Population-level impact of adjuvant trastuzumab emtansine on the incidence of metastatic breast cancer: an epidemiological prediction model of women with HER2-positive early breast cancer and residual disease following neoadjuvant therapy.

PURPOSE: Treating early-stage breast cancer (eBC) may delay or prevent subsequent metastatic breast cancer (mBC). In the phase 3 KATHERINE study, women with human epidermal growth factor receptor 2 (HER2)-positive eBC with residual disease following neoadjuvant therapy containing trastuzumab and a taxane experienced 50% reductions in disease recurrence or death when treated with adjuvant trastuzumab emtansine (T-DM1) vs adjuvant trastuzumab. We predicted the population-level impact of adjuvant T-DM1 on mBC occurrence in five European countries (EU5) and Canada from 2021-2030. METHODS: An epidemiological prediction model using data from national cancer registries, observational studies, and clinical trials was developed. Assuming 80% population-level uptake of adjuvant treatment, KATHERINE data were extrapolated prospectively to model projections. Robustness was evaluated in alternative scenarios. RESULTS: We projected an eligible population of 116,335 women in Canada and the EU5 who may be diagnosed with HER2-positive eBC and have residual disease following neoadjuvant therapy from 2021-2030. In EU5, the cumulative number of women projected to experience relapsed mBC over the 10-year study period was 36,009 vs 27,143 under adjuvant trastuzumab vs T-DM1, a difference of 8,866 women, equivalent to 25% fewer cases with the use of adjuvant T-DM1 in EU5 countries from 2021-2030. Findings were similar for Canada. CONCLUSION: Our models predicted greater reductions in the occurrence of relapsed mBC with adjuvant T-DM1 vs trastuzumab in the indicated populations in EU5 and Canada. Introduction of T-DM1 has the potential to reduce population-level disease burden of HER2-positive mBC in the geographies studied.

A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines.

Psychedelic indolethylamines have emerged as potential medicines to treat several psychiatric pathologies. Natural sources of these compounds include 'magic mushrooms' (Psilocybe spp.), plants used to prepare ayahuasca, and toads. The skin and parotid glands of certain toads accumulate a variety of specialized metabolites including toxic guanidine alkaloids, lipophilic alkaloids, poisonous steroids, and hallucinogenic indolethylamines such as DMT, 5-methoxy-DMT, and bufotenin. The occurrence of psychedelics has contributed to the ceremonial use of toads, particularly among Mesoamerican peoples. Yet, the biosynthesis of psychedelic alkaloids has not been elucidated. Herein, we report a novel indolethylamine N-methyltransferase (RmNMT) from cane toad (Rhinella marina). The RmNMT sequence was used to identify a related NMT from the common toad, Bufo bufo. Close homologs from various frog species were inactive, suggesting a role for psychedelic indolethylamine biosynthesis in toads. Enzyme kinetic analyses and comparison with functionally similar enzymes showed that recombinant RmNMT was an effective catalyst and not product inhibited. The substrate promiscuity of RmNMT enabled the bioproduction of a variety of substituted indolethylamines at levels sufficient for purification, pharmacological screening, and metabolic stability assays. Since the therapeutic potential of psychedelics has been linked to activity at serotonergic receptors, we evaluated binding of derivatives at 5-HT1A and 5-HT2A receptors. Primary amines exhibited enhanced affinity at the 5-HT1A receptor compared with tertiary amines. With the exception of 6-substituted derivatives, N,N-dimethylation also protected against catabolism by liver microsomes.

Impact of Pertuzumab and Ado-Trastuzumab Emtansine on Cumulative Avoidance of Recurrence Among Women Treated for Locally Advanced, Inflammatory, or Early-Stage Nonmetastatic HER2-Positive Breast Cancer in the United States.

