Publications by authors named "Dee W West"

91 Publications

Race/Ethnicity and Accuracy of Self-Reported Female First-Degree Family History of Breast and Other Cancers in the Northern California Breast Cancer Family Registry.

Cancer Epidemiol Biomarkers Prev 2019 11 5;28(11):1792-1801. Epub 2019 Sep 5.

Cancer Prevention Institute of California, Fremont, California.

Background: Few studies have evaluated accuracy of self-reported family history of breast and other cancers in racial/ethnic minorities.

Methods: We assessed the accuracy of cancer family history reports by women with breast cancer (probands) from the Northern California Breast Cancer Family Registry compared with 2 reference standards: personal cancer history reports by female first-degree relatives and California Cancer Registry records.

Results: Probands reported breast cancer in first-degree relatives with high accuracy, but accuracy was lower for other cancers. Sensitivity (percentage correctly identifying relatives with cancer) was 93% [95% confidence interval (CI), 89.5-95.4] when compared with the relatives' self-report of breast cancer as the reference standard and varied little by proband race/ethnicity and other demographic factors, except for marginally lower sensitivity for Hispanic white probands (87.3%; 95% CI, 78.0-93.1; = 0.07) than non-Hispanic white probands (95.1%; 95% CI, 88.9-98.0). Accuracy was also high when compared with cancer registry records as the reference standard, with a sensitivity of 95.5% (95% CI, 93.4-96.9) for breast cancer, but lower sensitivity for Hispanic white probands (91.2%; 95% CI, 84.4-95.2; = 0.05) and probands with low English language proficiency (80%; 95% CI, 52.8-93.5; < 0.01).

Conclusions: Non-Hispanic white, African American, and Asian American probands reported first-degree breast cancer family history with high accuracy, although sensitivity was lower for Hispanic white probands and those with low English language proficiency.

Impact: Self-reported family history of breast cancer in first-degree relatives is highly accurate and can be used as a reliable standard when other validation methods are not available.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825587PMC
November 2019

Enrollment and biospecimen collection in a multiethnic family cohort: the Northern California site of the Breast Cancer Family Registry.

Cancer Causes Control 2019 Apr 5;30(4):395-408. Epub 2019 Mar 5.

Cancer Prevention Institute of California, Fremont, CA, 94358, USA.

Purpose: Racial/ethnic minorities are often assumed to be less willing to participate in and provide biospecimens for biomedical research. We examined racial/ethnic differences in enrollment of women with breast cancer (probands) and their first-degree relatives in the Northern California site of the Breast Cancer Family Registry from 1996 to 2011.

Methods: We evaluated participation in several study components, including biospecimen collection, for probands and relatives by race/ethnicity, cancer history, and other factors.

Results: Of 4,780 eligible probands, 76% enrolled in the family registry by completing the family history and risk factor questionnaires and 68% also provided a blood or mouthwash sample. Enrollment was highest (81%) for non-Hispanic whites (NHWs) and intermediate (73-76%) for Hispanics, African Americans, and all Asian American subgroups, except Filipina women (66%). Of 4,279 eligible relatives, 77% enrolled in the family registry, and 65% also provided a biospecimen sample. Enrollment was highest for NHWs (87%) and lowest for Chinese (68%) and Filipinas (67%). Among those enrolled, biospecimen collection rates were similar for NHW, Hispanic, and African American women, both for probands (92-95%) and relatives (82-87%), but lower for some Asian-American subgroups (probands: 72-88%; relatives: 71-88%), foreign-born Asian Americans, and probands those who were more recent immigrants or had low English language proficiency.

Conclusions: These results show that racial/ethnic minority populations are willing to provide biospecimen samples for research, although some Asian American subgroups in particular may need more directed recruitment methods. To address long-standing and well-documented cancer health disparities, minority populations need equal opportunities to contribute to biomedical research.
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http://dx.doi.org/10.1007/s10552-019-01154-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548459PMC
April 2019

Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.

Int J Cancer 2017 06 28;140(12):2728-2733. Epub 2017 Mar 28.

Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.

Genome-wide association studies (GWAS) in ethnic/racial minority populations can help to fine-map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.3, associated with colon cancer risk (odds ratio 0.61 for the risk allele G, p = 2.4 × 10 ). The frequency of the G allele was 0.06 in African Americans, compared to <0.01 in Europeans, Asians and Amerindians in the 1000 Genomes project. In addition, a variant previously identified through fine-mapping in this GWAS in the region 19q13.1, rs7252505, was confirmed to be more strongly associated with CRC in the African American replication set than the variant originally reported in Europeans (rs10411210). The association between rs7252505 and CRC was of borderline significance (p = 0.05) in a Hispanic population GWAS with 1,611 CRC cases and 4,330 controls. With the three datasets combined, the odds ratio was 0.84 for the risk allele A (95% confidence interval 0.79-0.89, p = 3.7 × 10 ). This study further highlights the importance of conducting GWAS studies in diverse ancestry populations.
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http://dx.doi.org/10.1002/ijc.30687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505639PMC
June 2017

Population-Based Testing and Treatment Characteristics for Chronic Myelogenous Leukemia.

J Registry Manag 2016 ;41(3):134-142

Introduction: National and international hematology/oncology practice guidelines recommend testing for the BCR-ABL mutation for definitive diagnosis of chronic myeloid leukemia (CML) to allow for appropriate treatment with a tyrosine kinase inhibitor (TKI). The purpose of our study was to describe population-based testing and treatment practice characteristics for patients diagnosed with CML.

Methods: We analyzed cases of CML using 2011 data from 10 state registries that are part of the Centers for Disease Control and Prevention (CDC)'s National Program of Cancer Registries. We describe completeness of testing for the BCR-ABL gene and availability of outpatient treatment with TKIs and associated characteristics.

