Cost-effectiveness of adjuvant chemotherapy for high-risk stage II and stage III colon cancer in South Africa.

BACKGROUND: Colon cancer incidence is rising in low- and middle-income countries (LMICs), where resource limitations and cost often dictate treatment decisions. In this study, we evaluate the cost-effectiveness of adjuvant chemotherapy for high-risk stage II and stage III colon cancer treatment in South Africa (ZA) and illustrate how such analyses can inform cancer treatment recommendations in a LMIC. METHODS: We created a decision-analytic Markov model to compare lifetime costs and outcomes for patients with high-risk stage II and stage III colon cancer treated with three adjuvant chemotherapy regimens in a public hospital in ZA: capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, and capecitabine for 6 months, compared to no adjuvant treatment. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life-year (DALY) averted, at a willingness-to-pay (WTP) threshold equal to the 2021 ZA gross domestic product per capita (I$13,764/DALY averted). RESULTS: CAPOX for 3 months was cost-effective for both patients with high-risk stage II and patients with stage III colon cancer (ICER = I$250/DALY averted and I$1042/DALY averted, respectively), compared to no adjuvant chemotherapy. In subgroup analyses of patients by tumor stage and number of positive lymph nodes, for patients with high-risk stage II colon cancer and T4 tumors, and patients with stage III colon cancer with T4 or N2 disease. CAPOX for 6 months was cost-effective and the optimal strategy. The optimal strategy in other settings will vary by local WTP thresholds. Decision analytic tools can be used to identify cost-effective cancer treatment strategies in resource-constrained settings. CONCLUSION: Colon cancer incidence is increasing in low- and middle-income countries, including South Africa, where resource constraints can impact treatment decisions. This cost-effectiveness study evaluates three systemic adjuvant chemotherapy options, compared to surgery alone, for patients in South African public hospitals after surgical resection for high-risk stage II and stage III colon cancer. Doublet adjuvant chemotherapy (capecitabine and oxaliplatin) for 3 months is the cost-effective strategy and should be recommended in South Africa.

Multimorbidity and overall survival among women with breast cancer: results from the South African Breast Cancer and HIV Outcomes Study.

BACKGROUND: Breast cancer survival in South Africa is low, but when diagnosed with breast cancer, many women in South Africa also have other chronic conditions. We investigated the impact of multimorbidity (≥ 2 other chronic conditions) on overall survival among women with breast cancer in South Africa. METHODS: Between 1 July 2015 and 31 December 2019, we enrolled women newly diagnosed with breast cancer at six public hospitals participating in the South African Breast Cancer and HIV Outcomes (SABCHO) Study. We examined seven chronic conditions (obesity, hypertension, diabetes, HIV, cerebrovascular diseases (CVD), asthma/chronic obstructive pulmonary disease, and tuberculosis), and we compared socio-demographic, clinical, and treatment factors between patients with and without each condition, and with and without multimorbidity. We investigated the association of multimorbidity with overall survival using multivariable Cox proportional hazard models. RESULTS: Of 3,261 women included in the analysis, 45% had multimorbidity; obesity (53%), hypertension (41%), HIV (22%), and diabetes (13%) were the most common individual conditions. Women with multimorbidity had poorer overall survival at 3 years than women without multimorbidity in both the full cohort (60.8% vs. 64.3%, p = 0.036) and stage groups: stages I-II, 80.7% vs. 86.3% (p = 0.005), and stage III, 53.0% vs. 59.4% (p = 0.024). In an adjusted model, women with diabetes (hazard ratio (HR) = 1.20, 95% confidence interval (CI) = 1.03-1.41), CVD (HR = 1.43, 95% CI = 1.17-1.76), HIV (HR = 1.21, 95% CI = 1.06-1.38), obesity + HIV (HR = 1.24 95% CI = 1.04-1.48), and multimorbidity (HR = 1.26, 95% CI = 1.13-1.40) had poorer overall survival than women without these conditions. CONCLUSIONS: Irrespective of the stage, multimorbidity at breast cancer diagnosis was an important prognostic factor for survival in our SABCHO cohort. The high prevalence of multimorbidity in our cohort calls for more comprehensive care to improve outcomes for South African women with breast cancer.

