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Background: Cell-to-cell adhesion and angiogenesis are hallmarks of cancer. No studies have examined associations of adhesion molecules and angiogenesis biomarkers with clinical outcomes in colorectal cancer. Methods: In presurgery serum from n = 426 patients with colorectal cancer (stage I–III), we investigated associations of CRP, SAA, adhesion molecules (sICAM-1, sVCAM-1), and angiogenesis markers (VEGF-A and VEGF-D) with overall survival (OS), disease-free survival (DFS), and risk of recurrence. We computed HRs and 95% confidence intervals; adjusted for age, sex, BMI, stage, site, and study site, stratified by tumor site in exploratory analyses. Results: N = 65 (15%) were deceased, and 39 patients (14%) had a recurrence after a median follow-up of 31 months. We observed significant associations of biomarkers with OS, DFS, and risk of recurrence on a continuous scale and comparing top to bottom tertile, with HRs ranging between 1.19 and 13.92. CRP was associated with risk of death and recurrence in patients in the top tertile compared with patients in the bottom tertile, for example, risk of recurrence HRQ3-Q1: 13.92 (1.72–112.56). Significant heterogeneity between biomarkers and clinical outcomes was observed in stratified analysis by tumor site for CRP, SAA, sICAM-1, sVCAM-1, and VEGF-D. VEGF-D was associated with a 3-fold increase in risk of death for rectal cancer (HRlog2: 3.26; 95% CI, 1.58–6.70) compared with no association for colon cancer (HRlog2: 0.78; 95% CI, 0.35–1.73; Pheterogenity = 0.01). Conclusions: Adhesion molecules and angiogenesis biomarkers are independent prognostic markers for colorectal cancer, with differences by tumor site. Impact: There is need for tailored treatment for colon and rectal cancer.

Background Black people experience excess cervical and colorectal (CRC) cancer burden. Racial residential segregation, one measure of exposure to racism, is a potential driver of these inequities. To achieve cancer equity, it is crucial to better understand the role of racism and cancer prevention and early detection behaviors, including cancer screening. We assessed the association of exposure to Black residential segregation and cancer screening among Black and White adults. Methods This was a retrospective cohort study using electronic medical record data from patients who were members of the Population-based Research to Optimize the Screening Process (PROSPR) cohort. The sample included non-Hispanic (NH) Black or NH White average-risk urban adults at five U.S. healthcare settings who were eligible and due for cervical cancer screening (women aged 21-65 years) or CRC screening (50-75 years) when they had a primary care appointment (cohort entry) from 2010-2012. Black residential segregation was measured using sample-based quartiles of the local exposure and isolation (LEx/Is) metric comprising census-tract level data from 2008-2012 American Community Survey. The outcome was receipt of cervical cancer screening (completion of Pap or Pap/human papillomavirus [HPV] co-test) or CRC screening (completion of FIT/gFOBT, sigmoidoscopy, or colonoscopy) within 3 years of cohort entry. Multilevel logistic regression was used to calculate association of segregation and screening while adjusting for patient- and census-travel level covariates (age, race, sex, year of cohort entry, comorbidities, healthcare system, and census tract level poverty rate.) Results Of 164,238 and 652,719 patients eligible and due for cervical cancer or CRC screening respectively, 106,753 (65.0%) and 465,042 (71.2%) received timely screening. Black patients (6.4% of cervical screening and 15.7% of CRC screening sample), compared to White patients, were more likely to live in neighborhoods in the highest quartile of Black segregation (cervical sample: 44.1% vs. 17.6%; CRC sample: 51.8% vs. 19.4%). Greater exposure to segregation was associated with lower odds of cervical cancer screening (Quartile [Q]4 vs. Q1 odds ratio [OR]=0.92; 95% CI 0.89-0.94) and CRC screening (Q4 vs. Q1 OR=0.91; 95% CI 0.89-0.92) in unadjusted models; these associations were attenuated in adjusted models for cervical (Q4 vs. Q1 adjusted OR[aOR]=0.99; 95%CI=0.95-1.03) and CRC screening (Q4 vs. Q1 aOR=1.0; 95% CI 0.97-1.02). Notably, in adjusted models for both screening types, higher census tract level neighborhood poverty rate was associated with lower odds of screening, and Black (vs. White) race was associated with higher odds of cervical cancer screening but lower odds of CRC screening. Discussion In this study within five healthcare systems, Black residential segregation was not associated with screening after adjustment for other variables. Additional analyses will assess potential for effect measure modification by patient race, healthcare system, and other factors. Citation Format: Sandi L. Pruitt, Lynn N. Ibekwe, Kaitlin Todd, Erica S. Breslau, Andrea N. Burnett-Hartman, Cheryl R. Clark, Natalie J. Del Vecchio, Jennifer S. Haas, Stacey Honda, Christopher I. Li, Rachel L. Winer, Christine Neslund-Dudas, Rachel Issaka. Association of racial residential segregation and screening uptake for cervical and colorectal cancer among Black and White patients in five diverse U.S. healthcare systems [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A114.

