Clinic-based perspectives on the integration of patient-reported outcomes (PROs) in a tertiary cancer center.

PURPOSE: This study examines providers' and clinic staff's perspectives on patient-reported outcomes (PROs) implementation at an academic medical center. METHODS: An anonymous and voluntary survey was administered to Henry Ford Cancer providers and clinic staff 18 months after PROs program implementation in September 2020, to obtain their feedback on perceived barriers, impact on workflows, and PROs administration frequency in routine cancer care. RESULTS: A total of 180 providers and 40 clinic staff were invited to complete the survey; 31% and 63% completed the survey, respectively. Approximately 68% of providers reported that electronically integrated PROs scores were either beneficial or somewhat beneficial to their patients, while only 28% of the clinic staff reported that PROs were beneficial or somewhat beneficial to patients. According to the clinic staff, the most common barriers to PROs completion included lack of patients' awareness of the utility of the program with respect to their care, patients' health status at check-in, and PROs being offered too frequently. CONCLUSION: There is favorable acceptance of the PROs program by providers, but clinic staff found it less favorable. Interventions to address barriers and improve program engagement are needed to ensure broad adoption of PROs in oncology practice.

Lifetime alcohol consumption patterns and young-onset breast cancer by subtype among Non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women's Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50 years of age. METHODS: Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative). RESULTS: Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all ptrend ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all ptrend ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18 years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed. CONCLUSIONS: Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted.

Tobacco Cessation Motivations, Preferences, and Barriers Among Rural Smokers: Implications for Optimizing Referrals in Clinical Practice.

Introduction: Rural‒urban smoking disparities have widened in recent years because smoking prevalence reductions have been experienced disproportionately among urban adults. Tobacco cessation programs that work in urban settings may not be reaching rural smokers or may need tailoring to be effective. Identifying smoking cessation preferences and barriers among rural smokers can facilitate the implementation of acceptable programs to address rural smoking-related disparities. Thus, the aim of this study was to examine tobacco cessation motivations, preferences, and barriers among rural smokers and to assess smokers' likelihood to use various types of tobacco cessation programs. Methods: Using a cross-sectional study design, we distributed a self-administered survey to 100 smokers during regularly scheduled healthcare appointments at 3 rural Michigan practices from June to August 2019. We examined differences in participant characteristics by the readiness to quit using chi-square/Fisher's exact tests and described cessation motivations, preferences, and barriers to tobacco cessation among rural smokers. Results: Participants reporting readiness to quit were less likely to have smoking allowed in their home (31.7% vs. 75.0%; p=0.003) and had a higher prevalence of anxiety (62.1% vs. 6.3%; p=0.0001) and depression (49.2% vs. 18.8%; p=0.04) than those not ready to quit. Preferences were higher for nicotine replacement medications and reward-based approaches, with only 10% of participants being likely to use telephone-based quitlines. Conclusions: These findings suggest that provider referrals to nicotine replacement medications and reward-based approaches can be used to enhance tobacco cessation among rural smokers.

Awareness of alcohol as a breast cancer risk factor and intentions to reduce alcohol consumption among U.S. young adult women.

Alcohol consumption is prevalent in young adult women and linked with breast cancer risk. Research to inform interventions targeting alcohol consumption as a breast cancer prevention strategy is limited. We examined young women's awareness of alcohol use as a breast cancer risk factor, identified correlates of awareness, and determined how awareness and conceptual predictors relate to intentions to reduce drinking. Women aged 18-25 years who drank alcohol in the past month (N = 493) completed a cross-sectional survey. Measures captured sociodemographics, breast cancer risk factors, awareness of alcohol use as a breast cancer risk factor, intentions to reduce drinking, and conceptual predictors. Analyses examined correlates of awareness and associations between awareness, conceptual predictors, and intentions to reduce drinking. Awareness was low (28%) and intentions to reduce drinking were moderate (M = 2.60, SD = 0.73, range 1-4). In multivariable analyses, awareness was associated with greater worry about cancer, beliefs that there's not much one can do to reduce cancer risk and everything causes cancer, higher perceived breast cancer risk, and stronger beliefs that reducing drinking reduces breast cancer risk. Awareness was not associated with intentions to reduce drinking. Younger age, older age of alcohol initiation, negative attitudes towards alcohol, fewer friends consuming alcohol, and stronger self-efficacy were associated with intentions to reduce drinking. Few young women recognize alcohol consumption as a breast cancer risk factor. Researchers and policymakers can apply our findings to design new or refine existing interventions to optimize their impact on awareness and alcohol consumption in young women.