Data From a One-Stop-Shop Comprehensive Cancer Screening Center.

PURPOSE: Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit. METHODS: Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate. RESULTS: Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10). CONCLUSION: We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings.[Media: see text].

Modeling the Cost-Effectiveness of Adjuvant Chemotherapy for Stage III Colon Cancer in South African Public Hospitals.

PURPOSE: Cancer incidence is rising in low- and middle-income countries, where resource constraints often complicate therapeutic decisions. Here, we perform a cost-effectiveness analysis to identify the optimal adjuvant chemotherapy strategy for patients with stage III colon cancer treated in South African (ZA) public hospitals. METHODS: A decision-analytic Markov model was developed to compare lifetime costs and outcomes for patients with stage III colon cancer treated with six adjuvant chemotherapy regimens in ZA public hospitals: fluorouracil, leucovorin, and oxaliplatin for 3 and 6 months; capecitabine and oxaliplatin (CAPOX) for 3 and 6 months; capecitabine for 6 months; and fluorouracil/leucovorin for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Societal costs and utilities were obtained from literature. The primary outcome was the incremental cost-effectiveness ratio in international dollars (I$) per disability-adjusted life-year (DALY) averted, compared with no therapy, at a willingness-to-pay (WTP) threshold of I$13,006.56. RESULTS: CAPOX for 3 months was cost-effective (I$5,381.17 and 5.74 DALYs averted) compared with no adjuvant chemotherapy. Fluorouracil, leucovorin, and oxaliplatin for 6 months was on the efficiency frontier with 5.91 DALYs averted but, with an incremental cost-effectiveness ratio of I$99,021.36/DALY averted, exceeded the WTP threshold. CONCLUSION: In ZA public hospitals, CAPOX for 3 months is the cost-effective adjuvant treatment for stage III colon cancer. The optimal strategy in other settings may change according to local WTP thresholds. Decision analytic tools can play a vital role in selecting cost-effective cancer therapeutics in resource-constrained settings.

Spiritual Care, Pain Reduction, and Preferred Place of Death Among Advanced Cancer Patients in Soweto, South Africa.

CONTEXT: When religious and spiritual (R/S) care needs of patients with advanced disease are met, their quality of life (QoL) improves. We studied the association between R/S support and QoL of patients with cancer at the end of life in Soweto, South Africa. OBJECTIVES: To identify R/S needs among patients with advanced cancer receiving palliative care services and to assess associations of receipt of R/S care with patient QoL and place of death. METHODS: A prospective cohort study conducted from May 1, 2016 to April 30, 2018 at a tertiary hospital in Soweto, South Africa. Nurses enrolled patients with advanced cancer and referred them to the palliative care multidisciplinary team. Spiritual counselors assessed and provided spiritual care to patients. We compared sociodemographic, clinical, and R/S factors and QoL of R/S care recipients and others. RESULTS: Of 233 deceased participants, 92 (39.5%) had received R/S care. Patients who received R/S care reported less pain (2.82 ± 1.23 vs. 1.93 ± 1.69), used less morphine, and were more likely to die at home than patients who did not (57.5% compared with 33.7%). On multivariate logistic regression analysis, adjusting for significant confounding influences and baseline African Palliative Care Association Palliative care Outcome Scale scores, receipt of spiritual care was associated with reduced pain and family worry (odds ratio 0.33; 95% CI 0.11-0.95 and odds ratio 3.43; 95% CI 1.10-10.70, respectively). CONCLUSION: Patients with cancer have R/S needs. R/S care among our patients appeared to improve their end-of-life experience. More research is needed to determine the mechanisms by which R/S care may have improved the observed patient outcomes.