Background: Type II diabetes and certain diabetes treatments have been observed to impact breast cancer risk. However, their associations with different breast cancer molecular subtype defined by estrogen receptor (ER)/progesterone receptor (PR)/HER2 status are unclear. Methods: We conducted a retrospective multi-center population-based case–case study consisting of 4,557 breast cancer cases to evaluate the impact of type II diabetes and diabetes medications on the risk of different breast cancer molecular subtypes [ER+/HER2−, ER+/HER2+, triple negative (ER−/PR−/HER2−), and HER2 overexpressing (H2E, ER−/PR−/HER2+)]. Using ER+/HER2− cases as the reference group, we estimated ORs and corresponding 95% confidence intervals (CI) for each subtype using polytomous logistic regression. Results: Compared with those without a diabetes history, women with type II diabetes had a 38% (95% CI, 1.01–1.89) increased odds of triple-negative breast cancer (TNBC). Current and longer term recent metformin use (13–24 months of treatment within the 24-month period prior to breast cancer diagnosis) was associated with elevated odds of TNBC (OR = 1.54; 95% CI, 1.07–2.22 and OR = 1.80; 95% CI, 1.13–2.85, respectively). Conclusions: The odds of having a triple-negative rather than ER+/HER2− breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin. This finding is supported by some preclinical data suggesting that diabetes may be more strongly associated with risk of triple-negative disease. Impact: Our study provides novel evidence regarding potential differential effects of type II diabetes and metformin use on risk of different molecular subtypes of breast cancer.

Background: Incidence rates of in situ breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with in situ breast cancer later develop second primary breast cancers. Methods: In this population-based nested case–control study among in situ breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer. Results: First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous in situ breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05–1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15–3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24–2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status. Conclusions: Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous in situ breast cancer. Impact: Given the growing population of in situ breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. Cancer Epidemiol Biomarkers Prev; 27(3); 315–20. ©2018 AACR.

Background: Black, Hispanic, and Asian/Pacific Islander (API) women are disproportionately affected by less-common, more aggressive subtypes of breast cancer, and differences in reproductive factors may contribute to these disparities. We conducted a population-based case-case analysis comparing the risks of luminal B, triple-negative (TN), and HER2-overexpressing (H2E) breast cancer to the risk of luminal A breast cancer to better understand how reproductive risk factors influence the excess burden of aggressive breast cancer subtypes among racial/ethnic minority women. Methods: This case-case analysis was based on incident breast cancer cases, 20-69 years of age, diagnosed among residents within the respective catchment areas of two population-based cancer registries. Subtypes were defined by joint estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status: luminal A (ER+/HER2−), luminal B (ER+/HER2+), H2E (ER−/HER2+), and TN (ER−/PR−/HER2−). Data were collected through medical record reviews and structured interviewer-administered questionnaires. Categorical exposure variables included: parity, number of full-term pregnancies, history of breastfeeding, age at menopause, and age at menarche. Multinomial logistic regression models were fit to calculate odds ratios (OR) and associated 95% confidence intervals (95%CI) for each subtype relative to luminal A breast cancer, separately for non-Hispanic white, Hispanic white, Black, and Asian/Pacific Islander (API) women, and adjusting for age at diagnosis, study site, and year at diagnosis. Results: This sample included 4,557 women with breast cancer (2,047 luminal A, 335 luminal B, 1,559 TN, and 615 H2E). Among non-Hispanic white women, parity was more strongly associated with H2E than luminal A breast cancer (OR:1.24, 95%CI:0.99-1.53). Among Black and API women, parity was associated with a greater risk of TN (Black OR:1.41, 95%CI:0.72-2.78; API OR:2.43, 95%CI:1.12-5.29) and a greater risk of H2E (Black OR:2.14, 95%CI:1.78-2.57; API OR:3.73, 95%CI:2.18-6.37), relative to luminal A breast cancer. Breastfeeding was more strongly associated with the risk of luminal B than luminal A breast cancer among API women (OR:1.33, 95%CI:1.13-1.57). Older age at menarche was associated with an increased risk of TN breast cancer only among Black women. Conclusion: In this population-based study, the associations between some reproductive factors and less-common subtypes of breast cancer differed by race/ethnicity. The reproductive choices of women from different racial/ethnic groups are driven by a complex set of factors that seem to influence their subsequent risk of TN and H2E breast cancer. Future studies are needed to further clarify these mechanisms among Black and API women and to identify optimal points of intervention. Citation Format: Nicole C. Lorona, Linda S. Cook, Mei-Tzu C. Tang, Deirdre A. Hill, Charles L. Wiggins, Christopher I. Li. Relationship between reproductive factors and risk of luminal, triple-negative, and HER2-overexpressing breast cancer by race/ethnicity [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-185.