Results: A total of 685 cases of CML were identified; 55 percent (374) had a documented BCR-ABL gene test with 96 percent (360) of these being positive for the BCR-ABL gene and the remaining 4 percent (14) either testing negative or having a missing result. Registries were able to identify the use of TKIs in 54 percent (369) of patients, though only 43 percent (296) had a corresponding BCR-ABL gene test documented. One state registry reported a significantly lower percentage of patients being tested for the BCR-ABL gene (25 percent) and receiving TKI treatment (21 percent). Limiting analysis to CML case reports from the remaining 9 comparative effectiveness research registries, 78 percent (305) patients had a documented BCR-ABL gene test and 79 percent (308) had documented treatment with a TKI. Receipt of testing or treatment for these 9 states did not vary by sex, race, ethnicity, census tract poverty level, census tract urbanization, or insurance status; BCR-ABL testing varied by state of residence, and BCR-ABL testing and TKI therapy occurred less often with increasing age (BCR-ABL testing: odds ratio [OR], 0.97; 95 percent CI, 0.95-0.99; and TKI therapy: OR, 0.97; 95 percent CI, 0.96-0.99).

Conclusions: Collection of detailed CML data vary significantly by states. A majority of the case patients had appropriate testing for the BCR-ABL gene and treatment with tyrosine kinase inhibitors. However, BCR-ABL testing and TKI treatment decreased with increasing age. Further research is needed to understand CML coding, testing, and treatment disparities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291176PMC
September 2018

Association of Breast Cancer Knowledge With Receipt of Guideline-Recommended Breast Cancer Treatment.

J Oncol Pract 2016 06 10;12(6):e613-25. Epub 2016 May 10.

Dana-Farber Cancer Institute; Harvard Medical School; and Brigham and Women's Hospital, Boston, MA; and Public Health Institute, Sacramento, CA.

Purpose: Knowledge about one's breast cancer characteristics is poor, but whether this knowledge affects treatment is uncertain. Among women with breast cancer, we examined whether tumor knowledge was associated with adjuvant treatment receipt.

Methods: We surveyed a population-based sample of women in Northern California with stage 0 to III breast cancer diagnosed during 2010 to 2011 (participation rate, 68.5%). Interviews were conducted between 4 months and 3 years after diagnosis. Among 414 respondents with stage I to III disease, we examined receipt of guideline-recommended chemotherapy, radiation, and hormonal therapy by reporting correct information about one's tumor, including stage, estrogen receptor, human epidermal growth factor receptor 2 (HER2), and grade (using registry data for confirmation). We performed multivariate logistic regression to assess the probability of receiving each treatment in relevant patient groups, adjusting for patient and tumor characteristics, and examined the impact of reporting correct tumor information on treatment receipt.

Results: Among relevant treatment-eligible groups, 81% received chemotherapy, 91% received radiation, and 83% received hormonal therapy. In adjusted analyses, having correct (v incorrect) information for stage and HER2 were associated with chemotherapy receipt (odds ratio [OR], 4.45; 95% CI, 1.50 to 12.50 for stage; OR, 2.70; 95% CI, 1.02 to 7.18 for HER2). Correctly reporting estrogen receptor status was associated with hormonal therapy receipt (OR, 3.91; 95% CI, 1.73 to 8.86), and correctly reporting stage was associated with radiation receipt (OR, 2.76; 95% CI, 1.03 to 7.40).

Conclusion: Knowledge about one's tumor characteristics was strongly associated with receipt of recommended therapies. Interventions to improve patients' knowledge and understanding of their cancers should be tested as a strategy for improving receipt of care.
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http://dx.doi.org/10.1200/JOP.2015.008508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957257PMC
June 2016

Survival among Never-Smokers with Lung Cancer in the Cancer Care Outcomes Research and Surveillance Study.

Ann Am Thorac Soc 2016 Jan;13(1):58-66

8 Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.

Rationale: Differences in patient characteristics and outcomes have been observed among current, former, and never-smokers with lung cancer, but most prior studies included few never-smokers and were not prospective.

Objectives: We used data from a large, prospective study of lung cancer care and outcomes in the United States to compare characteristics of never-smokers and smokers with lung cancer and to examine survival among the never-smokers.

Methods: Smoking status at diagnosis was determined by self-report and survival was determined from medical records and cancer registries, with follow-up through June 2010 or later. Cox regression was used to examine the association between smoking and survival, and to identify predictors of survival among never-smokers.

Measurements And Main Results: Among 3,410 patients with lung cancer diagnosed between September 1, 2003 and October 14, 2005 who completed a baseline patient survey, there were 274 never-smokers (8%), 1,612 former smokers (47%), 1,496 current smokers or smokers who quit recently (44%), and 28 with missing information about smoking status (<1%). Never-smokers appeared more likely than former and current/recent smokers to be female and of Asian or Hispanic race/ethnicity, and to have adenocarcinoma histology, fewer comorbidities, private insurance, and higher income and education. Compared with never-smokers, the adjusted hazard of death from any cause was 29% higher among former smokers (hazard ratio, 1.29; 95% confidence interval, 1.08-1.55), and 39% higher among current/recent smokers (hazard ratio, 1.39; 95% confidence interval, 1.16-1.67). Factors predicting worse overall survival among never-smokers included Hispanic ethnicity, severe comorbidity, undifferentiated histology, and regional or distant stage. Never-smoking Hispanics appeared more likely to have regional or advanced disease at diagnosis and less likely to undergo surgical resection, although these differences were not statistically significant.

Conclusions: Never-smokers with lung cancer are more likely than ever-smokers to be female, Asian or Hispanic, and more advantaged socioeconomically, suggesting possible etiologic differences in lung cancer by smoking status. Among never-smokers, Hispanics with lung cancer had worse survival than non-Hispanic whites.
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http://dx.doi.org/10.1513/AnnalsATS.201504-241OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461981PMC
January 2016

testing and first-line treatment among patients diagnosed with metastatic colorectal cancer using population data from ten National Program of Cancer Registries in the United States.

