Showing papers in "Journal of the National Cancer Institute in 2013"
TL;DR: The overall trends in declining cancer death rates continue, however, increases in incidence rates for some HPV-associated cancers and low vaccination coverage among adolescents underscore the need for additional prevention efforts for HPV- associated cancers, including efforts to increase vaccination coverage.
Abstract: Institute (NCI), and the Nor th American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year’s report includes incidence trends for human papillomavirus (HPV)–associated cancers and HPV vaccination (recommended for adolescents aged 11–12 years). Methods Data on cancer incidence were obtained from the CDC, NCI, and NAACCR, and data on mor tality were obtained from the CDC. Long- (1975/1992–2009) and short-term (2000–2009) trends in age-standardized incidence and death rates for all cancers combined and for the leading cancers among men and among women were examined by joinpoint analysis. Prevalence of HPV vaccination coverage during 2008 and 2010 and of Papanicolaou (Pap) testing during 2010 were obtained from national surveys. Results Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1 .5% per year from 2000 to 2009. Overall incidence rates decreased in men but stabilized in women. Incidence rates increased for two HPV-associated cancers (oropharynx, anus) and some cancers not associated with HPV (eg, liver, kidney, thyroid). Nationally, 32.0% (95% confidence interval [CI] = 30.3% to 33.6%) of girls aged 13 to 17 years in 2010 had received three doses of the HPV vaccine, and coverage was statistically significantly lower among the uninsured (14.1%, 95% CI = 9.4% to 20.6%) and in some Southern states (eg, 20.0% in Alabama [95% CI = 13.9% to 27.9%] and Mississippi [95% CI = 13.8% to 28.2%]), where cervical cancer rates were highest and recent Pap testing prevalence was the lowest.
994 citations
TL;DR: The traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy, and opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients are offered.
Abstract: The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.
842 citations
TL;DR: Prospective risk estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers.
Abstract: Background: Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers. The aims of this study were to derive penetrance estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles. Methods: Prospective cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom. Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline, 1509 women were unaffected by ovarian cancer, and 651 had been diagnosed with unilateral breast cancer. Cumulative risks were obtained using Kaplan–Meier estimates. Associations between cancer risk and covariables of interest were evaluated using Cox regression. All statistical tests were two-sided. Results: The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60% (95% confidence interval [CI] = 44% to 75%) for breast cancer, 59% (95% CI = 43% to 76%) for ovarian cancer, and 83% (95% CI = 69% to 94%) for contralateral breast cancer. For BRCA2 carriers, the corresponding risks were 55% (95% CI = 41% to 70%) for breast cancer, 16.5% (95% CI = 7.5% to 34%) for ovarian cancer, and 62% (95% CI = 44% to 79.5%) for contralateral breast cancer. BRCA2 carriers in the highest tertile of risk, defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk, were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile (hazard ratio = 4.1, 95% CI = 1.2 to 14.5; P = .02). Conclusions: Prospective risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast, ovarian, and contralateral breast cancer. Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers.
793 citations
TL;DR: It is found that CRC case subjects had decreased overall microbial community diversity and lower relative abundance of Clostridia and increased carriage of Fusobacterium were found in case subjects compared with control subjects.
Abstract: We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity (P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI] = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.
723 citations
National Institutes of Health1, University of British Columbia2, University of Alberta3, University of Milan4, University of Auvergne5, Ontario Institute for Cancer Research6, University of Texas MD Anderson Cancer Center7, University of Edinburgh8, University of Michigan9, The Royal Marsden NHS Foundation Trust10
TL;DR: Substantial variability in Ki67 scoring was observed among some of the world's most experienced laboratories, and factors contributing to interlaboratory discordance included tumor region selection, counting method, and subjective assessment of staining positivity.
Abstract: Uncontrolled proliferation is a key feature of malignancy. The nuclear proliferation marker Ki67 is of interest for various potential uses in the clinical management of breast cancer (eg, prognosis, prediction, and monitoring of response) (1–9). The most commonly used assay to assess Ki67 is immunohistochemical (IHC) staining with the MIB-1 antibody. However, interlaboratory methodology is inconsistent, and, despite the apparent prognostic utility of Ki67, routine use of this tumor biomarker has not been widely recommended by consensus guidelines panels such as that convened by the American Society of Clinical Oncology, mainly because of concerns regarding analytical validity (10).
With the goal of harmonizing Ki67 analytical methodology, Dowsett et al., on behalf of the International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group, provided an overview of the current state of the art of Ki67 evaluation and proposed a set of guidelines for analysis and reporting of Ki67 (1). Although those guidelines aimed to reduce preanalytical and analytical variations, the Working Group recognized that actual scoring procedures varied substantially, contributing to a lack of consensus regarding optimal cutoffs that should be applied in various research and clinical decision-making settings. This lack of consistency has prevented direct comparisons of Ki67 across laboratories and clinical trials.
In an effort to harmonize Ki67 analysis, the Working Group studied intra- and interlaboratory reproducibility of IHC assays for Ki67 in breast cancer among a group of highly experienced pathology laboratories. A secondary aim was to identify key sources of variation, particularly those introduced by different scoring methodologies.
502 citations
TL;DR: This work reviews the major events in the development of the in vitro models and the emergence of new technologies that have revealed important issues and limitations concerning human cancer cell lines as models and develops new in vitro preclinical models that would substantially increase the success rate ofnew in vitro-assessed cancer treatments.