Background: Reproductive factors are among the most well-established risk factors for breast cancer. However, their associations with different breast cancer subtypes defined by joint estrogen receptor (ER)/progesterone receptor (PR)/HER2 status remain unclear. Methods: We assessed relationships between reproductive factors and risks of luminal A (ER+/HER2−), luminal B (ER+/HER2+), triple-negative (TN; ER−/PR−/HER2−), and HER2-overexpressing (H2E; ER−/HER2+) breast cancers in a population-based case–case study consisting of 2,710 women ages 20–69 years diagnosed between 2004 and 2012. ORs and 95% confidence intervals (CI) were estimated with luminal A cases serving as the reference group using polytomous logistic regression. Results: Earlier age at first full-term pregnancy and age at menopause were positively associated with odds of TN breast cancer (Ptrend: 0.003 and 0.024, respectively). Parity was associated with a 43% (95% CI, 1.08–1.89) elevated odds of H2E breast cancer, and women who had ≥3 full-term pregnancies had a 63% (95% CI, 1.16–2.29, Ptrend = 0.013) increased odds of this subtype compared with nulliparous women. Breast feeding for ≥36 months was associated with a 49% (OR 0.51; 95% CI, 0.27–0.99) lower odds of TN breast cancer. Conclusion: Our results suggest that reproductive factors contribute differently to risks of the major molecular subtypes of breast cancer. Impact: African American and Hispanic women have higher incidence rates of the more aggressive TN and H2E breast cancers and their younger average age at first pregnancy, higher parity, and less frequent breast feeding could in part contribute to this disparity. Cancer Epidemiol Biomarkers Prev; 25(9); 1297–304. ©2016 AACR.

There are approximately 16 million cancer survivors in the United States, and outcomes of major concern for these survivors are their risks of developing a cancer recurrence, a second primary cancer, and dying of cancer. While cancer registries routinely collect data on second cancers and mortality, they do not ascertain data on recurrences. Gold-standard data on recurrences currently relies on review of medical records, which is costly, time consuming, and does not include events that occur after the review takes place. Extracting data from administrative and electronic health records provides an opportunity to ascertain information on recurrences in real time. We are using two approaches to address this issue that leverage gold-standard data on recurrences we have ascertained through one of our large population-based studies of breast cancer. The first involves the development and implementation of an algorithm for breast cancer recurrences using medical claims data, and the second applies machine learning and artificial intelligence to text in electronic health records. Methods and progress related to these two approaches will be presented. Citation Format: Christopher I. Li. Use of administrative and electronic health records to identify cancer recurrences [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr IA13.

Background: Five-year breast cancer survival rates are lower among Hispanic and African-American women than among Non-Hispanic White women. Differences in breast cancer treatment likely play a role. Adjuvant hormonal therapies increase overall survival among women with hormone receptor-positive breast cancer. Methods: We examined racial/ethnic differences in use and duration of adjuvant hormonal therapy among 3,588 postmenopausal women enrolled in the Women's Health Initiative (WHI) Extension Study. Women diagnosed with hormone receptor-positive localized or regional stage breast cancer after study enrollment were surveyed between September 2009 and August 2010 and asked to recall prior use and duration of adjuvant hormonal breast cancer therapy. ORs comparing self-reported use and duration with race/ethnicity (Hispanic, African-American, Asian/Pacific Islander vs. Non-Hispanic White) were estimated using multivariable-adjusted logistic regression. Results: Of the 3,588 women diagnosed from 1994 to 2009; 3,039 (85%) reported any use of adjuvant hormonal therapy, and 67% of women reporting ever-use who were diagnosed before 2005 reported using adjuvant hormonal therapy for the optimal duration of 5 years or more. In adjusted analysis, no statistically significant differences in use or duration by race/ethnicity were observed. Conclusions: This study did not find significant differences in use or duration of use of adjuvant hormonal therapy by race/ethnicity. Impact: Findings should be confirmed in other population-based samples, and potential reasons for discontinuation of therapy across all racial/ethnic groups should be explored. Cancer Epidemiol Biomarkers Prev; 22(3); 365–73. ©2012 AACR.

