Understanding benign breast disease and subsequent breast cancer in Hispanic white females; a step closer to evidence-based management.

Background While Hispanic white females (HW) have lower incidence of breast cancer (BC) than non-Hispanic white females (NHW), BC risk is unclear for HW females after benign breast disease (BBD). Methods We compared BBD characteristics and subsequent BC risk among HW and NHW females in New Mexico using a population-based collection of benign breast biopsies (1996-2007). BBD was categorized as non-proliferative disease (NPD), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). BC risk was assessed as absolute risk (AR) using cumulative incidence and relative risk (RR) by comparing the number of BC events in BBDs to non-BBD. Results This study included 3,684 HW and 6,587 NHW females with BBD. HW females had similar proportions of NPD (58.6%vs.54.3%), PDWA (21.4%vs.23.5%), and AH (3.6%vs.3.3%) as NHW. BC risk among all females with BBD was higher than population-based expected rates (RR=1.87) and was similar for HW and NHW subgroups (RR=1.99vs.1.84). As expected, BC risk increased with increasing BBD severity, both overall [RR=1.81 (NPD), 1.85 (PDWA) and 3.10 (AH)] and in the HW and NHW subgroups. Adjusted AR of BC at 5 years also increased with the severity of BBD (HW vs. NHW;NPD: 1.4 vs. 2.1%; PDWA: 1.5 vs. 2.7%; AH: 6 vs. 4.8%). Conclusions We found similar BC RRs and ARs in HW and NHW. Risk counseling should ensure that HW females receive breast cancer clinical management warranted by their similar absolute risks. Impact The present population-based provides evidence for clinical management of HW females with BBD for the prevention of BC.

Social media use among adolescents with acne: A cross-sectional survey study.

Social media is increasingly used by patients for the management of skin conditions like acne, despite the potential risk for low-quality information. This study surveyed 45 participants between the ages of 12 and 17 years to investigate factors that could be associated with social media use among adolescents with acne. The likelihood of social media use was not significantly increased by clinical severity of acne, more severe physical barriers (greater than or equal to 20 miles to the dermatology clinic), more severe temporal barriers (waiting 12 or more weeks for a first dermatology appointment), or worsened quality of life (assessed via the Skindex-Teen score). This study increases understanding of adolescents' social media behaviors, particularly as a way to seek information for skin conditions like acne.

Understanding the Procedural Skills Needed in Rural Pediatric Practices: A Survey of Rural Pediatric Providers in the State of New Mexico.

OBJECTIVES: There is little data evaluating procedural skills in current rural pediatric practices. In order to prepare a cadre of pediatricians to work in rural settings, we require an understanding of the unique procedural skills needed by rural pediatric providers. Our objective was to determine how often pediatricians performed various procedural skills, determine the importance of these skills to current practice, and how they differ between rural and urban pediatric providers. METHODS: A survey evaluating pediatrician utilization of the 13 required Accreditation Council Graduate Medical Education procedural skills in current practice was developed and distributed to pediatric providers in New Mexico. Descriptive statistics were used to profile participants and describe survey responses. Chi-square tests were used to evaluate differences by urban setting or IHS. Fisher's exact test was employed to assess differences if cell sizes were less than five. All p-values were two sided with alpha=.05. Benjamini-Hochberg method was used to control for type 1 errors. RESULTS: Fifty-two of 216 pediatric providers responded. The majority surveyed performed each of the 13 procedures less than monthly but competency in many of these procedures is important. Thirty-two respondents submitted free-text responses recommending competence with tracheostomy changes, gastrostomy-tube changes/cares, and circumcision. CONCLUSION: Majority of surveyed pediatricians performed the required procedures less than monthly but deemed several procedures to be important. Rural pediatricians recommended specific procedural skills needed in rural practice. All trainees receive procedural skills training. However, trainees interested in rural practice may need additional training in specific skills different than their non-rural counterparts.

Clinical outcomes of pediatric osteomyelitis.