Neoadjuvant Chemotherapy Use for Nonmetastatic Breast Cancer at Five Public South African Hospitals and Impact on Time to Initial Cancer Therapy.

BACKGROUND: In the U.S., neoadjuvant chemotherapy (NAC) for nonmetastatic breast cancer (BC) is used with extensive disease and aggressive molecular subtypes. Little is known about the influence of demographic characteristics, clinical factors, and resource constraints on NAC use in Africa. MATERIALS AND METHODS: We studied NAC use in a cohort of women with stage I-III BC enrolled in the South African Breast Cancer and HIV Outcomes study at five hospitals. We analyzed associations between NAC receipt and sociodemographic and clinical factors, and we developed Cox regression models for predictors of time to first treatment with NAC versus surgery. RESULTS: Of 810 patients, 505 (62.3%) received NAC. Multivariate analysis found associations between NAC use and black race (odds ratio [OR] 0.49; 95% confidence limit [CI], 0.25-0.96), younger age (OR 0.95; 95% CI, 0.92-0.97 for each year), T-stage (T4 versus T1: OR 136.29; 95% CI, 41.80-444.44), N-stage (N2 versus N0: OR 35.64; 95% CI, 16.56-76.73), and subtype (triple-negative versus luminal A: OR 5.16; 95% CI, 1.88-14.12). Sites differed in NAC use (Site D versus Site A: OR 5.73; 95% CI, 2.72-12.08; Site B versus Site A: OR 0.37; 95% CI, 0.16-0.86) and time to first treatment: Site A, 50 days to NAC versus 30 days to primary surgery (hazard ratio [HR] 1.84; 95% CI, 1.25-2.71); Site D, 101 days to NAC versus 126 days to primary surgery (HR 0.49; 95% CI, 0.27-0.89). CONCLUSION: NAC use for BC at these South African hospitals was associated with both tumor characteristics and heterogenous resource constraints. IMPLICATIONS FOR PRACTICE: Using data from a large breast cancer cohort treated in South Africa's public healthcare system, the authors looked at determinants of neoadjuvant chemotherapy use and time to initiate treatment. It was found that neoadjuvant chemotherapy was associated with increasing tumor burden and aggressive molecular subtypes, demonstrating clinically appropriate care in a lower resource setting. Results of this study also showed that time to treatment differences between chemotherapy and surgery varied by hospital, suggesting that differences in resource limitations were influencing clinical decision making. Practice guidelines and care quality metrics designed for low- and middle-income countries should accommodate heterogeneity of available resources.

Primary care visit use after positive fecal immunochemical test for colorectal cancer screening.

BACKGROUND: For some patients, positive cancer screening test results can be a stressful experience that can affect future screening compliance and increase the use of health care services unrelated to medically indicated follow-up. METHODS: Among 483,216 individuals aged 50 to 75 years who completed a fecal immunochemical test to screen for colorectal cancer at a large integrated health care setting between 2007 and 2011, the authors evaluated whether a positive test was associated with a net change in outpatient primary care visit use within the year after screening. Multivariable regression models were used to evaluate the relationship between test result group and net changes in primary care visits after fecal immunochemical testing. RESULTS: In the year after the fecal immunochemical test, use increased by 0.60 clinic visits for patients with true-positive results. The absolute change in visits was largest (3.00) among individuals with positive test results who were diagnosed with colorectal cancer, but significant small increases also were found for patients treated with polypectomy and who had no neoplasia (0.36) and those with a normal examination and no polypectomy performed (0.17). Groups of patients who demonstrated an increase in net visit use compared with the true-negative group included patients with true-positive results (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.54-1.66), and positive groups with a colorectal cancer diagnosis (OR, 7.19; 95% CI, 6.12-8.44), polypectomy/no neoplasia (OR, 1.37; 95% CI, 1.27-1.48), and normal examination/no polypectomy (OR, 1.24; 95% CI, 1.18-1.30). CONCLUSIONS: Given the large size of outreach programs, these small changes can cumulatively generate thousands of excess visits and have a substantial impact on total health care use. Therefore, these changes should be included in colorectal cancer screening cost models and their causes investigated further. Cancer 2017;123:3744-3753. © 2017 American Cancer Society.