Background: The length of the interval between age at menarche and age at first birth is positively associated with breast cancer risk. We examined the risk of breast cancer in atomic bomb survivors to investigate whether women exposed to radiation between menarche and first birth had a higher risk of radiogenic breast cancer than women exposed at the same age but outside this interval. Methods: Women (n = 30,113) were classified into three reproductive status at the time of the bombings (ATB) categories (premenarche, between menarche and first birth, or after first birth). Poisson regression was used to test the primary hypothesis. Results: When the background rate of breast cancer was taken to depend on city, age ATB, and attained age only, the radiation-related excess relative risk (ERR) varied significantly among the three categories (P = 0.049). However, after controlling for significant heterogeneity in the baseline risk of breast cancer between reproductive status ATB groups (P < 0.001), no significant heterogeneity (P = 0.88) was observed in the ERR, with an ERR per Gy of 1.36 [95% confidence interval (CI), 0.54-2.75] for women exposed between menarche and first birth ATB, and 1.07 (95% CI, 0.22-3.62) and 1.53 (95% CI, 0.63-2.90) for those exposed premenarche or after first birth, respectively. Conclusions: The radiation-associated risk of breast cancer does not vary significantly by reproductive status ATB. Impact: It is possible that radiation exerts similar carcinogenic effects on the breast regardless of its stage of differentiation, or that the differences in radiosensitivity are too small to be detected in this cohort. Cancer Epidemiol Biomarkers Prev; 19(7); 1746–54. ©2010 AACR.

Background: Biological distinctions between histologic subtypes of breast cancer suggest etiologic differences, although few studies have been powered to examine such differences. We compared associations between several factors and risk of ductal, lobular, and mixed ductal-lobular breast cancers. Methods: We used risk factor data from the Breast Cancer Surveillance Consortium for 3,331,744 mammograms on 1,211,238 women, including 19,119 women diagnosed with invasive breast cancer following mammography (n = 14,818 ductal, 1,602 lobular, and 1,601 mixed ductal-lobular). Histologic subtype–specific risk factor associations were evaluated using Cox regression. Results: Significant positive associations with family history and breast density were similar across subtypes. Hormone therapy use was associated with increased risk of all subtypes, but was most strongly associated with lobular cancer [hazard ratio (HR) = 1.46; 95% confidence interval (CI), 1.25-1.70]. Relative to nulliparous women, parous women had lower risk of ductal and mixed but not lobular cancers (HR = 0.80; 95% CI, 0.76-0.84; HR = 0.79; 95% CI, 0.68-0.93; HR = 0.96; 95% CI, 0.81-1.15, respectively). Late age at first birth was associated with increased risk of all subtypes. Conclusions: Similarities in risk factor associations with ductal, lobular, and mixed breast cancer subtypes were more pronounced than differences. Distinctions between subtype-specific associations were limited to analyses of hormone therapy use and reproductive history. Impact: The results of this study indicate that the strongest risk factors for breast cancer overall (that is, family history and breast density) are not histologic subtype specific. Additional studies are needed to better characterize subtype-specific associations with genetic, hormonal, and nonhormonal factors. Cancer Epidemiol Biomarkers Prev; 19(6); 1643–54. ©2010 AACR.

Both migraine and breast cancer are hormonally mediated diseases, and it is biologically plausible that women with a history of migraine may have a reduced breast cancer risk. However, this relationship has only been assessed in a single relatively small study that was unable to assess the effect of migraine triggers, which are also well-established breast cancer risk factors (e.g., use of alcohol and exogenous hormones), on the inverse association observed. Utilizing data on 4,568 breast cancer cases and 4,678 controls who participated in a multicenter population-based case-control study in the United States, we evaluated the association between migraine history and breast cancer risk using unconditional logistic regression. Migraine history data were obtained from structured in-person interviews. Women with a history of migraine had a reduced risk of breast cancer [odds ratio, 0.74; 95% confidence interval (CI), 0.66-0.82]. This risk did not differ by menopausal status, age at migraine diagnosis, use of prescription migraine medications, or when analyses were restricted to women who avoided various migraine triggers (including alcohol, exogenous hormones, and smoking). These data support a previous finding that a history of migraine may be associated with a reduced risk of breast cancer. It extends the prior report in observing that this relationship holds for both premenopausal and postmenopausal women and is independent of exposure to common migraine triggers. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2030–4)