J Cancer Res Ther (Manch) 2016 30;5(2):7-13. Epub 2017 Jan 30.

Louisiana Tumor Registry and Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States.

Background: In 2011, the National Comprehensive Cancer Network (NCCN) recommended testing for metastatic colorectal cancer (mCRC) patients. Our study assessed testing prevalence and its association with socio-demographic and clinical factors and examined first-line treatment.

Methods: Ten state population-based registries supported by Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) collected detailed cancer information on mCRC cases diagnosed in 2011, including biomarker testing and first-line treatment from ten central cancer registries. Data were analyzed with Chi-square tests and multivariate logistic regression.

Results: Of the 3,608 mCRC cases, 27% (n = 992) had a documented test. Increased age at diagnosis (p < 0.0001), racial/ethnic minorities (p = 0.0155), public insurance (p = 0.0018), and lower census tract education (p = 0.0023) were associated with less testing. Significant geographic variation in testing (p < 0.0001) ranged from 46% in New Hampshire to 18% in California. After adjusting for all covariates, age and residence at diagnosis (both p < 0.0001) remained predictors of testing. Non-Hispanic Blacks had less testing than non-Hispanic Whites (OR = 0.77, 95% CI = 0.61-0.97). Among those tested and found to have normal (wild-type) , 7% received anti-EGFR treatment; none received such treatment among those with mutated gene.

Conclusions: Despite NCCN guideline recommendations, 73% of mCRC cases diagnosed in 2011 had no documented test. Disparities in testing existed based on age, race, and residence at diagnosis.

Impact: These findings show the capacity of monitoring testing in the US using cancer registry data and suggest the need to understand the low uptake of testing, and associated treatment choices during the first year since diagnosis.
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http://dx.doi.org/10.14312/2052-4994.2017-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472357PMC
January 2017

Higher Stage of Disease Is Associated With Bilateral Mastectomy Among Patients With Breast Cancer: A Population-Based Survey.

Clin Breast Cancer 2016 Apr 28;16(2):105-12. Epub 2015 Aug 28.

Harvard Medical School, Department of Health Care Policy, Boston, MA; Division of General Internal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.

Background: The reasons for increasing rates of bilateral mastectomy for unilateral breast cancer are incompletely understood, and associations of disease stage with bilateral surgery have been inconsistent. We examined associations of clinical and sociodemographic factors, including stage, with surgery type and reconstruction receipt among women with breast cancer.

Patients And Methods: We surveyed a diverse population-based sample of women from Northern California cancer registries with stage 0 to III breast cancer diagnosed during 2010-2011 (participation rate, 68.5%). Using multinomial logistic regression, we examined factors associated with bilateral and unilateral mastectomy (vs. breast-conserving surgery), adjusting for tumor and sociodemographic characteristics. In a second model, we examined factors associated with reconstruction for mastectomy-treated patients.

Results: Among 487 participants, 58% had breast-conserving surgery, 32% had unilateral mastectomy, and 10% underwent bilateral mastectomy. In adjusted analyses, women with stage III (vs. stage 0) cancers had higher odds of bilateral mastectomy (odds ratio [OR], 8.28; 95% confidence interval, 2.32-29.50); women with stage II and III (vs. stage 0) disease had higher odds of unilateral mastectomy. Higher (vs. lower) income was also associated with bilateral mastectomy, while age ≥ 60 years (vs. < 50 years) was associated with lower odds of bilateral surgery. Among mastectomy-treated patients (n = 206), bilateral mastectomy, unmarried status, and higher education and income were all associated with reconstruction (P < .05).

Conclusion: In this population-based cohort, women with the greatest risk of distant recurrence were most likely to undergo bilateral mastectomy despite a lack of clear medical benefit, raising concern for overtreatment. Our findings highlight the need for interventions to assure women are making informed surgical decisions.
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http://dx.doi.org/10.1016/j.clbc.2015.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538374PMC
April 2016

Racial/Ethnic Differences in Patients' Selection of Surgeons and Hospitals for Breast Cancer Surgery.

JAMA Oncol 2015 May;1(2):222-30

Harvard Medical School, Department of Health Care Policy, Boston, Massachusetts4Division of General Internal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Importance: Racial differences in breast cancer treatment may result in part from differences in the surgeons and hospitals from whom patients receive their care. However, little is known about differences in patients' selection of surgeons and hospitals.

Objective: To examine racial/ethnic differences in how women selected their surgeons and hospitals for breast cancer surgery.

Design, Setting, And Participants: We surveyed 500 women (222 non-Hispanic white, 142 non-Hispanic black, 89 English-speaking Hispanic, and 47 Spanish-speaking Hispanic) from northern California cancer registries with stage 0 to III breast cancer diagnosed during 2010 through 2011. We used multivariable logistic regression to assess the reasons for surgeon and hospital selection by race/ethnicity, adjusting for other patient characteristics. We also assessed the association between reasons for physician selection and patients' ratings of their surgeon and hospital.

Main Outcomes And Measures: Reasons for surgeon and hospital selection and ratings of surgeon and hospital.