BACKGROUND: Osteomyelitis in children may produce severe sequelae. However, the frequency and distribution of such complications by type of osteomyelitis (chronic or acute) is not well described. METHODS: We searched the HealthFacts® database (containing medical information on 68 million individual patients in the United States) with 238 International Classification of Diseases (ICD) version 10 codes for acute osteomyelitis and chronic osteomyelitis appearing in 2015. Outcomes were recorded for each subject, including development of limb length discrepancies, pathologic fractures, mortality, and need for multiple surgeries or prolonged orthopedic care (one to two years following diagnosis). Gender, age and season of diagnosis were also assessed. Chi-square tests were used to compare differences between categorical variables, and t-tests between continuous variables. RESULTS: Eight hundred sixty-nine subjects were included (57.4% male). Children with chronic osteomyelitis were older than those with acute osteomyelitis (median 9.5 years vs 12.0, respectively, p = .0004). Diagnoses were more common in winter (p = .0003). Four subjects died while hospitalized during the study period (two with acute osteomyelitis, two with chronic osteomyelitis). Limb length discrepancies were rare and similarly distributed between infection types (≤ 1.3% of subjects, p = .83). Subjects with chronic osteomyeltis were more likely to require long-term orthopedic follow-up (14.0% vs. 4.8% for acute osteomyelitis, p < .0001), suffer from pathologic fractures (1.5% vs < 1.0%, p = .003) and to require multiple surgeries (46.0% vs. 29.3%, p = .04). CONCLUSIONS: Though infrequent, serious outcomes from osteomyelitis are more common with chronic osteomyelitis than acute osteomyelitis.

The Association of Antimicrobial Prophylaxis With Return Visits After Dog Bites in Children.

OBJECTIVES: Dog bites occur frequently in the United States, yet there are no clear guidelines for prescribing antibiotic prophylaxis in healthy children after a dog bite. The aim of our study was to assess antibiotic prophylaxis and subsequent rates of infection after dog bites in children. We hypothesized a negative association between prophylactic prescription of any antimicrobial and return visit within 14 days for infection. METHODS: In this retrospective cohort study, we assessed the frequency of antibiotic prophylaxis prescribed after dog bite injuries in patients 0 to 18 years old and subsequent return visits for infection using 2016 to 2017 medical and pharmacy claims derived from the IBM MarketScan Research Databases. We used the International Classification of Diseases-10 code W54 for dog bites then used keyword searches to find diagnoses (including infection), wound descriptions, and medications. RESULTS: Over the 2-year period, 22,911 patients were seen for dog bites that were not coded as infected. The majority, 13,043 (56.9%), were prescribed an antibiotic at the initial visit and 9868 (43.1%) were not. Of those prescribed antibiotics, 98 (0.75%; 95% confidence interval [CI], 0.60-0.90) returned with an infection, compared with 59 (0.60%; 95% CI, 0.44-0.75) of those not prescribed antibiotics. Receiving an antibiotic prescription at the initial visit was associated with a reduced rate of return for wound infection only among children whose wounds were repaired or closed. Children not receiving a prescription whose wounds were repaired were more than twice as likely to return with an infection in the subsequent 14 days as children whose wounds were not repaired (odds ratio, 2.2; 95% CI, 1.2-4.0). CONCLUSIONS: Most children are prescribed antibiotics at an initial emergency department visit after a dog bite. However, very few return for infection independent of antimicrobial prophylaxis, which suggests antibiotics are overprescribed in this setting.

Genomic characterization of Staphylococcus aureus isolates causing osteoarticular infections in otherwise healthy children.

BACKGROUND: Pediatric osteoarticular infections are commonly caused by Staphylococcus aureus. The contribution of S. aureus genomic variability to pathogenesis of these infections is poorly described. METHODS: We prospectively enrolled 47 children over 3 1/2 years from whom S. aureus was isolated on culture-12 uninfected with skin colonization, 16 with skin abscesses, 19 with osteoarticular infections (four with septic arthritis, three with acute osteomyelitis, six with acute osteomyelitis and septic arthritis and six with chronic osteomyelitis). Isolates underwent whole genome sequencing, with assessment for 254 virulence genes and any mutations as well as creation of a phylogenetic tree. Finally, isolates were compared for their ability to form static biofilms and compared to the genetic analysis. RESULTS: No sequence types predominated amongst osteoarticular infections. Only genes involved in evasion of host immune defenses were more frequently carried by isolates from osteoarticular infections than from skin colonization (p = .02). Virulence gene mutations were only noted in 14 genes (three regulating biofilm formation) when comparing isolates from subjects with osteoarticular infections and those with skin colonization. Biofilm results demonstrated large heterogeneity in the isolates' capacity to form static biofilms, with healthy control isolates producing more robust biofilm formation. CONCLUSIONS: S. aureus causing osteoarticular infections are genetically heterogeneous, and more frequently harbor genes involved in immune evasion than less invasive isolates. However, virulence gene carriage overall is similar with infrequent mutations, suggesting that pathogenesis of S. aureus osteoarticular infections may be primarily regulated at transcriptional and/or translational levels.