INTRODUCTION: We assessed the impact of HER2-positive early breast cancer (EBC) treatment landscape changes following the introduction of pertuzumab and ado-trastuzumab emtansine (T-DM1) on cumulative population-level recurrences avoided since 2013 (first pertuzumab approval for EBC in the United States; US). METHODS: We constructed a multi-year epidemiologic population treatment-impact model to estimate annual recurrences between 2013 and 2031. Parameters were: BC incidence; stage I-III proportion; HER2-positive disease proportion; treatment proportions for neoadjuvant-only, adjuvant-only, and neoadjuvant-adjuvant continuation; and therapeutic agent proportions within each of those settings (chemotherapy only, trastuzumab ± chemotherapy, pertuzumab with trastuzumab ± chemotherapy, or T-DM1). The primary endpoint was cumulative recurrences, estimated by incorporating extrapolated clinical trial data for each regimen of interest into the model under four scenarios. RESULTS: Approximately 889,057 women were predicted to be diagnosed with stage I-III HER2-positive BC from 2006 to 2031 in the US and potentially indicated for HER2-targeted treatment. In steady-state equilibrium, the model estimated that real-world utilization of pertuzumab and T-DM1 will reduce the population-level number of recurrences by approximately 32%, with 7226 recurrences predicted in 2031 based on current utilization rates. In different modeled scenarios, use of neoadjuvant pertuzumab, continuation of pertuzumab in the adjuvant setting, and T-DM1 in the adjuvant setting in women with residual disease after neoadjuvant treatment were all predicted to reduce the number of recurrences. CONCLUSION: Given the improvement of HER2-targeted treatments, alongside increases in BC disease burden, we expect that the population-level impact of HER2-targeted treatments will accelerate over the next decade. Our results suggest that utilization of HER2-targeted treatments in the US has the potential to change the epidemiology of HER2-positive EBC by preventing a substantial number of women from experiencing disease recurrence. These improvements may help to inform our understanding of the future disease and economic burden of HER2-positive BC in the US.

We predicted whether two treatments for a type of breast cancer called "HER2-positive," that had not yet spread from the breast, could be used to avoid the cancer coming back in women in the United States (US), using computer modeling. The model estimated that approximately 889,057 women were predicted to be diagnosed with this type of breast cancer from 2006 to 2031, and that use of the treatments pertuzumab and ado-trastuzumab emtansine (T-DM1) would reduce the number of breast cancers that came back by around 32%. Treating with pertuzumab before surgery, continuing pertuzumab treatment after surgery, and giving T-DM1 after surgery (in the event that some of the breast cancer remained after being treated before surgery) were all predicted to reduce the number of breast cancers that come back. Overall, we expect use of pertuzumab and T-DM1 to keep lowering the number of breast cancers that come back over the next decade in the US.

Contributions of Social Factors to Disparities in Prostate Cancer Risk Profiles among Black Men and Non-Hispanic White Men with Prostate Cancer in California.

BACKGROUND: Black men are more likely than Non-Hispanic White (NHW) men to be diagnosed with high-risk prostate cancer. We examined the extent to which social factors were associated with differences in prostate cancer risk profiles between Black men and NHW men [using a modification to the original D'Amico risk groups based on prostate specific antigen (PSA), Gleason score (GS), and TNM stage (stage)], based on individual and combined clinicopathologic characteristics. METHODS: We conducted a cross-sectional population-based study of 23,555 Black men and 146,889 NHW men diagnosed with prostate cancer in the California Cancer Registry from 2004 to 2017. We conducted multivariable logistic regression to examine the association of year of diagnosis, block group-level neighborhood socioeconomic status (nSES), marital status, and insurance type on differences in prostate cancer risk profiles between Black and NHW men. RESULTS: High PSA (>20 ng/mL), GS, stage, individually and combined prostate cancer risk profiles were more common among Black men versus NHW men. In fully adjusted models, relative to NHW men, we observed a persistent 67% increased odds of high PSA among Black men. nSES was the factor most strongly associated with racial disparity in high PSA, accounting for 25% of the difference. Marital status was the factor that was second most associated with a racial disparity. CONCLUSIONS: nSES was the factor most strongly associated with racial disparities in high PSA prostate cancer. IMPACT: The influence of nSES on racial disparities in PSA, GS, stage, and prostate cancer risk profiles warrants further consideration.

Synthetic Access to Benzimidacarbocyanine Dyes to Tailor Their Aggregation Properties.

Developing structure-aggregation relationships of cyanine dyes is crucial for controlling their optical properties for various uses. This study develops a synthetic route and the structure-dependent self-assembly of a family of benzimidacarbocyanine dyes for J- or H-aggregation properties. It was found that both the presence and placement of halogen atoms play a defining role in the resulting supramolecular interactions of these compounds.

Cause of death during prostate cancer survivorship: A contemporary, US population-based analysis.