Alcohol use is common among young adult women and is linked to an increased risk of breast cancer later in life. This study aimed to identify factors linked to young women's awareness of alcohol as a breast cancer risk factor and factors linked to intentions to reduce drinking. We surveyed 493 women aged 18­25 who resided in Ohio and reported drinking alcohol in the past month. Only 28% of the women were aware that alcohol use increases breast cancer risk, and intentions to reduce drinking were moderate. Factors associated with awareness of alcohol use as a breast cancer risk factor included cancer worry, believing there's not much you can do to lower your risk of cancer, believing everything causes cancer, higher perceived risk of breast cancer, and stronger beliefs that drinking less reduces breast cancer risk. Factors linked to intentions to reduce drinking included younger age, older age at first drinking, more negative attitudes about alcohol, believing fewer friends drink, and higher confidence to reduce drinking. The findings can help researchers and policymakers create new interventions to educate young women about the link between alcohol consumption and breast cancer risk and reduce alcohol use as a breast cancer prevention strategy.

Trends in Diet and Cancer Research: A Bibliometric and Visualization Analysis.

Diet plays a critical role for patients across the cancer continuum. The World Cancer Research Fund International and the American Cancer Society have published evidence supporting the role of nutrition in cancer prevention. We conducted an analysis of the literature on dietary nutrients and cancer to uncover opportunities for future research. The objective of the bibliometric analysis was to describe trends in peer-reviewed publications on dietary components and cancer and to highlight research gaps. PubMed was queried for manuscripts with diet- and cancer-related keywords and Medical Subject Headings (MeSH) terms. Metadata covering 99,784 publications from 6469 journals were analyzed to identify trends since 1970 on diet topics across 19 tumor types. Publications focused largely on breast, colorectal, and liver cancer, with fewer papers linking diet with other cancers such as brain, gallbladder, or ovarian. With respect to "unhealthy" diets, many publications focused on high-fat diets and alcohol consumption. The largest numbers of publications related to "healthy" diets examined the Mediterranean diet and the consumption of fruits and vegetables. These findings highlight the need for additional research focused on under-investigated cancers and dietary components, as well as dietary studies during cancer therapy and post-therapy, which may help to prolong survivorship.

Embedding lifestyle interventions into cancer care: has telehealth narrowed the equity gap?

Lifestyle interventions targeting energy balance (ie, diet, exercise) are critical for optimizing the health and well-being of cancer survivors. Despite their benefits, access to these interventions is limited, especially in underserved populations, including older people, minority populations and those living in rural and remote areas. Telehealth has the potential to improve equity and increase access. This article outlines the advantages and challenges of using telehealth to support the integration of lifestyle interventions into cancer care. We describe 2 recent studies, GO-EXCAP and weSurvive, as examples of telehealth lifestyle intervention in underserved populations (older people and rural cancer survivors) and offer practical recommendations for future implementation. Innovative approaches to the use of telehealth-delivered lifestyle intervention during cancer survivorship offer great potential to reduce cancer burden.

Provider Confidence and Perceived Barriers when Recommending the Human Papillomavirus Vaccine to Parents.