Ex Vivo Toxicity of Commonly Used Topical Antiseptics and Antibiotics on Human Chondrocytes.

Topical povidone-iodine, chlorhexidine, bacitracin, and vancomycin are commonly used antiseptic and antimicrobial agents to reduce risk and treat surgical site infections in numerous orthopedic procedures. Chondrocytes potentially may be exposed to these agents during operative procedures. The impact of these topical agents on chondrocyte viability is unclear. The goal of this study is to determine human chondrocyte viability ex vivo after exposure to commonly used concentrations of these topical antiseptic and antimicrobial agents. Human osteochondral plugs were harvested from the knee joint of a human decedent within 36 hours of death. Individual human osteochondral plugs were exposed to normal saline as a control; a range of concentrations of povidone-iodine (0.25%, 0.5%, and 1%), chlorhexidine (0.01% and 0.5%), and bacitracin (10,000 units/L, 50,000 units/L, and 100,000 units/L) for 1-minute lavage; or a 48-hour soak in vancomycin (0.16 mg/mL, 0.4 mg/mL, and 1.0 mg/mL) with nutrient media. Chondrocyte viability was evaluated with a live/dead viability assay at 0, 2, 4, and 6 days after exposure to bacitracin at 0, 3, and 6 days). Control subjects showed greater than 70% viability at all time points. Povidone-iodine, 0.5% chlorhexidine, and vancomycin showed significant cytotoxicity, with viability dropping to less than 40% by day 6. Chondrocytes exposed to 0.01% chlorhexidine maintained viability. Chondrocytes exposed to bacitracin showed viability until day 3, when there was a large drop in viability. Commonly used topical concentrations of povidone-iodine, vancomycin, and bacitracin are toxic to human chondrocytes ex vivo. A low concentration of chlorhexidine appears safe. Caution should be used when articular cartilage may be exposed to these agents during surgery. [Orthopedics. 2022;45(5):e263-e268.].

Antihypertensive medications and risks of recurrence and mortality in luminal, triple-negative, and HER2-overexpressing breast cancer.

PURPOSE: Antihypertensives are commonly prescribed medications and their effect on breast cancer recurrence and mortality is not clear, particularly among specific molecular subtypes of breast cancer: luminal, triple-negative (TN), and HER2-overexpressing (H2E). METHODS: A population-based prospective cohort study of women aged 20-69 diagnosed with a first primary invasive breast cancer between 2004 and 2015 was conducted in the Seattle, Washington and Albuquerque, New Mexico greater metropolitan areas. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality associated with hypertension and antihypertensives. RESULTS: In this sample of 2,383 luminal, 1,559 TN, and 615 H2E breast cancer patients, overall median age was 52 (interquartile range, 44-60). Hypertension and current use of antihypertensives were associated with increased risks of all-cause mortality in each subtype. Current use of angiotensin-converting enzyme inhibitors was associated with increased risks of both recurrence and breast cancer-specific mortality among luminal patients (HR: 2.5; 95% CI: 1.5, 4.3 and HR: 1.9; 95% CI: 1.2, 3.0, respectively). Among H2E patients, current use of calcium channel blockers was associated with an increased risk of breast cancer-specific mortality (HR: 1.8; 95% CI: 0.6, 5.4). CONCLUSION: Our findings suggest that some antihypertensive medications may be associated with adverse breast cancer outcomes among women with certain molecular subtypes. Additional studies are needed to confirm these findings.