BACKGROUND: More than 3.6 million men in the United States harbor a diagnosis of prostate cancer (PCa). The authors sought to provide in-depth analyses of the causes of death for contemporary survivors. METHODS: The authors performed a population-based cohort study in the United States (2000-2016) to assess causes of death for men diagnosed with PCa stratified by demographics and tumor stage. Using general population data, they calculated standardized mortality ratios (SMRs) as observed-to-expected death ratios. RESULTS: In total, 752,092 men with PCa, including 200,302 who died (27%), were assessed. A total of 29,048 men with local/regional disease (17%) died of PCa, whereas more than 4-fold men died of other causes (n = 143,719 [83%]). SMRs for death from noncancer causes (0.77; 95% confidence interval [CI], 0.77-0.78) suggested that these men were less likely than the general population to die of most other causes. The most common noncancer cause of death was cardiac-related (23%; SMR, 0.76; 95% CI, 0.75-0.77). Among men with distant PCa, 90% of deaths occurred within 5 years of diagnosis. Although deaths due to PCa composed the majority of deaths (74%), SMRs suggested that men with distant PCa were at heightened risk for death from most other noncancer causes (1.50; 95% CI, 1.46-1.54) and, in particular, for cardiac-related death (SMR, 1.48; 95% CI, 1.41-1.54) and suicide (SMR, 2.32; 95% CI, 1.78-2.96). Further analyses demonstrated that causes of death varied by patient demographics. CONCLUSIONS: Causes of death during PCa survivorship vary by patient and tumor characteristics. These data provide valuable information regarding health care prioritization during PCa survivorship. LAY SUMMARY: Men with early-stage prostate cancer are 4-fold more likely to die of other causes, whereas those with advanced prostate cancer are at increased risk for several causes not related to prostate cancer in comparison with the general population. These findings can help guide physicians taking care of men with a diagnosis of prostate cancer.

ChicagO Multiethnic Prevention and Surveillance Study (COMPASS): Increased Response Rates Among African American Residents in Low Socioeconomic Status Neighborhoods.

African American (AA) populations experience persistent health disparities in the USA. Low representation in bio-specimen research precludes stratified analyses and creates challenges in studying health outcomes among AA populations. Previous studies examining determinants of bio-specimen research participation among minority participants have focused on individual-level barriers and facilitators. Neighborhood-level contextual factors may also inform bio-specimen research participation, possibly through social norms and the influence of social views and behaviors on neighbor's perspectives. We conducted an epidemiological study of residents in 5108 Chicago addresses to examine determinants of bio-specimen research participation among predominantly AA participants solicited for participation in the first 6 years of ChicagO Multiethnic Prevention and Surveillance Study (COMPASS). We used a door-to-door recruitment strategy by interviewers of predominantly minority race and ethnicity. Participants were compensated with a $50 gift card. We achieved response rates of 30.4% for non-AA addresses and 58.0% for AA addresses, with as high as 80.3% response among AA addresses in low socioeconomic status (SES) neighborhoods. After multivariable adjustment, we found approximately 3 times the odds of study participation among predominantly AA addresses in low vs. average SES neighborhoods (odds ratio (OR) = 3.06; 95% confidence interval (CI) = 2.20-4.24). Conversely, for non-AA addresses, we observed no difference in the odds of study participation in low vs. average SES neighborhoods (OR = 0.89; 95% CI = 0.69-1.14) after multivariable adjustment. Our findings suggest that AA participants in low SES neighborhoods may be recruited for bio-specimen research through door-to-door approaches with compensation. Future studies may elucidate best practices to improve bio-specimen research participation among minority populations.

Tobacco and marijuana use and their association with serum prostate-specific antigen levels among African American men in Chicago.

African American (AA) men experience more than twice the prostate cancer mortality as White men yet are under-represented in academic research involving prostate-specific antigen (PSA), a biomarker of prostate cancer aggressiveness. We examined the impact of self-reported tobacco (cigarette pack-years and current tobacco use including e-cigarettes) and current regular marijuana use on serum PSA level based on clinical laboratory testing among 928 AA men interviewed 2013-2018 in Chicago. We defined outcome of elevated PSA ≥ 4.0 ng/mL for logistic regression models and continuous PSA increases for general linear models. All models were adjusted for age, sociodemographic characteristics, healthcare utilization, body mass index, and self-reported health. Among 431 AA men age ≥ 55 years, we observed ∼ 5 times the odds of elevated PSA among those with > 1 pack-years of cigarette smoking vs. never-smokers (odds ratio [OR] = 5.09; 95% confidence interval [CI] = 1.57-16.6) and a quarter the odds of elevated PSA among current marijuana users vs. non-users (OR = 0.27; 95% CI = 0.08-0.96). PSA increased on average 1.20 ng/mL among other current tobacco users vs. non-users. Among older AA men, cigarette smoking history and current tobacco use were positively associated with an increase in PSA levels and current marijuana use were inversely associated with PSA levels. Future work with studies of diverse patient populations with cancer outcomes are needed to assess whether these behavioral characteristics contribute to racial/ ethnic disparities in prostate cancer outcomes. Our study provides novel evidence regarding potential differences in PSA levels among older AA men according to behavioral characteristics.

