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1.  Specificity of Clinical Breast Examination in Community Practice 
Millions of women receive clinical breast examination (CBE) each year, as either a breast cancer screening test or a diagnostic test for breast symptoms. While screening CBE had moderately high specificity (∼94%) in clinical trials, community clinicians may be comparatively inexperienced and may conduct relatively brief examinations, resulting in even higher specificity but lower sensitivity.
To estimate the specificity of screening and diagnostic CBE in clinical practice and identify patient factors associated with specificity.
Retrospective cohort study.
Breast-cancer-free female health plan enrollees in 5 states (WA, OR, CA, MA, and MN) who received CBE (N = 1,484).
Medical charts were abstracted to ascertain breast cancer risk factors, examination purpose (screening vs diagnostic), and results (true-negative vs false-positive). Women were considered “average-risk” if they had neither a family history of breast cancer nor a prior breast biopsy and “increased-risk” otherwise.
Among average- and increased-risk women, respectively, the specificity (true-negative proportion) of screening CBE was 99.4% [95% confidence interval (CI): 98.8–99.7%] and 97.1% (95% CI: 95.7–98.0%), and the specificity of diagnostic CBE was 68.7% (95% CI: 59.7–76.5%) and 57.1% (95% CI: 51.1–63.0%). The odds of a true-negative screening CBE (specificity) were significantly lower among women at increased risk of breast cancer (adjusted odds ratio 0.21; 95% CI: 0.10–0.46).
Screening CBE likely has higher specificity among community clinicians compared to examiners in clinical trials of breast cancer screening, even among women at increased breast cancer risk. Highly specific examinations, however, may have relatively low sensitivity for breast cancer. Diagnostic CBE, meanwhile, is relatively nonspecific.
PMCID: PMC1824753  PMID: 17356964
breast cancer; sensitivity and specificity; screening; physical examination
2.  Practical Applications for Clinical Breast Examination (CBE) and Breast Self-Examination (BSE) in Screening and Early Detection of Breast Cancer* 
Breast Care  2008;3(1):17-20.
The background and preliminary results in terms of stage distribution are given for a trial of Clinical Breast Examination and the teaching of Breast Self-Examination in Cairo, Egypt. A stage shift towards early diagnosis appears to have been achieved. This has encouraged the development of similar projects in other middle income developing countries.
PMCID: PMC2931013  PMID: 20824015
Breast cancer; Screening; breast examination, clinical; Breast self-examination
3.  IHC for Her2 with CBE356 antibody is a more accurate predictor of Her2 gene amplification by FISH than HercepTest™ in breast carcinoma 
Journal of Clinical Pathology  2005;58(10):1086-1090.
Background: Her2 (c-erbB-2/neu) overexpression in breast carcinoma predicts response to the anti-Her2 monoclonal antibody, trastuzumab, and is associated with a poor prognosis. When considering patients for trastuzumab treatment, Her2 protein expression is measured by imunohistochemistry (IHC) and, where staining is equivocal, by fluorescence in situ hybridisation (FISH) detection of Her2 gene amplification.
Aims: To compare IHC using CBE356 with IHC using the Food and Drug Administration approved HercepTest™.
Methods: CBE356 and HercepTest were analysed using 167 FISH characterised breast carcinomas. Immunohistochemical expression of Her2 was measured semiquantitatively. Sensitivity, specificity, predictive values, and overall accuracy were calculated for both IHC methods using gene amplification by FISH as the end point, and IHC and FISH assays were tested in Kaplan–Meier survival analysis.
Results: The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CBE356 positive (2+ and 3+) cases were 94%, 89%, 95%, 84%, and 97%, respectively, and of HercepTest positive (2+ and 3+) cases were 91%, 66%, 98%, 92%, and 91%, respectively. A positive result with CBE356, HercepTest, or FISH was associated with significantly decreased overall survival (log rank p = 0.005, p = 0.0017, and p = 0.0005, respectively).
Conclusions: Positive IHC staining for Her2 using CBE356 is 3% more accurate and 23% more sensitive at predicting Her2 gene amplification by FISH than positive staining with HercepTest. Negative IHC using CBE356 antibody is 6% more likely to represent a truly negative result than negative staining with HercepTest. Overall, CBE356 was a more accurate predictor of Her2 gene amplification by FISH than HercepTest.
PMCID: PMC1770743  PMID: 16189156
CBE356; immunohistochemistry; Her expression; breast carcinoma
4.  Effectiveness of Computer-Aided Detection in Community Mammography Practice 
Computer-aided detection (CAD) is applied during screening mammography for millions of US women annually, although it is uncertain whether CAD improves breast cancer detection when used by community radiologists.
