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Introduction: Reproductive history and breast cancer risk reportedly differ by the estrogen receptor (ER±) and by the joint expression of ER and the human epidermal growth factor-2 receptor (ER±/HER2±). However, large sample sizes are needed to identify risk factor associations for the relatively less common ER- subtypes. Material and Methods: We, therefore, linked two large-scale and population-based Danish registries to assess the associations for parity, number of live births, and age at first live birth (AFLB) with receptor-specific breast cancer risk. Relative risks (RRs) and 95% confidence intervals (CIs) for associations were estimated with Poisson regression models. Results: With nearly 31 million women-years of follow-up, there were 45786 Danish women between the ages 20-84 years who developed an invasive breast cancer during the study period 1992-2011. Parity significantly reduced risk for ER+ and ER+/HER2- subtypes (RR for ER+/HER2- = 0.92; 0.87, 0.98) and suggestively increased risk for ER- and ER-/HER2- subtypes (RR for ER-/HER2- = 1.16; 0.99, 1.36). RRs increased with advancing AFLB for ER+ cancers, especially among premenopausal women; and were elevated for ER- cancers among age groups 12-19 years and 30-34 years compared to the reference age group 20-24 years. Conclusion: Associations of breast cancer risk and reproductive history varied among Danish women by ER± and by ER±/HER2±, consistent with receptor-specific etiological heterogeneity. Risk estimates for ER+ and ER+/HER2- cancers were similar to the well-established associations for breast cancer overall, whereas relative risks for ER- and ER/HER2- cancers tended to be null or the inverse of ER+ associations. Citation Format: Anderson WF, Pfeiffer RM, Wohlfahrt J, Ejlertsen B, Jensen M-B, Kroman NT. Reproductive factors and subtype specific breast cancer risk. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-03.

Introduction: The clinical classification of breast cancer into at least four intrinsic subtypes has advanced targeted therapy and improved prognosis. However, for etiological classification, it has been proposed that breast cancer is comprised of just two main subtypes: basal-like and non-basal-like. Evidence for these two etiologic subtypes emerges strongly from bimodal age frequency distributions at diagnosis. In the absence of RNA-based intrinsic subtyping, estrogen receptor (ER) expression is a useful surrogate for these two distinct etiologic classes. Using data from the population-based Carolina Breast Cancer Study (CBCS), we examined evidence for a two-component (ER-positive vs. ER-negative) mixture model for breast cancer biologic/etiologic heterogeneity. Methods: Automated digital scoring of ER expression was performed on immunohistochemistry-stained tissue microarrays comprising 1,920 invasive breast cancer cases from CBCS. Clinical classification of ER status has changed over time as new data have emerged regarding optimal treatment-relevant thresholds, but optimal etiologic thresholds have not been established. Therefore, we considered ER status as a quantitative, categorical variable with cut points of Results: As expected for etiologically-distinct entities, ER-negative and highly ER-positive tumors showed predominantly unimodal early-onset and late-onset age distributions at diagnosis with peak frequencies near ages 50 and 70 years, respectively. However, tumors with low and intermediate positivity showed bimodal patterns, consistent with a mixture of two main subtypes. Consistent with these age distribution patterns, young age ( Conclusions: While etiologic differences between dichotomized ER-negative and ER-positive breast cancer categories have been well described in many epidemiologic studies, differences in breast cancer etiology across quantitative levels of ER expression have not been so well-characterized. In this study, we report that ER-positive tumors with low positivity share etiologic features of ER-negative tumors, including young age at diagnosis and aggressive tumor characteristics. These data provide additional support for a two-component breast cancer mixture model, with quantitative level of ER positivity reflecting the relative distributions of ER-positive and ER-negative tumor populations. Citation Format: Allott EH, Tse C-K, Carey L, Anderson WF, Olshan AF, Troester MA. Etiologic heterogeneity in breast cancer across quantitative levels of estrogen receptor expression. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-04.