Synthesis of Tetrathia-Oligothiophene Macrocycles.

The synthesis of six tetrathia-oligothiophene macrocycles is described with modest ring-closing yields between 21 and 55%. Single-crystal X-ray studies of four of the macrocycles indicated that encapsulated solvent or guest molecules were possible. A variety of guest molecules were explored for inclusion complexes via NMR, absorption, emission, and X-ray techniques. The solution-phase inclusion complexes were uninformative; yet the solid-state experiments revealed that solvent exchangeable channels exist through the macrocyclic pores.

Community clinical practice patterns and mortality in patients with intermediate oncotype DX recurrence scores: Who benefits from chemotherapy?

BACKGROUND: The Oncotype DX recurrence score (RS) is used as a tool for making decisions about chemotherapy for patients who have hormone receptor (estrogen receptor or progesterone receptor)-positive, HER2-negative breast cancer. There is no benefit from chemotherapy among patients aged ≥50 years who have lymph node-negative disease and an RS from 11 to 25, but the benefit of chemotherapy in the lymph node-positive group remains unknown. METHODS: On the basis of data from the National Cancer Data Base between 2010 and 2014, a nationwide, retrospective cohort study included 73,185 women who had stage I through IIIA breast cancer and an RS between 11 and 30. RESULTS: Receipt of chemotherapy was associated with a reduced risk of death among patients who had lymph node-positive breast cancer (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.45-0.74; P < .001) after adjusting for other prognostic factors in a multivariable Cox model. The 5-year survival gain ranged from 1.3% (RS 11-17 subgroup), to 3.3% (RS 18-25 subgroup), and to 6.7% (RS 26-30 subgroup). Among patients who had lymph node-negative disease, chemotherapy was associated with a reduced risk of death for those with an RS from 25 to 30 (HR, 0.68; 95% CI, 0.48-0.96; P = .03; 5-year survival gain, 1.8%), but there was no benefit from chemotherapy for patients who had an RS from 11 to 17 (HR, 0.97; 95% CI, 0.61-1.55; P = .90), and there was a marginally significant benefit for women who had an RS from 18 to 25 (HR, 0.79; 95% CI, 0.62-1.00; P = .05). Similar results were observed using propensity score-matching method. CONCLUSIONS: The benefit of chemotherapy for patients with breast cancer who have an intermediate RS is driven in a nonlinear fashion by RS: the higher the RS, the larger the absolute benefit. Findings from this study underscore the utility of real-world data to inform joint decision making in practice.

Acid-Catalyzed Electron Transfer Processes in Naphthalene peri-Dichalcogenides.

1,8-Naphthalene peri-dichalcogenides undergo protonation by Bronsted acids to produce electrophilic cations. Single electron transfer (SET) from the remaining unprotonated electron-rich peri-dichalcogenide to the cation then generates a radical cation and a radical. Thus, the formation of radical species results in severe peak broadening and coalescence of NMR signals when trifluoroacetic acid or other strong acids are added to the peri-dichalcogenide, and the process can be reversed by treatment with base. Further evidence for the formation of radicals stems from EPR, radical quencing with sodium dithionite, and computational experiments. The electron transfer is enhanced by the presence of 2,7-dialkoxy substituents that further increase the electron-donating ability of the dichalcogenides. This is an unusual example of a proton-coupled electron transfer process where an electron-rich molecule reacts with its own conjugate acid via a single electron transfer process.

Assessment of encapsulated dyes' distribution in silica nanoparticles and their ability to release useful singlet oxygen.