Results: The 500 participants represented a response rate of 47.8% and a participation rate of 69%. The most frequently reported reason for surgeon selection was referral by another physician (78%); the most frequently reported reason for hospital selection was because it was a part of a patient's health plan (58%). After adjustment, 79% to 87% of black and Spanish-speaking Hispanic women reported selecting their surgeon based on a physician's referral vs 76% of white women (P = .007). Black and Hispanic patients were less likely than white patients to report selecting their surgeon based on reputation (adjusted rates, 18% and 22% of black and Hispanic women, respectively, vs 32% of white women; P = .02). Black and Hispanic women were also less likely than white women to select their hospital based on reputation (adjusted rates, 7% and 15% vs 23%, respectively; P = .003). Women who selected their surgeon based on reputation more often rated the care from their surgeon as excellent (adjusted odds ratio, 2.21; 95% CI, 1.24-3.93); those reporting their surgeon was one of the only surgeons available through the health plan less often reported excellent quality of surgical care (adjusted odds ratio, 0.56; 95% CI, 0.34-0.91).

Conclusions And Relevance: Compared with white patients with breast cancer, minority patients were less actively involved in physician and hospital selection, relying more on physician referral and health plans rather than on reputation. Interventions to promote involvement in surgeon and hospital selection may have potential for addressing disparities related to lower-quality care from surgeons and hospitals.
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http://dx.doi.org/10.1001/jamaoncol.2015.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944092PMC
May 2015

Genome-wide association study of colorectal cancer identifies six new susceptibility loci.

Nat Commun 2015 Jul 7;6:7138. Epub 2015 Jul 7.

Harvard Medical School, Boston, Massachusetts 02114, USA.

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.
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http://dx.doi.org/10.1038/ncomms8138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967357PMC
July 2015

Racial/ethnic disparities in knowledge about one's breast cancer characteristics.

Cancer 2015 Mar 26;121(5):724-32. Epub 2015 Jan 26.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Understanding tumor characteristics is likely important, but little is known about breast cancer patients' knowledge of their own disease. The authors assessed women's knowledge about their tumor characteristics, whether racial/ethnic disparities in knowledge exist, and whether education and health literacy influence associations.

Methods: A population-based cohort of women in Northern California with stage 0 through III breast cancers diagnosed from 2010 to 2011 (participation rate 68.5%) was surveyed. Among 500 respondents (222 non-Hispanic white women, 142 non-Hispanic black women, and 136 Hispanic women), racial/ethnic differences in knowledge about tumor characteristics (estrogen receptor [ER] status, human epidermal growth factor receptor 2 [HER2] status, stage, grade) and correctness of tumor information (with California Cancer Registry data for confirmation) were examined. Multivariate logistic regression was used to assess the probability of: 1) knowing tumor stage, receptor status, and grade; and 2) correctly answering questions about tumor information by race/ethnicity. The impact of education and health literacy on findings was examined in sequential models.

Results: Overall, 32% to 82% of women reported knowing each of the 4 tumor characteristics of interest, and 20% to 58% correctly reported these characteristics. After adjustment, black and Hispanic women were less likely than white women to know and have correct responses for stage, ER status, and HER2 status (all P<.05). Education and health literacy were significantly associated with knowing and having correct information about some characteristics, but these variables did not eliminate most of the racial/ethnic differences observed.

Conclusions: Patient's knowledge about their own breast cancer was generally poor, particularly for minority women. Further study of how this knowledge may impact receipt of care and outcomes is warranted.
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http://dx.doi.org/10.1002/cncr.28977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946569PMC
March 2015

Enhancing cancer registry data for comparative effectiveness research (CER) project: overview and methodology.

J Registry Manag 2014 ;41(3):103-12

Following the Institute of Medicine's 2009 report on the national priorities for comparative effectiveness research (CER), funding for support of CER became available in 2009 through the American Recovery and Re-investment Act. The Centers for Disease Control and Prevention (CDC) received funding to enhance the infrastructure of population-based cancer registries and to expand registry data collection to support CER. The CDC established 10 specialized registries within the National Program of Cancer Registries (NPCR) to enhance data collection for all cancers and to address targeted CER questions, including the clinical use and prognostic value of specific biomarkers. The project also included a special focus on detailed first course of treatment for cancers of the breast, colon, and rectum, as well as chronic myeloid leukemia (CML) diagnosed in 2011. This paper describes the methodology and the work conducted by the CDC and the NPCR specialized registries in collecting data for the 4 special focused cancers, including the selection of additional data variables, development of data collection tools and software modifications, institutional review board approvals, training, collection of detailed first course of treatment, and quality assurance. It also presents the characteristics of the study population and discusses the strengths and limitations of using population-based cancer registries to support CER as well as the potential future role of population-based cancer registries in assessing the quality of patient care and cancer control.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524450PMC
June 2015

Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.

Nat Commun 2014 Aug 8;5:4613. Epub 2014 Aug 8.

Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.

The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10(-8)) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10(-9)), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.
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http://dx.doi.org/10.1038/ncomms5613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180879PMC
August 2014

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.

Breast Cancer Res 2014 Dec 23;16(6):3419. Epub 2014 Dec 23.

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.

Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.

Results: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).

Conclusions: These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.
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http://dx.doi.org/10.1186/s13058-014-0474-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352262PMC
December 2014

Treatment and Mortality in Men with Localized Prostate Cancer: A Population-Based Study in California.

Open Prost Cancer J 2013 ;6:1-9

Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA.

Purpose: To provide patients and physicians with population-based estimates of mortality from prostate cancer or other causes depending upon the primary treatment modality, stratified by patient age, tumor stage and grade.

Methods: We conducted a 10-year competing-risk analysis of 45,440 men diagnosed with clinically localized (T1 or T2) prostate cancer in California during 1995-1998. Information on patient characteristics, primary treatment and cause of death was obtained from the California Cancer Registry.