Abstract: Although advances in genomics during the last decade have opened new avenues for translational research and allowed the direct evaluation of clinical samples, there is still a need for reliable preclinical models to test therapeutic strategies. Human cancer-derived cell lines are the most widely used models to study the biology of cancer and to test hypotheses to improve the efficacy of cancer treatment. Since the development of the first cancer cell line, the clinical relevance of these models has been continuously questioned. Based upon recent studies that have fueled the debate, we review the major events in the development of the in vitro models and the emergence of new technologies that have revealed important issues and limitations concerning human cancer cell lines as models. All cancer cell lines do not have equal value as tumor models. Some have been successful, whereas others have failed. However, the success stories should not obscure the growing body of data that motivates us to develop new in vitro preclinical models that would substantially increase the success rate of new in vitro–assessed cancer treatments.
485 citations
TL;DR: EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings and should be considered as front-line therapy in EGFRmut(+) advanced NSCLC patients, supporting EGFR mutation assessment before initiation of treatment.
Abstract: known in 31% of patients. EGFR-TKIs treatment prolonged PFS in EGFRmut+ patients, and EGFR mutation was predictive of PFS in all settings: The front-line hazard ratio for EGFRmut+ was 0.43 (95% confidence interval [CI] = 0.38 to 0.49; P < .001), and the front-line hazard ratio for EGFRmut– was 1.06 (95% CI = 0.94 to 1.19; P = .35; Pinteraction < .001). The second-line hazard ratio for EGFRmut+ was 0.34 (95% CI = 0.20 to 0.60; P < .001), and the second-line hazard ratio for EGFRmut– was 1.23 (95% CI = 1.05 to 1.46; P = .01; Pinteraction < .001). The maintenance hazard ratio for EGFRmut+ was 0.15 (95% CI = 0.08 to 0.27; P < .001), and the maintenance hazard ratio for EGFRmut– was 0.81 (95% CI = 0.68 to 0.97; P = .02; Pinteraction < .001). EGFR-TKIs treatment had no impact on OS for EGFRmut+ and EGFRmut– patients. Conclusions EGFR-TKIs therapy statistically significantly delays disease progression in EGFRmut+ patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut+ advanced NSCLC patients. J Natl Cancer Inst;2013;105:595–605
474 citations
TL;DR: The DCIS Score quantifies IBErisk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria.
Abstract: The treatment of ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast is variable, with concerns about both overtreatment and undertreatment (1–4). DCIS is commonly detected on screening mammography in the asymptomatic woman. Most women with newly diagnosed DCIS are eligible for breast conservation surgery (ie, excision or lumpectomy), either with or without radiation treatment. Randomized clinical trials have demonstrated that adding radiation treatment after surgical excision reduces the risk of developing local recurrence and invasive local recurrence by approximately 50% (5–14). However, most patients will not develop local recurrence if treated using surgical excision without radiation, and many patients are treated in contemporary practice using surgical excision alone (3,5–12,14–17).
Several studies have used clinical and pathologic features to attempt to define patients at low risk after surgical excision without radiation, including a prospective trial conducted by the Eastern Cooperative Oncology Group (ECOG) E5194 (18–21). However, reproducible and reliable methods using clinical and pathologic factors to select patients for surgical excision alone have not been established. The 2009 National Institutes of Health State-of-the-Science Conference included the research recommendation to develop and validate risk stratification models for identifying patients who may be managed with less therapeutic intervention (1).
This study was performed to determine whether the prospectively defined, 12-gene Oncotype DX DCIS Score (hereafter referred to as the DCIS Score) quantifies local recurrence risk and provides risk information independent of traditional clinical and pathologic characteristics.
454 citations
TL;DR: It is found that there is no sufficient evidence to support inclusion of benign breast disease, uterine fibroids, or genitourinary malformations as diagnostic criteria, and revised, evidence-based diagnostic criteria are proposed covering the spectrum of PTEN-related clinical disorders.
Abstract: Background PTEN hamartoma tumor syndrome (PHTS) refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog (PTEN) gene. Diagnostic criteria for Cowden syndrome, the principal PTEN-related disorder, were first established in 1996 before the identification of the PTEN gene and the ability to molecularly confirm a clinical diagnosis. These consortium criteria were based on clinical experience and case reports in the existing literature, with their inherent selection biases. Although it was initially reported that approximately 80% of patients with Cowden syndrome had an identifiable germline PTEN mutation, more recent work has shown these diagnostic criteria to be far less specific. In addition, increasing evidence has documented the association of a broader spectrum of clinical features with PTEN mutations. Our goal was to develop revised, evidence-based diagnostic criteria and to include features of the broader spectrum of PTEN-related clinical syndromes. Methods W e performed a systematic search and review of the medical literature related to clinical features reported in
435 citations
TL;DR: Findings support the idea that APM defects are immune escape mechanisms that disrupt the tumor cells' ability to be recognized and killed by tumor antigen-specific cytotoxic CD8(+) T cells.
Abstract: The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to all CD8(+) T-cell adaptive immune responses, including those against tumors. The generation of peptides and their loading on MHC class I molecules is a multistep process involving multiple molecular species that constitute the so-called antigen processing and presenting machinery (APM). The majority of class I peptides begin as proteasome degradation products of cytosolic proteins. Once transported into the endoplasmic reticulum by TAP (transporter associated with antigen processing), peptides are not bound randomly by class I molecules but are chosen by length and sequence, with peptidases editing the raw peptide pool. Aberrations in APM genes and proteins have frequently been observed in human tumors and found to correlate with relevant clinical variables, including tumor grade, tumor stage, disease recurrence, and survival. These findings support the idea that APM defects are immune escape mechanisms that disrupt the tumor cells' ability to be recognized and killed by tumor antigen-specific cytotoxic CD8(+) T cells. Detailed knowledge of APM is crucial for the optimization of T cell-based immunotherapy protocols.