Working with silica nanoparticle encapsulated BODIPY and xanthene photosensitizers, we have determined that singlet oxygen spends up to 78% of its lifetime inside the nanocarriers. Our systematic investigation indicates that hydrophobicity rules the photosensitizer distribution in nanoparticles, which in turn dictates the ability of these structures to release singlet oxygen.

Racial disparities in omission of oncotype DX but no racial disparities in chemotherapy receipt following completed oncotype DX test results.

PURPOSE: To examine racial/ethnic disparities in Oncotype DX (ODX) testing among patients with node-negative, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers and possible racial/ethnic disparities in chemotherapy receipt following ODX testing within Recurrence Score (RS) category (Not Done, Low, Intermediate, High), as well as chemotherapy receipt time trends within RS categories. METHODS: A retrospective cohort list of 125,288 women who were potentially indicated for ODX testing from 2010 to 2014 was obtained using the National Cancer Database. We fit multivariate logistic regression predicting chemotherapy receipt, adjusting for clinical factors, patient demographic factors, and hospital-level factors, separately by RS category, and calculated odds ratios (OR) and 95% confidence intervals (CI), as well as time trends. RESULTS: Overall, ODX testing was completed for 46.1% of Non-Hispanic (NH) Whites, 43.9% of NH Blacks, and 41.7% of Hispanics. Among patients who did not receive ODX testing, NH Black and Hispanic women both experienced statistically significant increases in chemotherapy receipt relative to NH White women (NH Black OR 1.23; 95% CI 1.11-1.37; Hispanic OR 1.23; 95% CI 1.07-1.42). However, among patients with ODX results, no statistically significant racial/ethnic differences in chemotherapy receipt were observed within strata of RS category. Trend analyses demonstrated increasing adherence to national guidelines for ODX testing. CONCLUSIONS: We identified racial disparities in omission of ODX testing but no differences in chemotherapy receipt if ODX test results were obtained, suggesting increasing access to ODX testing may improve racial equality in efficacious use of adjuvant chemotherapy for ER-positive HER2-negative breast cancer.

De novo metastasis in breast cancer: occurrence and overall survival stratified by molecular subtype.

Breast cancer molecular subtypes, categorized jointly by hormone receptors (HR) and human epidermal growth factor-2 (HER2), are utilized to guide systemic therapy. We hypothesized distinct patterns of de novo metastasis and overall survival by molecular subtype using a retrospective cohort of 399,772 women in the National Cancer Database diagnosed with first primary invasive breast cancer between 2010 and 2014, of whom 13,924 were diagnosed with de novo metastasis from 2010 to 2013 and had follow up data. The relationship of molecular subtype with patient and tumor characteristics, including site of de novo metastasis, were examined using Chi-squared tests. Kaplan-Meier and Cox proportional hazards analyses were used to examine overall survival by molecular subtype. Bone was the most frequent de novo metastatic site for all molecular subtypes. Compared to HR+/HER2-, patients with HR-/HER2+ experienced 4.5, 3.0, and 6.0 times the de novo brain, lung, and liver metastasis respectively. In survival analyses of women diagnosed with de novo metastasis, the mortality risk relative to HR+/HER2- was twice as high for triple-negative (hazard ratio = 2.02, 95% CI 1.89-2.16) and modestly lower for HR+/HER2+ (hazard ratio = 0.83, 95% CI 0.78-0.88). The median survival difference between metastatic patients with and without chemotherapy was 28.6 months in HR+/HER2+ and 28.2 months in HR-/HER2+, but only 10.9 months in triple-negative and 5.2 months in HR+/HER2-. In conclusion, despite unfavorable patterns of de novo metastasis, HER2+ breast cancers had relatively better survival in recent years, probably due to treatment differences. Utilizing molecular subtype and site of de novo metastasis may predict prognosis and guide treatment.

Enhanced Glutathione Peroxidase Activity of Water-Soluble and Polyethylene Glycol-Supported Selenides, Related Spirodioxyselenuranes, and Pincer Selenuranes.

