Kaur, Judith S.

Validated measures of empowerment for cancer patients will be very useful for program interventions. In this editorial, the author reviews the 2 articles in this issue that used the Health Education Information Questionnaire and suggests other important populations to study.

Objectives. We examined geographic differences and trends in incidence and mortality of ovarian and uterine cancer in American Indian/Alaska Native (AI/AN) women. Methods. We linked mortality data (1990–2009) and incidence data (1999–2009) to Indian Health Service (IHS) records. Death (and incidence) rates for ovarian and uterine cancer were examined for AI/AN and White women; Hispanics were excluded. Analyses focused on Contract Health Service Delivery Area (CHSDA) counties. Results. AI/AN and White women had similar ovarian and uterine cancer death rates. Ovarian and uterine cancer incidence and death rates were higher for AI/ANs residing in CHSDA counties than for all US counties. We also observed geographic differences, regardless of CHSDA residence, in ovarian and uterine cancer incidence and death rates in AI/AN women by IHS region; Pacific Coast and Southern Plains women had higher ovarian cancer death rates and Northern Plains women had higher uterine cancer death rates. Conclusions. Regional differences in the incidence and mortality of ovarian and uterine cancers among AI/AN women in the United States were significant. More research among correctly classified AI/AN women is needed to understand these differences.

Objectives. We compared breast cancer death rates and mortality trends among American Indian/Alaska Native (AI/AN) and White women using data for which racial misclassification was minimized. Methods. We used breast cancer deaths and cases linked to Indian Health Service (IHS) data to calculate age-adjusted rates and 95% confidence intervals (CIs) by IHS-designated regions from 1990 to 2009 for AI/AN and White women; Hispanics were excluded. Mortality-to-incidence ratios (MIR) were calculated for 1999 to 2009 as a proxy for prognosis after diagnosis. Results. Overall, the breast cancer death rate was lower in AI/AN women (21.6 per 100 000) than in White women (26.5). However, rates in AI/ANs were higher than rates in Whites for ages 40 to 49 years in the Alaska region, and ages 65 years and older in the Southern Plains region. White death rates significantly decreased (annual percent change [APC] = −2.1; 95% CI = −2.3, −2.0), but regional and overall AI/AN rates were unchanged (APC = 0.9; 95% CI = 0.1, 1.7). AI/AN women had higher MIRs than White women. Conclusions. There has been no improvement in death rates among AI/AN women. Targeted screening and timely, high-quality treatment are needed to reduce mortality from breast cancer in AI/AN women.

Objectives. We used improved data on American Indian and Alaska Native (AI/AN) ancestry to provide an updated and comprehensive description of cancer mortality and incidence among AI/AN populations from 1990 to 2009. Methods. We linked the National Death Index and central cancer registry records independently to the Indian Health Service (IHS) patient registration database to improve identification of AI/AN persons in cancer mortality and incidence data, respectively. Analyses were restricted to non-Hispanic persons residing in Contract Health Service Delivery Area counties in 6 geographic regions of the United States. We compared age-adjusted mortality and incidence rates for AI/AN populations with White populations using rate ratios and mortality-to-incidence ratios. Trends were described using joinpoint analysis. Results. Cancer mortality and incidence rates for AI/AN persons compared with Whites varied by region and type of cancer. Trends in death rates showed that greater progress in cancer control was achieved for White populations compared with AI/AN populations over the last 2 decades. Conclusions. Spatial variations in mortality and incidence by type of cancer demonstrated both persistent and emerging challenges for cancer control in AI/AN populations.

Abstract Background: Breast cancer is not a homogeneous disease, but several different and unique subtypes defined by gene expression analysis. Incidence and mortality rates vary by almost 3-fold between Alaska (highest) and the Southwestern tribes (lowest). We hypothesized that these differences may be due to, in part, varying levels of biologic tumor aggressiveness. Methods: A biorepository of the North Central Cancer Treatment Group with 95 cases of American Indian and Alaska Native (AIAN) women with adenocarcinoma of the breast surgically treated from 1990 to 2000 was tested for several biomarkers. Comparison distributions of biomarker values across state of residence using t tests for continuous (p53, MIB-1, cyclin D) and ordinally scaled markers [EGF receptor (EGFR), BCL-2, Her2] and χ2 tests of significance for binary markers [estrogen receptor (ER), progesterone receptor (PR)] were done. Results: Significant regional differences in some biomarker expression levels were seen. No increase was observed in “triple-negative” breast cancer or Her2 overexpression in these cases. Conclusions: Despite a 3-fold difference in breast cancer mortality in Alaska Native versus Southwestern American Indians, standard biomarkers such as ER, PR, and Her2 neu expression did not explain the disparity. Impact: There is a need for research to understand the biologic basis of breast cancer disparities in AIAN women. Potential for a prospective trial will be explored with tribes. See all articles in this CEBP Focus section, “Community Network Program Centers.” Cancer Epidemiol Biomarkers Prev; 23(3); 409–15. ©2014 AACR.