We investigated the association between CAD use during film-screen screening mammography and specificity, sensitivity, positive predictive value, cancer detection rates, and prognostic characteristics of breast cancers (stage, size, and node involvement). Records from 684 956 women who received more than 1.6 million film-screen mammograms at Breast Cancer Surveillance Consortium facilities in seven states in the United States from 1998 to 2006 were analyzed. We used random-effects logistic regression to estimate associations between CAD and specificity (true-negative examinations among women without breast cancer), sensitivity (true-positive examinations among women with breast cancer diagnosed within 1 year of mammography), and positive predictive value (breast cancer diagnosed after positive mammograms) while adjusting for mammography registry, patient age, time since previous mammography, breast density, use of hormone replacement therapy, and year of examination (1998–2002 vs 2003–2006). All statistical tests were two-sided.
Of 90 total facilities, 25 (27.8%) adopted CAD and used it for an average of 27.5 study months. In adjusted analyses, CAD use was associated with statistically significantly lower specificity (OR = 0.87, 95% confidence interval [CI] = 0.85 to 0.89, P < .001) and positive predictive value (OR = 0.89, 95% CI = 0.80 to 0.99, P = .03). A non-statistically significant increase in overall sensitivity with CAD (OR = 1.06, 95% CI = 0.84 to 1.33, P = .62) was attributed to increased sensitivity for ductal carcinoma in situ (OR = 1.55, 95% CI = 0.83 to 2.91; P = .17), although sensitivity for invasive cancer was similar with or without CAD (OR = 0.96, 95% CI = 0.75 to 1.24; P = .77). CAD was not associated with higher breast cancer detection rates or more favorable stage, size, or lymph node status of invasive breast cancer.
CAD use during film-screen screening mammography in the United States is associated with decreased specificity but not with improvement in the detection rate or prognostic characteristics of invasive breast cancer.
PMCID: PMC3149041  PMID: 21795668
5.  A nurse-delivered intervention to reduce barriers to breast and cervical cancer screening in Chicago inner city clinics. 
Public Health Reports  1994;109(1):104-111.
An 18-month intervention was implemented to increase breast and cervical cancer screening among poor African-American women in Chicago. Breast and cervical cancer screening programs were set up in two public clinics, one community-based and the other hospital-based. Nurse clinicians and public health workers were used in these programs to recruit women in the clinics and in targeted community institutions to receive free breast and cervical cancer screening. The following barriers were specifically addressed by the intervention: accessibility of screening, knowledge about breast and cervical cancers, access to followup screening examinations, and access to treatment. A computerized followup system was specifically designed to track patients. During the 18 months of the intervention, 10,829 visits were made by 7,654 low-income women. A total of 84 cases of breast cancer and 9 cases of cervical cancer were detected. Awareness of the program, as measured by a survey after the completion of the intervention, increased in both clinics compared with baseline results. Knowledge about breast and cervical cancers also increased, as measured by scores on tests given before and after a class on breast and cervical cancers. Followup rates were 86 percent for women attending the programs. More than 90 percent of the women referred for evaluation of breast abnormalities kept an appointment. In summary, the intervention was successful in reducing barriers to breast and cervical cancer detection and in attracting a high-risk group of women.
PMCID: PMC1402249  PMID: 8303003
6.  An admixture scan in 1,484 African American women with breast cancer 
African American women with breast cancer present more commonly with aggressive tumors that do not express the estrogen receptor (ER) and progesterone receptor (PR) compared with European American women. Whether this disparity is the result of inherited factors has not been established. We performed an admixture-based genome-wide scan to search for risk alleles for breast cancer that are highly differentiated in frequency between African American and European American women and may contribute to specific breast cancer phenotypes, such as ER negative (ER−) disease. African American women with invasive breast cancer (n=1,484) were pooled from 6 population-based studies and typed at ~1,500 ancestry informative markers (AIMs). We investigated global genetic ancestry and performed a whole genome admixture scan searching for breast cancer predisposing loci in association with disease phenotypes. We found a significant difference in ancestry between ER+PR+ and ER−PR− women, with higher European ancestry among ER+PR+ individuals, after controlling for possible confounders (OR for a 0 to 1 change in European ancestry proportion=2.84, 95% CI: 1.13–7.14, p=0.026). Women with localized tumors had higher European ancestry than women with non-localized tumors (OR=2.65, CI: 1.11–6.35, p=0.029). No genome-wide statistically significant associations were observed between European or African ancestry at any specific locus and breast cancer, or in analyses stratified by ER/PR status, stage or grade. In summary, in African American women genetic ancestry is associated with ER/PR status and disease stage. However, we found little evidence that genetic ancestry at any one region contributes significantly to breast cancer risk or hormone receptor status.
PMCID: PMC2783219  PMID: 19843668
African Americans; breast cancer; admixture mapping; hormone receptor status; genetic ancestry
7.  Using a state cancer registry to recruit young breast cancer survivors and high-risk relatives: protocol of a randomized trial testing the efficacy of a targeted versus a tailored intervention to increase breast cancer screening 
BMC Cancer  2013;13:97.
The Michigan Prevention Research Center, the University of Michigan Schools of Nursing, Public Health, and Medicine, and the Michigan Department of Community Health propose a multidisciplinary academic-clinical practice three-year project to increase breast cancer screening among young breast cancer survivors and their cancer-free female relatives at greatest risk for breast cancer.