Provider recommendation for the HPV vaccine is considered a critical determinant of vaccine uptake compared to other interventions such as parent education. However, providers cite continued barriers to discuss the vaccines with parents including sexual concerns and other misconceptions. The purpose of this mixed methods study was to evaluate physician knowledge and comfort discussing the vaccine with parents and perceived barriers to vaccine uptake among pediatric residents and attending physicians at a university-affiliated county health clinic. Physicians completed surveys guided by HPV Roundtable information to assess HPV vaccine knowledge, comfortability, and parental barriers to administration. A total of 28 pediatric physicians (20 residents and 8 attendings) completed the survey. HPV vaccine knowledge was high among providers in this study, with 75% of providers reporting high confidence. The majority of physicians in this study reported being comfortable or very comfortable talking to parents about the HPV vaccine (82.1%), recommending the HPV vaccine (89.3%), and recommending the HPV vaccine specifically to hesitant parents (82.1%). Attendings were more comfortable than residents talking to (p = .009) and recommending the vaccine to parents (p = .002). However, physicians reported parents' sexual concerns, vaccine safety, and misconceptions as the predominant barriers. These findings suggest that persistent stigma about the HPV vaccine as prevention for sexually transmitted infection, rather than the HPV vaccine as cancer prevention persist. Findings from this study suggest the need for HPV vaccine education for parents and provider training on targeted communication strategies.

Culturally targeted message framing and colorectal cancer screening preferences among African Americans.

OBJECTIVE: The current study investigated whether culturally targeted message frames alter preferences for specific colorectal cancer (CRC) screening modalities among African Americans. METHOD: African Americans who were eligible for CRC screening (N = 457) viewed a video about CRC risks, prevention, and recommended screening options. Participants then received a gain or loss-framed message about screening, with half of participants viewing an additional culturally targeted message about overcoming disparities in CRC through screening. Participants reported their desired thoroughness in CRC screening and preferences for being screened using colonoscopy, sigmoidoscopy, or stool-based fecal immunochemical testing. RESULTS: Relative to gain-framing, loss-framed messaging enhanced desired thoroughness in CRC screening. Targeted loss-framing enhanced preferences for colonoscopy and decreased preferences for stool-based FIT screening. CONCLUSIONS: Findings demonstrate that message framing and culturally targeted messaging can impact CRC screening preferences. Altering preferences may carry implications for reducing CRC screening disparities among African Americans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Lifetime personal cigarette smoking and risk of young-onset breast cancer by subtype among non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). METHODS: Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. RESULTS: YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. CONCLUSION: Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.

Cancer disparities in the context of rurality: risk factors and screening across various U.S. rural classification codes.

PURPOSE: Prior cancer research is limited by inconsistencies in defining rurality. The purpose of this study was to describe the prevalence of cancer risk factors and cancer screening behaviors across various county-based rural classification codes, including measures reflecting a continuum, to inform our understanding of cancer disparities according to the extent of rurality. METHODS: Using an ecological cross-sectional design, we examined differences in cancer risk factors and cancer screening behaviors from the Behavioral Risk Factor Surveillance System and National Health Interview Survey (2008-2013) across rural counties and between rural and urban counties using four rural-urban classification codes for counties and county-equivalents in 2013: U.S. Office of Management and Budget, National Center for Health Statistics, USDA Economic Research Service's rural-urban continuum codes, and Urban Influence Codes. RESULTS: Although a rural-to-urban gradient was not consistently evident across all classification codes, the prevalence of smoking, obesity, physical inactivity, and binge alcohol use increased (all ptrend < 0.03), while colorectal, cervical and breast cancer screening decreased (all ptrend < 0.001) with increasing rurality. Differences in the prevalence of risk factors and screening behaviors across rural areas were greater than differences between rural and urban counties for obesity (2.4% vs. 1.5%), physical activity (2.9% vs. 2.5%), binge alcohol use (3.4% vs. 0.4%), cervical cancer screening (6.8% vs. 4.0%), and colorectal cancer screening (4.4% vs. 3.8%). CONCLUSIONS: Rural cancer disparities persist across multiple rural-urban classification codes, with marked variation in cancer risk factors and screening evident within rural regions. Focusing only on a rural-urban dichotomy may not sufficiently capture subpopulations of rural residents at greater risk for cancer and cancer-related mortality.

The impact of race and ethnicity in breast cancer-disparities and implications for precision oncology.

Breast cancer is the most commonly diagnosed cancer worldwide and is one of the leading causes of cancer death. The incidence, pathological features, and clinical outcomes in breast cancer differ by geographical distribution and across racial and ethnic populations. Importantly, racial and ethnic diversity in breast cancer clinical trials is lacking, with both Blacks and Hispanics underrepresented. In this forum article, breast cancer researchers from across the globe discuss the factors contributing to racial and ethnic breast cancer disparities and highlight specific implications of precision oncology approaches for equitable provision of breast cancer care to improve outcomes and address disparities.