Spreading depolarization may represent a novel mechanism for delayed fluctuating neurological deficit after chronic subdural hematoma evacuation.

OBJECTIVE: Most patients with chronic subdural hematoma (cSDH) recover after surgical evacuation with a straightforward course. There is a subset of patients who develop transient and fluctuating deficits not explained by seizures, stroke, or mass effect after evacuation. The objective of this study was to investigate whether these postoperative neurological deficits may be related to temporary brain dysfunction caused by cortical spreading depolarizations (SDs). METHODS: The authors conducted a prospective observational study of 40 patients who underwent cSDH evacuation. At the time of surgery, a 1 × 6 subdural electrode strip was placed on the cortex parallel to the subdural drain. Clinical outcomes were assessed utilizing the Markwalder Grading Scale, need for clinical EEG for new deficit, and presence of new deficits. RESULTS: Definitive SD was detected in 6 (15%) of 40 patients. Baseline and cSDH characteristics did not differ between patients with and without SD. More patients experienced postoperative neurological deterioration if they had SD (50%) compared to those without SD (8.8%; p = 0.03). Only 2 patients in the entire cohort demonstrated early neurological deterioration, both of whom had SD. One of these cases demonstrated a time-locked new focal neurological deficit (aphasia) at the start of a series of multiple clusters of SD. CONCLUSIONS: This is the first observation of SD occurring after cSDH evacuation. SD occurred at a rate of 15% and was associated with neurological deterioration. This may represent a novel mechanism for otherwise unexplained fluctuating neurological deficit after cSDH evacuation. This could provide a new therapeutic target, and SD-targeted therapies should be evaluated in prospective clinical trials.

Advancing Pan-cancer Gene Expression Survial Analysis by Inclusion of Non-coding RNA.

Non-coding RNAs occupy a significant fraction of the human genome. Their biological significance is backed up by a plethora of emerging evidence. One of the most robust approaches to demonstrate non-coding RNA's biological relevance is through their prognostic value. Using the rich gene expression data from The Cancer Genome Altas (TCGA), we designed Advanced Expression Survival Analysis (AESA), a web tool which provides several novel survival analysis approaches not offered by previous tools. In addition to the common single-gene approach, AESA computes the gene expression composite score of a set of genes for survival analysis and utilizes permutation test or cross-validation to assess the significance of log-rank statistic and the degree of over-fitting. AESA offers survival feature selection with post-selection inference and utilizes expanded TCGA clinical data including overall, disease-specific, disease-free, and progression-free survival information. Users can analyse either protein-coding or non-coding regions of the transcriptome. We demonstrated the effectiveness of AESA using several empirical examples. Our analyses showed that non-coding RNAs perform as well as messenger RNAs in predicting survival of cancer patients. These results reinforce the potential prognostic value of non-coding RNAs. AESA is developed as a module in the freely accessible analysis suite MutEx. Abbreviation: ACC: Adrenocortical Carcinoma (n = 92); BLCA: Bladder Urothelial Carcinoma (n = 412); BRCA: Breast Invasive Carcinoma (n = 1098); CESC: Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (n = 307); CHOL: Cholangiocarcinoma (n = 51); COAD: Colon Adenocarcinoma (n = 461); DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (n = 58); ESCA: Oesophageal Carcinoma (n = 185); GBM: Glioblastoma Multiforme (n = 617); HNSC: Head and Neck Squamous Cell Carcinoma (n = 528); KICH: Kidney Chromophobe (n = 113); KIRC: Kidney Renal Clear Cell Carcinoma (n = 537); KIRP: Kidney Renal Papillary Cell Carcinoma (n = 291); LAML: Acute Myeloid Leukaemia (n = 200); LGG: Brain Lower Grade Glioma (n = 516); LIHC: Liver Hepatocellular Carcinoma (n = 377); LUAD: Lung Adenocarcinoma (n = 585); LUSC: Lung Squamous Cell Carcinoma (n = 504); MESO: Mesothelioma (n = 87); OV: Ovarian Serous Cystadenocarcinoma (n = 608) PAAD: Pancreatic Adenocarcinoma (n = 185); PCPG: Pheochromocytoma and Paraganglioma (n = 179); PRAD: Prostate Adenocarcinoma (n = 500); READ: Rectum Adenocarcinoma (n = 172); SARC: Sarcoma (n = 261); SKCM: Skin Cutaneous Melanoma (n = 470); STAD: Stomach Adenocarcinoma (n = 443); TGCT: Testicular Germ Cell Tumours (n = 150); THCA: Thyroid Carcinoma (n = 507) THYM: Thymoma (n = 124); UCEC: Uterine Corpus Endometrial Carcinoma (n = 560); UCS: Uterine Carcinosarcoma (n = 57); UVM: Uveal Melanoma (n = 80).