Background: Serous tubal intraepithelial carcinoma (STIC) is hypothesized to give rise to many cancers that have been historically classified as ovarian primaries. Although STIC is gaining status as a diagnostic entity, similar appearing lesions would likely have been reported as fallopian tubal carcinoma in-situ (FT-CIS) in the past. Accordingly to characterize patterns of reporting and behavior for tubal cancers, we analyzed population-based data for incidence rate trends, co-occurrence with cancer at other sites and survival of FT-CIS and invasive fallopian tube carcinoma (FT-Inv). Methods: We analyzed data for FT-CIS and FT-Inv included within 33 registries using the Cancer Incidence in North America Deluxe Analytical Files provided by the North American Association of Central Cancer Registries (1995-2012). Primary site of invasive carcinomas were defined according to the International Classification of Diseases for Oncology (3rd edition) topography codes (ovarian (C56.9), fallopian tube (C57.0), and primary peritoneal cancers (C48.1-.2, 48.8)). We excluded cancers with non-epithelial histology. Total counts, incidence rates per 1 million adjusted to the 2000 standard US population and age-standardized stage-specific survival were computed. Temporal incidence rate patterns were analyzed by joinpoint regression with estimates of annual percentage change (APC). Results: Cases in which the first cancer diagnosis was FT-CIS, included 98 FT-CIS alone; 27 FT-CIS followed by another cancer diagnosis within 1 year and 172 cases in which FT-CIS was diagnosed concurrently with another cancer as compared with 5513 invasive tubal carcinomas over the same period. The incidence rate of FT-CIS was stable from 1995-2002, then significantly increased from 2002-2012 [APC (95% CI) = 16.2% (10.9-21.7)]. Rates of early stage high-grade serous FT-Inv increased significantly from 2002-2012 [10.4% (6.1-14.9)] and rates of late stage high-grade serous FT-Inv rose sharply from 2002-2012 [20.0% (17.5-22.6)]. Five-year age-standardized survival for women with FT-CIS only was 75.6% overall, reflecting 89.1% survival for women less than 50 years and 70.9% for women 50 years or older; survival for high-grade early stage serous FT-Inv was 77.8%. Conclusions: Diagnoses of FT-CIS and FT-Inv have increased dramatically, likely reflecting changes in diagnostic pathology practice. Developing standardized reporting for FT-CIS (and in the future, STIC) when present with concurrent invasive cancer are needed, given that this occurs often. Based on limited data, 5-year survival for FT-CIS and early stage FT-Inv are similar, but future studies to evaluate data for STIC will be required, which will likely be achievable only through national registries that are large enough to capture sufficient cases. Citation Format: Mark E. Sherman, Sally B. Coburn, Hannah Yang, William Anderson, Philip Rosenberg, Gretchen Gierach, Nicolas Wentzensen, Kathy Cronin, Britton Trabert. Incidence rates and outcomes of fallopian tube carcinomas: Data from the North American Association of Central Cancer Registries [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 260. doi:10.1158/1538-7445.AM2017-260