Barriers to Access for Cervical and Breast Cancer Screenings Among Female Latinx Migrant Farmworkers in the US: A Scoping Literature Review.

Identification of barriers to cancer screening among female migrant farmworkers is needed to inform intervention development and healthcare policy. Thus, our purpose was to systematically review and summarize findings from prior studies of barriers faced by Latinx migrant farmworkers in accessing cervical and breast cancer screenings in the US. Medline and Embase were used to identify literature through October 2021 using the search terms "migrant farmworkers AND. . .cancer; healthcare access; breast; cervical; federally qualified health centers," and "migrant cancer screening" and "migrant farmworker cancer screening." Snowball sampling by reviewing citations in each selected article was also used. Exclusion criteria included those articles that focused on specific types of cancer other than breast or cervical, those not within the US, not referencing Latinx migrants, not referencing cancer screening, or those focused on pediatric populations. Data was synthesized by 3 authors and selected articles were assessed for common themes. Nineteen articles met inclusion criteria. Common themes about barriers to cancer screening included: lack of cancer knowledge, cost/inability to pay, lack of health insurance coverage, cultural perceptions, fear, language difficulties, and transportation and time constraints. Findings suggest that barriers to cancer screening among migrant farmworkers may be addressed by providing education about cancer screening and treatment, addressing fear, language, and cultural barriers, and providing transportation and health insurance coverage. Consideration of these barriers is necessary to effectively address cancer disparities in this vulnerable population of female farmworkers.

Implementation of Physical Activity Programs for Rural Cancer Survivors: Challenges and Opportunities.

Physical activity after cancer diagnosis has been consistently associated with improvements in quality of life and prognosis. However, few cancer survivors meet physical activity recommendations, and adherence is even lower among those living in rural settings. The purpose of this quasi-experimental study was to evaluate the implementation of a clinic-based physical activity program for cancer survivors at a rural community oncology setting. We also examined changes in quality-of-life measures among 24 cancer survivors participating in the physical activity program and described challenges and opportunities to optimize future implementation efforts in rural settings. Significant pre- to post-program improvements in fatigue (5.5 to 6.8; p = 0.03), constipation (7.7 to 9.0; p = 0.02), pain (6.7 to 8.0; p = 0.007), and sleep quality (p = 0.008) were observed. Participants also reported improved nausea, stamina, depression, stress, and overall physical health after participation in the physical activity program, although the differences were not statistically significant (all p-values > 0.13). However, the reach of the physical activity program was limited, with only 0.59% of cancer survivors participating. Fidelity to the physical activity program was relatively high, with 72.7% of survivors participating in at least five classes. Our findings suggest that physical activity programs in oncological settings may need tailoring to effectively reach rural cancer survivors.

Effects of culturally targeted message framing on colorectal cancer screening among African Americans.

OBJECTIVE: This study examined how standard and culturally targeted versions of gain and loss-framed messaging affect African Americans' colorectal cancer (CRC) screening receptivity and behavior, as well as their anticipation of experiencing racism in undertaking CRC screening. METHOD: Screening-deficient African Americans (N = 457) viewed an informational video about CRC risks, prevention, and screening and were randomized to receive a gain or loss-framed message about screening. Half of participants viewed an additional culturally targeted message about overcoming racial disparities in CRC by obtaining screening. Using the Theory of Planned Behavior, we measured general receptivity to CRC screening. We also measured arousal of anticipatory racism in response to messaging. Finally, we offered participants a no-cost fecal immunochemical testing kit (FIT Kit) and measured uptake and use. RESULTS: Message framing interacted with culturally targeted messaging to affect CRC screening receptivity and behavior. Participants were no more receptive to CRC screening when standard loss-framing was used, but were more favorable if loss-framing was culturally targeted. Targeted loss-framing also reduced anticipatory racism, which partially mediated effects on screening receptivity. Finally, although participants least often accepted a FIT Kit with standard loss-framing, effects of messaging on FIT Kit uptake and use were not significant. CONCLUSION: This study adds to growing recognition of important cultural nuance in effective use of message framing. Current finding also suggest that targeted and framed messaging could synergistically impact the extent to which African Americans engage in CRC screening, although specific impacts on FIT Kit screening are less certain. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dermal Lymphatic Invasion, Survival, and Time to Recurrence or Progression in Inflammatory Breast Cancer.