Abstract Purpose: The study has two related purposes. To: 1. describe breast cancer risk factors and screening patterns in a sample of American Indian and Alaska Native (AI/AN) women from four tribes in the Northern Plains region; and 2. ascertain associations between women's risk factors and their adherence to mammographic screening guidelines with the intention of using the results to develop future interventions to increase screening, especially in higher risk non-adherent women. Background: The Indian Health Service (IHS) has noted that challenging economic factors make increases in AI/AN women's screening participation difficult. In this light, understanding the relationship between risk factors and screening adherence is an important first step in developing low-cost interventions to improve screening participation, especially for women at higher risk of breast cancer. Lending importance to the role of screening in reducing breast cancer deaths in Northern Plains AI/AN women are high rates of later stage (regional or distant disease) diagnoses that are equal to the Non-Hispanic White (NHW) population (95.8 and 95.4/100,000 respectively). Later stage at diagnosis is associated with worse survival profiles. We hypothesized that women at higher risk as compared to women at lower risk on the factors analyzed would be more likely to adhere to annual screening guidelines promoted by their clinics. Procedures/Methods: Criteria for inclusion in this study were: women with no history of breast cancer who were ≥ 40 years of age, and had at least one mammogram on file. We reviewed the charts of a representative sample of ∼20% of eligible women in four tribes (1250 records, 1088 of of which met inclusion criteria). The study collected Gail Model risk factor data and also assigned BIRADS scores to an early and late mammogram where they were available (888 pairs) for each woman. In addition, we collected age at menopause as an additional risk factor. For each Gail Model risk factor (age, age at menarche, age at first live birth, number of first degree relatives with a breast cancer history, breast biopsy—number of biopsies, history of atypical hyperplasia), women were assigned to higher or lower risk categories by comparison with calculated scores for women of the same age. Overall five-year and lifetime Gail Model risk scores, using standard criteria, also were calculated for each woman and compared with predicted risk for women of equivalent ages. For breast density, women were determined to be at lower risk if their BIRADS score was 1 or 2, and at higher risk if they were scored 3 or 4. To ascertain levels of screening adherence, we followed American Cancer Society (ACS) guidelines which recommend an annual mammogram beginning at age 40. We used this standard because it is the recommendation given to women in the clinics where the study was conducted. All women who received screening exams within 1.5 years (18 months) were considered adherent. Results are age-adjusted for each tribal site and across sites. Summary of Findings: Only P-values for older age at menopause (0.02), older chronological age (0.005), and 5-year Gail Model risk scores (0.02) were consistent with our hypotheses that women at higher risk would be more adherent with screening guidelines. There was no significant association between screening adherence and life-time risk (0.12), family history (0.28), age at menarche (0.99), age at first live birth (0.68), biopsy history (0.99), or BIRADS density scores (0.16). Conclusions: The minimal relationship between risk factors and adherence suggests that generally neither individual risk factors nor overall risk predict women's screening decisions. This suggests that personal and clinic-centered mediators should be identified to guide future interventions to increase the proportion of women who adhere to screening guidelines, especially women who are at greater risk. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B95.

Patients with cancer often have complex needs that must be met within a short intervention window. The authors highlight opportunities for improved multidisciplinary care for patients with advanced cancer and their families.

