Data Sources

Incident data of endometrial cancer for Puerto Rico were obtained from the incidence case file [8] from 1992-2003. The Puerto Rico Central Cancer Registry is the fourth oldest population-based cancer registry in the world [9] collecting information in Puerto Rico since 1951. Since 1997, the Puerto Rico Central Cancer Registry has been part of the CDC's National Program of Cancer Registry and uses the SEER and the North American Association of Central Cancer Registries (NAACCR) standards for coding data; thus, the registry is fully comparable with both SEER and NAACCR data. In the year 2003, a CDC audit concluded that 95.3% of all cancer cases diagnosed or treated in hospital facilities in Puerto Rico were appropriately reported to the Puerto Rico Central Cancer Registry; a result comparable to the United States median (95%) [10]. All cancer cases diagnosed since 2001 are reported using the third edition of the International Classification of Disease for Oncology (ICD-O-3) [11]. Cases from 1992 to 2000 which were originally reported using previous editions of ICD-O were converted to ICD-O-3 codes. Incident cases of endometrial cancer for NHW, NHB, and Hispanics in the United States for the period from 1992 to 2003 were obtained from the SEER 13 [SEER Stat 6.3.5 software] [12].The database SEER 13 represents 13.8% of the total US population; the Hispanic category represents 21.8% of the total US Hispanic population and includes persons from multiple Hispanic sub-groups (i.e. Mexicans, Puerto Ricans, Cubans, among others living in the US). Incidence data for Hispanics are based on the NAACCR Hispanic Identification Algorithm (NHIA) [13].

Endometrial cancer mortality information for Puerto Rico and the United States (NHW, NHB, Hispanics) from 1992-2003 was obtained, respectively, from the Puerto Rico Central Cancer Registry as reported by death certificates prepared by the Puerto Rico Department of Health [14] and from the SEER program as reported by the National Center for Health Statistics (NCHS) [15]. Causes of death were coded and classified according to the International Classification of Diseases (ICD-10) [16].

Women diagnosed with a primary cancer of the endometrium (ICD-O3 C54.1 with histological valid codes from 8000-8576 or by death certificate from cancer associated to the endometrium or corpus and uterus, not otherwise specified (NOS) (ICD-10 C54-C55; ICD-9 179, 182)), between 1992 and 2003 were eligible for our study. For incidence statistics, the analysis was limited to primary cases of malignant endometrial cancer confirmed microscopically, with a positive histology, positive exfoliative cytology with no positive histology, a positive laboratory test/marker study or direct visualization without microscopic confirmation, radiography without microscopic confirmation, clinical diagnosis only or those diagnosed solely by death certificates. Cases of carcinoma in situ and uterine sarcomas were excluded. For mortality statistics, cases with cause of death stated as corpus and uterus, NOS were eligible for analysis. Mortality from endometrial cancer was evaluated combining corpus and NOS categories as these categories are usually combined to reflect non-cervical carcinoma of the uterus and given that cases diagnosed through death certificates are more likely to have NOS classification. Data quality across all sub-groups was good, as the proportion of death certificate only cases was low across all racial/ethnic groups (<1%) (data not shown).

Statistical Analysis

Incidence and mortality rates

5-year survival

The observed 5-year survival from endometrial cancer was 78.4% (95% CI = 77.9%-78.9%) among NHW, 79.5% (95% CI = 77.9%-81.0%) among Hispanics, 63.1% (95% CI = 60.1%-65.9%) in Puerto Rico and 56.8 (95% CI = 54.7%-58.9%) for NHB (Figure 1). Significant differences in the survival curves were observed across racial/ethnic groups (Log-rank X² = 817.94, p <.0001), with the 20^th percentile of the survival function (based on the failure probability) being higher for Hispanics and NHW (58 and 53 months, respectively) than for NHB and Puerto Ricans (14 and 23 months, respectively) (data not shown). Thus, in NHB and Puerto Ricans there is more than a 20% probability of death by months 14 and 23 after endometrial cancer diagnosis, respectively. Meanwhile, for Hispanics and NHW there is more than a 20% probability of death by months 55 and 51, correspondingly. In addition, the age-adjusted Cox proportional hazards model showed that compared with women in Puerto Rico, Hispanic women in the United States had 37% lower mortality risk4(HR = 0.63, 95% CI = 0.56-0.71) and NHW had 53% lower mortality risk (HR = 0.47, 95% CI = 0.43-0.52) after 5 years of diagnosis. NHB women had 22% higher mortality risk than women in Puerto Rico (HR = 1.22, 95% CI = 1.09-1.36).