Background: Estrogen receptor (ER) status in breast cancer is strongly associated with etiologic factors, prognosis and treatment response. Data suggest that population-based incidence rates of ER-positive (ER+) tumors are increasing and ER-negative (ER-) cancers have fallen over time in the United States (US), Denmark and Scotland. Whether these trends are consistent in other populations with different etiologic exposures and across ER±/HER2± subtypes is unknown. We, therefore, analyzed breast cancer secular trends in Ireland by ER expression; and for the first time, by joint expression of ER±/HER2±, a well-established clinical marker of uncertain etiological significance. Methods: This study included invasive breast cancers (n=24,845; 2004-2013) among women aged 20-84 years within the population-based National Cancer Registry of Ireland (97% coverage). The general population at risk (n=10,401,986) was obtained from the Irish Central Statistics Office. Using a validated approach to account for missing ER/HER2-status, we assessed ER± and ER±/HER2± secular trends with age-standardized incidence rates (ASR) and estimated annual percentage change (EAPC) with 95% confidence intervals (95%CI). Results: Over the 10-year follow-up period, 19,264 ER+ and 4,161 ER- breast cancers were diagnosed (1,420 were ER-unknown). ASRs increased significantly for ER+ (EAPC: 2.20%/year (95%CI: 0.97, 3.45%/year)) and decreased significantly for ER- cancers (EAPC: -3.43%/year (95%CI: -5.05, -1.78%/year)). The ER-specific trends were qualitatively similar among three age groups ( Conclusion: Secular trends for ER± cancers in Ireland were similar to those previously observed in the US and Denmark. Further, trends for ER/HER2 followed those for ER, although rates were constant for ER+/HER+ tumors. The divergence of cancer incidence patterns by ER among independent populations over time could reflect comparable changes in risk factor exposures with dual or opposite effects for risk of ER+ and ER- cancers (e.g., obesity, age at first birth/parity). Additionally, although HER2 is a well-established clinical predictive and prognostic marker for breast cancer outcome, it did not appear to substantively impact breast cancer incidence trends. Citation Format: Maeve Mullooly, Jeanne Murphy, Gretchen L. Gierach, Brittny Davis, Paul Walsh, Sandra Deady, Thomas I. Barron, Mark E. Sherman, Philip S. Rosenberg, William F. Anderson. Estrogen receptor positive and negative breast cancer secular trends in Ireland (2004-2013) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 257. doi:10.1158/1538-7445.AM2017-257

Introduction: There are three distinct South-East Asian ethnic groups in Sarawak, Malaysia (Chinese, Malay, and natives) whose breast cancer incidence rates and the distribution of tumor subtypes were reported to be significantly different. It remains unclear whether survival varies among breast cancer cases in these ethnic groups. We aimed to evaluate the relationship between survival and ethnicity when taking into account tumor characteristics. Methods: We analyzed incident breast cancer cases who were enrolled and treated in Sarawak General Hospital, Malaysia, between 1992 and 2014. The association of ethnicity with survival (relapse-free survival and overall survival) was evaluated using multivariate Cox-proportional hazard model. Subgroup analysis was conducted for each tumor subtype defined by hormone receptor (HR+, ER+ or PR+; HR-, ER- and PR-) and HER2 status (HR+/HER2-, HR+/HER2+, HR-/HER2-, and HR-/HER2+). Results: Among 2,758 eligible cases (median follow-up years, 2.90 years), there were 636 deceased and 423 relapsed cases. While there was no significant difference in disease recurrence, overall survival varied significantly by ethnicity. Compared with Chinese women, Malay women had a higher proportion of mortality (HR = 1.50; 95% CI = 1.14-1.96; P = 0.0037). This disparity remained significant only among cases with HR+ tumors (HR = 1.91; 95% CI = 1.17-3.11; P = 0.0091 among HR+/HER2-; HR = 2.74; 95% CI = 1.30-5.77; P = 0.0079 among HR+/HER2+). There was no difference in survival between Chinese and native women overall or stratified by subtype. Conclusions: Our results showed that Malay women experienced worse survival compared to Chinese women particularly among cases with HR+ tumors. Future studies are needed to clarify the underlying factors for this association in order to develop intervention strategies to reduce disparity. Citation Format: Hyuna Sung, C.R. Beena Devi, Jennifer Guida, Tieng Swee Tang, William F. Anderson, Xiaohong R. Yang. Ethnic disparities in breast cancer survival in Sarawak, Malaysia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3414.