Results: In this population-based cohort, the most common primary treatment was surgery (40.4%), followed by radiotherapy (29.1%), conservative management (20.8%), and androgen deprivation therapy (ADT) monotherapy (9.8%). Prostate cancer mortality differed significantly (p < 0.0001) across treatment groups among patients <80 years at diagnosis with moderately or poorly differentiated disease; the 10-year disease-specific mortality rates were generally highest for men treated with ADT monotherapy [range: 3.3% (95% CI=0.8-12.5%) to 53.8% (95% CI=34.4-72.2%)], intermediate for men treated with conservative management [range: 1.7% (95% CI=0.7-4.6%) to 30.0% (95% CI=16.2-48.8%] or radiotherapy [range: 3.2% (95% CI=1.8-5.5%) to 18.3% (95% CI=15.1-22.0%)], and lowest for men treated with surgery [range: 1.2% (95% CI=0.8-1.7%) to 11.0% (95% CI=8.4-14.2%)].

Conclusion: The cause-specific mortality estimates provided by this observational study can help patients and physicians better understand the expected long-term outcomes of localized prostate cancer given the initial treatment choice and practice patterns in the general population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758138PMC
January 2013

Validity of Race, Ethnicity, and National Origin in Population-based Cancer Registries and Rapid Case Ascertainment Enhanced With a Spanish Surname List.

Med Care 2016 Jan;54(1):e1-8

*Epidemiology Program, County of Marin, San Rafael, CA†School of Community Health Sciences, University of Nevada, Reno, Reno, NV‡Department of Health Research and Policy, Stanford School of Medicine, Stanford, CA§Brigham and Women's Hospital∥Department of Health Policy, Harvard Medical School, Boston, MA¶Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands#Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive, Cancer Center, University of Southern California, Los Angeles**Cancer Prevention Institute of California, Fremont††The RAND Corporation, Santa Monica‡‡UCLA School of Medicine, Los Angeles, CA.

Background: Accurate information regarding race, ethnicity, and national origins is critical for identifying disparities in the cancer burden.

Objectives: To examine the use of a Spanish surname list to improve the quality of race-related information obtained from rapid case ascertainment (RCA) and to estimate the accuracy of race-related information obtained from cancer registry records collected by routine reporting.

Subjects: Self-reported survey responses of 3954 participants from California enrolled in the Cancer Care Outcomes Research and Surveillance Consortium.

Measures: Sensitivity, specificity, positive predictive value, and percent agreement. We used logistic regression to identify predictors of underreporting and overreporting of a race/ethnicity.

Results: Use of the Spanish surname list increased the sensitivity of RCA for Latino ethnicity from 37% to 83%. Sensitivity for cancer registry records collected by routine reporting was ≥95% for whites, blacks, and Asians, and specificity was high for all groups (86%-100%). However, patterns of misclassification by race/ethnicity were found that could lead to biased cancer statistics for specific race/ethnicities. Discordance between self-reported and registry-reported race/ethnicity was more likely for women, Latinos, and Asians.

Conclusions: Methods to improve race and ethnicity data, such as using Spanish surnames in RCA and instituting data collection guidelines for hospitals, are needed to ensure minorities are accurately represented in clinical and epidemiological research.
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http://dx.doi.org/10.1097/MLR.0b013e3182a30350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449309PMC
January 2016

Cancer incidence among specific Asian and Pacific Islander populations in the Unites States.

J Natl Cancer Inst 2013 Aug 22;105(15):1073-5. Epub 2013 Jul 22.

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http://dx.doi.org/10.1093/jnci/djt196DOI Listing
August 2013

Diagnostic chest X-rays and breast cancer risk before age 50 years for BRCA1 and BRCA2 mutation carriers.

Cancer Epidemiol Biomarkers Prev 2013 Sep 12;22(9):1547-56. Epub 2013 Jul 12.

Cancer Prevention Institute of California, 2201 Walnut Avenue, Suite 300, Fremont, CA 94538-2334, USA.

Background: The effects of low-dose medical radiation on breast cancer risk are uncertain, and few studies have included genetically susceptible women, such as those who carry germline BRCA1 and BRCA2 mutations.

Methods: We studied 454 BRCA1 and 273 BRCA2 mutation carriers ages younger than 50 years from three breast cancer family registries in the United States, Canada, and Australia/New Zealand. We estimated breast cancer risk associated with diagnostic chest X-rays by comparing mutation carriers with breast cancer (cases) with those without breast cancer (controls). Exposure to chest X-rays was self-reported. Mammograms were not considered in the analysis.

Results: After adjusting for known risk factors for breast cancer, the ORs for a history of diagnostic chest X-rays, excluding those for tuberculosis or pneumonia, were 1.16 [95% confidence interval (CI), 0.64-2.11] for BRCA1 mutations carriers and 1.22 (95% CI, 0.62-2.42) for BRCA2 mutations carriers. The OR was statistically elevated for BRCA2 mutation carriers with three to five diagnostic chest X-rays (P = 0.01) but not for those with six or more chest X-rays. Few women reported chest fluoroscopy for tuberculosis or chest X-rays for pneumonia; the OR estimates were elevated, but not statistically significant, for BRCA1 mutation carriers.

Conclusions: Our findings do not support a positive association between diagnostic chest X-rays and breast cancer risk before the ages of 50 years for BRCA1 or BRCA2 mutation carriers.

Impact: Given the increasing use of diagnostic imaging involving higher ionizing radiation doses, further studies of genetically predisposed women are warranted.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-0189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015518PMC
September 2013

Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans.

Hum Mol Genet 2013 Dec 12;22(24):5048-55. Epub 2013 Jul 12.

Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.