Relationship between Insurance Type at Diagnosis and Hepatocellular Carcinoma Survival.

BACKGROUND: For individuals with hepatocellular carcinoma (HCC), type of insurance may be an important prognostic factor because of its impact on access to care. This study investigates the relationship between insurance type at diagnosis and stage-specific survival. METHODS: This retrospective cohort analysis used data from 18 Surveillance, Epidemiology, and End Results Program cancer registries. Individuals ages 20 to 64 years, diagnosed with primary HCC between 2010 and 2015, with either private, Medicaid, or no insurance were eligible for cohort inclusion. Adjusted Cox proportional-hazards regression models were used to generate HRs and 95% confidence intervals (CI) for associations between insurance type at diagnosis and overall survival. All models were stratified by stage at diagnosis. RESULTS: This analysis included 14,655 cases. Compared with privately insured individuals with the same stage of disease, those with Medicaid had a 43% (HR = 1.43; 95% CI, 1.13-1.32), 22% (HR = 1.22; 95% CI, 1.13-1.32), and 7% higher risk of death for localized, regional, and distant stage, respectively. Uninsured individuals had an 88% (HR = 1.88; 95% CI, 1.65-2.14), 59% (HR = 1.59; 95% CI, 1.41-1.80), and 35% (HR = 1.35; 95% CI, 1.18-1.55) higher risk of death for localized, regional, and distant stage, respectively, compared with privately insured individuals. CONCLUSIONS: Disparities in survival exist by the type of insurance that individuals with HCC have at the time of diagnosis. IMPACT: These findings support the need for additional research on access to and quality of cancer care for Medicaid and uninsured patients.

Temporal trends in breast cancer survival by race and ethnicity: A population-based cohort study.

INTRODUCTION: Differences in breast cancer survival by race and ethnicity are often assumed to be a fairly recent phenomenon, and are hypothesized to have arisen due to gaps in receipt of screening or therapy. The emergence of these differences in calendar time have implications for identification of their origin. We sought to determine whether breast cancer survival differences by race or ethnicity arose in tandem with the advent of screening or therapeutic advances. MATERIALS AND METHODS: A cohort of women diagnosed with invasive breast cancer from 1975-2009 in 18 population-based registries were followed for five-year breast cancer cause-specific survival. Differences in survival according to race/ethnicity and estrogen receptor status were quantified in Cox proportional hazards models, with estimation of hazard ratios (HR), 95% confidence intervals (CI), and absolute risk differences. For 2010, we also assessed differences in survival by breast cancer subtypes defined by hormone receptor and Her2/neu status. RESULTS: Among over 930,000 women, initial differences in five-year breast cancer-specific survival by race became apparent among 1975-1979 diagnoses and continued to be evident, with stronger disparities apparent in those of Black vs. White Non-Hispanic (WNH) race and among estrogen-receptor positive vs. negative disease. Within breast cancer subtype, all included race/ethnic groups experienced disparate survival in comparison with WNH women for triple-negative disease. Black women had a consistent gap in absolute survival of .10-.12, compared with WNH women, from 1975-1979 through all included time periods, such that 5- year survival of Black women diagnosed in 2005-09 lagged more than 20 years behind that of WNH women. DISCUSSION: Survival differed by race for diagnoses that predate the introduction of mammographic screening and most therapeutic advances. Absolute differences in survival by race and ethnicity have remained almost constant over 40 years of observation, suggesting early origins for some contributors.