Background: Prostate-specific antigen testing (PSA) has dramatically changed the composition of prostate cancer, making it difficult to assess incidence trends. By defining fatal prostate cancer as the underlying cause of death from disease within 10 years of diagnosis, we have been able to conduct an in-depth analysis of “clinically relevant” prostate cancer incidence trends. Methods: We extracted incident prostate cancer cases, causes of death and survival among men aged 45-84 years using the US Surveillance, Epidemiology, and End Results (SEER) database (1975-2002). In addition to standard descriptive analyses, the ability to distinguish prostate cancer cases that were ultimately fatal enabled us to fit age-period-cohort models. Results: Among 51,682 fatal prostate cancer cases, incidence increased 1% per year prior to 1992, declined 15% per year from 1992-1995, and further declined by 5% per year through 2002. Age-specific incidence rates of fatal disease decreased over 2% per year among men aged 55 years and older, yet increased up to 1% per year among younger men. Fatal disease rates were more than 2-fold higher in black men compared with white men, a racial disparity that increased to 3-6 fold among younger men. Conclusion: In the United States, after widespread use of PSA screening and advances in prostate cancer treatment, fatal prostate cancer rates have substantially declined. Yet, rates of fatal prostate cancer among younger men have remained relatively stable, suggesting the need for additional attention to early-onset prostate cancer that has the potential to result in death. This study also highlights the persistent black-to-white racial disparity in fatal prostate cancer, underscoring the need for a greater understanding of the causes of this difference so that strategies may be implemented to reduce, and ultimately eliminate, racial disparities in prostate cancer. Citation Format: Scott P. Kelly, Philip S. Rosenberg, William F. Anderson, Sean D. Cleary, Naji Younes, Gabriella Andreotti, Michael B. Cook. Trends in fatal prostate cancer incidence by race among US men. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5208.

BACKGROUND: During the next several decades, 40 million American women born between 1946 through 1964 will face very high absolute risks of post-menopausal breast cancer, and 56 million women currently in their 20s and 30s will face substantial risks of pre-menopausal breast cancer. No study to date has predicted the future annual incidence rate and burden (number) of new cases in the United States (US) of both invasive and in-situ female breast cancers stratified by the estrogen receptor (ER) status of the tumor. However, such forecasts could help the oncology community develop a proactive roadmap to optimize prevention and treatment strategies. METHODS: We constructed forecasts for women ages 30 through 84 in 2011 through 2030 using cancer incidence data from the Surveillance Epidemiology and End Results Program, novel age-period-cohort (APC) forecasting models, and population projections from the US Census Bureau. We modelled 16 subsets of breast tumors defined by positive versus negative ER status (a correlate of tumor biology and standard clinical predictive marker), invasive versus in-situ behavior, and four age group (two pre-menopausal groups 30 - 39 and 40 - 49, and two post-menopausal groups 50 - 69 and 70 - 84). Screening mammography is recommended for women ages 50 - 74 by the US Preventive Services Task Force and starting at age 40 by the American Cancer Society; the age-group-specific models allowed the APC model parameters to implicitly reflect screening effects in the population. For each subset we applied a second-generation APC forecasting model incorporating JoinPoint regression of breast cancer birth cohort effects. RESULTS: The incidence of both invasive and in-situ ER+ tumors is expected to increase significantly during our forecast period. In contrast, the incidence of both invasive and in-situ ER- tumors is expected to decrease significantly. The total number of new tumors (invasive plus in-situ) is expected to rise more than 50% from 283,000 in 2011 to 441,000 in 2030 (plausible range from 353,000 to 466,700 cases). The proportion of new cases ages 70 - 84 is expected to increase from 24% to 35%, while the proportion ages 50 - 69 is expected to decrease from 55% to 44%. The proportion of ER+ invasive cancers is expected to remain the same near 63%, whereas the proportion of ER+ in-situ cancers is expected to increase from 19% to 29%. The proportion of ER- cancers (invasive and in-situ) is expected to decrease from 17% to 9%. CONCLUSIONS: Breast cancer will continue to rise in the US through 2030, especially for ER+ in-situ tumors among older women. In contrast, ER- invasive and in-situ tumors will continue to fall. These results highlight a need to optimize case management among older women, and to better understand etiological factors responsible for declining ER- incidence rates. Citation Format: Philip S. Rosenberg, Kimberly A. Barker, William F. Anderson. Estrogen receptor status and the future burden of invasive and in-situ breast cancers in the United States. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3699. doi:10.1158/1538-7445.AM2015-3699