Diaryl selenides containing o-hydroxymethylene substituents function as peroxide-destroying mimetics of the antioxidant selenoenzyme glutathione peroxidase (GPx), via oxidation to the corresponding spirodioxyselenuranes with hydrogen peroxide and subsequent reduction back to the original selenides with glutathione. Parent selenides with 3-hydroxypropyl or 2,3-dihydroxypropyl groups produced the novel compounds 10 and 11, respectively, with greatly improved aqueous solubility and catalytic activity. The phenolic derivative 28 displayed similarly ameliorated properties and also modest radical-inhibiting antioxidant activity, as evidenced by an assay based on phenolic hydrogen atom transfer to the stable free radical DPPH. In contrast, several selenides that afford pincer selenuranes (e.g., 20 and 21) instead of spiroselenuranes upon oxidation showed inferior catalytic activity. Several selenide analogues were attached to polyethylene glycol (PEG) oligomers, as PEG substituents can improve water solubility and bioavailability, while retarding clearance. Again, the PEG derivatives afforded remarkable activity when oxidation generated spirodioxyselenuranes and diminished activity when pincer compounds were produced. Several such compounds proved to be ca. 10- to 100-fold catalytically superior to the diaryl selenides and their spirodioxyselenurane counterparts investigated previously. Finally, an NMR-based assay employing glutathione in D2O was designed to accommodate the faster reacting water-soluble mimetics and to more closely duplicate in vivo conditions.

Residential cancer cluster investigation nearby a Superfund Study Area with trichloroethylene contamination.

PURPOSE: Trichloroethylene (TCE) is an industrial solvent associated with liver cancer, kidney cancer, and non-Hodgkin's lymphoma (NHL). It is unclear whether an excess of TCE-associated cancers have occurred surrounding the Middlefield-Ellis-Whisman Superfund site in Mountain View, California. We conducted a population-based cancer cluster investigation comparing the incidence of NHL, liver, and kidney cancers in the neighborhood of interest to the incidence among residents in the surrounding four-county region. METHODS: Case counts and address information were obtained using routinely collected data from the Greater Bay Area Cancer Registry, part of the Surveillance, Epidemiology, and End Results program. Population denominators were obtained from the 1990, 2000, and 2010 US censuses. Standardized incidence ratios (SIRs) with two-sided 99 % confidence intervals (CIs) were calculated for time intervals surrounding the US Censuses. RESULTS: There were no statistically significant differences between the neighborhood of interest and the larger region for cancers of the liver or kidney. A statistically significant elevation was observed for NHL during one of the three time periods evaluated (1996-2005: SIR = 1.8, 99 % CI 1.1-2.8). No statistically significant NHL elevation existed in the earlier 1988-1995 (SIR = 1.3, 99 % CI 0.5-2.6) or later 2006-2011 (SIR = 1.3, 99 % CI 0.6-2.4) periods. CONCLUSION: There is no evidence of an increased incidence of liver or kidney cancer, and there is a lack of evidence of a consistent, sustained, or more recent elevation in NHL occurrence in this neighborhood. This evaluation included existing cancer registry data, which cannot speak to specific exposures incurred by past or current residents of this neighborhood.

Effects of methoxy substituents on the glutathione peroxidase-like activity of cyclic seleninate esters.

Cyclic seleninate esters function as mimetics of the antioxidant enzyme glutathione peroxidase and catalyze the reduction of hydrogen peroxide with a stoichiometric thiol. While a single electron-donating methoxy substituent para to the selenium atom enhances the catalytic activity, m-methoxy groups have little effect and o-methoxy substituents suppress activity. The effects of multiple methoxy groups are not cumulative. This behavior can be rationalized by opposing mesomeric and steric effects. Oxidation of the product disulfide via its thiolsulfinate was also observed.

Outcomes after diagnosis of mycosis fungoides and Sézary syndrome before 30 years of age: a population-based study.

IMPORTANCE: Mycosis fungoides and Sézary syndrome (MF/SS) are rare in children and young adults, and thus the incidence and outcomes in this patient population are not well studied. OBJECTIVE: To assess the incidence and outcomes of MF/SS in patients diagnosed before 30 years of age. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 2 population-based cancer registries-the California Cancer Registry (n = 204) and 9 US cancer registries of the Surveillance, Epidemiology, and End Results program (SEER 9; n = 195)-for patients diagnosed with MF/SS before 30 years of age. MAIN OUTCOMES AND MEASURES: Overall survival was calculated by the Kaplan-Meier method. The risk of a second cancer was assessed by calculating the standard incidence ratio (SIR) comparing observed cancer incidence in patients with MF/SS with the expected incidence in the age-, sex-, and race-standardized general population. RESULTS: The incidence of MF/SS is rare before 30 years of age, with an incidence rate of 0.05 per 100,000 persons per year before age 20 years and 0.12 per 100,000 persons per year between ages 20 and 29 years in the California Cancer Registry. At 10 years, patients with MF/SS had an overall survival of 94.3% (95% CI, 89.6%-97.2%) in the California Cancer Registry and 88.9% (95% CI, 82.4%-93.2%) in SEER 9. In SEER 9, there was a significant excess risk of all types of second cancers combined (SIR, 3.40; 95% CI, 1.55-6.45), particularly lymphoma (SIR, 12.86; 95% CI, 2.65-37.59) and melanoma (SIR, 9.31; 95% CI, 8.75-33.62). In the California Cancer Registry, the SIR for risk of all types of second cancers was similar to that in SEER 9 (SIR, 3.45; 95% CI, 0.94-8.83), although not statistically significant. CONCLUSIONS AND RELEVANCE: Young patients with MF/SS have a favorable outcome, despite a strong suggestion of an increased risk of second primary cancers. Prolonged follow-up is warranted to definitively assess their risk of developing second cancers in a lifetime.