Incidence and mortality rates

Puerto Rican women showed a significant increase in the incidence of endometrial cancer during the study period; this rapid increase suggests changes in environmental exposures and lifestyle factors within this population. Obesity and diabetes, two of the major risk factors associated with endometrial cancer [2], have increased among Puerto Rican women in the last decade [23, 24]. Moreover, although the prevalence of obesity in Puerto Rican women (22.3%) is similar to that in the United States, the prevalence of diabetes in Puerto Rico (12.5%, 95% CI = 11.3%-13.7%) is the highest of all states and territories in the United States [23]. In addition, other factors related to Western lifestyle, such as sedentary behavior, low physical activity and changes in dietary factors (i.e. low fruit and vegetable consumption) may also contribute to the increased incidence [23, 24]. Similar increases have been observed in Puerto Rico on the incidence of breast [25] and colorectal [26] cancer and support the notion that as our population acquires Western lifestyles, cancer risk is likely to follow those of industrialized societies. The fastest increase in the incidence of endometrial cancer observed among women aged 20-34 years in Puerto Rico from 1992 to 2003 is of special interest as this is not a common event among younger women [27]. This increasing trend in incidence was also observed among NHW, NHB, and Hispanic women in the United States. Again, some of the strongest identified risk factors for endometrial cancer, obesity and diabetes [2] have increased among young Puerto Rican and United States cohorts (25-34 years), and may account for this increase among young women [23, 24]. Nonetheless, these results need to be interpreted with caution, as the number of cases for this age group was relatively small across all racial/ethnic groups.

Other potential explanations for the increase in endometrial cancer incidence rates are the changes in hormonal and reproductive factors, such as parity and age at menarche [2], over the last decades in Puerto Rico. Fertility rate among Puerto Rican women has decreased. The average number of children born to women 15 to 49 years of age in Puerto Rico decreased from 6.4 children in 1932 to 2.1 children in 1998 [28, 29]. In fact, Puerto Rico's current fertility rate (2.0 children per woman) is slightly lower than that of the United States (2.1 per woman) [30]. The fact that the median age of menarche has decreased in young Puerto Rican women (13.2 years: 1935-1939 to 12.7 years: 1965-1967) [28, 31] may in part also explain the observed increases in the incidence trends in this population, as these increase the lifetime exposure to exogenous and endogenous estrogens, respectively [32]. Nonetheless, although historical data is limited, studies suggest that age at natural menopause, another factor related to endometrial cancer risk [2], is currently similar between Puerto Rican women in Puerto Rico (51.3 years) [31] and women from the United States (51.4 years) [30]; suggesting that the time of exposure to endogenous estrogen is similar in these populations [33].

Regarding hormone therapy, after reports of increased risk of endometrial cancer with use of estrogen replacement therapy in the 1980's, declines in prescriptions for estrogen and subsequent declines in endometrial cancer incidence were observed in the United States [34]. Although recent evidence supports that hormone therapy for postmenopausal women without a hysterectomy should consist of both estrogen and progesterone, to reduce the risk of endometrial hyperplasia [35], accelerated decreases in the use of hormone therapy have again been observed in the United States after the 2002 Women's Health Initiative report of greater harm than benefit of combined conjugated equine estrogens plus progestin [36]. Nonetheless, to our knowledge, population-based data on the impact of these more recent decreases in hormone therapy use on endometrial cancer trends in the United States has not yet been published and in fact, these changes in hormone use would not impact the time period studied in this analysis (1992-2003). For Puerto Rico, the fact that no population-based data on historical use of hormone therapy has been published, limits our ability to hypothesize on the impact of hormone therapies on endometrial cancer incidence trends in this population. Given the increasing trends observed in the incidence of endometrial cancer in Puerto Rico, particularly among younger women, future analytical epidemiologic studies should assess the impact of changes in lifestyle factors in the occurrence of endometrial cancer in Puerto Rico. Also, multiethnic studies should access the reasons for the increases in endometrial cancer that were also observed among NHW, NHB and Hispanic young women in the United States.

