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Objectives We report cancer incidence, mortality, and stage distributions among Asians and Pacific Islanders (API) residing in the U.S. and note health disparities, using the cancer experience of the non-Hispanic white population as the referent group. New databases added to publicly available SEER*Stat software will enable public health researchers to further investigate cancer patterns among API groups. Methods Cancer diagnoses among API groups occurring from 1 January 1998 to 31 December 2002 were included from 14 Surveillance, Epidemiology, and End Results (SEER) Program state and regional population-based cancer registries covering 54% of the U.S. API population. Cancer deaths were included from the seven states that report death information for detailed API groups and which cover over 68% of the total U.S. API population. Using detailed racial/ethnic population data from the 2000 decennial census, we produced incidence rates centered on the census year for Asian Indians/Pakistanis, Chinese, Filipinos, Guamanians, Native Hawaiians, Japanese, Kampucheans, Koreans, Laotians, Samoans, Tongans, and Vietnamese. State vital records offices do not report API deaths separately for Kampucheans, Laotians, Pakistanis, and Tongans, so mortality rates were analyzed only for the remaining API groups. Results Overall cancer incidence rates for the API groups tended be lower than overall rates for non-Hispanic whites, with the exception of Native Hawaiian women (All cancers rate = 488.5 per 100,000 vs. 448.5 for non-Hispanic white women). Among the API groups, overall cancer incidence and death rates were highest for Native Hawaiian and Samoan men and women due to high rates for cancers of the prostate, lung, and colorectum among Native Hawaiian men; cancers of the prostate, lung, liver, and stomach among Samoan men; and cancers of the breast and lung among Native Hawaiian and Samoan women. Incidence and death rates for cancers of the liver, stomach, and nasopharynx were notably high in several of the API groups and exceeded rates generally seen for non-Hispanic white men and women. Incidence rates were lowest among Asian Indian/Pakistani and Guamanian men and women and Kampuchean women. Asian Indian and Guamanian men and women also had the lowest cancer death rates. Selected API groups had less favorable distributions of stage at diagnosis for certain cancers than non-Hispanic whites. Conclusions Possible disparities in cancer incidence or mortality between specific API groups in our study and non-Hispanic whites (referent group) were identified for several cancers. Unfavorable patterns of stage at diagnosis for cancers of the colon and rectum, breast, cervix uteri, and prostate suggest a need for cancer control interventions in selected groups. The observed variation in cancer patterns among API groups indicates the importance of monitoring these groups separately, as these patterns may provide etiologic clues that could be investigated by analytic epidemiological studies.

Paul Boutros, Robert Bristow and colleagues report a molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer. They find that multifocal tumors are highly heterogeneous, and they identify a novel recurrent amplification of MYCL1 . Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL , which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Sales and profit margins are two popular earnings components discussed in the media. We study properties of one-year-ahead analyst forecasts of these two components. As sales are in dollar amounts and profit margin is a ratio, we propose robust statistical methods to assess and contrast their forecast properties. We find that four performance properties associated with earnings forecasts—optimism, relative accuracy with respect to benchmark model forecasts, forecast suboptimality, and serial correlation of forecast errors—apply to both sales and profit margins. Sales forecasts, in general, perform better than profit margin forecasts. Further evidence also shows that sales forecasts perform better than profit margin forecasts in terms of how their forecast errors explain earnings forecast errors and how realized surprises affect adjustments of the respective forecasts. We also find that a better information environment, surrogated by size, improves sales forecasts more than profit margin forecasts. All of these findings suggest that forecasting profit margins is inherently more difficult than forecasting sales.

Clinical prognostic groupings for localised prostate cancers are imprecise, with 30–50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1–9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65–0·76]) and radical prostatectomy (4·0 [1·6–9·7]; p=0·0024; AUC 0·57 [0·52–0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2–12]; p=0·019; AUC 0·67 [0·61–0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0–19]; p=0·0015; AUC 0·74 [95% CI 0·65–0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4–6·0]; p=0·0039; AUC 0·68 [95% CI 0·63–0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.

A general consensus in the literature is that financial analysts make optimistic forecasts. That is, they tend to underreact to negative but overreact to positive information. In this study, we invoke this idea to provide an explanation for the distress risk puzzle, the phenomenon that high distress risk firms deliver anomalously low subsequent returns. We find that analysts underestimate the implication of the poor performance of higher distress risk firms, and thus make EPS and sales forecasts that are generally more optimistic than those for the lower distress risk firms. Because market respond to the analyst forecasts, investors initially overvalue the high distress risk firms; later on, when those firms report less than expected performance, analysts revise their forecasts downwards that in turn cause the high distress risk firms to earn low future returns composing of both immediate-forecast-revision responses and post-forecast-revision price drifts. We further document that (quarter) earnings announcements convey a substantial amount of information that roughly drives more than 60% of the analyst forecast revisions and 30% of the revision-related market responses.

Jorge Reis-Filho and colleagues identify recurrent mutations in PRKD1 in 73% of polymorphous low-grade adenocarcinoma, a malignant tumor of the minor salivary glands. The mutations cause activation of the PRKD1 serine-threonine kinase. Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.