The study has three specific aims: 1) Identify and survey 3,000 young breast cancer survivors (diagnosed at 20–45 years old) regarding their breast cancer screening utilization. 2) Identify and survey survivors’ high-risk relatives regarding their breast cancer screening utilization. 3) Test two versions (Targeted vs. Enhanced Tailored) of an intervention to increase breast cancer screening among survivors and relatives. Following approval by human subjects review boards, 3,000 young breast cancer survivors will be identified through the Michigan Cancer Registry and mailed an invitation letter and a baseline survey. The baseline survey will obtain information on the survivors’: a) current breast cancer screening status and use of genetic counseling; b) perceived barriers and facilitators to screening; c) family health history. Based on the family history information provided by survivors, we will identify up to two high-risk relatives per survivor. Young breast cancer survivors will be mailed consent forms and baseline surveys to distribute to their selected high-risk relatives. Relatives’ baseline survey will obtain information on their: a) current breast cancer screening status and use of genetic counseling; and b) perceived barriers and facilitators to screening. Young breast cancer survivors and high-risk relatives will be randomized as a family unit to receive two versions of an intervention aiming to increase breast cancer screening and use of cancer genetic services. A follow-up survey will be mailed 9 months after the intervention to survivors and high-risk relatives to evaluate the efficacy of each intervention version on: a) use of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing cancer genetic and screening services; d) family support related to screening; e) knowledge of breast cancer genetics; and f) satisfaction with the intervention.
The study will enhance efforts of the state of Michigan surrounding cancer prevention, control, and public health genomics.
Trial registration
PMCID: PMC3599993  PMID: 23448100
Breast cancer screening; Familial breast cancer; Young breast cancer survivors; High-risk relatives; Randomized trial; Targeted and enhanced tailored intervention; Screening mammography; Genetic testing; Cancer registry; State-wide community-based sample
8.  Breast Cancer Risk Prediction and Mammography Biopsy Decisions 
Controversy continues about screening mammography, in part because of the risk of false-negative and false-positive mammograms. Pre-test breast cancer risk factors may improve the positive and negative predictive value of screening.
To create a model that estimates the potential impact of pre-test risk prediction using clinical and genomic information on the reclassification of women with abnormal mammograms (BI-RADS3 and BI-RADS4 [Breast Imaging-Reporting and Data System]) above and below the threshold for breast biopsy.
The current study modeled 1-year breast cancer risk in women with abnormal screening mammograms using existing data on breast cancer risk factors, 12 validated breast cancer single nucleotide polymorphisms (SNPs), and probability of cancer given the BI-RADS category. Examination was made of reclassification of women above and below biopsy thresholds of 1%, 2%, and 3% risk. The Breast Cancer Surveillance Consortium data were collected from 1996 to 2002. Data analysis was conducted in 2010 and 2011.
Using a biopsy risk threshold of 2% and the standard risk factor model, 5% of women with a BI-RADS3 mammogram had a risk above the threshold, and 3% of women with BIRADS4A mammograms had a risk below the threshold. The addition of 12 SNPs in the model resulted in 8% of women with a BI-RADS3 mammogram above the threshold for biopsy and 7% of women with BI-RADS4A mammograms below the threshold.
The incorporation of pre-test breast cancer risk factors could change biopsy decisions for a small proportion of women with abnormal mammograms. The greatest impact comes from standard breast cancer risk factors.
PMCID: PMC3527848  PMID: 23253645
9.  Association between mammographic density and basal-like and luminal A breast cancer subtypes 
Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer.
We estimated associations between mammographic density and breast cancer risk according to breast cancer subtype. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). A total of 491 cases had mammograms within five years prior to and one year after diagnosis and 528 controls had screening or diagnostic mammograms close to the dates of selection into CBCS. Mammographic density was reported to the CMR using Breast Imaging Reporting and Data System categories. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 1 and 2 (HER1 and HER2), and cytokeratin 5/6 (CK5/6) were assessed by immunohistochemistry and dichotomized as positive or negative, with ER+ and/or PR+, and HER2- tumors classified as luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors classified as basal-like breast cancer. Triple negative tumors were defined as negative for ER, PR and HER2. Of the 491 cases 175 were missing information on subtypes; the remaining cases included 181 luminal A, 17 luminal B, 48 basal-like, 29 ER-/PR-/HER2+, and 41 unclassified subtypes. Odds ratios comparing each subtype to all controls and case-case odds ratios comparing mammographic density distributions in basal-like to luminal A breast cancers were estimated using logistic regression.
Mammographic density was associated with increased risk of both luminal A and basal-like breast cancers, although estimates were imprecise. The magnitude of the odds ratio associated with mammographic density was not substantially different between basal-like and luminal A cancers in case–control analyses and case-case analyses (case-case OR = 1.08 (95% confidence interval: 0.30, 3.84)).
These results suggest that risk estimates associated with mammographic density are not distinct for separate breast cancer subtypes (basal-like/triple negative vs. luminal A breast cancers). Studies with a larger number of basal-like breast cancers are needed to confirm our findings.