415 citations
TL;DR: In this article, the expression profiles of circulating miRNAs reflect miRNA profiles of tumor tissues and to the best of our knowledge, no systematic investigation of the relationship between miRNA profile in body fluids vs matched primary colorectal cancer patients has been undertaken.
Abstract: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. In the United States, CRC is the third most common cancer, with more than 143000 new cases and more than 52000 deaths each year (1). Several CRC screening tests, including fecal occult-blood testing and colonoscopy, have been available for years (2) and have aided in reducing the mortality associated with this disease (3–5). However, compliance with these screening tests has been far from adequate. Patients with metastatic disease frequently receive expensive cytotoxic chemotherapeutic regimens coupled with targeted monoclonal antibodies but with relatively modest benefits (6). Without a priori knowledge of which patients will experience tumor recurrence, there is inevitable overtreatment with agents associated with toxic side effects (7). These limitations underscore the need for novel biomarkers, particularly noninvasive biomarkers in serum or plasma, for diagnosis, prognosis, and prediction of response to chemotherapy.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that play a central role in the regulation of mRNA expression (8). The discovery that miRNA expression is frequently dysregulated in a cancer-specific manner provides an opportunity to develop these RNAs as biomarkers for cancer detection (9). Although most previous studies on miRNA expression have been performed on tissue specimens, some studies have shown diagnostic and prognostic potential for circulating miRNAs (10–14) because tumor-derived miRNAs can be present in blood and appear to be stably protected from endogenous ribonuclease activity in the circulation (15). Nonetheless, it is unclear whether expression profiles of circulating miRNAs reflect miRNA profiles of tumor tissues and to the best of our knowledge, no systematic investigation of the relationship between miRNA profiles in body fluids vs matched primary CRCs has thus far been undertaken. This is critical because increased expression of circulating miRNAs could be indicative of miRNAs secreted from a tumor, raising the overall diagnostic specificity of the biomarker.
MiR-21 is an oncogenic miRNA that modulates the expression of multiple cancer-related target genes such as PTEN, TPM1, and PDCD and has been shown to be overexpressed in various human tumors (16–18). In addition, miR-21 expression is upregulated in CRC tissues, is elevated during tumor progression, and is also associated with poor survival and response to chemotherapy (19–22). The clinical significance of circulating miR-21 levels in CRC remains unclear at this time. Although an earlier study was unable to use plasma miR-21 as a biomarker because of low levels of detection using a direct amplification method (10), a more recent study demonstrated statistically significantly elevated plasma miR-21 expression in CRC patients using TaqMan-based approaches (23). On the other hand, miR-31 is another miRNA frequently overexpressed in CRC tissues and has been shown to be associated with tumor prognosis (19,24). Additionally, both miR-21 and miR-31 are frequently upregulated, even in premalignant lesions such as colonic adenomas, which are the target lesions of CRC screening (25–27). In light of these observations, we hypothesized that these two miRNAs might be good candidates for exploration as circulating biomarkers for the early detection and prognosis of CRC, assuming that the expression pattern for these miRNAs in serum mirrors that in the neoplastic tissues.
We have systematically investigated the expression of miR-21 and miR-31 in a two-phase study. In the first phase, we determined whether cultured CRC cells secrete these miRNAs into the culture medium, establishing their secretory potential. We then performed quantitative analyses of these miRNAs in a subset of serum samples from CRC patients and healthy control subjects to determine the feasibility of their detection in the circulation. In the second phase, using a large validation cohort comprised of matched serum and tissue samples from patients with colorectal neoplasia and serum from healthy control subjects, we evaluated the clinical significance of these miRNAs as potential biomarkers for diagnosis and prognosis of CRC patients.
TL;DR: Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification and no evidence existed for a differential prognostic role of BRAF mutation by MSI status.
Abstract: BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses’ Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAF–wild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF–wild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60 (95% confidence interval [CI] =1.12 to 2.28; P = .009), 0.48 (95% CI = 0.27 to 0.87; P = .02), and 0.25 (95% CI = 0.12 to 0.52; P .50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification.
TL;DR: MRI accurately detects residual tumor after neoadjuvant chemotherapy and is more accurate than mammography; however, studies comparing MRI and ultrasound are required.
Abstract: Background It has been proposed that magnetic resonance imaging (MRI) be used to guide breast cancer surgery by dif ferentiating residual tumor from pathologic complete response (pCR) after neoadjuvant chemotherapy. This metaanalysis examines MRI accuracy in detecting residual tumor, investigates variables potentially affecting MRI performance, and compares MRI with other tests. Methods A systematic literature searc h was undertaken. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate (relative) diagnostic odds ratios ([R]DORs). Summary sensitivity (correct identification of residual tumor), specificity (correct identification of pCR), and areas under the SROC curves (AUCs) were derived. All statistical tests were two-sided. Results F orty-four studies (2050 patients) were included. The overall AUC of MRI was 0.88. Accuracy was lower for “standard” pCR definitions (referent category) than “less clearly described” (RDOR = 2.41, 95% confidence interval [CI] = 1.11 to 5.23) or “near-pCR” definitions (RDOR = 2.60, 95% CI = 0.73 to 9.24; P = .03.) Corresponding AUCs were 0.83, 0.90, and 0.91. Specificity was higher when negative MRI was defined as contrast enhancement less than or equal to normal tissue (0.83, 95% CI = 0.64 to 0.93) vs no enhancement (0.54, 95% CI = 0.39 to 0.69; P = .02), with comparable sensitivity (0.83, 95% CI = 0.69 to 0.91; vs 0.87, 95% CI = 0.80 to 0.92; P = .45). MRI had higher accuracy than mammography (P = .02); there was only weak evidence that MRI had higher accuracy than clinical examination (P = .10). No difference in MRI and ultrasound accuracy was found (P = .15). Conclusions MRI accurately detects residual tumor af ter neoadjuvant chemotherapy. Accuracy was lower when pCR was more rigorously defined, and specificity was lower when test negativity thresholds were more stringent; these definitions require standardization. MRI is more accurate than mammography; however, studies comparing MRI and ultrasound are required.