Background: The frequency of migraine headache changes at various times of a woman's reproductive cycle. Menarche, menses, pregnancy, and perimenopause may carry a different migraine risk conceivably because of fluctuating estrogen levels, and in general, migraine frequency is associated with falling estrogen levels. Given the strong relationship between endogenous estrogen levels and breast cancer risk, migraine sufferers may experience a reduced risk of breast cancer.Methods: We combined data from two population-based case-control studies to examine the relationship between migraine and risk of postmenopausal invasive breast cancer among 1,199 ductal carcinoma cases, 739 lobular carcinoma cases, and 1,474 controls 55 to 79 years of age. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).Results: Women who reported a clinical diagnosis of migraine had reduced risks of ductal carcinoma (OR, 0.67; 95% CI, 0.54-0.82) and lobular carcinoma (OR, 0.68; 95% CI, 0.52-0.90). These associations were primarily limited to hormone receptor–positive tumors as migraine was associated with a 0.65-fold (95% CI, 0.51-0.83) reduced risk of estrogen receptor–positive (ER+)/progesterone receptor–positive (PR+) ductal carcinoma. The reductions in risk observed were seen among migraine sufferers who did and did not use prescription medications for their migraines.Conclusions: These data suggest that a history of migraine is associated with a decreased risk of breast cancer, particularly among ER+/PR+ ductal and lobular carcinomas. Because this is the first study to address an association between migraine history and breast cancer risk, additional studies are needed to confirm this finding. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3116–22)

Although the clinical relevance of molecular subtypes of breast cancer has been documented, little is known about risk factors for different tumor subtypes, especially the HER2-overexpressing and the triple-negative subtypes that have poor prognoses. Obesity may be differentially related to the risk of different subtypes given the various potential mechanisms underlying its association with breast cancer. We pooled two population-based case-control studies of postmenopausal breast cancer for an analysis, including 1,447 controls and 1,008 luminal (hormone receptor positive), 39 HER2-overexpressing (hormone receptor negative, HER2 positive), and 77 triple-negative (hormone receptor and HER2 negative) cases. Associations between anthropometric factors and the risk of different breast cancer subtypes were evaluated using polytomous logistic regression. Among women not currently using menopausal hormone therapy, body mass index (BMI) and weight were associated with the risk of luminal tumors [odds ratio (OR) comparing highest versus lowest quartiles, 1.7; 95% confidence interval (95% CI), 1.2-2.4 and OR, 1.7; 95% CI, 1.2-2.4, respectively] and suggestively associated with risk of triple-negative tumors (OR, 2.7; 95% CI, 1.0-7.5 and OR, 5.1; 95% CI, 1.1-23.0, respectively). Neither BMI nor weight was associated with the risk of any tumor subtype among hormone therapy users. The positive relationship between BMI and luminal tumors among postmenopausal women not using hormone therapy is well characterized in the literature. Although our sample size was limited, body size may also be related to the risk of postmenopausal triple-negative breast cancer among nonusers of hormone therapy. Given the expanding obesity epidemic, the widespread cessation of hormone therapy use, and the poor prognosis of triple-negative tumors, this novel finding merits confirmation. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2078–86)

Background: Histamine2-receptor antagonist (H2 blocker) medications are used to treat heartburn, gastroesophageal reflux disease, and ulcers. Some H2 blockers, specifically cimetidine and ranitidine, also increase serum prolactin concentrations. Given the positive relationship between prolactin levels and postmenopausal breast cancer risk, use of H2 blockers is a potential breast cancer risk factor. The few previous studies evaluating this association have been null but have been limited by small sample sizes, and none have evaluated risk by either histologic type or estrogen receptor/progesterone receptor status. Methods: Combining data from two population-based case-control studies conducted in western Washington, we assessed the relationship between use of H2 blockers and risk of different types of breast cancer among 1,941 cases and 1,476 controls 55 to 79 years old. Odds ratios and 95% confidence intervals (95% CI) were calculated using polytomous logistic regression. Results: Current use of H2 blockers overall, cimetidine, and famotidine was not associated with an increased risk of either invasive ductal or invasive lobular breast cancer. Current users of ranitidine had a 2.2-fold (95% CI, 1.1-4.3) increased risk of ductal carcinoma that was confined to a 2.4-fold (95% CI, 1.2-4.9) increased risk of estrogen receptor–positive/progesterone receptor–positive ductal carcinoma. Conclusions: Use of H2 blockers in general is not associated with an increased risk of breast cancer, although current use of ranitidine may increase risk of hormone receptor–positive ductal carcinoma. Further studies to confirm this finding are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(1):67–72)

Background: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types.Methods: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression.Results: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma.Conclusions: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(5):946–54)