PMCID: PMC3978452  PMID: 24008056
Mammographic density; Breast cancer; Subtypes; Basal-like; Epidemiology
10.  Delivery of Cancer Screening 
Archives of internal medicine  2007;167(6):580-585.
Patients and physicians strongly endorse the importance of preventive or periodic health examinations (PHEs). However, the extent to which PHEs contribute to the delivery of cancer screening is uncertain.
In a retrospective cohort study, we determined the association between receipt of a PHE and cancer testing in a population-based sample of enrollees in a Washington State health plan who were aged 52 to 78 years and eligible for colorectal, breast, or prostate cancer screening in 2002–2003 (N = 64 288). Outcomes included completion of any colorectal cancer testing (fecal occult blood testing, sigmoidoscopy, colonoscopy, or barium enema), screening mammography, and prostate-specific antigen testing.
More than half (52.4%) of the enrollees received a PHE during the study period. After adjusting for demographics, comorbidity, number of outpatient visits, and historical preventive service use before January 1, 2002, receipt of a PHE was significantly associated with completion of colorectal cancer testing (incidence difference, 40.4% [95% confidence interval (CI), 39.4%–41.3%]; relative incidence, 3.47 [95% CI, 3.34–3.59]), screening mammography [incidence difference, 14.2% [95% CI, 12.7%–15.7%]; relative incidence, 1.23 [95% CI, 1.20–1.25]), and prostate-specific antigen testing (incidence difference, 39.4% [95% CI, 38.3%–40.5%]; relative incidence, 3.06 [95% CI, 2.95–3.18]).
Among managed care enrollees eligible for cancer screening, PHE receipt is associated with completion of colorectal, breast, and prostate cancer testing. In similar populations, the PHE may serve as a clinically important forum for the promotion of evidence-based colorectal cancer and breast cancer screening and of screening with relatively less empirical support, such as prostate cancer screening.
PMCID: PMC3443471  PMID: 17389289
11.  Patient-Provider Communication and Cancer Screening among Unmarried Women 
Patient education and counseling  2008;73(2):251-255.
Unmarried women are less likely than married women to receive recommended cancer screenings. Patient-provider communication is a consistent predictor of cancer screening among women. The purpose of this study was to investigate the relationship between patient-provider communication, barriers to cancer screening, and on-schedule breast and cervical cancer screening (BCCS) among unmarried women.
Data were from the Cancer Screening Project for Women, a 2003-2005 survey examining cancer screening practices. We computed polytomous logistic regression models to examine the relationship between communication (communication about tests, communication about sexual and intimate relationships), barriers to screening, and on-schedule BCCS among unmarried women.
A total of 630 women were enrolled, and 605 women completed the baseline questionnaire. Overall, more than 60% reported on-schedule BCCS. More than half reported that their providers communicated about BCCS most or all of the time. Fewer than half communicated about sexual history and intimate relationships. Women who reported that their providers communicated about screening tests and their sexual and intimate relationships were more likely to be on-schedule for BCCS.
Patient-provider communication in multiple areas may encourage women to remain on-schedule for their recommended cancer screenings. Longitudinal research should be conducted to examine whether communication predicts BCCS, and to examine how patient and provider characteristics may influence communication in order to promote adherence to screening guidelines for unmarried women.
Practice Implications:
Comprehensive communication that goes beyond information about screening tests may impact adherence to cancer screening guidelines.
PMCID: PMC2648309  PMID: 18723307
cancer screening; patient-provider communication
12.  Efficiency of palpation in clinical detection of breast cancer. 
An annual clinical screening test for breast cancer must be simple, brief and efficient. The traditional physical examination of the breast is time-consuming, mainly because of the complicated maneuvers necessary to inspect for retraction. Palpation with the patient supine, however, can be performed quickly. Of 286 primary breast cancers 96% (275) were palpable as a lump, and this was the only clinical sign in 55%. Retraction was the sole clinical sign in only 1%. The combination of retraction and a solid lump is a very specific but not very sensitive test for breast cancer. Retraction in this series was not related to the size of the primary tumour but among the women with a cancerous breast lump was significantly more likely to be found in those over 44 years of age, being present in 52% of these women but only 10% of the younger women. Inspection of the breast can therefore safely be detected from screening breast examinations, whether performed by the physician or the patient.
PMCID: PMC1862403  PMID: 7139488
13.  Interventions to Enhance Breast Cancer Screening, Diagnosis, and Treatment among Racial and Ethnic Minority Women 
Medical care research and review : MCRR  2007;64(5 Suppl):195S-242S.
The authors conduct a systematic review of the literature to identify interventions designed to enhance breast cancer screening, diagnosis, and treatment among minority women. Most trials in this area have focused on breast cancer screening, while relatively few have addressed diagnostic testing or breast cancer treatment. Among patient-targeted screening interventions, those that are culturally tailored or addressed financial or logistical barriers are generally more effective than reminder-based interventions, especially among women with fewer financial resources and those without previous mammography. Chart-based reminders increase physician adherence to mammography guidelines but are less effective at increasing clinical breast examination. Several trials demonstrate that case management is an effective strategy for expediting diagnostic testing after screening abnormalities have been found. Additional support for these and other proven health care organization-based interventions appears justified and may be necessary to eliminate racial and ethnic breast cancer disparities.