TL;DR: This study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA and suggests that these fatty acids are involved in prostate tumorigenesis.
Abstract: Results Compared with men in the lowest quartiles of LCω-3PUFA, men in the highest quartile had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Associations were similar for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response. Conclusions This study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA. The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LCω-3PUFA intake should consider its potential risks. J Natl Cancer Inst Inflammation plays a role in the etiology of many cancers. The strongest evidence for an inflammatory component in prostate carcinogenesis is based on the characteristics of a precursor lesion, proliferative inflammatory atrophy, which is an area of highly proliferative but atrophic epithelial cells with notable inflammatory infiltrates (1,2). Considerable research has addressed whether factors that affect inflammation are associated with prostate cancer risk. With the exception of obesity, which is associated with increased inflammation and higher risks of high-grade prostate cancer (3,4) and prostate cancer death (5,6), studies on lifestyle factors associated with reduced inflammation, including use of aspirin (7,8) and nonsteroidal anti-inflammatory drugs (8) and statins (9) and consumption of long-chain ω-3 fatty acids (10–12) (here defined as eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids), have been inconsistent. We recently reported, using data and serum collected in the Prostate Cancer Prevention Trial, that high concentration of serum phospholipid long-chain ω-3 fatty acids, which is a biomarker of usual ω-3 fatty acid intake (13), was associated with a large increase in the risk of high-grade prostate cancer (14). We also found that high concentrations of trans-fatty acids, which are associated with increased inflammation (15,16), were associated with reduced risk of high-grade prostate cancer (14). These findings were counter to expectations but raised the possibility that high intakes of ω-3 fatty acids, for example through use of fish oil supplements, could increase the risk of clinically significant, highgrade prostate cancer. Here we replicate these analyses using data and plasma collected in the Selenium and Vitamin E Cancer Prevention Trial (SELECT; trial registration: clinicaltrials.gov identifier NCT00006392]. Given the widespread use of ω-3 fatty acid supplements (17,18), an ongoing clinical trial testing ω-3 fatty acid supplementation for cancer and cardiovascular disease prevention (19), and the purported health benefits of consuming fatty fish (20,21), it is important to further investigate whether high consumption of ω-3 fatty acids could contribute to prostate cancer risk.
TL;DR: The hypothesis that active smoking is associated with increased breast cancer risk for women who initiate smoking before first birth is supported and suggesting that smoking might play a role in breast cancer initiation is suggested.
Abstract: Background The relationship between active cigarette smoking and breast cancer risk remains controversial because of unresolved issues of confounding and dose response. Methods To investigate these issues further, we analyzed data from 73 388 women in the American Cancer Society's Cancer Prevention Study II (CPS-II) Nutrition Cohort. Analyses were based on 3721 invasive breast cancer case patients identified during a median follow-up of 13.8 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from multivariable-adjusted Cox proportional hazard regression models. P values were two-sided. We also conducted meta-analyses of our results with those published from 14 other cohort studies. Results In CPS-II, incidence was higher in current (HR = 1.24, 95% CI = 1.07 to 1.42) and former smokers (HR =1.13, 95% CI = 1.06 to 1.21) than in never smokers. Women who initiated smoking before menarche (HR = 1.61, 95% CI = 1.10 to 2.34) or after menarche but 11 or more years before first birth (HR = 1.45, 95% CI = 1.21 to 1.74) had higher risk (P trend = .03). No relationships were observed with other smoking parameters. Alcohol consumption did not confound associations with smoking status, although neither current nor former smoking were associated with risk among never drinkers (P interaction = .11). In meta-analyses, current (HR = 1.12, 95% CI = 1.08 to 1.16) and former smoking (HR = 1.09, 95% CI = 1.04 to 1.15) were weakly associated with risk; a stronger association (HR = 1.21, 95% CI = 1.14 to 1.28) was observed in women who initiated smoking before first birth. Conclusions These results support the hypothesis that active smoking is associated with increased breast cancer risk for women who initiate smoking before first birth and suggest that smoking might play a role in breast cancer initiation.
TL;DR: The overall burden of cancer in CF patients remains low; however they have an increased risk of digestive tract cancer, particularly following transplantation, and decreased risk of melanoma.
Abstract: Background Many patients with cystic fibrosis (CF) now reach adulthood, at which time the risk of cancer is increased. The aim of this study was to determine cancer risks in nontransplanted and transplanted CF patients. Methods From 1990 to 2009, we followed 41,188 patients who received care at one of the 250 CF care center programs in the United States and compared the observed number of cancers in nontransplanted and transplanted patients with that expected in the general US population. Results In 344,114 patient-years of observation of nontransplanted patients, the overall cancer risk was similar to the background risk (standardized incidence ratio [SIR] = 1.1, 95% confidence interval [CI] = 1.0 to 1.3). However, we observed an elevated risk of digestive tract cancer (SIR = 3.5, 95% CI = 2.6 to 4.7) involving the esophago-gastric junction, biliary tract, small bowel, and colon. There was also an increased risk of testicular cancer (SIR = 1.7, 95% CI = 1.02 to 2.7) and lymphoid leukemia (SIR = 2.0, 95% CI = 1.2 to 3.1) and a decreased risk of malignant melanoma (SIR = 0.4, 95% CI = 0.2 to 0.9). In 8235 patient-years of observation of transplanted patients, 26 tumors were observed compared with 9.6 expected (SIR = 2.7, 95% CI = 1.8 to 3.9). The increased risk was particularly high for digestive tract cancers (SIR = 17.3, 95% CI = 10.7 to 26.5), with most cases arising in the bowel. Conclusions The overall burden of cancer in CF patients remains low; however they have an increased risk of digestive tract cancer, particularly following transplantation. They also have increased risk of lymphoid leukemia and testicular cancer, and decreased risk of melanoma.