OBJECTIVES: Dermal lymphatic invasion (DLI) with tumor emboli is a common pathologic characteristic of inflammatory breast cancer (IBC), although its presence is not required for diagnosis. We examined whether documented DLI on skin biopsy was associated with survival and time to recurrence or progression in IBC. MATERIALS AND METHODS: A total of 340 women enrolled in the IBC Registry at Dana-Farber Cancer Institute between 1997 and 2019 were included in this study. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for associations of DLI and overall survival, time to locoregional recurrence/progression, and distant metastasis by stage at presentation. RESULTS: DLI was detected in 215 (63.2%) of IBC cases overall. At disease presentation, IBC with DLI had a higher prevalence of de novo metastases (37.7% vs. 26.4%), breast skin ulceration (6.1% vs. 2.4%), and lymphovascular invasion within the breast parenchyma (52.9% vs. 25.5%) and a lower prevalence of palpable breast mass (48.2% vs. 70.6%) than IBC without DLI. Over a median follow-up of 2.0 years, 147 deaths occurred. DLI was not associated with survival or recurrence in multivariable models (all P ≥0.10). For example, among women with stage III disease, hazard ratios (95% confidence intervals) for DLI presence was 1.29 (0.77-2.15) for overall survival, 1.29 (0.56-3.00) for locoregional recurrence, and 1.71 (0.97-3.02) for distant metastasis. CONCLUSION: Although the extent of tumor emboli in dermal lymphatics may be associated with biological features of IBC, DLI was not an independent prognostic marker of clinical outcomes in this study.

Improving Colorectal Cancer Screening in a Rural Setting: A Randomized Study.

INTRODUCTION: Colorectal cancer screening has been shown to prevent or detect early colorectal cancer and reduce mortality; yet, adherence to screening recommendations remains low, particularly in rural settings. STUDY DESIGN: RCT. SETTING/PARTICIPANTS: Adults (n=7,812) aged 50-75 years and due for colorectal cancer screening in a largely rural health system were randomly assigned to either the intervention (n=3,906) or the control (n=3,906) group in September 2016, with analysis following through 2018. INTERVENTION: A mailed motivational messaging screening reminder letter with an option to call and request a free at-home fecal immunochemical screening test (intervention) or the standard invitation letter detailing that the individual was due for screening (control). Multifaceted motivational messaging emphasized colorectal cancer preventability and the ease and affordability of screening, and communicated a limited supply of test kits. MAIN OUTCOME MEASURES: Colorectal cancer screening participation within 6 months after mailed invitation was ascertained from the electronic medical record. RESULTS: Colorectal cancer screening participation was significantly improved in the intervention (30.1%) vs the usual care control group (22.5%; p<0.001). Individuals randomized to the intervention group had 49% higher odds of being screened over follow-up than those randomized to the control group (OR=1.49, 95% CI=1.34, 1.65). A total of 13.2 screening invitations were needed to accomplish 1 additional screening over the usual care. Of the 233 fecal immunochemical test kits mailed to participants, 154 (66.1%) were returned, and 18 (11.7%) tested positive. CONCLUSIONS: A mailed motivational messaging letter with a low-cost screening alternative increased colorectal cancer screening in this largely rural community with generally poor adherence to screening recommendations. Mailed colorectal cancer screening reminders using motivational messaging may be an effective method for increasing screening and reducing rural colorectal cancer disparities.

Racial/ethnic disparities in inflammatory breast cancer survival in the Michigan Cancer Surveillance Program.

