospective studies have assessed whether there exists an association between lung cancer and the use of non-steroidal anti-inflammatory drugs (NSAIDs). In the present study, the association between fatal lung cancer and NSAIDs was investigated using cohort data from the Third National Health and Nutrition Examination Study (NHANES III). Baseline data were collected on smoking, NSAID use and other lifestyle factors for 10,735 participants during 1988-1994, with cause-specific mortality status ascertained through probabilistic record matching based on the National Death Index until 2006. Cox proportional hazards regression models were conducted to estimate hazard ratios (HRs) and confidence intervals (CIs) for NSAID use and death from lung cancer, controlling for current smoking and other covariates. During the 18 years of follow-up, 269 participants succumbed to lung cancer, of whom 252 (93.6%) reported a history of cigarette smoking. Since all but 17 of the 269 fatal lung cancer cases occurred among current or former smokers, estimates of NSAID effects were ascertained from a sub-cohort of 5,882 individuals who reported a history of past or current cigarette smoking. Multivariate regression models revealed that regular use of ibuprofen resulted in a 48% reduced risk of lung cancer mortality (HR=0.52, 95% CI: 0.33-0.82, P<0.01). The main effects of other compounds tested, such as aspirin or acetaminophen, were not statistically significant. Our results suggest that high-risk subgroups of smokers may benefit from the regular use of specific NSAIDs, which may prove to be a useful strategy for lung cancer prevention.

Costs of Diagnostic Assessment for Lung Cancer: A Medicare Claims Analysis.

PURPOSE: To assess the diagnostic costs leading up to a lung cancer diagnosis in patients with abnormal computed tomography (CT) scans. PATIENTS AND METHODS: A retrospective cohort study using the 5% Medicare claims data (January 1, 2009, to December 31, 2011) was conducted. Patients aged 65 to 74 years with an abnormal chest CT scan were identified. Index was defined as the date of the abnormal chest CT scan. Outcomes assessed over a 12-month follow-up after index included lung cancer diagnosis rate and the use and associated costs of follow-up diagnostic tests up to diagnosis of lung cancer. RESULTS: Of 8979 patients identified with an abnormal chest CT scan (mean age, 69.3 ± 2.9 years), 13.9% were diagnosed with lung cancer over 12 months. Chest x-rays were the most common diagnostic test. Of the 19% who underwent a biopsy, 43.6% were not diagnosed with lung cancer during follow-up. The average total diagnostic assessment cost per patient was higher for those with versus without lung cancer ($7567 vs. $3558). Among patients not diagnosed with lung cancer, the median diagnostic cost per patient for those with versus without biopsy was ∼ 28 times higher. Adverse events significantly increased the average cost per biopsy (approximately 4-fold). CONCLUSION: Total lung cancer diagnostic cost was $38.3M in the defined study sample, of which 43.1% was accounted for by biopsied patients without a lung cancer diagnosis. Additional risk stratification is required to decrease unnecessary biopsy referrals and costs. Further, adverse events significantly increased costs.

Prospective evaluation of C-reactive protein, smoking and lung cancer death in the Third National Health and Nutrition Examination Survey.

Chronic inflammation plays an important role in lung carcinogenesis. Few prospective studies have examined associations between lung cancer, serum C-reactive protein (CRP), a measure of systemic inflammation, and inflammatory lifestyle factors, such as smoking and obesity. This study prospectively examined the relationship between CRP and lung cancer death and its interrelationships with several lifestyle factors. Baseline data on smoking and other lifestyle variables were collected for 8,950 participants in the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994). Baseline CRP levels were measured in serum samples by nephelometry. Mortality status was ascertained through probabilistic record matching using the National Death Index through 2006. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for CRP and lung cancer death, with adjustment for smoking and other variables. During 18 years of follow-up, 219 individuals died from lung cancer. Multivariate regression models revealed a dose-response effect for elevated CRP and risk of lung cancer death when adjusting for age, gender, BMI and smoking. Compared to individuals with CRP <3 mg/l, lung cancer death was significantly associated with elevated levels of CRP: HR=1.63 (95% CI=1.15-2.26) for 3-7 mg/l and HR=2.44 (95% CI=1.81­3.45) for CRP >7 mg/l, P-trend <0.0001). The risk of lung cancer death for smokers increased 9-fold in adjusted models (P<0.0001). When stratified by gender and smoking status the effects of CRP were similar for smokers and males but did not reach statistical significance for females and non-smokers. This study supports a dose-dependent relationship between lung cancer death and CRP for males and smokers, but additional efforts are needed to better elucidate these relationships in women and non-smokers. The results suggest that CRP may emerge as a valuable tool in identifying high-risk subgroups of smokers for lung cancer prevention strategies.