The ancestral makeup of Hispanic women in the United States is complex; they form an admixed population including European (EUR), Amerindian (AI), and African (AFR) ancestry. Studies have demonstrated differences in the distribution of molecular subtypes of breast cancer between non-Hispanic white women and Hispanic women. To better understand the relationship of breast cancer biomarkers/molecular subtypes and ancestry in a U.S. Hispanic population, we assessed histologic characteristics, tumor cell protein expression by immunohistochemistry (IHC), gene expression using the Affymetrix Human HTA 2.0 array, and ancestry by ancestry informative markers (AIMs) in a cohort of 331 Hispanic women diagnosed with breast cancer in either Washington or New Mexico. To assess individual ancestry, we genotyped a panel of 215 AIMs in 260 women with available DNA. We ran ancestry analyses using one to ten populations in the model; three populations gave the lowest cross-validation error (0.53). In this cohort, we observed the largest contribution from EUR ancestry (mean=58.6%; range=8.3-97.6%), followed by AI ancestry (mean=33.6%; range=0-89.5%) and AFR ancestry (mean=7.9%; range=0-83.9%). We did not see significant associations between ancestry proportion and individual IHC markers ER, PR, HER2, CK5/6, EGFR, or tumor grade. However, three markers (tumor lymphocyte response, p53 positivity, high Ki67 positivity) were associated with ancestry: greater AFR ancestry with higher lymphocyte response (OR=1.045 per 1% increase in AFR ancestry, 95% CI: 1.004-1.087, p=0.03) and an increasing AI ancestry with high Ki67 positivity (OR=1.032 per 1% increase in AI ancestry, 95% CI: 1.005-1.061, p=0.02) and high p53 expression (OR=1.035 per 1% increase in AI ancestry, 95% CI: 1.008-1.062, p=0.01). We compared St. Gallen IHC subtypes with ancestry and observed a positive association between the ER-/PR-/HER2+ subtype and AI ancestry. Specifically, for every 1% increase in AI ancestry, we observed a 4.2% (95% CI: 0.2%-8.3%) increased risk for ER-/PR-/HER2+ disease compared to patients with Luminal A (ER+/PR+/HER2-) disease (p=0.04). Gene expression intrinsic subtyping by PAM50 was also suggestive of this association: an increasing proportion of AI ancestry was associated with increased odds of having the HER2-enriched subtype compared with Luminal A subtype (OR=1.030, 95% CI: 0.995-1.067, p=0.09). In conclusion, ancestry in this population of Hispanic women with breast cancer was mixed. Greater AI ancestry was associated with increased odds of ER-/PR-/HER2+ disease and of two markers of aggressive breast cancer, high tumor cell proliferation and p53 expression. There was no association identified between ancestry and triple negative breast cancer. Other studies have identified that HER2+ breast cancer rates in Hispanic women are higher than those in non-Hispanic white women. These data highlight the ancestral heterogeneity of the Hispanic population and the need to fully understand which subgroups of Hispanic women might be at an increased risk for specific breast cancer types, especially those that are aggressive and associated with poor outcomes. Citation Format: Jamie Guenthoer, Xiaoyu Chai, Karen W. Makar, Chris S. Carlson, Rania Bakkar, Irena B. King, Huining Kang, Beti Thompson, Christopher I. Li, Li Hsu, Linda S. Cook, Peggy L. Porter. Relationship of ancestry and breast cancer subtypes in Hispanic women from New Mexico and Washington State. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C56.

Background: Although Latinas have lower breast cancer rates compared to non-Hispanic Whites (NHW), breast cancer is the top cancer killer of Latinas. There are many reasons for this, some involve biology, types of breast cancer found in Latinas, metabolic increases thought to be due to adoption of western diets, and lack of screening for early detection. In a large breast cancer program examining such cancers in Latinas, we overcame a number of challenges in each of four studies examining the fore-named factors. Methods: Four projects and four cores made up our Center for Population Health and Health Disparities (CPHHD). Using a community-based participatory research (CBPR) model, we recruited Latinas to participate in studies investigating the various factors related to breast cancer. Projects used robust methodologies to assess the relationship between elevated risks of triple negative breast cancers; the effects of a typical US diet compared to a traditional Mexican diet; the role of genetic ancestry on breast cancer in Latinas; and the effectiveness of a lay health worker intervention to increase breast cancer screening. As part of the program, we asked investigators to identify challenges encountered and how they were resolved. Results: All four projects were completed on time. Overall results of each project will be presented. Challenges in each project will be described as well as how the challenges were overcome. The role of the Community Advisory Board will be described and how its suggestions for sending results back to participants were adopted and incorporated in the program. Discussion: Embarking on a large transdisciplinary program to understand Latinas' breast cancer risks and to translate those risks to the population of interest has been stimulating and thought-provoking. Addressing challenges as they emerged and finding solutions required a team effort. By obtaining perspectives from a variety of disciplines, we were able to solve the challenges. This team approach is recommended for similar studies. Citation Format: Beti Thompson, Shirley AA Beresford, Gloria D. Coronado, Marian Neuhouser, Christopher I. Li, Linda S. Cook, Peggy Porter. Understanding and preventing breast cancer disparities in Latinas. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA13.

