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Purpose: Estrogen receptor (ER) + /progesterone receptor (PR) – or ER−/PR + breast cancer prognosis has not been well-described outside of clinical trials. We evaluated the relationship between ER/PR (ER + /PR−, ER−/PR + , ER + /PR + , ER−/PR−) subgroups and breast cancer-specific mortality within a general community setting in the US. Methods: A Retrospective cohort of 11,737 women diagnosed with breast cancer between 1990 and 2016 within US integrated healthcare systems (median follow-up = 7 years; 1,104 breast cancer-specific deaths) were included in this analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for site, demographic and clinicopathological characteristics, and treatment (surgery/radiotherapy, chemotherapy, endocrine therapy). Results: Breast cancer-specific mortality was higher for those with ER + /PR− (n = 1,233) compared with ER + /PR + tumors (n = 8,439) before (HR = 1.43; 95% CI = 1.17–1.75) and after treatment adjustment (HR = 1.58; 95% CI = 1.27–1.97). ER + /PR− breast cancer-specific mortality remained higher than ER + /PR + tumors when stratified by treatment received. Breast cancer-specific mortality was similar in ER–/PR + (n = 161) compared with ER + /PR + tumors. Conclusion: Our findings suggest that ER + /PR− tumors may have worse breast cancer-specific mortality than ER + /PR + tumors in a community setting. [ABSTRACT FROM AUTHOR]

Background: Brain and other central nervous system (CNS) cancers are the leading cause of U.S. pediatric cancer mortality. Incidence trends can provide etiologic insight. We report trends in incidence rates of pediatric malignant CNS cancers and pilocytic astrocytoma (nonmalignant but historically registered) in the United States. Methods: Age-standardized incidence rates and annual percent changes (APC) in rates during 1998 to 2013 were calculated for children aged 0 to 19, stratified by subtype, age, sex, and for gliomas, histology and location. We estimated the absolute change in number of cases diagnosed U.S.-wide during 2013 compared with the expected number of cases had 1998 rates remained stable. Results: Rates of all pediatric malignant CNS cancer combined (n = 18,612) did not change [APC: 0.16; 95% confidence interval (CI): -0.21-0.53]. There were statistically significant changes in several subtypes; however, glioma incidence (n = 10,664) increased by 0.77% per year (95% CI: 0.29-1.26), embryonal cancer rates (n = 5,423) decreased by 0.88% per year (95% CI: -1.33 to -0.43), and pilocytic astrocytoma rates (n = 6,858) increased by 0.89% per year (95% CI: 0.21-1.58). Of the 1,171 malignant tumors and 450 pilocytic astrocytomas diagnosed in U.S. children in 2013, we estimated 120 excess gliomas, 94 excess pilocytic astrocytomas, and 72 fewer embryonal CNS tumors than would be expected had 1998 rates remained stable. Conclusions: The gradual changes in incidence we observed for specific types of pediatric CNS cancers are likely due to a combination of changes in classification and diagnosis and true changes in CNS cancer. Impact: Continued surveillance of pediatric CNS tumors should remain a priority, given their significant contribution to pediatric cancer-related deaths. [ABSTRACT FROM AUTHOR]

Despite decades of epidemiological research, it remains uncertain whether ionizing radiation can cause lymphomas. Most epidemiological studies of lymphoma risk following non-uniform exposure used dose to red bone marrow (RBM), constituting a small fraction of the lymphocytes, as a surrogate of dose to the lymphocytes. We developed a method to estimate dose to the lymphocytes using the reference distribution of lymphocytes throughout the body and Monte Carlo simulations of computational human phantoms. We applied our method to estimating lymphocyte doses for a pediatric CT patient cohort in the United Kingdom. Estimated dose to the RBM was greater than lymphocyte dose for most scan types (up to 2.6-fold higher, a 5-year-old brain scan) except abdomen scan (RBM dose was about half the lymphocyte dose, a 5-year-old abdomen scan). The lymphocyte dose in the UK cohort showed that T-spine and whole body scans delivered the highest lymphocyte doses (up to 22.4 mGy). [ABSTRACT FROM AUTHOR]