Assessment of the effects of severe obesity and lifestyle risk factors on stage of endometrial cancer.

BACKGROUND: Lifestyle risk factors, including obesity, have been associated with increased risk of endometrial cancer (EC). Women with higher obesity levels tend to have less aggressive EC disease stage and histology. This study further investigated associations between nonmodifiable risk factors, such as age, race, and grade, and modifiable lifestyle factors, such as diet and physical activity expenditure, in relation to severe obesity and late versus early EC stage at diagnosis. METHODS: Demographic, anthropometric, and lifestyle surveys were administered to 177 women with histologically confirmed EC. Logistic regression analyses assessed the relationship between obesity and other risk factors on EC stage at diagnosis. RESULTS: In multivariate models, body mass index (BMI) < 35 was not significantly associated with late EC stage at diagnosis (OR = 1.67, P = 0.219) when adjusting for grade and age. Grade was significantly associated with EC stage when controlling for BMI and age (OR = 8.48, P = .000). Women more than the age of 60 had a fourfold increased risk of diagnosis at late versus early EC stage when adjusting for other risk factors. Age had a confounding effect on the obesity-EC stage association. CONCLUSIONS: Our results corroborate those of past studies showing that BMI is not an independent risk factor for EC stage and that age may have confounded the obesity-EC stage association. Because of mixed results and implications for treatment outcomes, however, further research examining these variables is warranted. IMPACT: Our results provide further insight into the obesity EC-stage association, especially the confounding effect of age. Future studies should examine modifiable lifestyle factors in larger and more diverse populations.

Effects of tomato- and soy-rich diets on the IGF-I hormonal network: a crossover study of postmenopausal women at high risk for breast cancer.

To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone-binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 µmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 µmol/L (P < 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted.

Health-related quality of life in long-term breast cancer survivors: differences by adjuvant chemotherapy dose in Cancer and Leukemia Group B study 8541.

BACKGROUND: The Survivor's Health and Reaction (SHARE) study examined health-related quality of life (HRQL) in breast cancer patients who had participated in Cancer and Leukemia Group B Trial 8541 from 1985 to 1991. METHODS: In total, 245 survivors (78% of eligible patients) who were 9.4 to 16.5 years postdiagnosis (mean, 12.5 years postdiagnosis) completed HRQL surveys relating to 5 domains. Analyses examined HRQL domains according to 3 different chemotherapy dose levels that were administered in the original treatment trial: low-dose cyclophosphamide, doxorubicin, and fluorouracil (CAF) at 300 mg/m(2), 30 mg/m(2), and 300 x 2 mg/m(2), respectively, over 4 cycles; standard-dose CAF at 400 mg/m(2), 40 mg/m(2), and 400 x 2 mg/m(2), respectively, over 6 cycles; and high-dose CAF at 600 mg/m(2), 60 mg/m(2) and 600 x 2 mg/m(2), respectively, over 4 cycles. RESULTS: In univariate analyses, a statistically significant difference was observed on the Medical Outcomes Study 36-item short form Physical Role Functioning subscale by treatment group, with lower mean scores in the standard treatment arm (mean, 65.05) compared with mean scores in the low-dose arm (mean, 74.66) and the high-dose arm (mean, 84.94; P.0001). However, multivariate analysis revealed that treatment arm no longer was statistically significant, whereas the following factors were associated with decreased physical role functioning: age >or=60 years (odds ratio [OR], 3.55; P = .006), increased comorbidity interference total score (OR, 1.64; P = .005), lower vitality (OR, 1.05; P = .0002), and increased menopausal symptoms (OR, 1.04 P = .02). CONCLUSIONS: At 9.4-16.5 years after their original diagnosis, differences in physical role functioning among breast cancer survivors who had received 3 different dose levels of chemotherapy were explained by clinical and demographic variables, such as age, fatigue, menopausal symptoms, and comorbidities. Prospective studies are needed to further assess the role of these factors in explaining HRQL and physical role functioning among long-term survivors.

Arm/hand swelling and perceived functioning among breast cancer survivors 12 years post-diagnosis: CALGB 79804.