Obesity and survival among a cohort of breast cancer patients is partially mediated by tumor characteristics.

Obesity exerts adverse effects on breast cancer survival, but the means have not been fully elucidated. We evaluated obesity as a contributor to breast cancer survival according to tumor molecular subtypes in a population-based case-cohort study using data from the Surveillance Epidemiology and End Results (SEER) program. We determined whether obese women were more likely to be diagnosed with poor prognosis tumor characteristics and quantified the contribution of obesity to survival. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated via Cox multivariate models. The effect of obesity on survival was evaluated among 859 incident breast cancers (subcohort; 15% random sample; median survival 7.8 years) and 697 deaths from breast cancer (cases; 100% sample). Obese women had a 1.7- and 1.8-fold increased risk of stage III/IV disease and grade 3/4 tumors, respectively. Obese women with Luminal A- and Luminal B-like breast cancer were 1.8 (95% CI 1.3-2.5) and 2.2 (95% CI 0.9-5.0) times more likely to die from their cancer compared to normal weight women. In mediation analyses, the proportion of excess mortality attributable to tumor characteristics was 36.1% overall and 41% and 38% for Luminal A- and Luminal B-like disease, respectively. Obesity was not associated with breast cancer-specific mortality among women who had Her2-overexpressing or triple-negative tumors. Obesity may influence hormone-positive breast cancer-specific mortality in part through fostering poor prognosis tumors. When tumor biology is considered as part of the causal pathway, the public health impact of obesity on breast cancer survival may be greater than previously estimated.

Relationship between Diabetes and Diabetes Medications and Risk of Different Molecular Subtypes of Breast Cancer.

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.

Recent Use of Oral Contraceptives and Risk of Luminal B, Triple-Negative, and HER2-Overexpressing Breast Cancer.

Oral contraceptive use is a well-established risk factor for breast cancer and is common among reproductive-aged women in the USA. Its relationship with less common, more aggressive, molecular subtypes is less clear. A population-based case-case analysis was conducted comparing three less common molecular subtypes to luminal A breast cancer among 1701 premenopausal cases aged 21-49 diagnosed with a first primary invasive breast cancer between 2004 and 2015. Medical record reviews and structured interviewer-administered questionnaires were used to collect data on oral contraceptive use. Multinomial logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for recency of oral contraceptive use for each subtype of breast cancer. Current use of oral contraceptives and use within 5 years before diagnosis was associated with lower odds of H2E tumors compared with luminal A tumors [OR = 0.5, 95% CI: 0.3, 0.9 and OR = 0.5, 95% CI: 0.4, 0.8, respectively] with increasing duration associated with decreasing odds (p for trend < 0.05). Oral contraceptive use was not associated with risks of TN or luminal B breast cancer. Oral contraceptive use may be more strongly positively associated with risks of luminal A, luminal B, and TN breast cancer than with risk of H2E tumors. These findings contribute to the etiological understanding of different molecular subtypes of breast cancer.

Alcohol, smoking, and risk of Her2-overexpressing and triple-negative breast cancer relative to estrogen receptor-positive breast cancer.

Epidemiological evidence is limited on how alcohol consumption and smoking are associated with risk of different subtypes of breast cancer, such as triple-negative (TN) and human epidermal growth factor receptor 2-overexpressing (H2E) breast cancers, which may have different etiologies from more common luminal (estrogen receptor [ER+]) breast cancers. In this population-based case-case study, we evaluated the association between alcohol, smoking, and risk of H2E and TN breast cancer, compared with ER+ breast cancers, among women aged 20-69 years. Using polytomous regression, associations between alcohol consumption, smoking, and breast cancer risk were evaluated in 909 ER+, 1,290 TN, and 489 H2E breast cancer patients, with ER+ breast cancer patients as the reference group. Current alcohol consumption at diagnosis was associated with a lower risk of H2E breast cancer (odds ratio = 0.74, 95% confidence interval: 0.58-0.92) relative to ER+ cancers. No difference in association was observed by menopausal status. No association between alcohol consumption and TN breast cancer relative to ER+ breast cancer was observed. Women who smoked did not have an altered risk of TN or H2E breast cancer, relative to ER+ cancer. Our results suggest that alcohol is associated with lower risk of H2E breast cancer relative to ER+ breast cancer. This study adds to the body of epidemiologic evidence that breast cancer etiology differs by breast cancer subtype.