Association Between Complementary and Alternative Medicine Use and Breast Cancer Chemotherapy Initiation: The Breast Cancer Quality of Care (BQUAL) Study.

IMPORTANCE: Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation. OBJECTIVE: To determine whether complementary and alternative medicine (CAM) use is associated with decreased breast cancer chemotherapy initiation. DESIGN, SETTING, AND PARTICIPANTS: In this multisite prospective cohort study (the Breast Cancer Quality of Care [BQUAL] study) designed to examine predictors of breast cancer treatment initiation and adherence, 685 women younger than 70 years with nonmetastatic invasive breast cancer were recruited from Columbia University Medical Center, Kaiser Permanente Northern California, and Henry Ford Health System and enrolled between May 2006 and July 31, 2010. Overall, 306 patients (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network guidelines. Participants were followed for up to 12 months. EXPOSURES: Baseline interviews assessed current use of 5 CAM modalities (vitamins and/or minerals, herbs and/or botanicals, other natural products, mind-body self-practice, mind-body practitioner-based practice). CAM use definitions included any use, dietary supplement use, mind-body use, and a CAM index summing the 5 modalities. MAIN OUTCOMES AND MEASURES: Chemotherapy initiation was assessed via self-report up to 12 months after baseline. Multivariable logistic regression models examined a priori hypotheses testing whether CAM use was associated with chemotherapy initiation, adjusting for demographic and clinical covariates, and delineating groups by age and chemotherapy indication. RESULTS: A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among women for whom chemotherapy was indicated, dietary supplement users and women with high CAM index scores were less likely than nonusers to initiate chemotherapy (odds ratio [OR], 0.16; 95% CI, 0.03-0.51; and OR per unit, 0.64; 95% CI, 0.46-0.87, respectively). Use of mind-body practices was not related to chemotherapy initiation (OR, 1.45; 95% CI, 0.57-3.59). There was no association between CAM use and chemotherapy initiation among women for whom chemotherapy was discretionary. CONCLUSIONS AND RELEVANCE: CAM use was high among patients with early-stage breast cancer enrolled in a multisite prospective cohort study. Current dietary supplement use and higher number of CAM modalities used but not mind-body practices were associated with decreased initiation of clinically indicated chemotherapy. Oncologists should consider discussing CAM with their patients during the chemotherapy decision-making process.

Survivorship care plans and adherence to lifestyle recommendations among breast cancer survivors.

PURPOSE: The effectiveness of survivorship care plans has not been widely tested. We evaluated whether a one-time brief lifestyle consultation as part of a broader survivorship care plan was effective at changing diet and lifestyle patterns. METHODS: A diverse sample of women with stage 0-III breast cancer were randomized to control or intervention groups within 6 weeks of completing adjuvant treatment. Both groups received the National Cancer Institute publication, "Facing Forward: Life after Cancer Treatment." The intervention group also met with a nurse (1 h) and a nutritionist (1 h) to receive personalized lifestyle recommendations based upon national guidelines. Diet, lifestyle, and perceived health were assessed at baseline, 3 and 6 months. Linear regression analyses evaluated the effects of the intervention adjusted for covariates. RESULTS: A total of 126 women completed the study (60 control/66 intervention, 61 Hispanic/65 non-Hispanic). At 3 months, the intervention group reported greater knowledge of a healthy diet (P = 0.047), importance of physical activity (P = 0.03), and appropriate use of dietary supplements (P = 0.006) and reported lower frequency of alcohol drinking (P = 0.03) than controls. At 6 months, only greater knowledge of a healthy diet (P = 0.01) persisted. The intervention was more effective among non-Hispanics than Hispanics on improving attitude towards healthy eating (P = 0.03) and frequency of physical activity (P = 0.006). CONCLUSIONS: The intervention changed lifestyle behaviors and knowledge in the short-term, but the benefits did not persist. IMPLICATIONS FOR CANCER SURVIVORS: Culturally competent long-term behavioral interventions should be tested beyond the survivorship care plan to facilitate long-term behavior change among breast cancer survivors.