Background: Breast cancer is a heterogeneous disease, divisible into a variable number of clinical subtypes depending upon the analytical approach. A fundamental question is how many etiological subtypes underlie the spectrum of clinical breast tumors? A clinical subtype represents a grouping according to prognosis (outcome) or prediction (expected treatment response), whereas an etiological subtype reflects a common set of causes. Methods: We initiated a systematic literature review to examine the historical, epidemiological, biostatistical, and molecular evidence for breast cancer etiology. Information sources included CANCERLIT, Index Medicus, and PubMed. Data resources included the Surveillance, Epidemiology, and End Results program. Results: A bimodal age distribution at diagnosis was a fundamental characteristic of breast cancer for important tumor characteristics, risk factor profiles, molecular markers, and prognosis; suggestive of a ‘mixture’ of two main etiological subtypes in varying proportions in different populations. The first breast cancer tended to arise early in life with modal age-at-diagnosis near 50 years and generally behaved aggressively. The second breast cancer occurred later in life with modal age near 70 years, and usually portended a more indolent clinical course. Conclusion: Epidemiological and molecular patterns suggest that breast cancer etiology reflects a bimodal breast cancer mixture model, possibly emerging from two stem cells of origin. Notwithstanding, the potential added value of more detailed categorizations and personalized approaches for the targeted treatment of breast cancer, we suggest that the development of criteria to better identify the two proposed main etiologic types would advance etiologic research and the prevention of breast cancer. Citation Format: William F. Anderson, Philip S. Rosenberg, Aleix Prat, Charles M. Perou, Mark E. Sherman. How many epidemiological types of breast cancer: Two, three, four, or more. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 266. doi:10.1158/1538-7445.AM2014-266

Introduction: Breast cancer incidence rates are much lower in Asian women than in Western women. However, the incidence rates in Asian countries are rapidly increasing in the recent decades and this dramatic rise has been largely attributed to a strong birth-cohort effect. For example, some of the well-established breast cancer risk factors may interact with age which may in turn lead to differential cohort effect among early- and late-onset breast cancers. Methods: We analyzed the incidence and population data (1988 through 2009) among Chinese women obtained from population-based cancer registries in different countries or geographical areas (urban China, rural China, Singapore, and the United States). The cohort relative risks adjusted for age and period effects were estimated separately for women younger than 50 years (30-49) and women age 50 or older (50-79) using the respective mid-year birth cohort as referent (1934 for older and 1960 for younger women, respectively). Results: Breast cancer incidence has increased in all Chinese populations examined, particularly in women aged 50-79 years with estimated annual percentage change (EAPC) ranging from 2.00%/year (95% CI, 0.95-3.07) for Chinese American to 6.24%/year (95% CI, 4.95-7.55) for rural China. In contrast, rates for younger women aged 30-49 were stable or increased at a slower rate with EAPC from -0.33%/year (95% CI, -1.39-1.08) for Chinese American to 4.72%/year (95% CI, 3.92-5.52) for rural China. The cohort relative risks of breast cancer in older women rose significantly in successive birth cohorts in all Chinese populations with the most dramatic 4.0-fold (95% CI, 3.07-5.24) increase seen in rural China and a more modest 1.7-fold (95% CI, 1.24-2.23) increase among Chinese American women born from 1934 to 1958. In contrast, the increases in cohort relative risk among younger women were markedly lower or non-significant in all Chinese populations except for rural Chinese women (2.1-fold; 95% CI, 1.36-3.17) born from 1960 to 1978. Consistently, the projection of future incidence also showed a greater increase in late-onset breast cancer than in early-onset breast cancer. Conclusions: Our findings suggest that cohort effect-driven risk of breast cancer attributed to rapid socioeconomic development and concurrent westernization in Asian countries has and will continue to result in an upsurge in breast cancer incidence, especially in older women. Our data further supports the previous hypothesis that early- and late-onset breast cancers might derive from distinct etiologic pathways. Citation Format: Hyuna Sung, Philip S. Rosenberg, Wan-Qing Chen, Mikael Hartman, Wei-yen Lim, Kee Seng Chia, Oscar Wai-kong Mang, Shelly Lap-ah Tse, William F. Anderson, Xiaohong R. Yang. Differential cohort effect on early- and late-onset breast cancer incidence among Chinese women in different populations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-288. doi:10.1158/1538-7445.AM2014-LB-288