TL;DR: These data fill a critical knowledge gap concerning the cancer experience of Asian American groups and highlight where increased preventive, screening, and surveillance efforts are needed-in particular, lung cancer among Filipina and Korean women and Asian Indian/Pakistani men, breast cancer among all women, and liver cancer among Vietnamese, Laotian, and Kampuchean women and Filipino, Kampukhean, and Vietnamese men.
Abstract: The Asian American population grew faster than that of any racial group in the United States over the last decade (1), with Asian Americans currently representing 5.6% of the population (2). Two-thirds of Asian Americans are foreign-born, and 25% immigrated within the past decade (3). Asian Americans come from heterogeneous socioeconomic backgrounds (1) and vary in English proficiency, insurance coverage, and use of health services (4,5), factors that play important roles in cancer risk. Despite the Asian American population being comprised of numerous diverse groups originating from more than 50 different countries and speaking more than 100 languages, the dominant research literature tends to aggregate these groups (6). As a population with bimodal distributions of socioeconomic status (5,7–10), Asian Americans are generally portrayed as a “model minority” (11), a misleading narrative that obscures their diversity and complexity (8,9,12–14).
An appreciation for the heterogeneity of these populations (15) is evident in the increase in publications reporting cancer incidence data for specific Asian American groups (13,16–39). The existence of the National Cancer Institute’s Surveillance, Epidemiology, End Results (SEER) Program, an integrated program of population-based cancer registries (40–42), facilitates cancer surveillance among specific Asian American populations (43). Examining the descriptive epidemiology of cancer among Asian American groups is critical to the identification of opportunities for targeted cancer control and to informing cancer etiology (36).
Although cancer incidence trends over time have been presented for Asian Americans in California (13,16,20,23,30,31,33,37,39,44–46), the lack of detailed annual population estimates has precluded an examination of national trends. We report results from the first analysis of national trends in cancer incidence for the eight largest Asian American groups—Asian Indians and Pakistanis (combined), Chinese, Filipinos, Japanese, Kampucheans (Cambodians), Koreans, Laotian, and Vietnamese—from 1990 through 2008.
TL;DR: A higher volume of aerobic or combined exercise is achievable and safe during breast cancer chemotherapy and may manage declines in physical functioning and worsening symptoms better than standard volumes.
Abstract: BACKGROUND: Exercise improves physical functioning and symptom management during breast cancer chemotherapy, but the effects of different doses and types of exercise are unknown. METHODS: A multicenter trial in Canada randomized 301 breast cancer patients to thrice-weekly supervised exercise during chemotherapy consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was physical functioning assessed by the Medical Outcomes Survey-Short Form (SF)-36. Secondary endpoints were other physical functioning scales, symptoms, fitness, and chemotherapy completion. All statistical tests were linear mixed model analyses, and the P values were two-sided. RESULTS: Follow-up assessment of patient-reported outcomes was 99.0%. Adjusted linear mixed-model analyses showed that neither HIGH (+0.8; 95% confidence interval [CI] = -0.8 to 2.4; P = .30) nor COMB (+0.5; 95% CI = -1.1 to 2.1; P = .52] were superior to STAN for the primary outcome. In secondary analyses not adjusted for multiple comparisons, HIGH was superior to STAN for the SF-36 physical component summary (P = .04), SF-36 bodily pain (P = .02), and endocrine symptoms (P = .02). COMB was superior to STAN for endocrine symptoms (P = .009) and superior to STAN (P < .001) and HIGH (P < .001) for muscular strength. HIGH was superior to COMB for the SF-36 bodily pain (P = .04) and aerobic fitness (P = .03). No differences emerged for body composition or chemotherapy completion. CONCLUSIONS: A higher volume of aerobic or combined exercise is achievable and safe during breast cancer chemotherapy and may manage declines in physical functioning and worsening symptoms better than standard volumes.
TL;DR: Recent studies on PI3K/Akt-regulated cell motility in both physiological and pathological settings are discussed with the aim of a better understanding of how activities of the PI3 kappa-Akt axis initiate and transmit "migratory signals" that stimulate cell movement.
Abstract: The prosurvival activity of phosphoinositide 3 kinase (PI3K)/Akt (also known as protein kinase B, PKB) pathway has been investigated in great detail in human physiology and disease. Accumulating evidence is emerging that this signaling axis also actively engages with the migratory process in motile cells, including metastatic cancer cells. Interference with the role of PI3K/Akt-mediated cell motility impairs cellular development and attenuates malignant progression of cancer metastasis. Because metastasis is responsible for 90% of mortality in cancer patients, the acceleration of cancer cell spreading observed in association with hyperactivation of the PI3K pathway, triggered for example by chemotherapy/radiotherapy in the clinic, has heightened awareness of the conflict between "good drugs" and unfavorable effects. Here, we discuss recent studies on PI3K/Akt-regulated cell motility in both physiological and pathological settings, with the aim of a better understanding of how activities of the PI3K/Akt axis initiate and transmit "migratory signals" that stimulate cell movement. We focus in particular on its direct influence on cell migration and invasion, epithelial-mesenchymal transition, and cancer metastasis.
TL;DR: In clinical trials, RT protocol deviations are associated with increased risks of treatment failure and overall mortality.
Abstract: Background
Noncompliance with radiotherapy (RT) protocol guidelines has been linked to inferior clinical outcomes. We performed a meta-analysis of cooperative group trials to examine the association between RT quality assurance (QA) deviations and disease control and overall survival (OS).