Psychosocial factors related to non-persistence with adjuvant endocrine therapy among women with breast cancer: the Breast Cancer Quality of Care Study (BQUAL).

Non-adherence to adjuvant endocrine therapy (ET) for breast cancer (BC) is common. Our goal was to determine the associations between psychosocial factors and ET non-persistence. We recruited women with BC receiving care in an integrated healthcare system between 2006 and 2010. Using a subset of patients treated with ET, we investigated factors related to ET non-persistence (discontinuation) based on pharmacy records (≥90 days gap). Serial interviews were conducted at baseline and every 6 months. The Functional Assessment of Cancer Therapy (FACT), Medical Outcomes Survey, Treatment Satisfaction Questionnaire (TSQM), Impact of Events Scale (IES), Interpersonal Processes of Care measure, and Decision-making beliefs and concerns were measured. Multivariate models assessed factors associated with non-persistence. Of the 523 women in our final cohort who initiated ET and had a subsequent evaluation, 94 (18 %) were non-persistent over a 2-year follow-up. The cohort was primarily white (74.4 %), stage 1 (60.6 %), and on an aromatase inhibitor (68.1 %). Women in the highest income category had a lower odds of being non-persistent (OR 0.43, 95 % CI 0.23-0.81). Quality of life and attitudes toward ET at baseline were associated with non-persistence. At follow-up, the FACT, TSQM, and IES were associated with non-persistence (p < 0.001). Most women continued ET. Women who reported a better attitude toward ET, better quality of life, and more treatment satisfaction, were less likely to be non-persistent and those who reported intrusive/avoidant thoughts were more likely to be non-persistent. Interventions to enhance the psychosocial well-being of patients should be evaluated to increase adherence.

Latent class analysis suggests four distinct classes of complementary medicine users among women with breast cancer.

BACKGROUND: Breast cancer patients commonly report using >1 form of complementary and alternative medicine (CAM). However, few studies have attempted to analyze predictors and outcomes of multiple CAM modalities. We sought to group breast cancer patients by clusters of type and intensity of complementary and alternative medicine (CAM) use following diagnosis. METHODS: Detailed CAM use following breast cancer diagnosis was assessed in 2002-2003 among 764 female residents of Long Island, New York diagnosed with breast cancer in 1996-1997. Latent class analysis (LCA) was applied to CAM modalities while taking into account frequency and intensities. RESULTS: Four distinct latent classes of CAM use emerged: 1) "Low-dose supplement users" (40%), who used only common nutritional supplements; 2) "Vitamin/mineral supplement users" (39%), using an abundance of supplements in addition to other practices; 3) "Mind-body medicine users" (12%), with near-universal use of supplements, mind-body medicine techniques, and massage; and 4) "Multi-modality high-dose users" (9%), who were highly likely to use nearly all types of CAM. Predictors of membership in classes with substantial CAM use included younger age, more education, higher income, Jewish religion, ideal body mass index, higher fruit and vegetable intake, higher levels of physical activity, receipt of adjuvant chemotherapy, and prior use of oral contraceptives. CONCLUSIONS: LCA identified important subgroups of breast cancer patients characterized by varying degrees of complementary therapy use. Further research should explore the reproducibility of these classes and investigate the association between latent class membership and breast cancer outcomes.

Phase Ib Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Patients with Barrett's Esophagus.