Background: Long-term breast cancer trends in incidence in the United States (US) show rising ER positive rates and falling ER negative rates. We hypothesized that these divergent trends reflect etiologic heterogeneity and that comparable trends should be observed in other countries with similar risk factor profiles. Methods: We analyzed invasive female breast cancers in Denmark from 1993-2010. We summarized the overall trend in age-standardized rates with the estimated annual percentage change (EAPC) statistic, and used age-period-cohort models to estimate age-specific EAPCs, cohort rate ratios (CRRs), and projections for future time periods (2011-2018). Results: In Denmark, the overall rate of ER positive cancers rose between 1993 and 2010 by 3·0%/year (95% CI: 2·8 to 3·3%/yr) while the overall rate of ER negative cancers fell by 2·1%/year (95% CI: -2·5 to -1·6%/yr). The ER positive rate increased fastest among postmenopausal women and the ER negative rate decreased fastest among premenopausal women, reflecting that cohorts born after 1944 were at relatively higher risk of ER positive tumors and lower risk of ER negative tumors. If current trends continue, ER positive cancers will increase at least 13% and ER negative cancers will fall as much as 15% by 2018. Conclusion: Divergent ER-specific trends are consistent with distinct etiologic pathways. If trends in known risk factors are responsible, the Danish and US experience may foreshadow a common pattern worldwide. Citation Format: William F. Anderson, Philip Rosenberg, Lucia Petito, Hormuzd A. Katki, Bent Ejlertsen, Marianne Ewertz, Birgitte B. Rasmussen, Maj-Britt Jensen, Niels Kroman. Divergent estrogen receptor positive and negative breast cancer trends and etiologic heterogeneity in Denmark . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 132. doi:10.1158/1538-7445.AM2013-132

Breast cancer incidence in the United States rose until 1999 then fell. This decline was most apparent among older women with easier-to-treat estrogen receptor (ER) positive tumors; reported incidence of more aggressive ER negative cancers was stable. However, these analyses did not account for missing ER data, which can reduce statistical power and more importantly bias the observed trends. We, therefore, developed an imputation method to correct for missing ER using a national sample of 379,323 breast cancers diagnosed from 1992 through 2007. After correction, current incidence of ER positive tumors was surprisingly similar to pre-1999 incidence, whereas ER negative cancers fell steadily by 1.8% per year. We show for the first time that the recent national decline in breast cancer overall reflects an unexpected drop in ER negative rates more than any changes in ER positive rates. These refined results challenge past interpretations and have the potential to better gauge breast cancer trends. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-445. doi:10.1158/1538-7445.AM2011-LB-445