TL;DR: Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period, and studies to increase knowledge to guide the role of gINSeng to improve CRF are needed.
Abstract: Additional participating institutions include: Siouxland Hematology-Oncology Associates, Sioux City, IA (Donald Wender, MD); Toledo Community Hospital Oncology Program (Rex B. Mowat, MD); Medical College of Georgia, Augusta, GA (Anand P. Jillella MD); Iowa Oncology Research Association CCOP, Des Moines, IA (Robert J. Behrens, MD); Rapid City Regional Hospital, Inc, Rapid City, SD (Richard Charles Tenglin, MD); Columbus CCOP, Columbus, OH (J. Philip Kuebler, MD, PhD); Michigan Cancer Research Consortium, Ann Arbor, MI (Philip J. Stella, MD); Meritcare Hospital CCOP, Fargo, ND (Preston D. Steen, MD); Geisinger Clinic & Medical Center CCOP, Danville, PA (Albert M. Bernath Jr, MD); Montana Cancer Consortium CCOP, Billings, MT (Benjamin T. Marchello, MD); Sioux Community Cancer Consortium, Sioux Falls, SD (Miroslaw Muzurczak, MD); Lehigh Valley Hospital, Allentown, PA (Suresh Nair, MD); Colorado Cancer Research Program, Denver, CO (Eduardo R. Pajon Jr, MD); Mayo Clinic Arizona, Scottsdale, AZ (Michele Y. Halyard, MD); Medcenter One Health Systems, Bismarck, ND (Edward J. Wos, DO); Carle Cancer Center CCOP, Urbana, IL (Kendrith M. Rowland Jr, MD); Cedar Rapids Oncology Project CCOP, Cedar Rapids, IA (Martin Wiesenfeld, MD); Hematology & Oncology of Dayton, Inc, Dayton, OH (Howard M. Gross, MD); Essentia Duluth CCOP, Duluth, MN (Daniel A. Nikcevich, MD); Altru Health Systems, Grand Forks, ND (Grant Seeger, MD); Grand Rapids Clinical Oncology Program, Grand Rapids, MI (Martin J. Bury, MD); Grand Rapids Clinical Oncology Program, Grand Rapids, MI; St. Vincent Regional Cancer Center CCOP, Green Bay, WI (Anthony J. Jaslowski, MD); Hawaii Minority-Based CCOP (William S. Loui, MD); Heartland Cancer Research CCOP, St. Louis, MO (Alan P. Lyss, MD); Edward Comprehensive Cancer Center, Huntington, WV (Maria Rosalia B. Tri Tirona, MD); Marshfield Clinical Research Foundation, Minocqua, WI (Matthias Weiss, MD); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, MN (Patrick J. Flynn, MD); Missouri Valley Cancer Consortium, Omaha, NE (Gamini S. Soori, MD); University of New Mexico, Albuquerque, NM (Zoneddy R. Dayao, MD); Northern Indiana Cancer Research Consortium CCOP, South Bend, IN (Robin T. Zon, MD); Cancer Care Associates, Tulsa, OK (Alan M. Keller, MD); Illinois Oncology Research Assn. CCOP, Peoria, IL (John W. Kugler, MD); Columbia River Oncology Program, Portland, OR (Janet C. Ruzich, MD); CentraCare Clinic, St. Cloud, MN (Donald J. Jurgens, MD); Cancer Research for the Ozarks, Springfield, MO (Robert L. Carolla, MD).
TL;DR: The findings suggest that although BMI is not an independent prognostic factor for CSM after controlling for stage and grade, tumors developing in an obesogenic environment may be more indolent.
Abstract: Renal cell carcinoma (RCC) comprises 85% of kidney cancer and its incidence is increasing, potentially because of more widespread use of diagnostic imagining, with a trend toward smaller tumors being diagnosed (1). Mortality from RCC, however, has not decreased in parallel, suggesting that perhaps not all small tumors are indolent. More than 40% of RCC is attributable to obesity as measured by body mass index (BMI). Recent meta-analyses from prospective observational studies estimate that RCC risk increases by 24% for men and 34% for women for every 5kg/m2 rise in BMI (2). Putative mechanisms through which larger body size increases risk of kidney cancer include chronic tissue hypoxia, altered hormonal milieu, and increased inflammatory response (3). Because these processes can both induce and promote carcinogenesis (4,5), one might expect higher BMI to be an adverse prognostic factor for kidney cancer. Remarkably, a recent systematic review and meta-analysis found overweight and obese kidney cancer patients experienced statistically significantly longer survival than normal-weight patients (6). This phenomenon, known as the “obesity paradox,” has been described among patients on dialysis (7) and with other hemodynamic and metabolic disorders such as heart failure (8), hypertension (9), coronary heart disease (10), diabetes (11), and chronic kidney disease (12), but not among other obesity-related cancers including prostate, colorectal, and postmenopausal breast cancer (13).
The impact of obesity on RCC survival has not been adequately examined, and mechanisms underlying the associations have not been explored. It is not clear whether the obesity paradox is spurious and influenced by detection bias or whether tumors developing in heavier patients are less aggressive and therefore confer a survival advantage. Given that one in three American adults is obese (14) and the incidence of kidney cancer is increasing (1), a better understanding of the obesity paradox is critical to inform secondary prevention efforts and maximize weight management strategies for kidney cancer patients. The purpose of this analysis was to examine the influence of presurgical BMI on stage at presentation and cancer-specific mortality (CSM), while considering the impact of detection bias, nutritional status, and molecular tumor features.