Colorectal cancer incidence in Asian populations in California: effect of nativity and neighborhood-level factors.

OBJECTIVES: Heritable and environmental factors may contribute to differences in colorectal cancer (CRC) incidence across populations. We capitalized on the resources of the California Cancer Registry (CCR) and California's diverse Asian population to perform a cohort study exploring the relationships between CRC incidence, nativity, and neighborhood-level factors across Asian subgroups. METHODS: We identified CRC cases in the CCR from 1990 to 2004 and calculated age-adjusted CRC incidence rates for non-Hispanic Whites and US-born vs. foreign-born Asian ethnic subgroups, stratified by neighborhood socioeconomic status (SES) and "ethnic enclave." Trends were studied with joinpoint analysis. RESULTS: CRC incidence was lowest among foreign-born South Asians (22.0/100,000; 95% confidence interval (CI): 19.7-24.5/100,000) and highest among foreign-born Japanese (74.6/100,000; 95% CI: 70.1-79.2/100,000). Women in all Asian subgroups except Japanese, and men in all Asian subgroups except Japanese and US-born Chinese, had lower CRC incidence than non-Hispanic Whites. Among Chinese men and Filipino women and men, CRC incidence was lower among foreign-born than US-born persons; the opposite was observed for Japanese women and men. Among non-Hispanic Whites, but not most Asian subgroups, CRC incidence decreased over time. CRC incidence was inversely associated with neighborhood SES among non-Hispanic Whites, and level of ethnic enclave among Asians. CONCLUSIONS: CRC incidence rates differ substantially across Asian subgroups in California. The significant associations between CRC incidence and nativity and residence in an ethnic enclave suggest a substantial effect of acquired environmental factors. The absence of declines in CRC incidence rates among most Asians during our study period may point to disparities in screening compared with Whites.

Immigration factors and prostate cancer survival among Hispanic men in California: does neighborhood matter?

BACKGROUND: Hispanics are more likely than other racial/ethnic groups in the United States to be diagnosed with later stage of prostate cancer, yet they have lower prostate cancer mortality rates. The authors evaluated the impact of nativity and neighborhood-level Hispanic ethnic enclave on prostate cancer survival among Hispanics. METHODS: A total of 35,427 Hispanic men diagnosed with invasive prostate cancer from 1995 through 2008 in the California Cancer Registry were studied; vital status data were available through 2010. Block group-level neighborhood measures were developed from US Census data. Stage-stratified Cox proportional hazards models were used to assess the effect of nativity and ethnic enclave on prostate cancer survival. RESULTS: In models adjusted for neighborhood socioeconomic status and other individual factors, foreign-born Hispanics were found to have a significantly lower risk of prostate cancer survival (hazards ratio [HR], 0.81; 95% confidence interval [95% CI], 0.75-0.87). Living in an ethnic enclave appeared to modify this effect, with the survival advantage slightly more pronounced in the high ethnic enclave neighborhoods (HR, 0.78; 95% CI, 0.71-0.86) compared with low ethnic enclave neighborhoods (HR, 0.86; 95% CI, 0.76-0.98). CONCLUSIONS: Despite lower socioeconomic status, Hispanic immigrants have better survival after prostate cancer than US-born Hispanics and this pattern was more striking among those living in ethnic enclaves. Identifying the modifiable individual and neighborhood-level factors that facilitate this survival advantage in Hispanic immigrants may help to inform specific interventions to improve survival among all patients.