Background and aims: Age-specific analyses for noncardia gastric cancer reveal divergent trends among United States (U.S.) whites: rates are declining in older adults (over age 40) but rising in younger persons. To further investigate this heterogeneity, we evaluated incidence trends by anatomic subsite, age, and race/ethnicity. Methods: Gastric cancer incidence data for 1976-2007 were obtained from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Incidence rates and estimated annual percentage change (EAPC) were obtained by gastric subsite, age group (25-39, 40-59, and 60-84 years), and race/ethnicity. Results: Based on data from the nine oldest SEER registries (covering about 10% of the U.S. population), long term age-specific incidence rates for corpus cancer increased between 1976 and 2007 with EAPCs of 1.0%/yr (95% CI, 0.1-1.9) for whites and 3.5%/yr (95% CI, 1.8-5.2) for blacks. All other subsite-specific rates decreased in whites and blacks, whereas all noncardia subsites including corpus cancer declined among other races. In the shorter term, age-specific analyses using combined data from NPCR and SEER registries (covering 89.4% of the U.S. population), corpus cancer significantly increased among younger and middle-aged whites from 1999 to 2007; in ethnic-specific analyses, the increase was significant among non-Hispanic whites aged 40-59 years. Age-specific rates for all subsites declined or were stable in this period among blacks and other races. Conclusions: Long- and short-term incidence trends for noncardia gastric cancers indicate a shifting distribution by anatomic subsite, age and race/ethnicity, consistent with changing risk factor exposures and warranting further investigation. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention and the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1916. doi:10.1158/1538-7445.AM2011-1916

Cutaneous malignant melanoma incidence rates have been increasing among young women in the United States. Given that tan-seeking behaviors have increased ultraviolet radiation exposures in anatomic sites usually covered by clothing, i.e., trunk among women, we further assessed melanoma incidence trends by gender and anatomic site. Case and population data among Whites were obtained from the Surveillance, Epidemiology, and End Results Tumor Registries (SEER 9, 1975-2006). Age-period-cohort models were used to assess age, calendar-period, and birth-cohort effects. Net drift, the sum of linear trends in the period and cohort effects, was used to show differential secular trends due to period and/or cohort effects such as screening, case ascertainment, sun exposure, etc. Longitudinal age trend (LAT), the sum of the linear trends in the age and period effects, was used to show differential age-related biological effects. There were 105,829 melanomas diagnosed from 1975 through 2006 in the SEER 9 Registries. The overall age-adjusted incidence rate (IR) was 17.70 per 100,000, with a male to female incidence rate ratio (IRR) of 1.40 (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 866.

INTRODUCTION: Previous research has noted that cancer mortality rates are higher for males than females, but no extensive analysis of this has been conducted. We wanted to study the extent of sex disparities in cancer mortality and if these disparities persist after adjustment for characteristics of the person and cancer. METHODS: We extracted U.S. vital statistics mortality data and cancer incidence and survival data from the SEER*Stat system for 36 cancers and undertook age-adjusted mortality rates and survival analyses. For the age-adjusted mortality rate analyses we extracted mortality count, person-years, and mortality rate per 100,000 for each cancer, stratified by sex and age for the period 1977-2006. Male-to-female mortality rate ratios (MRRs) were calculated. For each cancer, we plotted sex-specific mortality rates and male-to-female MRRs. For the survival analyses, we extracted patient id, age and date of diagnosis, sex, primary site, stage, grade, survival time, vital status and cause of death. Relative hazards for the 5-year period following diagnosis were estimated from Cox proportional hazard models adjusted for age, stage, grade, and year of diagnosis. RESULTS: For the vast majority of cancers, age-adjusted mortality rates were higher among males than females; the 5 cancers with the highest male-to-female MRR were lip (5.51, 95% confidence interval (CI):5.05-6.03), larynx (5.37, 95%CI:5.29-5.45), hypopharynx (4.47, 95%CI:4.30-4.65), esophagus (4.08, 95%CI:4.05-4.11) and urinary bladder (3.36, 95%CI:3.34-3.39). Only 3 cancers had a higher mortality rate among females than males: peritoneum, omentum and mesentery (MRR=0.39, 95%CI:0.38-0.41); gallbladder (0.56, 95%CI:0.55-0.57); and anus, anal canal and anorectum (0.78, 95%CI:0.75-0.81). The survival analyses indicated that males had a significantly increased risk of death, relative to females, for the cancers: anus, anal canal and anorectum (hazard ratio: 1.21, 95%CI:1.03-1.44); colon and rectum (1.08, 95%CI:1.07-1.09); floor of mouth (1.29, 95%CI:1.04-1.59); larynx (1.09, 95%CI:1.01-1.18); liver and intrahepatic bile duct (1.20, 95%CI:1.14-1.26); lung and bronchus (1.19, 95%CI:1.17-1.20); pancreas (1.06, 95%CI:1.03-1.08); small intestine (1.16, 95%CI:1.04-1.29); and soft tissue including heart (1.12, 95%CI:1.03-1.21). Females had higher mortality risks for the cancers tongue (0.87, 95%CI:0.81-0.94) and urinary bladder (0.83, 95%CI:0.81-0.86). DISCUSSION: Male cancer mortality rates were higher than equivalent female rates for the majority of cancers studied. Moreover, males also had higher risk of cancer mortality following diagnosis, relative to females, for many cancers even after adjustment for age of diagnosis, stage, grade and year of diagnosis. These observations indicate that there are sex differences in exposure and/or endogenous metabolic processes which modify risk of both cancer incidence and cancer mortality following diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1834.