Genome-wide association studies of colorectal cancer (CRC) in Europeans and Asians have identified 21 risk susceptibility regions [29 index single-nucleotide polymorphisms (SNPs)]. Characterizing these risk regions in diverse racial groups with different linkage disequilibrium (LD) structure can help localize causal variants. We examined associations between CRC and all 29 index SNPs in 6597 African Americans (1894 cases and 4703 controls). Nine SNPs in eight regions (5q31.1, 6q26-q27, 8q23.3, 8q24.21, 11q13.4, 15q13.3, 18q21.1 and 20p12.3) formally replicated in our data with one-sided P-values <0.05 and the same risk directions as reported previously. We performed fine-mapping of the 21 risk regions (including 250 kb on both sides of the index SNPs) using genotyped and imputed markers at the density of the 1000 Genomes Project to search for additional or more predictive risk markers. Among the SNPs correlated with the index variants, two markers, rs12759486 (or rs7547751, a putative functional variant in perfect LD with it) in 1q41 and rs7252505 in 19q13.1, were more strongly and statistically significantly associated with CRC (P < 0.0006). The average per allele risk was improved using the replicated index variants and the two new markers (odds ratio = 1.14, P = 6.5 × 10(-16)) in African Americans, compared with using all index SNPs (odds ratio = 1.07, P = 3.4 × 10(-10)). The contribution of the two new risk SNPs to CRC heritability was estimated to be 1.5% in African Americans. This study highlights the importance of fine-mapping in diverse populations.
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http://dx.doi.org/10.1093/hmg/ddt337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836473PMC
December 2013

Enrollment of patients with lung and colorectal cancers onto clinical trials.

J Oncol Pract 2013 Mar;9(2):e40-7

Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USA.

Purpose: Only 2% to 5% of adult patients with cancer enroll onto clinical trials. We assessed simultaneously characteristics of patients and their physicians that may be independently associated with participation.

Methods: CanCORS, a National Cancer Institute (NCI) -funded population-based observational cohort study of newly diagnosed patients with lung and colorectal cancers, sampled patients across five geographic areas, five health care delivery systems, and 15 Veterans Administration hospitals. We linked patient survey and medical record data with physician survey data to examine correlates of trial enrollment.

Results: Among 9,901 patients, 5.3% enrolled onto trials. Of the 9,901 patients, we linked 6,506 patients to one medical oncologist, surgeon, or radiation oncologist (physicians, N = 1,325) who responded to the physician survey and was considered their primary cancer clinician decision maker. Patient age, race, disease stage, geographic region, and health insurance were independently associated with trial enrollment. Physician factors independently associated with patient trial enrollment were being a medical oncologist, practicing at an NCI-designated cancer center, taking the lead in discussing trials with patients, and receiving increased income from trial enrollment. After simultaneously adjusting for patient and physician characteristics, only being a physician practicing at an NCI-designated cancer center (odds ratio [OR], 1.65; 95% CI, 1.19 to 2.27) and patient female sex (OR, 1.36; 95% CI, 1.10 to 1.68), age > 70 versus < 50 years (OR, 0.28; 95% CI, 0.16 to 0.48), and advanced disease (OR, 1.85; 95% CI, 1.45 to 2.37) remained independently associated with trial enrollment.

Conclusion: Both practice environment and patient clinical and demographic characteristics are associated with cancer clinical trial enrollment; simultaneous intervention may be required when trying to increase enrollment rates.
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http://dx.doi.org/10.1200/JOP.2012.000598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595449PMC
March 2013

Changes in health status among aging survivors of pediatric upper and lower extremity sarcoma: a report from the childhood cancer survivor study.

Arch Phys Med Rehabil 2013 Jun 1;94(6):1062-73. Epub 2013 Feb 1.

Department of Pediatrics, Stanford University & Lucile Packard Children's Hospital, Palo Alto, CA, USA.

Objective: To evaluate health status and participation restrictions in survivors of childhood extremity sarcomas.

Design: Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003, or 2007 were included.

Setting: Cohort study of survivors of extremity sarcomas.

Participants: Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5% white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986.

Interventions: Not applicable.

Main Outcome Measures: Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age.

Results: In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation.

Conclusions: Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age.
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http://dx.doi.org/10.1016/j.apmr.2013.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913046PMC
June 2013

Chemotherapy use and patient treatment preferences in advanced colorectal cancer: a prospective cohort study.

Cancer 2013 Feb 12;119(4):854-62. Epub 2012 Sep 12.

Duke Cancer Institute, Durham, North Carolina 27710, USA.

Background: The objective of this study was to determine how patient preferences guide the course of palliative chemotherapy for advanced colorectal cancer.

Methods: Eligible patients with metastatic colorectal cancer (mCRC) were enrolled nationwide in a prospective, population-based cohort study. Data were obtained through medical record abstraction and patient surveys. Logistic regression analysis was used to evaluate patient characteristics associated with visiting medical oncology and receiving chemotherapy and patient characteristics, beliefs, and preferences associated with receiving >1 line of chemotherapy and receiving combination chemotherapy.

Results: Among 702 patients with mCRC, 91% consulted a medical oncologist; and among those, 82% received chemotherapy. Patients ages 65 to 75 years and aged ≥75 years were less likely to visit an oncologist, as were patients who were too sick to complete their own survey. In adjusted analyses, patients aged ≥75 years who had moderate or severe comorbidity were less likely to receive chemotherapy, as were patients who were too sick to complete their own survey. Patients received chemotherapy even if they believed that chemotherapy would not extend their life (90%) or that chemotherapy would not likely help with cancer-related problems (89%), or patients preferred treatment focusing on comfort even if it meant not living as long (90%). Older patients were less likely to receive combination first-line therapy. Patient preferences and beliefs were not associated with receipt of >1 line of chemotherapy or combination chemotherapy.

Conclusions: The majority of patients received chemotherapy even if they expressed negative or marginal preferences or beliefs regarding chemotherapy. Patient preferences and beliefs were not associated with the intensity or number of chemotherapy regimens.
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http://dx.doi.org/10.1002/cncr.27815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548062PMC
February 2013

Identification of BRCA1/2 founder mutations in Southern Chinese breast cancer patients using gene sequencing and high resolution DNA melting analysis.

PLoS One 2012 7;7(9):e43994. Epub 2012 Sep 7.