Objective: To describe the medical conditions associated with the use of CT in children or young adults with no previous cancer diagnosis. Methods: Radiologist reports for scans performed in 1995–2008 in non-cancer patients less than 22 years of age were collected from the radiology information system in 44 hospitals of Great Britain. By semantic search, an automated procedure identified 185 medical conditions within the radiologist reports. Manual validation of a subsample by a paediatric radiologist showed a satisfactory performance of the automatic coding procedure. Results: Medical information was extracted for 37,807 scans; 19.5% scans were performed in children less than 5 years old; 52.0% scans were performed in 2000 or after. Trauma, diseases of the nervous (mainly hydrocephalus) or the circulatory system were each mentioned in 25–30% of scans. Hydrocephalus was mentioned in 19% of all scans, 59% of scans repeated ≥5 times in a year, and was the most frequent condition in children less than 5 years of age. Congenital diseases/malformations, disorders of the musculoskeletal system/connective tissues and infectious or respiratory diseases were each mentioned in 5–10% of scans. Suspicionor diagnosis of benign or malignant tumour was identified in 5% of scans. Conclusion: This study describes the medical conditions that likely underlie the use of CT in children in Great Britain. It shows that patients with hydrocephalus may receive high cumulative radiation exposures from CT in early life, i.e. at ages when they are most sensitive to radiation. Advances in knowledge: The majority of scans were unrelated to cancer suspicion. Repeated scans over time were mainly associated with the management of hydrocephalus. [ABSTRACT FROM AUTHOR]

Background: We previously reported evidence of a dose-response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings.Methods: We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer-predisposing conditions or previous unreported cancers and compared the dose-response analyses with our original results.Results: We obtained information from the RIS and death certificates for about 40% of the cohort (n∼180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose-response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend=0.02) and by 30% from 0.023 to 0.016 (P-trend<0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases.Conclusions: Although there was evidence of some bias in our original risk estimates, re-analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients. [ABSTRACT FROM AUTHOR]

Tamoxifen-associated mammographic density (MD) reductions are linked to improved breast cancer survival. We evaluated MD at six time points to determine the timing of greatest reduction following tamoxifen initiation. We sampled 40 Kaiser Permanente Northwest estrogen receptor (ER)-positive breast cancer patients from a prior study of MD change, according to tamoxifen use duration and age at diagnosis: <4 years tamoxifen and ⩾50 years (N = 6) or >50 years (N = 10) old; ⩾4 years tamoxifen and ⩾50 years (N = 13) or >50 years (N = 11) old. A single reader evaluated percent MD in the contralateral breast on baseline (pre-diagnosis) and five approximately yearly post-diagnostic (T1 to T5)mammograms. Mean MD change was calculated. Interactions with age (⩾50 and >50 years), tamoxifen duration (<4 and ⩾4 years), and baseline MD (tertiles) were tested in linear regression models. Overall, the largest MD decline occurred by T1 (mean 4.5%) with little additional decline by T5. Declines differed by tertile of baseline MD (Pinteraction < 0.01). In the highest tertile, the largest reduction occurred by T1 (mean 14.9%), with an additional reduction of 3.6% by T5. Changes were smaller in the middle and lowest baseline MD tertiles, with cumulative reductions of 3.0% and 0.4% from baseline to T5, respectively. There were no differences by age (Pinteraction = 0.36) or tamoxifen duration (Pinteraction = 0.42). Among ER-positive patients treated with tamoxifen and surviving ⩾5 years, most of the MD reduction occurred within approximately 12 months of tamoxifen initiation, suggesting that MD measurement at a single time point following tamoxifen initiation can identify patients with substantial density declines. [ABSTRACT FROM AUTHOR]

The role of lifestyle risk factors in prostate cancer risk remains elusive despite a large number of epidemiologic studies. In a pooled analysis of data from South and East Asian countries published in this issue, Fowke et al. (Am J Epidemiol. 2015;182(5):381-389) found no evidence for an association between prostate cancer mortality and obesity, alcohol, or smoking. Prostate cancer screening is very uncommon in these countries, and previous evidence for associations with lifestyle factors comes primarily from studies carried out in North America, where screening is very common. Fowke et al. concluded that screening biases are likely to explain the differences in study results. In this commentary, we discuss the potential influence of population-based cancer screening programs in estimates of association from epidemiologic studies. This highlights the importance of carefully considering the impact of screening in the analysis and interpretation of results, in order to advance our understanding of the etiology of cancers that can be detected by screening. [ABSTRACT FROM AUTHOR]