Purpose: Because of its rarity, male breast cancer is often compared to female breast cancer.Materials and Methods: To compare and contrast male and female breast cancers, we obtained case and population data from the NCI's Surveillance, Epidemiology, and End Results program for breast cancers diagnosed from 1973 through 2005. Standard descriptive epidemiology was supplemented with age-period-cohort models and breast cancer survival analyses.Results: Men with breast cancer comprised less than 1% of all breast cancers. Male compared to female breast cancers occurred later in life with higher stage, lower grade, and more estrogen receptor positive tumors. Recent breast cancer incidence and mortality rates declined over time for men and women, both overall and within each age group, but these trends were greater for women than men. Comparing cases diagnosed in 1996 through 2005 versus 1976 through 1985, and adjusting for age, stage, and grade, cause-specific hazard rates for breast cancer death declined by 28% among men (p = 0.03) and by 42% among women (p ∼ 0).Conclusion: There were three intriguing results. Age-specific incidence patterns showed that the biology of male breast cancer resembled the late-onset and hormone sensitive type of female breast cancer. Similar breast cancer incidence trends among men and women suggested that there are common breast cancer risk factors that affect both sexes, especially hormone positive breast cancer. Finally, breast cancer mortality and survival rates have improved significantly over time for male breast cancer, but progress has lagged behind for men compared to women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2075.

Abstract #2086 Background: Although breast cancer incidence rates are higher among Blacks than Whites prior to age 40 years, the reverse is true after age 40 years. This so-called Black to White ethnic crossover has been described but never systematically studied. Materials and Methods: To further assess the Black to White incidence rate crossover, we obtained data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Invasive female breast cancers were stratified by Black and White race and estrogen receptor (ER) expression. Standard descriptive epidemiology was supplemented with “comparative” age-period-cohort (APC) models. Results:]We observed “qualitative” (reversing or crossing) age-interactions by race, stratified by birth-cohort and adjusted for calendar-period. For example, APC fitted age-at-onset curves were higher among Blacks than Whites prior to age 40 years, and then rates crossed, after which age-specific rates were higher for Whites (p ∼ 0 for difference). In contrast to age-related differences, secular trends were similar for Blacks and Whites (net drifts, p = 0.85 for difference). For all time periods and age groups, ER negative incidence rates were higher among Blacks, whereas ER positive rates were higher among Whites. Conclusion: When viewed as a qualitative (crossing) age-interaction, the Black to White ethnic crossover reflects the reversal of incidence rate ratios for early-onset/poor prognosis and late-onset/good prognosis breast cancer types. Blacks have more early-onset and ER-negative tumors, even after adjustment for calendar-period (screening) and birth-cohort (exposure) effects. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2086.