PMCID: PMC2657605  PMID: 17881627
breast cancer; screening; diagnosis; treatment; race; ethnicity; intervention
14.  Caregiving associated with selected cancer risk behaviors and screening utilization among women: cross-sectional results of the 2009 BRFSS 
BMC Public Health  2012;12:685.
Informal caregiving is increasingly common as the U.S. population ages, and there is concern that caregivers are less likely than non-caregivers to practice health-promoting behaviors, including cancer screening. We examined caregiving effects on cancer risk behaviors and breast and cervical cancer screening in the 2009 Behavioral Risk Factor Surveillance System.
Women age ≥41 with data on breast and cervical cancer screening were included (weighted frequency 3,478,000 women). Cancer screening was classified according to American Cancer Society guidelines. We evaluated the association of caregiving with cancer risk behaviors (obesity, physical activity, alcohol intake, smoking status, and fruit/vegetable consumption) and cancer screening (mammography, clinical breast exam [CBE], and Pap test) using logistic regression overall and with stratification on age (<65, ≥65) or race (white, non-white).
Caregivers had greater odds of being obese, physically active, and current smokers. Subgroup analyses revealed that caregiving was associated with obesity in younger women and whites, and with less obesity in older women. Also, caregiving was associated with smoking only among younger women and non-whites. Caregivers had greater odds of ever having had a mammogram or CBE, yet there was no association with mammogram, CBE, or Pap test within guidelines.
Caregiving was associated with some health behaviors that increase cancer risk, yet not with cancer screening within guidelines. Effects of caregiving by age and race require confirmation by additional studies.
PMCID: PMC3499215  PMID: 22908937
Caregiving; Mammography; Pap test; Health behaviors
15.  Using Clinical Factors and Mammographic Breast Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model 
Annals of internal medicine  2008;148(5):337-347.
Current models for assessing breast cancer risk are complex and do not include breast density, a strong risk factor for breast cancer that is routinely reported with mammography.
To develop and validate an easy-to-use breast cancer risk prediction model that includes breast density.
Empirical model based on Surveillance, Epidemiology, and End Results incidence, and relative hazards from a prospective cohort.
Screening mammography sites participating in the Breast Cancer Surveillance Consortium.
1 095 484 women undergoing mammography who had no previous diagnosis of breast cancer.
Self-reported age, race or ethnicity, family history of breast cancer, and history of breast biopsy. Community radiologists rated breast density by using 4 Breast Imaging Reporting and Data System categories.
During 5.3 years of follow-up, invasive breast cancer was diagnosed in 14 766 women. The breast density model was well calibrated overall (expected–observed ratio, 1.03 [95% CI, 0.99 to 1.06]) and in racial and ethnic subgroups. It had modest discriminatory accuracy (concordance index, 0.66 [CI, 0.65 to 0.67]). Women with low-density mammograms had 5-year risks less than 1.67% unless they had a family history of breast cancer and were older than age 65 years.
The model has only modest ability to discriminate between women who will develop breast cancer and those who will not.
A breast cancer prediction model that incorporates routinely reported measures of breast density can estimate 5-year risk for invasive breast cancer. Its accuracy needs to be further evaluated in independent populations before it can be recommended for clinical use.
PMCID: PMC2674327  PMID: 18316752
16.  Differences in Knowledge of Breast Cancer Screening Among African American, Arab American, and Latina Women 
Preventing Chronic Disease  2010;8(1):A20.
We examined differences in knowledge and socioeconomic factors associated with 3 types of breast cancer screening (breast self-examination, clinical breast examination, and mammogram) among African American, Arab, and Latina women.
Community health workers used a community-based intervention to recruit 341 women (112 Arab, 113 Latina, and 116 African American) in southeastern Michigan to participate in a breast cancer prevention intervention from August through October 2006. Before and after the intervention, women responded to a previously validated 5-item multiple-choice test on breast cancer screening (possible score range: 0 to 5) in their language of preference (English, Spanish, or Arabic). We used generalized estimating equations to analyze data and to account for family-level and individual correlations.
Although African American women knew more about breast cancer screening at the baseline (pretest median scores were 4 for African American, 3 for Arab and 3 for Latina women), all groups significantly increased their knowledge after participating in the breast cancer prevention intervention (posttest median scores were 5 for African American and 4 for Arab and Latina women). Generalized estimating equations models show that Arab and Latina women made the most significant gains in posttest scores (P < .001).
Racial/ethnic differences in knowledge of breast cancer screening highlight the need for tailored information on breast cancer screening for African American, Arab, and Latina women to promote adherence to breast cancer screening guidelines.