It has been reported that age-specific breast cancer rates vary by estrogen receptor and progesterone receptor status. We report breast cancer rates for age-at-diagnosis, stage-at-diagnosis, histological grade and type by estrogen (ER) and progesterone (PgR) receptor status in six major racial/ethnic groups. The average annual age-adjusted rates for breast cancers with estrogen receptor positive (ER+), ER-, progesterone receptor positive (PgR+), PgR-, ER+PgR+, ER+PgR-, ER-PgR+ and ER-PgR- are determined from 123,732 breast cancers with known ER status, diagnosed from 1992 to 1998 from 11 Surveillance, Epidemiology, and End Results (SEER) cancer registries. For each racial/ethnic group, their ER+ (ER+PgR+ and ER+PgR-) age-specific rates increased with age (but at a slower pace after ages 50-54) while their ER- (ER- PgR+ and ER-PgR-) age-specific rates did not increase after ages 50-54. The rank orders of the rates among the racial/ethnic groups varied by ER/PgR status. The stage I rates were greater than the stage II rates for the ER/PgR groups except for ER- and ER- PgR- cancers. The grade 2 (moderately differentiated) rates were greater than the grades 3 and 4 (poorly differentiated and undifferentiated cancers) rates for ER+ cancers, but not for ER- cancers. These results suggest that although breast cancer is a disease with enormous heterogeneity, the multiple types of breast cancer can be separated into distinct subgroups by their ER status, and perhaps by their ER/PgR status, and their cancer characteristics may be important in understanding the multiple nature of breast cancer.

Objective: Analysis of 3359 Danish breast cancer cases indicated that menopause exerted a greater protective effect on estrogen-receptor negative (ER-) breast cancer than on estrogen-receptor positive (ER+) breast cancer. We examined US age-specific breast cancer rates by hormone receptor status in white and black women and men to investigate this unexpected result. Methods: Age-specific breast cancer incidence rates from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were analyzed by joint estrogen receptor and progesterone receptor (ER/PR) status of 101,140 white female and 8870 black female cases and by ER status in 706 white male and black male cases diagnosed from 1992 to 1998. Changes in the rate of increase in rates with age were identified using Poisson regression analyses. Results: For both white women and black women the age-specific rates of ER- breast cancer cease increasing after 50 years of age, but age-specific rates of ER+ breast cancer continue to increase after 50 years of age. For men the incidence of ER- cancers may increase at a slower rate than incidence of ER+ cancers in older ages. In women the black rates of ER+ cancers are greater than white rates only until age 35, but black rates of ER- cancers are greater than white rates for all ages. Conclusions: Differences in age-specific breast cancer incidence patterns by hormone receptor status are similar for black women and white women. The incidence pattern for ER- cancers is consistent with a paracrine model for hormone-stimulated growth in normal breast tissue. The continued increase in ER+ cancers after menopause may be explained by both the paracrine growth model and an increase in the proliferation rate of ER+ cells with age.

In the 1990s, U.S. cancer mortality rates declined due to reductions in tobacco use among men and beneficial cancer interventions, such as mammography and Pap smears. We examined the cancer rates by racial/ethnic group, socioeconomic status and time period to identify disparities underlying the overall mortality trend. We examined racial/ethnic disparities by measuring excess cancer burden [rate ratio (RR) and ratio differences (RD)] and trends in their cancer rates for nine cancer sites. The trend (T) is calculated as a ratio of the average annual cancer mortality rate for 1995-2000 relative to the rate for 1990-1994 for three levels of poverty (counties with <10% living below the poverty level, 10% - <20% and > or =20%) for the major racial/ethnic populations. We also compared the trend for each racial/ethnic SES group to the trend for lowest SES white group (TD). Blacks have RR disparities relative to whites for each cancer site examined, except for female lung cancer, while the other minorities had RR disparities for cervical cancer (RR>1). There are increases in RR disparities from 1990-1994 to 1995-2000 (RD>0) for colorectal cancer, prostate cancer and breast cancer for each racial/ethnic minority. Whites and blacks had declining trends for every SES group (T<1) and positive high SES gradients (the highest SES group had the best trend and the lowest SES group had the worst trend) at each cancer site, except female lung cancer (T>1). In contrast, American Indians/Alaska natives, Hispanics and Asians/ Pacific Islanders had increasing trends for some of their cancer sites, and their trends did not have the SES gradients. Increases in racial/ethnic disparities (RD>0) for colorectal, breast and prostate cancer were largest in the lowest SES groups. At some cancer sites, the highest SES group for minorities had worse trend results than the trends for the lowest SES white group (TD>0).

Background: The National Cancer Institute created the Special Population Network (SPN) to develop cancer awareness, research and training with partnerships from community and research organizations. Methods: Eighteen SPNs were funded with the goals of enlisting community partnerships, enhancing training opportunities for minority scientists, and conducting pilot research projects. Results: The SPN program concluded in 2005 after achieving many major milestones. Conclusion: This paper provides background information about the SPN and one of its programs, the Pacific Islander Cancer Control Network.