Department of Surgery, The University of Hong Kong, Hong Kong SAR.

Background: Ethnic variations in breast cancer epidemiology and genetics have necessitated investigation of the spectra of BRCA1 and BRCA2 mutations in different populations. Knowledge of BRCA mutations in Chinese populations is still largely unknown. We conducted a multi-center study to characterize the spectra of BRCA mutations in Chinese breast and ovarian cancer patients from Southern China.

Methodology/principal Findings: A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive BRCA1 and BRCA2 mutation screening was performed using bi-directional sequencing of all coding exons of BRCA1 and BRCA2. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM) analysis. Among the 451 probands analyzed, 69 (15.3%) deleterious BRCA mutations were identified, comprising 29 in BRCA1 and 40 in BRCA2. The four recurrent BRCA1 mutations (c.470_471delCT, c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT) accounted for 34.5% (10/29) of all BRCA1 mutations in this cohort. The four recurrent BRCA2 mutations (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA) accounted for 40% (16/40) of all BRCA2 mutations. Haplotype analysis was performed to confirm 1 BRCA1 and 3 BRCA2 mutations are putative founder mutations. Rapid HRM mutation screening for a panel of the founder mutations were developed and validated.

Conclusion: In this study, our findings suggest that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Southern Chinese population. Knowing the spectrum and frequency of the founder mutations in this population will assist in the development of a cost-effective rapid screening assay, which in turn facilitates genetic counseling and testing for the purpose of cancer risk assessment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043994PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436879PMC
May 2013

Examining the association between socioeconomic status and invasive colorectal cancer incidence and mortality in California.

Cancer Epidemiol Biomarkers Prev 2012 Oct 21;21(10):1814-22. Epub 2012 Aug 21.

Epidemiology Program, University of Hawai'i Cancer Center, University of Hawai'i, Honolulu, Hawaii 96813, USA.

Background: Colorectal cancer (CRC) incidence and mortality rates vary across race/ethnicity. Socioeconomic status (SES) also influences CRC rates; however, these associations might be inconsistent across racial/ethnic groups and tumor subsite. We examined associations between area-level SES and CRC incidence and mortality in a population-based registry study of non-Hispanic Whites, African Americans, Hispanics, and Asians/Pacific Islanders from California.

Methods: Data on 52,608 incident CRC cases (1998-2002) and 14,515 CRC deaths (1999-2001) aged ≥50 years were obtained from the California Cancer Registry. Based on 2000 U.S. Census data, each cancer case and death was assigned a multidimensional census tract-level SES index. SES-specific quintiles of CRC incidence and mortality rates, incidence rate ratios (IRR) and mortality rate ratios, and 95% confidence intervals (CI) were estimated. Analyses were stratified by anatomical site, including left- versus right-sided tumors, race/ethnicity, and stage of disease.

Results: Overall CRC incidence and SES did not show a clear association, yet patterns of associations varied across tumor subsite and race/ethnicity. Positive associations between SES and CRC incidence were found in Hispanics [SES Q5 v. Q1: IRR = 1.54, CI = 1.39-1.69], irrespective of the subsite. For Whites [SES Q5 v. Q1: IRR = 0.80, CI = 0.77-0.83], and African Americans [SES Q5 v. Q1: IRR = 0.83, CI = 0.70-0.97] inverse associations were observed, predominantly for left-sided tumors. Mortality rates declined with increasing SES in Whites, whereas in Hispanics mortality rates significantly increased with SES.

Conclusions: Our findings show that SES differences in CRC incidence and mortality vary considerably across anatomical subsite and race/ethnicity.

Impact: Studies combining area- and individual-level SES information are warranted.
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http://dx.doi.org/10.1158/1055-9965.EPI-12-0659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738465PMC
October 2012

Effect of Massachusetts health insurance reform on mammography use and breast cancer stage at diagnosis.

Cancer 2013 Jan 25;119(2):250-8. Epub 2012 Jul 25.

Division of General Internal Medicine, Brigham and Women's Hospital, and Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts 02115, USA.

Background: Massachusetts law requires all residents to maintain a minimum level of health insurance, and rates of uninsurance in that state decreased from 6.4% in 2006 to 1.9% in 2010. The authors of this report assessed whether health insurance expansion was associated with use of mammography and earlier stage at breast cancer diagnosis.

Methods: By using a prereform/postreform design with a concurrent control (California), mammography rates in the last year were assessed using the Behavioral Risk Factor Surveillance System survey and the diagnosis of stage I (vs II/III/IV) breast cancers based on cancer registry data among women ages 41 to 64. Propensity score analyses were used to compare California women who were most similar to women in Massachusetts with Massachusetts women.

Results: Among propensity-weighted cohorts, adjusted mammography rates in Massachusetts were 69.2% in 2006, 69.5% in 2008, and 69.0% in 2010. In California, the rates were 59% in 2006, 60.3% in 2008, and 56.2% in 2010 (P = .89 for interaction by state for 2010 vs 2006). Among propensity-weighted cohorts, adjusted rates of diagnosis with stage I cancers were 52.2% in 2006, 53.5% in 2007, and 52.4% in 2008 in Massachusetts versus 46.4% in 2006, 46.3% in 2007, and 45.7% in 2008 in California (P = .58 for interaction by state for 2010 vs 2006).

Conclusions: Health insurance reform in Massachusetts was not associated with increased rates of mammography or earlier stage at diagnosis compared with California, possibly because of insurance and mammography rates that already were high. Additional research is needed to assess the impact of insurance expansions in other populations, especially those with higher uninsurance rates.
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http://dx.doi.org/10.1002/cncr.27757DOI Listing
January 2013

Breast cancer risk factors differ between Asian and white women with BRCA1/2 mutations.