PMCID: PMC3044031  PMID: 21159232
17.  Sociodemographic Characteristics, Distance to the Clinic, and Breast Cancer Screening Results 
Timely detection and follow-up of abnormal cellular changes can aid in early diagnosis of breast cancer, thus leading to better treatment outcomes. However, despite substantial breast cancer screening initiatives, the proportion of female breast cancer cases diagnosed at late stages remains high. Distance to screening clinics may affect access to care, particularly for women living in impoverished areas with limited means of reliable transportation. Utilizing breast cancer screening data collected by the Illinois Breast and Cervical Cancer Program between 1996 and 2010, we examined the effect of travel distance to the clinic from which women received breast cancer screening tests on stage of diagnosis.
The proportion of abnormal mammograms in White women (1.6%) was higher than in Black women (1.1%) or Hispanic women (0.5%). The average distance traveled to a clinic was also farthest among White women (6.7 mi) than for Hispanic (5.3 mi) or Black women (4.4 mi). Distance to a clinic was significantly associated with increased odds of having abnormal results. When distance to clinic was controlled for, the observed disparity in odds of having an abnormal mammogram between White and Black women was no longer statistically significant. Individual and neighborhood sociodemographic characteristics were significantly associated with distance to clinic, but were not associated with increased odds of having an abnormal mammogram, controlling for distance to the clinic.
Findings showed that individual and neighborhood sociodemographic characteristics are directly and indirectly associated with abnormal mammogram results, and that distance to a clinic may mediate, in part, the effects of individual characteristics and neighborhood disadvantage on the probability of having an abnormal mammogram.
PMCID: PMC3898539  PMID: 24466505
Breast cancer screening; travel distance; abnormal mammogram
18.  Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts 
European Radiology  2009;20(3):734-742.
Mammography, the standard method of breast cancer screening, misses many cancers, especially in dense-breasted women. We compared the performance and diagnostic yield of mammography alone versus an automated whole breast ultrasound (AWBU) plus mammography in women with dense breasts and/or at elevated risk of breast cancer.
AWBU screening was tested in 4,419 women having routine mammography (Trial Registration: Identifier: NCT00649337). Cancers occurring during the study and subsequent 1-year follow-up were evaluated. Sensitivity, specificity and positive predictive value (PPV) of biopsy recommendation for mammography alone, AWBU and mammography with AWBU were calculated.
Breast cancer detection doubled from 23 to 46 in 6,425 studies using AWBU with mammography, resulting in an increase in diagnostic yield from 3.6 per 1,000 with mammography alone to 7.2 per 1,000 by adding AWBU. PPV for biopsy based on mammography findings was 39.0% and for AWBU 38.4%. The number of detected invasive cancers 10 mm or less in size tripled from 7 to 21 when AWBU findings were added to mammography.
AWBU resulted in significant cancer detection improvement compared with mammography alone. Additional detection and the smaller size of invasive cancers may justify this technology’s expense for women with dense breasts and/or at high risk for breast cancer.
PMCID: PMC2822222  PMID: 19727744
Mammography; Ultrasound; Breast cancer; Screening; Automated
19.  Bias in estimating accuracy of a binary screening test with differential disease verification 
Statistics in medicine  2011;30(15):1852-1864.
Sensitivity, specificity, positive and negative predictive value are typically used to quantify the accuracy of a binary screening test. In some studies it may not be ethical or feasible to obtain definitive disease ascertainment for all subjects using a gold standard test. When a gold standard test cannot be used an imperfect reference test that is less than 100% sensitive and specific may be used instead. In breast cancer screening, for example, follow-up for cancer diagnosis is used as an imperfect reference test for women where it is not possible to obtain gold standard results. This incomplete ascertainment of true disease, or differential disease verification, can result in biased estimates of accuracy. In this paper, we derive the apparent accuracy values for studies subject to differential verification. We determine how the bias is affected by the accuracy of the imperfect reference test, the percent who receive the imperfect reference standard test not receiving the gold standard, the prevalence of the disease, and the correlation between the results for the screening test and the imperfect reference test. It is shown that designs with differential disease verification can yield biased estimates of accuracy. Estimates of sensitivity in cancer screening trials may be substantially biased. However, careful design decisions, including selection of the imperfect reference test, can help to minimize bias. A hypothetical breast cancer screening study is used to illustrate the problem.
PMCID: PMC3115446  PMID: 21495059
Bias; Predictive values; Screening; Sensitivity; Specificity
20.  Nonadherence to Breast and Cervical Cancer Screening: What Are the Linkages to Chronic Disease Risk? 
Preventing Chronic Disease  2003;1(1):A04.
Several preventive practices that reduce chronic disease risk have been associated with breast and cervical cancer screening, including maintenance of normal weight and avoidance of cigarette smoking. A history of certain chronic illnesses such as diabetes and cardiovascular disease has also been related to cancer screening. Nevertheless, studies that have attempted to identify women who are less likely to have had a recent breast or cervical cancer screening test have infrequently examined the associations of breast and cervical cancer screening with multiple health factors that influence chronic disease risk.