TL;DR: Application of the IASLC/ATS/ERS lung ADC histologic subtyping classification identifies the presence of an MIP component of 5% or greater as independently associated with the risk of recurrence in patients treated with LR.
Abstract: Background We sought to analyze the prognostic significance of the new International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) lung adenocarcinoma (ADC) classification for patients undergoing resection for small (≤2 cm) lung ADC and to investigate whether histologic subtyping can predict recurrence after limited resection (LR) vs lobectomy (LO). Methods Comprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification on all consecutive patients who underwent LR or LO for small lung ADC between 1995 and 2009 at Memorial Sloan-Kettering Cancer Center. Clinical characteristics and pathologic data were retrospectively evaluated for 734 consecutive patients (LR: 258; LO: 476). Cumulative incidence of recurrence (CIR) was calculated using competing risks analysis and compared across groups using Grey’s test. All statistical tests were two-sided. Results Application of IASLC/ATS/ERS lung ADC histologic subtyping to predict recurrence demonstrates that, in the LR group but not in the LO group, micropapillary (MIP) component of 5% or greater was associated with an increased risk of recurrence, compared with MIP component of less than 5% (LR: 5-year CIR = 34.2%, 95% confidence interval [CI] = 23.5% to 49.7% vs 5-year CIR = 12.4%, 95% CI = 6.9% to 22.1%, P < .001; LO: 5-year CIR = 19.1%, 95% CI = 12.0% to 30.5% vs 15-year CIR = 12.9%, 95% CI = 7.6% to 21.9%, P = .13). In the LR group, among patients with tumors with an MIP component of 5% or greater, most recurrences (63.4%) were locoregional; MIP component of 5% or greater was statistically significantly associated with increased risk of local recurrence when the surgical margin was less than 1 cm (5-year CIR = 32.0%, 95% CI = 18.6% to 46.0% for MIP ≥ 5% vs 5-year CIR = 7.6%, 95% CI = 2.3% to 15.6% for MIP < 5%; P = .007) but not when surgical margin was 1 cm or greater (5-year CIR = 13.0%, 95% CI = 4.1% to 22.1% for MIP ≥ 5% vs 5-year CIR = 3.4%, 95% CI = 0% to 7.7% for MIP < 5%; P = .10). Conclusions Application of the IASLC/ATS/ERS classification identifies the presence of an MIP component of 5% or greater as independently associated with the risk of recurrence in patients treated with LR.
TL;DR: The results suggest that the definition of clinically insignificant PCa might be worth re-examining and that more than 50% of cancers in ASI and nearly 25% of surgeries in CAU men have a GS of 7 or greater.
Abstract: BACKGROUND Substantial geographical differences in prostate cancer (PCa) incidence and mortality exist, being lower among Asian (ASI) men compared with Caucasian (CAU) men. We prospectively compared PCa prevalence in CAU and ASI men from specific populations with low penetrance of prostate-specific antigen screening. METHODS Prostate glands were prospectively obtained during autopsy from men who died from causes other than PCa in Moscow, Russia (CAU), and Tokyo, Japan (ASI). Prostates were removed en-block and analyzed in toto. We compared across the 2 populations PCa prevalence, number and Gleason score (GS) of tumour foci, pathological stage, spatial location, and tumor volume using χ(2), Mann-Whitney-Wilcoxon tests, and multiple logistic regression. All statistical tests were two-sided. RESULTS Three hundred twenty prostates were collected, 220 from CAU men and 100 from ASI mean. The mean age was 62.5 in CAU men and 68.5 years in ASI men (P < .001). PCa prevalences of 37.3% in CAU men and 35.0% in ASI men were observed (P = .70). Average tumor volume was 0.303cm(3). In men aged greater than 60 years, PCa was observed in more than 40% of prostates, reaching nearly 60% in men aged greater than 80 years. GS 7 or greater cancers accounted for 23.1% and 51.4% of all PCa in CAU and ASI men, respectively, (P = .003). When adjusted for age and prostate weight, ASI men still had a greater probability of having GS 7 or greater PCa (P = .03). CONCLUSIONS PCa is found on autopsy in a similar proportion of Russian and Japanese men. More than 50% of cancers in ASI and nearly 25% of cancers in CAU men have a GS of 7 or greater. Our results suggest that the definition of clinically insignificant PCa might be worth re-examining.
TL;DR: These data highlight statistically and clinically significant disparities in the quality of ovarian cancer care and overall survival, independent of NCCN guidelines, along racial and SES parameters.
Abstract: cancer diagnosed in the period from 1998 to 2002 was done using data from patients classified as white or black. Adherence to National Comprehensive Cancer Network (NCCN) guideline care was defined by stage-appropriate surgical procedures and recommended chemotherapy. The main outcome measures were differences in adherence to NCCN guidelines and overall survival according to race and SES and were analyzed using binomial logistic regression and multilevel survival analysis. Results A total of 47 160 patients (white = 43 995; black = 3165) were identified. Non-NCCN-guideline-adherent care was an independent predictor of inferior overall survival (hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.38 to 1.47). Demographic characteristics independently associated with a higher likelihood of not receiving NCCN guideline-adherent care were black race (odds ratio [OR] = 1.36, 95% CI = 1.25 to 1.48), Medicare payer status (OR = 1.20, 95% CI = 1.12 to 1.28), and not insured payer status (OR = 1.33, 95% CI = 1.19 to 1.49). After controlling for disease and treatment-related variables, independent racial and SES predictors of survival were black race (HR = 1.29, 95% CI = 1.22 to 1.36), Medicaid payer status (HR = 1.29, 95% CI = 1.20 to 1.38), not insured payer status (HR = 1.32, 95% CI = 1.20 to 1.44), and median household income less than $35 000 (HR = 1.06, 95% CI = 1.02 to 1.11). Conclusions These data highlight statistically and clinically significant disparities in the quality of o varian cancer care and overall survival, independent of NCCN guidelines, along racial and SES parameters. Increased efforts are needed to more precisely define the patient, provider, health-care system, and societal factors leading to these observed disparities and guide targeted interventions.