This study was conducted to determine the safety and efficacy of the green tea-derived Polyphenon E (Poly E) in patients with Barrett's Esophagus (BE). Subjects were randomized to a 6-month, twice daily (BID) oral treatment of placebo or Poly E (200, 400, or 600 mg). Endoscopic evaluation, including biopsies, was performed before and after treatment. The primary objective was to demonstrate safety; secondary objectives investigated catechin accumulation and effects in clinical specimens. Of the 44 enrolled subjects, 11 received placebo, and 33 received Poly E. No dose-limiting toxicities were encountered, and a maximum tolerated dose (MTD) was not reached. The recommended phase II dose was 600 mg twice daily. The most common treatment-related adverse events (AE) in Poly E-treated subjects were grade I and II nausea, grade I belching, and grade I lactate dehydrogenase (LDH) elevation. No treatment-related AEs were reported in placebo-treated subjects, aside from grade I laboratory abnormalities. Pill counts and subject diaries were not consistently collected, and compliance was difficult to determine. However, on the basis of an intention-to-treat analysis, there was a significant relationship between Poly E dose and esophageal EGCG level--mean changes (pmol/g) of 0.79 (placebo), 6.06 (200 mg), 35.67 (400 mg), and 34.95 (600 mg); P = 0.005. There was a possible relationship between Poly E dose and urine PGE-M concentration. In conclusion, Poly E was well-tolerated, and treatment with Poly E (400 and 600 mg) but not Poly E (200 mg) or placebo resulted in clinically relevant and detectable EGCG accumulation in the target organ, esophageal mucosa.

Polyunsaturated fatty acid interactions and breast cancer incidence: a population-based case-control study on Long Island, New York.

PURPOSE: Experimental studies demonstrate that ω-3 polyunsaturated fatty acids (PUFAs) inhibit inflammatory eicosanoids generated by ω-6 PUFAs. Epidemiologic studies on dietary ω-3 PUFA intake show consistent inverse associations with breast cancer incidence among Asian populations, where ω-3, relative to ω-6, intake is high. In contrast, associations are inconsistent among Western populations, where intake of ω-3, relative to ω-6, is low. We hypothesized that examining interactions between ω-3 and ω-6 would help elucidate the PUFA-breast cancer association in the United States. METHODS: In a Long Island, New York, population-based study of 1463 breast cancer cases and 1500 controls, we estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression to examine interactions between ω-3 and ω-6 intake. RESULTS: We observed a super-additive interaction (relative excess risk due to interaction = 0.41; 95% confidence interval = 0.06-0.76) between ω-3 and ω-6 intake in association with breast cancer incidence, although the CIs for the joint exposure of low ω-3/high ω-6 compared to high ω-3/low ω-6 intake were wide (odds ratio = 1.20; 95% confidence interval = 0.85-1.69). CONCLUSIONS: Breast cancer risk reduction may be possible for U.S. women with dietary consumption of higher ω-3, which has anti-inflammatory properties, in concert with lower ω-6, which induces inflammation. Replication from future U.S.-based investigations is needed.

Dietary intake of fish, polyunsaturated fatty acids, and survival after breast cancer: A population-based follow-up study on Long Island, New York.

BACKGROUND: In laboratory experiments, ω-3 polyunsaturated fatty acids (PUFAs) have been found to reduce inflammatory eicosanoids resulting from ω-6 PUFA metabolism via competitive inhibition, and the ω-3-induced cytotoxic environment increases apoptosis and reduces cell growth in breast cancer cells. To the authors' knowledge, epidemiologic investigations regarding whether dietary ω-3 PUFA intake benefits survival after breast cancer are limited and inconsistent. METHODS: The authors used resources from a population-based follow-up study conducted on Long Island, New York, among 1463 women newly diagnosed with first primary breast cancer who were interviewed an average of approximately 3 months after diagnosis to assess risk and prognostic factors, including dietary intake (using a food frequency questionnaire). Vital status was determined through 2011, yielding a median follow-up of 14.7 years and 485 deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards regression. RESULTS: All-cause mortality was reduced among women with breast cancer reporting the highest quartile of intake (compared with never) for tuna (HR, 0.71; 95% CI, 0.55-0.92), other baked/broiled fish (HR, 0.75; 95% CI, 0.58-0.97), and the dietary long-chain ω-3 PUFAs docosahexaenoic acid (HR, 0.71; 95% CI, 0.55-0.92) and eicosapentaenoic acid (HR, 0.75; 95% CI, 0.58-0.97). CONCLUSIONS: All-cause mortality was reduced by 16% to 34% among women with breast cancer who reported a high intake of fish and long-chain ω-3 PUFAs. Long-chain ω-3 PUFA intake from fish and other dietary sources may provide a potential strategy to improve survival after breast cancer.

Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk.

PURPOSE: Studies of vitamin D-pathway genetic variants in relation to cancer risk have been inconsistent. We examined the associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk. METHODS: In a population-based case-control study of 967 incident breast cancer cases and 993 controls, we genotyped 25 polymorphisms encoding the vitamin D receptor (VDR) gene, 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D-binding protein (GC) and measured plasma 25(OH)D. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: Among CYP24A1 polymorphisms, rs6068816 was associated with a 72 % reduction in breast cancer risk (TT vs. CC, OR 0.28, 95 % CI 0.10-0.76; p trend = 0.01), but for rs13038432, the 46 % decrease included the null value (GG vs. AA, OR 0.54, 95 % CI 0.17-1.67; p trend = 0.03). Increased risk that included the null value was noted for CYP24A1 rs3787557 (CC vs. TT, OR 1.34, 95 % CI 0.92-1.89). The VDR polymorphism, TaqI (rs731236), was associated with a 26 % risk reduction (TT vs. CC, OR 0.74, 95 % CI 0.56-0.98; p trend = 0.01). For other polymorphisms, ORs were weak and included the null value. The inverse association for plasma 25(OH)D with breast cancer was more pronounced (OR 0.43, 95 % CI 0.27-0.68) among women with the common allele for CYP24A1, rs927650 (p for interaction on a multiplicative scale = 0.01). CONCLUSION: Breast cancer risk may be associated with specific vitamin D-related polymorphisms, particularly CYP24A1. Genetic variation in the vitamin D pathway should be considered when designing potential intervention strategies with vitamin D supplementation.

Changes in vitamin and mineral supplement use after breast cancer diagnosis in the Pathways Study: a prospective cohort study.

BACKGROUND: Vitamin and mineral supplement use after a breast cancer diagnosis is common and controversial. Dosages used and the timing of initiation and/or discontinuation of supplements have not been clearly described. METHODS: We prospectively examined changes in use of 17 vitamin/mineral supplements in the first six months following breast cancer diagnosis among 2,596 members (28% non-white) of Kaiser Permanente Northern California. We used multivariable logistic regression to examine demographic, clinical, and lifestyle predictors of initiation and discontinuation. RESULTS: Most women used vitamin/mineral supplements before (84%) and after (82%) diagnosis, with average doses far in excess of Institute of Medicine reference intakes. Over half (60.2%) reported initiating a vitamin/mineral following diagnosis, 46.3% discontinuing a vitamin/mineral, 65.6% using a vitamin/mineral continuously, and only 7.2% not using any vitamin/mineral supplement before or after diagnosis. The most commonly initiated supplements were calcium (38.2%), vitamin D (32.01%), vitamin B6 (12.3%) and magnesium (11.31%); the most commonly discontinued supplements were multivitamins (17.14%), vitamin C (15.97%) and vitamin E (45.62%). Higher education, higher intake of fruits/vegetables, and receipt of chemotherapy were associated with initiation (p-values <0.05). Younger age and breast-conserving surgery were associated with discontinuation (p-values <0.05). CONCLUSIONS: In this large cohort of ethnically diverse breast cancer patients, high numbers of women used vitamin/mineral supplements in the 6 months following breast cancer diagnosis, often at high doses and in combination with other supplements. The immediate period after diagnosis is a critical time for clinicians to counsel women on supplement use.