To clarify relationships between cancer screening and health behaviors and other factors that influence chronic disease risk, we examined the self-reported breast and cervical cancer screening practices of women in the United States by using data from the 1999 Behavioral Risk Factor Surveillance System. The women were described according to their recent use of mammography and the Papanicolaou test, physician visits within the past year, health insurance coverage, and preventive practices that reduce chronic disease risk.
Overall, 74.5% (95% CI, 73.9%-75.1%) of the women in this sample aged 40 years or older (n = 56,528) had received a mammogram within the past 2 years. The percentage of women who had been screened for breast cancer, however, varied widely by factors associated with reducing the risk of chronic disease (e.g., cholesterol check in the past 2 years, blood pressure check in the past 2 years, normal weight, avoidance of cigarette smoking) and having access to health care (e.g., health insurance coverage, recent physician visit). Similarly, 84.4% (95% CI, 83.9%-84.9%) of all women aged 18 years or older who had not undergone a hysterectomy (n = 69,113) had received a Papanicolaou test in the past 3 years, and factors associated with reduced chronic disease risk and health care access were related to having had a recent Papanicolaou test.
The results of this study suggest that underscreened women who are at risk for breast and cervical cancer are likely to benefit from programs that identify and address coexisting prevention needs. The identification of coexisting prevention needs might assist in developing interventions that address multiple risks for chronic disease among women and might subsequently help improve the efficiency and effectiveness of prevention programs.
PMCID: PMC544527  PMID: 15634366
21.  Weighing the Benefits and Burdens of Mammography Screening Among Women Age 80 Years or Older 
Journal of Clinical Oncology  2009;27(11):1774-1780.
To examine outcomes of mammography screening among women ≥ 80 years to inform decision making.
Patients and Methods
We conducted a cohort study of 2,011 women without a history of breast cancer who were age ≥ 80 years between 1994 and 2004 and who received care at one academic primary care clinic or two community health centers in Boston, MA. Medical record data were abstracted on all screening and diagnostic mammograms, breast ultrasounds and biopsies performed, all breast cancers diagnosed through December 31, 2006, and on sociodemographics. Date and cause of death were confirmed using the National Death Index.
The majority of patients (78.6%) were non-Hispanic white and 51.4% (n = 1,034) had been screened with mammography since age 80 years. Among women who were screened, eight were diagnosed with ductal carcinoma in situ, 16 with early stage disease (1.5%), two with late stage disease, and one died as a result of breast cancer. Many (110; 11%) experienced a false-positive screening mammogram that led to 19 benign breast biopsies, eight refused work-up, and three experienced a false-negative screening mammogram; 97 were screened within 2 years of their death from other causes. There were no significant differences in the rate, stage, recurrence rate, or deaths due to breast cancer between women who were screened and those who were not screened.
The majority of women ≥ 80 years are screened with mammography yet few benefit. Meanwhile, 12.5% experience a burden from screening. The data from this study can be used to inform elderly women's decision making and potentially lead to more rational use of screening.
PMCID: PMC2668704  PMID: 19255318
22.  Culture, Emotion, and Cancer Screening: an Integrative Framework for Investigating Health Behavior 
Although health disparity research has investigated social structural, cultural, or psychological factors, the interrelations among these factors deserve greater attention.
This study aims to examine cancer screening emotions and their relations to screening fatalism as determinants of breast cancer screening among women from diverse socioeconomic and ethnic backgrounds.
An integrative conceptual framework was used to test the multivariate relations among socioeconomic status, age, screening fatalism, screening emotions, and clinical breast exam compliance among 281 Latino and Anglo women, using multi-group structural equation causal modeling.
Screening emotions and screening fatalism had a negative, direct influence on clinical breast exam compliance for both ethnic groups. Still, ethnicity moderated the indirect effect of screening fatalism on clinical breast exam compliance through screening emotions.
Integrative conceptual frameworks and multivariate methods may shed light on the complex relations among factors influencing health behaviors relevant to disparities. Future research and intervention must recognize this complexity when working with diverse populations.
PMCID: PMC3584161  PMID: 21472484
Emotions; Culture; Fatalism; Breast cancer screening; Health disparities
23.  Screening for Breast Cancer 
Breast cancer screening in community practices may be different from that in randomized controlled trials. New screening modalities are becoming available.
To review breast cancer screening, especially in the community and to examine evidence about new screening modalities.
Data Sources and Study Selection
English-language articles of randomized controlled trials assessing effectiveness of breast cancer screening were reviewed, as well as meta-analyses, systematic reviews, studies of breast cancer screening in the community, and guidelines. Also, studies of newer screening modalities were assessed.