Abstract Purpose: The purpose of this study was to describe breast cancer risk factors and screening patterns in a sample of American Indian and Alaska Native (AI/AN) women from four tribes within the Bemidji Area of the Indian Health Service (Northern Plains region), and to ascertain the association between risk factors and adherence to mammographic screening guidelines. The IHS has noted that economic factors make increases in screening participation difficult. In this light, understanding the relationship between risk factors and screening adherence is an important first step in developing interventions to improve screening participation, especially for women at higher risk of breast cancer. Lending importance to the role of screening in reducing breast cancer deaths in Northern Plains AI/AN women are rates of later stage (regional or distant disease) diagnoses that are equal to the Non-Hispanic White (NHW) population (95.8 and 95.4/100,000 respectively). Later stage at diagnosis is associated with worse survival profiles. Procedures/Methods: Criteria for inclusion in this study were: ≥ 40 years of age, at least one mammogram on file, and no history of breast cancer. We reviewed the charts of 20% of eligible women in four tribes (1190 records). The study collected Gail Model risk factor data and also assigned BIRADS scores to at least one mammogram for each woman. For each Gail Model risk factor (age, age at menarche, age at first live birth, number of first degree relatives with a breast cancer history, breast biopsy, number of biopsies, history or atypical hyperplasia), women were assigned to higher or lower risk categories by comparison with calculated scores for women of the same age. Overall five-year and lifetime Gail Model risk scores also were calculated for each woman and compared with predicted risk for women of equivalent ages. For breast density, women were determined to be at lower risk if their BIRADS score was 1 or 2, and at higher risk if they were scored 3 or 4. To ascertain levels of screening adherence, we followed American Cancer Society (ACS) guidelines which recommend an annual mammogram beginning at age 40. We used this standard because it is the recommendation given to women in the clinics where the study was conducted. All women who received screening exams within 1.2 years (14.4 months) were considered adherent. Summary of Findings: There was no significant difference between overall Gail Model 5-year risk scores of Bemidji Area AI/AN women and the predicted scores. Bemidji Area women have a significantly lower lifetime risk than what is predicted. For individual risk factors, high screening adherence was significantly associated only with chronological age (p = 0.04) and history of biopsy (p =0.02). There was no significant association between screening adherence and BIRADS density scores. Conclusions: Absence of a relationship between risk and adherence, which is low generally, suggests that women are not using their individual risk factors or their overall risk to guide their screening decisions. This suggests that personal and clinic-centered mediators should be identified to guide future interventions to increase the proportion of women who adhere to screening guidelines, especially women who are at greater risk. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B106.

Abstract Introduction: Breast cancer is a major cause of cancer mortality in American Indian and Alaska Native (AIAN) women. However regional differences are striking with lowers rates in Arizona and highest in Alaska with almost a three-fold difference in incidence and mortality between the two states. These differences may be due in part to varying levels of biologic tumor aggressiveness. To evaluate this, we compared a panel of biomarkers on consecutively diagnosed AIAN breast cancer cases from AZ (N=53) and AK (N=42). Methods: Retrospective analysis of tissue blocks measured expression levels for the following panel of biomarkers: ER and PR (ordinally coded as positive vs. negative); her2, BCL-2, and EGFR (coded 0.1.2. and 3+) and P53, MIB-1 and cyclin D (continuous percent of cells stained). Distributions of biomarker values were compared across state of residence using t-tests for continuous and ordinally scaled markers and chi-square tests of significance for binary markers. Age adjusted analyses were also carried out using linear and logistic regression models as appropriate to account for possible differences in age at diagnosis across states. Chart reviews recorded demographics and treatment characteristics. Results: The following demographics were observed with 95 cases of AIAN women with breast cancer analyzed. Average age at diagnosis was similar in the two states (mean, 58.4 for AZ vs. 56.1 for AK, t-test p value=0.45). 74% presented with a palpable mass. 32% had lumpectomy and axillary node dissection. 28% were premenopausal. 8% had a first-degree relative with breast cancer. 46% received adjuvant chemotherapy. 54% received adjuvant hormonal therapy. Cases from AK had higher levels of p53 staining (40.3 vs. 18.5, p=0.004) and lower levels of both EGFR (mean ordinal scaling 0.15 vs. 0.53, p=0.02) and Her2 (mean ordinal scaling 0.81 vs. 1.32, p=0.02) tan those from AZ. No differences in distribution were observed for MIB-1, Cyclin D, BCL-2, ER or PR. When examined together, the triple negative combination of ER/PR/Her2 also did not differ across states (12% for AK vs.13%forAZ, p=0.85). Conclusions: Our findings indicate that regional differences in biomarker expression levels of P53, EGFR and Her2 may exist in AIAN women. Further research is needed to confirm our results and determine to what extent these differences may explain the observed differences in mortality. Genetic testing for BRCA1,2 or other genetic associations with breast cancer have not been done in these populations and may also be useful to examine the reasons for differences in incidence and mortality. In addition, AIAN women are more likely to present with palpable masses representing higher risk stages of breast cancer. Outreach activities in this population continue to be highly important to change mortality. Supported in part by NCI U01 114609 Spirit of Eagles Community Network Program Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A55.

Abstract Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (103–109 TCID50). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54–277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3–38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients. Cancer Res; 70(3); 875–82