PURPOSE: While racial disparities in inflammatory breast cancer (IBC) incidence are fairly well documented, with black women having significantly higher rates compared to white women; less is known about whether IBC prognosis differs by race/ethnicity. Therefore, the objective of this study was to assess racial/ethnic disparities in survival among women diagnosed with IBC in the Michigan Cancer Surveillance Program (MCSP) from 1998 to 2014. METHODS: We examined the frequency and percentage of breast cancer cases coded to the various IBC codes in the MCSP registry over the study period. We used age-adjusted and multivariable Cox Proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of race/ethnicity with all-cause mortality. RESULTS: Using a comprehensive case definition of IBC, 1324 IBC patients were identified from women diagnosed with invasive breast cancer in the MCSP [Non-Hispanic Black (NHB) = 227; Non-Hispanic White (NHW) = 984; Hispanic = 86; other = 27]. The percentage of all breast cancer cases defined as IBC in the MCSP registry differs considerably across registry codes from 0.02 to 1.1%. We observed significantly higher risk of death among NHB compared with NHW [HR (95% CI), 1.21 (1.01-1.45)], while no significant survival differences were observed between NHW and Hispanics or other racial/ethnic minorities. CONCLUSIONS: A comprehensive case definition should be utilized to avoid underestimation of IBC and to better understand this aggressive disease. Further research is needed to identify underlying causes and develop effective interventions to reduce IBC survival disparities between NHB and NHW women.

Erythrocyte membrane fatty acids and breast cancer risk: a prospective analysis in the nurses' health study II.

The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996 and 1999, and breast cancer risk in a nested case-control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n = 794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI ≥ 25), several odd-chain saturated (SFA, e.g. 17:0, ORQ4vsQ1 (95% CI) =1.85 (1.18-2.88), ptrend =0.006 pint <0.001), trans (TFA, e.g. 18:1, ORQ4vsQ1 (95% CI) =2.33 (1.45-3.77), ptrend <0.001, pint =0.007) and dairy-derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n-7t; ORQ4vsQ1 (95% CI) =1.83(1.16-2.89), ptrend =0.005, pint <0.001) were positively associated, and n-3 polyunsaturated fatty acids (n-3 PUFA, e.g. alpha-linolenic acid; ORQ4vsQ1 (95% CI) =0.57 (0.36-0.89), ptrend =0.017, pint =0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI < 25 (ORQ4vsQ1 (95% CI) =0.68 (0.46-0.98), ptrend =0.05, pint =0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy-derived fatty acids and inverse associations of n-3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted.

Assessment of Ki67 expression for breast cancer subtype classification and prognosis in the Nurses' Health Study.

PURPOSE: Ki67 is a proliferation marker commonly assessed by immunohistochemistry in breast cancer, and it has been proposed as a clinical marker for subtype classification, prognosis, and prediction of therapeutic response. However, the clinical utility of Ki67 is limited by the lack of consensus on the optimal cut point for each application. METHODS: We assessed Ki67 by immunohistochemistry using Definiens digital image analysis (DIA) in 2653 cases of incident invasive breast cancer diagnosed in the Nurses' Health Study from 1976 to 2006. Ki67 was scored as continuous percentage of positive tumor cells, and dichotomized at various cut points. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models for distant recurrence, breast cancer-specific mortality and overall mortality in relation to luminal subtypes defined with various Ki67 cut points, adjusting for breast cancer prognostic factors, clinico-pathologic features and treatment. RESULTS: DIA was highly correlated with manual scoring of Ki67 (Spearman correlation ρ = 0.86). Mean Ki67 score was higher in grade-defined luminal B (12.6%), HER2-enriched (17.9%) and basal-like (20.6%) subtypes compared to luminal A (8.9%). In multivariable-adjusted models, luminal B tumors had higher breast cancer-specific mortality compared to luminal A cancer classified using various cut points for Ki67 positivity including the 14% cut point routinely reported in the literature (HR 1.38, 95% CI 1.11-1.72, p = 0.004). There was no significant difference in clinical outcomes for ER- tumors according to Ki67 positivity defined at various cut points. CONCLUSIONS: Assessment of Ki67 in breast tumors by DIA was a robust and quantitative method. Results from this large prospective cohort study provide support for the clinical relevance of using Ki67 at the 14% cut point for luminal subtype classification and breast cancer prognosis.