Background: Guidelines for the management of early stage invasive breast cancer include locoregional and systemic treatments that, on average, prolong disease-free and overall survival. Yet, a considerable proportion of women do not receive some or all of the guideline recommended breast cancer care. Disparities in the receipt of radiation therapy, chemotherapy, and endocrine therapy by patient and treatment facility characteristics may contribute to demographic differences in breast cancer survival. Methods: This population-based cohort study enrolled women aged 20 – 69 years, diagnosed with stage I, II, or IIIA breast cancer in the Seattle-Puget Sound area between 2004 and 2011, who were identified through the local Surveillance Epidemiology and End Results cancer registry. Concordance with National Comprehensive Cancer Network (NCCN) guideline recommendations and American Society of Clinical Oncology (ASCO)/NCCN Quality Measures (QMs) was assessed for 1,344 women using data collected from cancer registry records, pathology reports, and patient self-report from a telephone interview. Multivariable logistic regression was used to estimate the association between patient and facility characteristics, barriers and facilitators to care, and non-concordance with NCCN guidelines and QMs. Results: Compared to women with uninterrupted insurance coverage, women who did not have insurance at some point during their breast cancer treatment had a 3.5-fold (95% CI: 1.0-10.5) higher likelihood of non-concordance with NCCN guidelines for radiation therapy, and a 3.5-fold (95 % CI 1.2-10.5) higher likelihood of non-concordance with NCCN guidelines for chemotherapy. Low income was consistently associated with risk of non-concordance, with multivariate odds ratios of 2.3 (95% CI: 1.0-4.9) for radiation therapy guidelines, 4.6 (95% CI: 1.8-11.6) for chemotherapy guidelines, and 3.7 (95% CI: 1.4-9.7) for endocrine therapy guidelines associated with an annual family income of Conclusions: Economic factors were associated with non-receipt of most forms of recommended treatment. Our results and those of previous studies documenting socioeconomic disparities in the receipt of guideline recommended chemotherapy warrant further study of the root causes of these inequities, and of the effectiveness of interventions, such as patient navigation, designed to improve guideline concordance among uninsured, underinsured, and low-income women. This abstract is also presented as Poster A85. Citation Format: Jean A. McDougall, Noel S. Weiss, Kenneth J. Kopecky, Beti Thompson, Hannah M. Linden, Christopher I. Li. Socioeconomic determinants of the receipt of guideline-concordant breast cancer treatment. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PR8. doi:10.1158/1538-7755.DISP13-PR8

While the use of self-reported treatment data is common in cancer disparities research, it is unknown whether their accuracy varies by study participant's income or education. Using data collected from a population-based case-control study of contralateral breast cancer, we compared the concordance between participant responses to a telephone questionnaire and medical record data obtained from all facilities where a participant received breast cancer treatment. This analysis included women age 40 – 79 diagnosed with contralateral breast cancer (n=256) or only a single breast cancer (n = 533) between 1990 and 2005. Concordance was evaluated by calculating the percent agreement, Kappa statistic and its 95% confidence interval (CI) for the agreement between self-report and medical record data for the type of breast cancer surgery received, receipt and start date (month and year) of chemotherapy and radiation, and type of hormonal therapy received of all 789 participants stratified by highest level of education received (≤ high school, some college, ≥ college graduate) and annual household income ( .90). However, some variation with respect to treatment start date was observed. For radiation start date, concordance was lower among women reporting an income of Citation Format: Jean A. McDougall, Kathleen E. Malone, Mei-Tzu C. Tang, Christopher I. Li. Concordance between self-reported and medical record breast cancer treatment data by income and education. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B50.