Breast cancer survival, survival disparities, and guideline-based treatment.

PURPOSE: The role of appropriate therapy in breast cancer survival and survival disparities by race/ethnicity has not been fully elucidated. We investigated whether lack of guideline-recommended therapy contributed to survival differences overall and among Hispanics relative to non-Hispanic white (NHW) women in a case-cohort study. METHODS: The study included a 15% random sample of female invasive breast cancer patients diagnosed from 1997 to 2009 in 6 New Mexico counties and all deaths due to breast cancer-related causes. Information was obtained from comprehensive medical chart reviews. National Comprehensive Cancer Network (NCCN®) guideline-recommended treatment was assessed among white women aged < 70 who were free of contraindications for recommended therapy, had stage I-III tumors, and survived ≥ 12 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer death were estimated using Cox proportional hazards models. RESULTS: Included women represented 4635 patients and 449 breast cancer deaths. Women who did not receive radiotherapy (HR 2.3; 95% CI 1.2-4.4) or endocrine therapy (HR 2.0; 95% CI 1.0-4.0) as recommended by guidelines had an increased risk of breast cancer death, relative to those treated appropriately. Receipt of guideline-recommended therapy did not differ between Hispanic and NHW women for chemotherapy (84.2% vs. 81.3%, respectively), radiotherapy (89.2% vs. 91.1%), or endocrine therapy (89.2% vs. 85.8%), thus did not influence Hispanic survival disparities. CONCLUSIONS: Lack of guideline-recommended radiotherapy or endocrine therapy contributed to survival as strongly as other established prognostic indicators. Hispanic survival disparities in this population do not appear to be attributable to treatment differences.

Breast Biopsy Intensity and Findings Following Breast Cancer Screening in Women With and Without a Personal History of Breast Cancer.

Importance: There is little evidence on population-based harms and benefits of screening breast magnetic resonance imaging (MRI) in women with and without a personal history of breast cancer (PHBC). Objective: To evaluate biopsy rates and yield in the 90 days following screening (mammography vs magnetic resonance imaging with or without mammography) among women with and without a PHBC. Design, Setting, and Participants: Observational cohort study of 6 Breast Cancer Surveillance Consortium (BCSC) registries. Population-based sample of 812 164 women undergoing screening, 2003 through 2013. Exposures: A total of 2 048 994 digital mammography and/or breast MRI screening episodes (mammogram alone vs MRI with or without screening mammogram within 30 days). Main Outcomes and Measures: Biopsy intensity (surgical greater than core greater than fine-needle aspiration) and yield (invasive cancer greater than ductal carcinoma in situ greater than high-risk benign greater than benign) within 90 days of a screening episode. We computed age-adjusted rates of biopsy intensity (per 1000 screening episodes) and biopsy yield (per 1000 screening episodes with biopsies). Outcomes were stratified by PHBC and by BCSC 5-year breast cancer risk among women without PHBC. Results: We included 101 103 and 1 939 455 mammogram screening episodes in women with and without PHBC, respectively; MRI screening episodes included 3763 with PHBC and 4673 without PHBC. Age-adjusted core and surgical biopsy rates (per 1000 episodes) doubled (57.1; 95% CI, 50.3-65.1) following MRI compared with mammography (23.6; 95% CI, 22.4-24.8) in women with PHBC. Differences (per 1000 episodes) were even larger in women without PHBC: 84.7 (95% CI, 75.9-94.9) following MRI and 14.9 (95% CI, 14.7-15.0) following mammography episodes. Ductal carcinoma in situ and invasive biopsy yield (per 1000 episodes) was significantly higher following mammography compared with MRI episodes in women with PHBC (mammography, 404.6; 95% CI, 381.2-428.8; MRI, 267.6; 95% CI, 208.0-337.8) and nonsignificantly higher, but in the same direction, in women without PHBC (mammography, 279.3; 95% CI, 274.2-284.4; MRI, 214.6; 95% CI, 158.7-280.8). High-risk benign lesions were more commonly identified following MRI regardless of PHBC. Higher biopsy rates and lower cancer yield following MRI were not explained by increasing age or higher 5-year breast cancer risk. Conclusions and Relevance: Women with and without PHBC who undergo screening MRI experience higher biopsy rates coupled with significantly lower cancer yield findings following biopsy compared with screening mammography alone. Further work is needed to identify women who will benefit from screening MRI to ensure an acceptable benefit-to-harm ratio.