INTRODUCTION: Lymphedema is an under-reported and debilitating consequence of axillary node dissection among breast cancer survivors. This study describes the characteristics of arm and hand swelling in relation to perceived physical and mental health functioning among breast cancer survivors 9-16 years post-diagnosis who previously participated in a clinical trial coordinated by the Cancer and Leukemia Group B (CALGB 8541). METHODS: Eligible survivors of CALGB 8541 completed questionnaires assessing demographics, arm/hand swelling, perceived physical functioning, and mental health. RESULTS: Two hundred forty-five women (94% white, mean age = 63, on average 12.4 years post-diagnosis) completed questionnaires (participation rate = 78%). Seventy-five women (31%) reported arm/hand swelling since their surgery. Of these women, 76% reported current swelling and half reported constant swelling, mainly in the upper arm. Swelling was reported as mild or moderate in 88% of the women. Women who reported severe swelling had significantly worse physical functioning and trended toward worse depressive symptoms and poorer mental health (lower mental SF-36 scores) as well. Activity-limiting swelling was also significantly associated with worse physical functioning. Although swelling interfered with wearing clothing (36%) and perceptions about general appearance (32%), only 37% of women sought treatment for swelling. CONCLUSIONS: Arm/hand swelling is a chronic problem for a subgroup of long-term survivors of breast cancer, negatively affecting physical functioning. IMPLICATIONS FOR CANCER SURVIVORS: Educational efforts are needed as part of a comprehensive survivorship care plan to raise awareness about lymphedema so that survivors may identify this complication, seek treatment early, and potentially improve their physical functioning.

Randomized trial of an intervention to improve mammography utilization among a triracial rural population of women.

INTRODUCTION: Mammography is underused by certain groups of women, in particular poor and minority women. We developed a lay health advisor (LHA) intervention based on behavioral theories and tested whether it improved mammography attendance in Robeson County, NC, a rural, low-income, triracial (white, Native American, African American) population. METHODS: A total of 851 women who had not had a mammogram within the past year were randomly assigned to the LHA intervention (n = 433) or to a comparison arm (n = 418) during 1998-2002. Rates of mammography use after 12-14 months (as verified by medical record review) were compared using a chi-square test. Baseline and follow-up (at 12-14 months) surveys were used to obtain information on demographics, risk factors, and barriers, beliefs, and knowledge about mammography. Linear regression, Mantel-Haenszel statistics, and logistic regression were used to compare barriers, beliefs, and knowledge from baseline to follow-up and to identify baseline factors associated with mammography. RESULTS: At follow-up, 42.5% of the women in the LHA group and 27.3% of those in the comparison group had had a mammogram in the previous 12 months (relative risk = 1.56, 95% confidence interval [CI] = 1.29 to 1.87). Compared with those in the comparison group, women in the LHA group displayed statistically significantly better belief scores (difference = 0.46 points on a 0-10 scale, 95% CI = 0.15 to 0.77) and reduced barriers at follow-up (difference = -0.77 points, 95% CI = -1.02 to -0.53), after adjusting for baseline scores. CONCLUSIONS: LHA interventions can improve mammography utilization. Future studies are needed to assess strategies to disseminate effective LHA interventions to underserved populations.

Racial differences in knowledge, attitudes, and cancer screening practices among a triracial rural population.

BACKGROUND: Low-income, minority, and rural women face a greater burden with regard to cancer-related morbidity and mortality and are usually underrepresented in cancer control research. The Robeson County Outreach, Screening and Education Project sought to increase mammography use among low-income, minority, and rural women age > 40 years. The current article reports on racial disparities and barriers to screening, especially those related to knowledge, attitudes, and behaviors. METHODS: A baseline survey was administered to 897 women age > 40 years who lived in rural Robeson County in North Carolina. The sample consisted of three principal racial groups: whites, African Americans, and Native Americans. Survey comparisons were made among racial groups with respect to knowledge, attitudes, and behaviors regarding breast and cervical carcinoma screening. RESULTS: Overall, Native American and African-American women had lower levels of knowledge, more inaccurate beliefs, and more barriers to screening compared with white women. Among the notable findings were that 43% of the patient population did not mention mammograms and 53% did not mention Pap smears as breast and cervical carcinoma screening tests, respectively; furthermore, compared with white women, significantly fewer African-American and Native American women mentioned these tests (P < 0.001). Sixty-seven percent of all women reported that a physician had never encouraged them to receive a mammogram, although 75% reported having received a regular checkup in the preceding year. CONCLUSIONS: Although all low-income rural women experienced significant barriers to receiving cancer screening tests, these barriers were more common for minority women compared with white women. More research is needed to identify ways to overcome such barriers, especially among Native American women. The results of the current study have important implications with respect to the designing of interventions aimed at improving cancer screening for all women.