TL;DR: Short telomere length is associated with reduced survival after cancer but not with cancer risk, which contrasts with findings from recent meta-analyses.
Abstract: Background Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer. Methods We measured leukocyte telomere length in a prospective study of 47 102 Danish general population participants from the Copenhagen City Heart Study and the Copenhagen General Population Study. Participants were followed for up to 20 years for cancer diagnosis and death. Follow-up was 100% complete. All statistical tests were two-sided. Results Telomere length decreased linearly with increasing age (P <.001). During follow-up, we observed 3142 first cancers and, among these individuals, 1730 deaths. Decreasing quartiles of telomere length were associated with decreasing survival after cancer (log-rank P <.001). Multivariable-adjusted hazard ratios of early death were 1.31 (95% confidence interval [CI] = 1.14 to 1.52) in individuals in the quartile and 1.43 (95% CI = 1.13 to 1.80) in individuals in the decile with the shortest telomeres vs the longest. Unadjusted hazard ratios of cancer risk were 1.74 (95% CI = 1.58 to 1.93) and 2.00 (95% CI = 1.70 to 2.35) in individuals in the quartile and decile with the shortest vs longest telomeres; however, multivariable adjustment changed these hazard ratios to 0.98 (95% CI = 0.88 to 1.08) and 0.95 (95% CI = 0.80 to 1.11), mainly because of age adjustment. Conclusions Short telomere length is associated with reduced survival after cancer but not with cancer risk. The latter contrasts with findings from recent meta-analyses.
University of Florida1, University of Texas MD Anderson Cancer Center2, National Institutes of Health3, University of Texas Southwestern Medical Center4, Duke University5, Medical College of Wisconsin6, University of New Mexico7, New York University8, University of Colorado Denver9, University of California, San Francisco10
TL;DR: Findings indicate strong associations between inherited genetic variation and ALL susceptibility in children and shed new light on ALL molecular etiology in diverse ancestry.
Abstract: Heng Xu, Wenjian Yang, Virginia Perez-Andreu, Meenakshi Devidas, Yiping Fan, Cheng Cheng, Deqing Pei, Paul Scheet, Esteban Gonzalez Burchard, Celeste Eng, Scott Huntsman, Dara G. Torgerson, Michael Dean, Naomi J. Winick, Paul L. Martin, Bruce M. Camitta, W. Paul Bowman, Cheryl L. Willman, William L. Carroll, Charles G. Mullighan, Deepa Bhojwani, Stephen P. Hunger, Ching-Hon Pui, William E. Evans, Mary V. Relling, Mignon L. Loh, Jun J. Yang
TL;DR: None of the IHC4 markers provided statistically significant prognostic information in years 5 to 10, except for nodal status and tumor size, which may help select patients who could benefit most from hormonal therapy beyond 5 years of treatment.
Abstract: Adjuvant chemotherapy and endocrine therapy for early breast cancer have had a considerable impact on outcomes (1), but a substantial number of women, especially those with estrogen receptor (ER)–positive tumors, remain at risk for late recurrences. The annual rate is in excess of 2% for at least 15 years, even after 5 years of tamoxifen therapy (2), and currently it is not possible to identify a group of such women who can be considered as cured (3,4). This remains true for at least 10 years for women treated for 5 years with an aromatase inhibitor (5).
Most of the studies of prevention of late relapse have been performed in women receiving tamoxifen as initial adjuvant endocrine therapy for early ER-positive breast cancer. The MA17 trial clearly showed that extended adjuvant therapy with letrozole after 5 years of tamoxifen prolongs disease-free survival and overall survival, regardless of the patient’s nodal status involvement (6). Brewster et al. (7) found that ER positivity, nodal involvement, and grade were all associated with increased risk of late recurrence. It is of importance to determine to what extent the newer immunohistochemical and molecular scores can help in predicting late recurrence.
Recent publications from the transATAC (Anastrozole, Tamozifen, Alone or in Combination) cohort have demonstrated that the Oncotype DX recurrence score (RS) (8), the immunohistochemical (IHC4) score (9) and the PAM50-based risk of recurrence (ROR) score (10) all provide additional information beyond that available for clinical variables, summarized in the clinical treatment score (CTS), about the risk of distant recurrence in postmenopausal women with hormone receptor–positive breast cancer treated with anastrozole or tamoxifen, but it is unknown how much of this effect extends beyond 5 years. Here, we investigate the relationship between clinical variables, immunohistochemical markers, and these scores for the prediction of distant recurrence separately in years 0 to 5 and years 5 to 10 after diagnosis for postmenopausal women with early hormone receptor–positive breast cancer.
TL;DR: Some circulating inflammation marker levels are associated with prospective lung cancer risk, and a cross-validated inflammation score using four independent markers provided good separation in 10-year lung cancer cumulative risks among former smokers.
Abstract: Methods We conducted a nested case–control study (n = 526 lung cancer patients and n = 592 control subjects) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Control subjects were matched to lung cancer case patients on age, sex, follow-up time (median = 2.9 years), randomization year, and smoking (pack-years and time since quitting). Serum levels of 77 inflammation markers were measured using a Luminex bead-based assay. Conditional logistic regression and weighted Cox models were used to estimate odds ratios (ORs) and cumulative risks, respectively.
TL;DR: Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence and prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, and increased breastcancer mortality can be expected.
Abstract: Background In the Women’s Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied. Methods We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariableadjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided. Results After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers. Conclusions Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.