Underutilization of Supplemental Magnetic Resonance Imaging Screening Among Patients at High Breast Cancer Risk.

BACKGROUND: Women at high lifetime breast cancer risk may benefit from supplemental breast magnetic resonance imaging (MRI) screening, in addition to routine mammography screening for earlier cancer detection. MATERIALS AND METHODS: We performed a cross-sectional study of 422,406 women undergoing routine mammography screening across 86 Breast Cancer Surveillance Consortium (BCSC) facilities during calendar year 2012. We determined availability and use of on-site screening breast MRI services based on woman-level characteristics, including >20% lifetime absolute risk using the National Cancer Institute risk assessment tool. Multivariate analyses were performed to determine sociodemographic characteristics associated with on-site screening MRI use. RESULTS: Overall, 43.9% (2403/5468) of women at high lifetime risk attended a facility with on-site breast MRI screening availability. However, only 6.6% (158/2403) of high-risk women obtained breast MRI screening within a 2-year window of their screening mammogram. Patient factors associated with on-site MRI screening use included younger (<40 years) age (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.34-4.21), family history (OR = 1.72, 95% CI: 1.13-2.63), prior breast biopsy (OR = 2.09, 95% CI: 1.22-3.58), and postsecondary education (OR = 2.22, 95% CI: 1.04-4.74). CONCLUSIONS: While nearly half of women at high lifetime breast cancer risk undergo routine screening mammography at a facility with on-site breast MRI availability, supplemental breast MRI remains widely underutilized among those who may benefit from earlier cancer detection. Future studies should evaluate whether other enabling factors such as formal risk assessment and patient awareness of high lifetime breast cancer risk can mitigate the underutilization of supplemental screening breast MRI.

Utilization of breast cancer screening with magnetic resonance imaging in community practice.

BACKGROUND: Breast cancer screening with magnetic resonance imaging (MRI) may be a useful adjunct to screening mammography in high-risk women, but MRI uptake may be increasing rapidly among low- and average-risk women for whom benefits are unestablished. Comparatively little is known about use of screening MRI in community practice. OBJECTIVE: To assess relative utilization of MRI among women who do and do not meet professional society guidelines for supplemental screening, and describe utilization according to breast cancer risk indications. DESIGN: Prospective cohort study conducted between 2007 and 2014. PARTICIPANTS: In five regional imaging registries participating in the Breast Cancer Surveillance Consortium (BCSC), 348,955 women received a screening mammogram, of whom 1499 underwent screening MRI. MAIN MEASURES: Lifetime breast cancer risk (< 20% or ≥ 20%) estimated by family history of two or more first-degree relatives, and Gail model risk estimates. Breast Imaging Reporting and Data System breast density and benign breast diseases also were assessed. Relative risks (RR) for undergoing screening MRI were estimated using Poisson regression. KEY RESULTS: Among women with < 20% lifetime risk, which does not meet professional guidelines for supplementary MRI screening, and no first-degree breast cancer family history, screening MRI utilization was elevated among those with extremely dense breasts [RR 2.2; 95% confidence interval (CI) 1.7-2.8] relative to those with scattered fibroglandular densities and among women with atypia (RR 7.4; 95% CI 3.9-14.3.) or lobular carcinoma in situ (RR 33.1; 95% CI 18.0-60.9) relative to women with non-proliferative disease. Approximately 82.9% (95% CI 80.8%-84.7%) of screening MRIs occurred among women who did not meet professional guidelines and 35.5% (95% CI 33.1-37.9%) among women considered at low-to-average breast cancer risk. CONCLUSION: Utilization of screening MRI in community settings is not consistent with current professional guidelines and the goal of delivery of high-value care.