Despite increasing incidence trends, mortality trends of endometrial cancer in Puerto Rico have remained relatively constant. These constant mortality trends were also seen among all age-groups of Hispanic and NHB women in the United States, and are consistent with SEER data from similar time periods [37]. Decreasing trends in mortality from endometrial cancer were only observed among NHW women aged 65 years and older. These results suggest that contrary to NHW, advances in treatment have not significantly benefited Puerto Ricans and other racial/ethnic minority populations in the United States. Disease stage at diagnosis, histologic type of the tumor, access to care, and differences in pharmacogenomics and response to treatment across these racial/ethnic groups should be evaluated in order to determine their impact on mortality trends.

Regarding the SRR's, consistent with studies performed in the 70's and 80's [4, 5], the incidence of endometrial cancer in Puerto Rico from 1999-2003 was significantly lower than that of NHW and NHB. Although we observed similar incidence rates between Puerto Rican and Hispanic women, recent studies suggest that Puerto Ricans are the Hispanic subgroup most affected by cancer in the United States [38], and that endometrial cancer in island Puerto Ricans is in fact lower than that of mainland Puerto Ricans [38, 39]; a pattern also consistent with historical data [5]. Thus, future analytic studies between mainland and island Puerto Ricans should help elucidate the risk factors and the potential gene-environment interactions that occur among Puerto Ricans once they migrate to the continental United States, and that result in increased incidence of the disease in this group. Our study also showed that women in Puerto Rico had higher age-adjusted mortality rate from endometrial cancer from 1999-2003 than Hispanic women living in the United States (although similar to NHW and lower than that of NHB). This result also warrants further attention and elucidation, particularly given the lack of data comparing endometrial cancer mortality statistics across these populations.

Survival

Puerto Rican and NHB women had a poorer 5-year survival from endometrial cancer compared to NHW and Hispanic women in the United States (1992 to 2002). These results are consistent with previous studies which have reported a survival disadvantage among NHB women compared to NHW women [40]. A potential explanation for this disparity is differences in medical access and treatment [40]. Nonetheless, disparities seem to remain independent of treatment, suggesting that other factors, including cancer biology, socioeconomic and cultural factors should be evaluated [41]. We also observed that although the SRR for mortality showed that Puerto Ricans and NHW had similar mortality rates from endometrial cancer, the hazard ratio from the age-adjusted Cox model showed that NHW had a clear advantage over Puerto Ricans regarding their five-year survival. The lower five-year survival from endometrial cancer among Puerto Ricans in our study (as compared to NHW), suggests a health disparity for this group in areas such as quality of care and/or differences in terms of stage at diagnosis and associated comorbidities. Given the limited availability of data, future studies should define what social and clinical indicators might be influencing the observed disparities in endometrial cancer survival in Puerto Rico. In addition, given that research suggests that women with private medical insurance coverage are diagnosed at an earlier stage, and their pattern of care differs from those of women with other types of health insurance [42], future studies should also address the impact of the introduction of the Health Care Reform legislation in Puerto Rico in 1993 on endometrial cancer survival. This model shifted medically indigent persons from direct care by public sector institutions to managed care arrangements through the private sector [43, 44]; even though this model (which covers approximately 40% of the population) made available health insurance for underserved populations, it restricts the referrals to specialists and limits the use of more expensive diagnostic and treatment options [44].

A limitation of this study is the lack of adjustment by hysterectomy rates which might have resulted in an underestimation in our estimates of disease occurrence [45]. The prevalence of hysterectomy in the United States (21%-24%) [46], and in Puerto Rico is high (13.1% for women 35 to 49 years and 32.5% for women ≥ 50 years; [unpublished data, Estudio Continuo de Salud, Ramos G. et al, 2002]. Also, although common, the practice of combining corpus and NOS categories, some of which are of cervical origin, could have overestimated our statistics of endometrial cancer mortality. Finally, even though Puerto Rico is a Hispanic population, Hispanics in the United States constitute an heterogeneous group of persons from a variety of Hispanic origins (i.e. Mexican, Cubans, Puerto Ricans), that in fact show substantial variability in cancer rates across subpopulations [38]. Also, Hispanics may differ by degree of acculturation or socioeconomic status and cancer occurrence and risk factors can vary among Hispanics because of regional, behavioral, or genetic differences [47]. Thus, we highlight that the Hispanic population residing in the United States described in this study is not directly comparable to the Puerto Rican population living in Puerto Rico; nonetheless, the comparison between these and other racial/ethnic groups helps to further understand health disparities among racial/ethnic minorities in the United States.