Fam Cancer 2012 Sep;11(3):429-39

Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

The prevalence and penetrance of BRCA1 and BRCA2 (BRCA1/2) mutations may differ between Asians and whites. We investigated BRCA1/2 mutations and cancer risk factors in a clinic-based sample. BRCA1/2 mutation carriers were enrolled from cancer genetics clinics in Hong Kong and California according to standardized entry criteria. We compared BRCA mutation position, cancer history, hormonal and reproductive exposures. We analyzed DNA samples for single-nucleotide polymorphisms reported to modify breast cancer risk. We performed logistic regression to identify independent predictors of breast cancer. Fifty Asian women and forty-nine white American women were enrolled. BRCA1 mutations were more common among whites (67 vs. 42 %, p = 0.02), and BRCA2 mutations among Asians (58 vs. 37 %, p = 0.04). More Asians had breast cancer (76 vs. 53 %, p = 0.03); more whites had relatives with breast cancer (86 vs. 50 %, p = 0.0003). More whites than Asians had breastfed (71 vs. 42 %, p = 0.005), had high BMI (median 24.3 vs. 21.2, p = 0.04), consumed alcohol (2 drinks/week vs. 0, p < 0.001), and had oophorectomy (61 vs. 34 %, p = 0.01). Asians had a higher frequency of risk-associated alleles in MAP3K1 (88 vs. 59 %, p = 0.005) and TOX3/TNRC9 (88 vs. 55 %, p = 0.0002). On logistic regression, MAP3K1 was associated with increased breast cancer risk for BRCA2, but not BRCA1 mutation carriers; breast density was associated with increased risk among Asians but not whites. We found significant differences in breast cancer risk factors between Asian and white BRCA1/2 mutation carriers. Further investigation of racial differences in BRCA1/2 mutation epidemiology could inform targeted cancer risk-reduction strategies.
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http://dx.doi.org/10.1007/s10689-012-9531-9DOI Listing
September 2012

Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry.

Breast Cancer Res Treat 2012 Aug 25;134(3):1209-20. Epub 2012 Apr 25.

Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St., 7th Floor, New York, NY 10032, USA.

Epidemiologic studies of histologic types of breast cancer including mucinous, medullary, and tubular carcinomas have primarily relied on International Classification of Diseases-Oncology (ICD-O) codes assigned by local pathologists to define histology. Using data from the Breast Cancer Family Registry (BCFR), we compared histologic agreement between centralized BCFR pathology review and ICD-O codes available from local tumor registries among 3,260 breast cancer cases. Agreement was low to moderate for less common histologies; for example, only 55 and 26 % of cases classified as mucinous and medullary, respectively, by centralized review were similarly classified using ICD-O coding. We then evaluated risk factors for each histologic subtype by comparing each histologic case group defined by centralized review with a common set of 2,997 population-based controls using polytomous logistic regression. Parity [odds ratio (OR) = 0.4, 95 % confidence interval (95 % CI): 0.2-0.9, for parous vs. nulliparous], age at menarche (OR = 0.5, 95 % CI: 0.3-0.9, for age ≥13 vs. ≤11), and use of oral contraceptives (OCs) (OR = 0.5, 95 % CI: 0.2-0.8, OC use >5 years vs. never) were associated with mucinous carcinoma (N = 92 cases). Body mass index (BMI) (OR = 1.05, 95 % CI: 1.0-1.1, per unit of BMI) and high parity (OR = 2.6, 95 % CI: 1.1-6.0 for ≥3 live births vs. nulliparous) were associated with medullary carcinoma (N = 90 cases). We did not find any associations between breast cancer risk factors and tubular carcinoma (N = 86 cases). Relative risk estimates from analyses using ICD-O classifications of histology, rather than centralized review, resulted in attenuated, and/or more imprecise, associations. These findings suggest risk factor heterogeneity across breast cancer tumor histologies, and demonstrate the value of centralized pathology review for classifying rarer tumor types.
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http://dx.doi.org/10.1007/s10549-012-2056-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470278PMC
August 2012

Accuracy of BRCA1/2 mutation prediction models for different ethnicities and genders: experience in a southern Chinese cohort.

World J Surg 2012 Apr;36(4):702-13

Division of Breast Surgery, Department of Surgery, The University of Hong Kong, Hong Kong, China.

Background: BRCA1/2 mutation prediction models (BRCAPRO, Myriad II, Couch, Shattuck-Eidens, BOADICEA) are well established in western cohorts to estimate the probability of BRCA1/2 mutations. Results are conflicting in Asian populations. Most studies did not account for gender-specific prediction. We evaluated the performance of these models in a Chinese cohort, including males, before BRCA1/2 mutation testing.

Methods: The five risk models were used to calculate the probability of BRCA mutations in probands with breast and ovarian cancers; 267 were non-BRCA mutation carriers (247 females and 20 males) and 43 were BRCA mutation carriers (38 females and 5 males).

Results: Mean BRCA prediction scores for all models were statistically better for carriers than noncarriers for females but not for males. BRCAPRO overestimated the numbers of female BRCA1/2 mutation carriers at thresholds ≥20% but underestimated if <20%. BRCAPRO and BOADICEA underestimated the number of male BRCA1/2 mutation carriers whilst Myriad II underestimated the number of both male and female carriers. In females, BRCAPRO showed similar discrimination, as measured by the area under the receiver operator characteristic curve (AUC) for BRCA1/2 combined mutation prediction to BOADICEA, but performed better than BOADICEA in BRCA1 mutation prediction (AUC 93% vs. 87%). BOADICEA had the best discrimination for BRCA1/2 combined mutation prediction (AUC 87%) in males.

Conclusions: The variation in model performance underscores the need for research on larger Asian cohorts as prediction models, and the possible need for customizing these models for different ethnic groups and genders.
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http://dx.doi.org/10.1007/s00268-011-1406-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299960PMC
April 2012
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