Purpose: Prior studies suggest that recent oral contraceptive (OC) use is associated with a modest increased risk of breast cancer among young women. However, the majority of these reports have relied on self-reported use and have not characterized risks associated with newer OC formulations. Methods: We conducted a nested case-control study among health plan enrollees at a large health maintenance organization, Group Health Cooperative, which serves the greater Seattle-Puget Sound region. Cases consisted of 1,102 women 20–49 years of age diagnosed with invasive breast cancer from 1990–2009. We randomly selected 21,952 controls matched on age, year, and enrollment length. Detailed information on recent OC use, including formulation, dose, and duration was ascertained from electronic pharmacy records. Multivariate-adjusted conditional logistic regression was used to calculate odds ratios (ORs) as estimates of relative risks and 95% confidence intervals (CIs). Results: Recent OC use (within 1 year of diagnosis) was associated with a 60% (95% CI = 1.3–1.9) increased breast cancer risk. The association was slightly stronger for estrogen receptor (ER) positive compared to ER-negative disease (ER-positive OR = 1.7, 95% CI = 1.3–2.1 and ER-negative OR = 1.2, 95% CI = 0.8–1.8), though this difference was not statistically significant. The ORs varied somewhat by OC formulation, with recent use of OCs containing the progestin ethynodiol diacetate (OR = 2.6, 95% CI = 1.4–4.7) or high dose estrogen (OR = 2.7, 95% CI = 1.2–6.4) associated with particularly elevated risk estimates compared to non-use of OCs in the prior year. In contrast, risk estimates for recent use of OCs with the progestin norgestimate or low dose estrogen suggested either a modest association or no association (OR = 1.2, 95% CI = 0.6–2.2 and OR = 1.0, 95% CI = 0.6–1.7, respectively). Conclusions: These results suggest that recent use of contemporary OC formulations is associated with an elevated risk of breast cancer among women ages 20–49, with associations varying somewhat by OC formulation. Although breast cancer is rare among young women, the potential risk of breast cancer associated with certain formulations could impact OC recommendations by providers if these findings are confirmed. This abstract is one of the 20 highest scoring abstracts of those submitted for presentation at the 36th Annual ASPO meeting held March 4–6, 2012, in Washington, DC.

Introduction: Few studies have examined the distribution of breast cancer outcomes among Hispanics by race (i.e. Hispanic Black, Hispanic White). Understanding the diversity of breast cancer characteristics among Hispanic women is key to explaining the differences in breast cancer outcomes. Purpose: To assess the distribution of tumor stage, joint estrogen receptor (ER)/progesterone receptor (PR) status, and breast cancer-specific mortality with race and ethnicity, among Hispanic Black, Hispanic White, non-Hispanic Black (NHB), non-Hispanic White (NHW) women using Surveillance, Epidemiology, and End Results (SEER) Program data. Methods: We used data on 441,742 women aged 20–79 years who were diagnosed with primary invasive breast cancer between January 1992 and December 2008, with no prior history of cancer, and who were identified through the SEER 17 population-based registries. Women less than 20 and older than 79 years of age were excluded from the study. The primary outcomes of interest were: AJCC tumor stage, joint estrogen receptor (ER)/progesterone receptor (PR) status, and breast cancer-specific mortality. Our primary exposure of interest was race/ethnicity, which was categorized into four groups, based on SEER data: non-Hispanic White, non-Hispanic Black, Hispanic White, and Hispanic Black. Covariates included age at diagnosis, year of diagnosis, % population below poverty level, % population with less than a high school education, % foreign born, % non-English language, SEER registry, and treatment (surgery and/or radiation therapy). Results: Hispanic Blacks had the highest risk of being diagnosed with stage III and IV tumors compared to NHWs (RRR=2.4 [95% CI:1.9-3.1] and RRR=2.0 [95% CI:1.4-2.8], respectively; p Conclusion: Hispanic Black women have disproportionately higher rates of late stage invasive breast cancer diagnoses, ER–/PR– breast disease, and breast cancer-specific mortality compared to non-Hispanic White women. Furthermore, RRR estimates suggest that the increased risk associated with late stage and ER–/PR– may be greater than or equal to those estimates observed for non-Hispanic Black and Hispanic White women. The findings from this study will be among the first studies to present information on breast cancer characteristics and outcomes in both Hispanic Black and Hispanic White. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B66.

This study aimed to investigate the relationship between income and the receipt and adherence to adjuvant hormonal therapy (AHT) in a cohort of estrogen receptor (ER)-positive, invasive breast cancer cases. Women age 20 to 45 with a first primary diagnosis of invasive breast cancer between 2004 and 2010 were identified from the Cancer Surveillance System of Western Washington and given a telephone interview to ascertain data on breast cancer risk factors, demographic characteristics, and treatment history. A total of 602 invasive ER-positive cases were available for this analysis which uses logistic regression to compare the odds of starting and discontinuing AHT, such as Tamoxifen, Letrozole, Anastrozole, or Leuprolide, by categories of annual household income adjusting for household size and age. 72% of women received any AHT and 14% of women had discontinued AHT by the time of the interview. Of those who discontinued AHT, 53% had discontinued after less than one year of starting. There were no differences in the likelihood of starting AHT by income. However, women with an income of less than $50,000 were 2.4 times more likely to report discontinuing use than women with an income of $50,000 or more (Odds ratio(OR)=2.42; 95% Confidence interval(CI)=1.32-4.41). The income disparity in the likelihood of discontinuing AHT is particularly stark when comparing women with an income of ≥$90,000 to those with an income of Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A107.