Background: A prior analysis of postmenopausal breast cancer patients linked a decline in mammographic density (MD) following the initiation of tamoxifen treatment with improved survival, but excluded premenopausal women, for whom tamoxifen is the primary anti-endocrine therapy. Therefore, we evaluated change in MD after tamoxifen and breast cancer death among patients age 32 to 87 years. Methods: This case-control study included 349 estrogen receptor (ER)--positive breast cancer patients who were treated with tamoxifen at Kaiser Permanente Northwest (1990-2008): 97 who died from breast cancer (case patients) and 252 who did not (control patients), matched on age and year at diagnosis and disease stage. Percent MD in the unaffected breast was measured at baseline (mean six months before tamoxifen initiation) and follow-up (mean 12 months after initiation). Associations between change in MD and breast cancer death were estimated using conditional logistic regression. Results: Patients in the highest tertile of MD decline had a lower risk of breast cancer death when compared with women in the lowest tertile (odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.22 to 0.88); results were similar after adjustment for baseline MD (OR = 0.49, 95% CI = 0.23 to 1.02). Reductions in death were observed only among patients in the middle and upper tertiles of baseline MD. Associations did not differ by age, tamoxifen use duration, estrogen and/or progestin use, body mass index, or receipt of chemotherapy or radiotherapy. Conclusion: These data suggest that younger and older ER-positive breast cancer patients who experience large reductions in MD following tamoxifen initiation have an improved prognosis. [ABSTRACT FROM AUTHOR]

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Background: We examined the relationship between estimated radiation dose from CT scans and subsequent Hodgkin lymphoma in the UK pediatric CT scans cohort. Methods: A retrospective, record linkage cohort included patients ages 0 to 21 years who underwent CT scans between 1980 and 2002 and were followed up for cancer or death until 2008. Poisson regression analysis was used to evaluate the relationship between estimated radiation dose (lagged by 2 years) and incident Hodgkin lymphoma diagnosed at least 2 years after the first CT scan. Results: There were 65 incident cases of Hodgkin lymphoma in the cohort of 178,601 patients. Neither estimated red bone marrow dose nor mean lymphocyte dose from CT scans was clearly associated with an increased risk of Hodgkin lymphoma (RR for 20+ mGy vs. <5 mGy = 0.92 (0.38-2.22) Ptrend > 0.5 and 1.44 (0.60-3.48) Ptrend > 0.5), respectively. Conclusions: Radiation exposure from pediatric CT scans 2 or more years before diagnosis was not associated with Hodgkin lymphoma in this large UK cohort. Impact: These findings are consistent with the majority of previous studies, which do not support a link between ionizing radiation and Hodgkin lymphoma. The results contrast our previous positive findings in this cohort for brain tumors and leukemia, both of which are known to be strongly linked to radiation exposure during childhood. [ABSTRACT FROM AUTHOR]

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995–2009; Adventist Health Study 2, 2002–2008; Black Women's Health Study, 1995–2009; Cancer Prevention Study II, 1982–2008; Multiethnic Cohort Study, 1993–2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993–2009; Southern Community Cohort Study, 2002–2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30–104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25–27.4, 27.5–29.9, 30–34.9, 35–39.9, 40–49.9, and 50–60 kg/m2 were 1.02 (0.92–1.12), 1.06 (0.95–1.18), 1.32 (1.18–1.47), 1.54 (1.29–1.83), 1.93 (1.46–2.56), and 1.93 (0.80–4.69), respectively among men and 1.06 (0.99–1.15), 1.15 (1.06–1.25), 1.24 (1.15–1.34), 1.58 (1.43–1.74), 1.80 (1.60–2.02), and 2.31 (1.74–3.07) respectively among women (reference category 22.5–24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans. [ABSTRACT FROM AUTHOR]

The article focuses on use of pooling data from cohort studies of cancer incidences for investigating second cancer etiology. It mentions the study which reveals that second solid cancers in adults occur due to radiotherapy. It adds that second cancers cause morbidity and mortality among cancer survivors.