General descriptive studies (00350): Following decades of rising breast cancer incidence in the U.S. there were abrupt declines circa 2000 that stabilized during 2003-2004. The fall in breast cancer rates occurred mostly among older women with ER positive cancers, following the Womens Health Initiative announcement that reported statistically significant breast cancer risks among women using hormone replacement therapy. Much less attention was given to falling ER negative cancer rates, especially since hormonal exposures were not expected to affect ER negative tumors. Subsequent studies in the U.S., however, confirmed that ER negative breast cancers had declined while ER positive cancers were rising over the long-term;consistent with etiologic heterogeneity due to secular changes in different risk factor profiles for ER positive and ER negative cancers. The observation of similar trends in other countries with similar risk factor patterns would support the view that US trends reflect changes in the prevalence of exposures linked to different breast cancer subtypes. Denmark was an excellent test case. Subsequent results showed that trends in breast cancer incidence rates in Demark and U.S. were similar and consistent with dynamic changes in etiologically distinct breast cancer subtypes over time. ER positive cancers had increased among middle-aged and older Danish women in earlier birth-cohorts (or generations), implying a confluence of risk factor exposures during the peri-menopausal through the post-menopausal periods. On the other hand, ER negative cancers had decreased among younger women in more recent cohorts. The Danish and US experience may foreshadow a common pattern worldwide. Emerging data suggest that ovarian cancers differ by tumor grade. However, the reliability of microscopic grade from paraffin tissue in the general medical community and as reflected in population-based cancer registries is unknown. We examined grade agreement between two gynecologic pathologists and the NCIs Surveillance Epidemiology and End Results (SEER) Residual Tissue Repository (SEER). Grade agreement was fair at best between the study pathologists and SEER;and therefore, recorded grade in SEER should be used with caution and is probably not a reliable metric for ovarian cancer epidemiology in the general population. We investigated risk factors for inflammatory breast cancer in a nested case-control study in the Breast Cancer Surveillance Consortium database (1994-2009). Associations between high BMI and inflammatory breast cancer were particularly striking and suggest a different etiology for this clinically distinct breast cancer. After a report from the Womens Health Initiative (WHI) in 2002, a precipitous decline in menopausal hormonal therapy (MHT) use in the United States was linked to a decline in breast cancer incidence rates. Given that MHT use is also associated with increased ovarian cancer risk, we tested whether ovarian cancer incidence rates changed after 2002 using the North American Association of Central Cancer Registries (NAACCR) database. After a marked reduction in MHT use around 2002, ovarian cancer incidence rates demonstrated an accelerated decline, with the largest changes for endometrioid carcinomas. This strong temporal association, although not proving a causal role of hormones in ovarian carcinogenesis, suggests a role for hormonal exposures on the development and behavior of certain ovarian cancer subtypes. Although ovarian cancer incidence rates have declined in the United States, less is known of ovarian cancer trends among survivors of breast cancer. Therefore, we examined second primary ovarian cancers after first primary breast cancer in SEER. Persistently elevated SIRs along with decreasing absolute rates over the entire study period suggest that ovarian cancers in both the general population and survivors of breast cancer are declining in parallel, possibly because of common risk factor exposures. The SEER program incidence data were utilized in several additional projects. In a study of biliary tract cancers, a female excess of gallbladder cancer was apparent among all racial/ethnic groups, in contrast to a male excess for extrahepatic bile duct and ampulla of Vater cancers. The temporal trends differed by site, with rates for gallbladder cancer declining and those for extrahepatic bile duct rising in many of the gender/racial/ethnic groups. These findings indicate that these cancers likely are etiologically distinct. The incidence of potentially HPV-related preinvasive and invasive neoplasms in the US was investigated to document the patterns before widespread HPV vaccination. Incidence of preinvasive squamous tumors of the cervix, vagina, and penis rose rapidly over time and decreased for invasive neoplasms. The most rapid increases occurred for both preinvasive and invasive anal tumors. Patterns were generally similar among the various racial/ethnic groups, with the exception of invasive head and neck tumor rates which increased exclusively among white males. The rising rates support an urgent need for vaccination given the absence of effective screening modalities for tumors at these sites. The increases in thyroid cancer overall and in the predominant papillary type have been well-documented, but trends for follicular thyroid cancer, a less common but more aggressive variant, have not been as well characterized. Follicular thyroid cancer rates among both women and men rose more rapidly for regional than localized stage disease;rates increased for all tumor sizes among women but primarily for smaller size tumors among men. These results add to the evidence that rising thyroid cancer rates are not only due to improvements in detection and that the thyroid types should be evaluated separately in future studies. The thyroid cancer incidence rates in Sao Paulo, Brazil, known to be among the highest in the world, were compared with those in the U.S. SEER program. Overall incidence rates increased over time in both populations and were higher in Sao Paulo than in the US among both females and males, by 65% and 23%, respectively. The female/male incidence rate ratio was higher in Sao Paulo (4.17) than in SEER (3.10), and it did not change over time. Both diagnostic activity and iodine nutrition status may be contributing to these patterns. Both the SEER and NAACCR data were used to assess state-level uterine corpus cancer incidence rates by race/ethnicity corrected for hysterectomy prevalence and to identify potential correlation with state-level obesity prevalence. Corpus cancer rates rose 30%-100% with correction for hysterectomy, and a modest association with obesity became apparent. For most states, hysterectomy correction diminished or reversed the black/white deficit and accentuated the Hispanic/white deficit. Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of African descent were assessed using publicly available IARC data and collected data from the Men of African Descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium. Prostate cancer incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in sub-Saharan Africa. The proportion of prostate tumors that were stage T1 was higher in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. Although cancer of the prostate appears to be under diagnosed and/or under reported in sub-Saharan men, prostate cancer incidence and mortality represent a significant public health problem in men of African descent around the world.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010183-11
Application #
8763632
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2013
Total Cost
$167,685
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
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