Data Synthesis
All major US medical organizations recommend screening mammography for women aged 40 years and older. Screening mammography reduces breast cancer mortality by about 20% to 35% in women aged 50 to 69 years and slightly less in women aged 40 to 49 years at 14 years of follow-up. Approximately 95% of women with abnormalities on screening mammograms do not have breast cancer with variability based on such factors as age of the woman and assessment category assigned by the radiologist. Studies comparing full-field digital mammography to screen film have not shown statistically significant differences in cancer detection while the impact on recall rates (percentage of screening mammograms considered to have positive results) was unclear. One study suggested that computer-aided detection increases cancer detection rates and recall rates while a second larger study did not find any significant differences. Screening clinical breast examination detects some cancers missed by mammography, but the sensitivity reported in the community is lower (28% to 36%) than in randomized trials (about 54%). Breast self-examination has not been shown to be effective in reducing breast cancer mortality, but it does increase the number of breast biopsies performed because of false-positives. Magnetic resonance imaging and ultrasound are being studied for screening women at high risk for breast cancer but are not recommended for screening the general population. Sensitivity of magnetic resonance imaging in high-risk women has been found to be much higher than that of mammography but specificity is generally lower. Effect of the magnetic resonance imaging on breast cancer mortality is not known. A balanced discussion of possible benefits and harms of screening should be undertaken with each woman.
In the community, mammography remains the main screening tool while the effectiveness of clinical breast examination and self-examination are less. New screening modalities are unlikely to replace mammography in the near future for screening the general population.
PMCID: PMC3149836  PMID: 15755947
24.  Prospective screening study of 0.5 Tesla dedicated magnetic resonance imaging for the detection of breast cancer in young, high-risk women 
BMC Women's Health  2006;6:10.
Evidence-based screening guidelines are needed for women under 40 with a family history of breast cancer, a BRCA1 or BRCA2 mutation, or other risk factors. An accurate assessment of breast cancer risk is required to balance the benefits and risks of surveillance, yet published studies have used narrow risk assessment schemata for enrollment. Breast density limits the sensitivity of film-screen mammography but is not thought to pose a limitation to MRI, however the utility of MRI surveillance has not been specifically examined before in women with dense breasts. Also, all MRI surveillance studies yet reported have used high strength magnets that may not be practical for dedicated imaging in many breast centers. Medium strength 0.5 Tesla MRI may provide an alternative economic option for surveillance.
We conducted a prospective, nonrandomized pilot study of 30 women age 25–49 years with dense breasts evaluating the addition of 0.5 Tesla MRI to conventional screening. All participants had a high quantitative breast cancer risk, defined as ≥ 3.5% over the next 5 years per the Gail or BRCAPRO models, and/or a known BRCA1 or BRCA2 germline mutation.
The average age at enrollment was 41.4 years and the average 5-year risk was 4.8%. Twenty-two subjects had BIRADS category 1 or 2 breast MRIs (negative or probably benign), whereas no category 4 or 5 MRIs (possibly or probably malignant) were observed. Eight subjects had BIRADS 3 results, identifying lesions that were "probably benign", yet prompting further evaluation. One of these subjects was diagnosed with a stage T1aN0M0 invasive ductal carcinoma, and later determined to be a BRCA1 mutation carrier.
Using medium-strength MRI we were able to detect 1 early breast tumor that was mammographically undetectable among 30 young high-risk women with dense breasts. These results support the concept that breast MRI can enhance surveillance for young high-risk women with dense breasts, and further suggest that a medium-strength instrument is sufficient for this application. For the first time, we demonstrate the use of quantitative breast cancer risk assessment via a combination of the Gail and BRCAPRO models for enrollment in a screening trial.
PMCID: PMC1553433  PMID: 16800895
25.  Specificity of screening in United Kingdom trial of early detection of breast cancer. 
BMJ : British Medical Journal  1992;304(6823):346-349.
OBJECTIVES--To study the specificity of screening for breast cancer by clinical examination with or without mammography and to estimate the extra breast biopsies resulting from a population screening programme. DESIGN--Non-randomised, population based study. SETTING--Two screening districts (Edinburgh and Guildford) and four comparison districts (Dundee, Oxford, Southmead, and Stoke). SUBJECTS--49,956 women aged 45-64 in the screening districts and 127,109 women in the comparison districts. INTERVENTIONS--The screening districts offered women annual screening by clinical examination, with mammography in alternate years for seven years. MAIN OUTCOME MEASURES--Numbers of true positive, false positive, true negative, and false negative results; specificity and predictive value of screening; numbers of benign and malignant biopsy specimens. RESULTS--At their first mammographic and clinical screen 94% (30,035/31,997) of women without breast cancer were correctly classified as negative; 6% (1962) were referred for further investigation, but only 321 (1%) required a biopsy to establish that the suspicious lesion was not malignant. At subsequent screens specificity improved to 96%, and only 0.4% of women without cancer received biopsy. After the first screen the ratio of benign to malignant biopsy specimens was the same as that among women in the comparison centres, but because mammographic screening increased the number of women with both malignant and benign disease referred the number of biopsies was increased up to twofold in the years women were offered screening by mammography. CONCLUSION--Our provision of a prompt, highly specialised assessment of women with suspicious lesions at screening may have contributed to the relatively low specificities, while at the same time probably mitigating the adverse effects of low specificity.
PMCID: PMC1881232  PMID: 1540731

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