Nutrient pathways and breast cancer risk: the Long Island Breast Cancer Study Project.

The relative importance of biochemical pathways has not been previously examined when considering the influence of diet on breast cancer risk. To address this issue, we used interview data from a population-based sample of 1463 breast cancer cases and 1500 controls. Dietary intake was assessed shortly after diagnosis using a 101-item food frequency questionnaire. Age- and energy-adjusted odds ratios (ORs) for individual micro- and macronutrients were estimated with logistic regression. Hierarchical modeling was used to account for biologically plausible nutrient pathways (1-carbon metabolism, oxidative stress, glycemic control, and phytoestrogens). Effect estimates from hierarchical modeling were more precise and plausible compared to those from multivariable models. The strongest relationship observed was for the glycemic control pathway, but confidence intervals (CI) were wide [OR (95% CI): 0.86 (0.62, 1.21)]. Little or no effect was observed for the 1-carbon metabolism, oxidative stress, and phytoestrogen pathways. Associations were similar when stratified by supplement use. Our approach that emphasizes biochemical pathways, rather than individual nutrients, revealed that breast cancer risk may be more strongly associated with glycemic control factors than those from other pathways considered. Our study emphasizes the importance of accounting for multiple nutrient pathways when examining associations between dietary intake and breast cancer.

Noninitiation of adjuvant chemotherapy in women with localized breast cancer: the breast cancer quality of care study.

PURPOSE: For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. PATIENTS AND METHODS: We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years. RESULTS: Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor- and progesterone receptor-negative status) were associated with increased chemotherapy initiation. CONCLUSION: Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.

Use of adjuvant 5-fluorouracil and radiation therapy after gastric cancer resection among the elderly and impact on survival.

PURPOSE: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. METHODS AND MATERIALS: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. RESULTS: Among 1,993 patients who received combined chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. CONCLUSIONS: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.

Prevalence and predictors of antioxidant supplement use during breast cancer treatment: the Long Island Breast Cancer Study Project.

BACKGROUND: Although many patients take antioxidant dietary supplements during breast cancer treatment, the benefits of such supplementation are unproven. The authors of this report analyzed the prevalence of and factors associated with antioxidant supplement use during breast cancer (BC) treatment among women who participated in the Long Island Breast Cancer Study Project. METHODS: From 2002 through 2004, women with BC who had participated a case-control study from 1996 to 1997 were invited to participate in a follow-up interview. Antioxidant supplement use was defined as any self-reported intake of supplemental vitamin C, vitamin E, beta-carotene, or selenium in individual supplements or multivitamins. RESULTS: Follow-up interview participants were younger, more predominantly white, and of higher socioeconomic status than women who did not respond. Among 764 participants who completed the follow-up interview, 663 (86.8%) reported receiving adjuvant treatment for their BC. Of those 663 women, 401 (60.5%) reported using antioxidants during adjuvant treatment: One hundred twenty of 310 women (38.7%) used antioxidants during chemotherapy, 196 of 464 women (42.2%) used them during radiation, and 286 of 462 women (61.9%) used them during tamoxifen therapy. Of 401 antioxidant users, 278 women (69.3%) used high doses (doses higher than those contained in a Centrum multivitamin). The factors that were associated with high antioxidant supplement use during treatment were higher fruit and vegetable intake at diagnosis (relative risk [RR], 1.71; 95% confidence interval [CI], 1.13-2.59), tamoxifen use (RR, 3.66; 95% CI, 2.32-5.78), ever using herbal products (RR, 3.49; 95% CI, 2.26-5.38), and ever engaging in mind-body practices (RR, 1.72; 95% CI, 1.13-2.64). CONCLUSIONS: Given the common use of antioxidant supplements during BC treatment, often at high doses and in conjunction with other complementary therapies, future research should address the effects of antioxidant supplementation on BC outcomes.