Mark Dignan

Individual and Combined Effects of Age, Breast Density, and Hormone Replacement Therapy Use on the Accuracy of Screening Mammography

Context High breast density increases breast cancer risk and the difficulty of reading mammograms. Breast density decreases with age and increases with postmenopausal hormone therapy use. The interplay of breast density, age, and hormone therapy use on the accuracy of mammography is uncertain. Contribution For women with fatty breasts, the sensitivity of mammography was 87% and the specificity was 96.9%. For women with extremely dense breasts, the sensitivity of mammography was 62.9% and the specificity was 89.1%. Sensitivity increased with age. Hormone therapy use was not an independent predictor of accuracy. Implications The accuracy of screening mammography is best in older women and in women with fatty breasts. Postmenopausal hormone therapy affects mammography accuracy only through its effects on breast density. The Editors Mammographic breast density may be the most undervalued and underused risk factor in studies investigating breast cancer occurrence (1). The risk for breast cancer is four to six times higher in women with dense breasts (2, 3). Breast density may also decrease the sensitivity and, thus, the accuracy of mammography. Radiographically dense breast tissue may obscure tumors, which increases the difficulty of detecting breast cancer. In addition, dense breast tissue may mimic breast cancer on mammography (4), which increases recall rates (4-12), reduces specificity, and compromises the benefit of screening in women with dense breasts (such as women who use HRT or who are premenopausal) (6, 8, 13). Breast density is affected by age, use of hormone replacement therapy (HRT), menstrual cycle phase, parity, body mass index, and familial or genetic tendency (4, 5, 14-21). Studies show that the sensitivity of mammography increases with age (6-8), especially in postmenopausal women whose breasts are less dense (8). Earlier research has examined the individual effect of each factor we have described, but most studies could not adequately examine the interaction of these factors because of insufficient sample size (4-15). Studies conducted in the 1970s with data from the Breast Cancer Detection Demonstration Project (22) and New York Health Insurance Plan (23) are based on mammographic examinations that are very different from those performed using current technology. The Mammography Quality Standards Act (24) and the standardized reporting efforts of the American College of Radiology (25) have resulted in important improvements in mammography that necessitate reexamination. We used data from the National Cancer Institutes Breast Cancer Surveillance Consortium (BCSC) (26) on 329 495 women in the United States who had 463 372 screening mammograms, which were linked to 2223 cases of breast cancer. Our goal was to examine the individual and combined effects of age, breast density, and HRT use on mammographic accuracy. This large data set provides a unique opportunity to examine these issues in women undergoing screening mammography in the United States, especially women younger than 50 years of age and older than 80 years of age. We chose to study a sample that had been recently screened (within the previous 2 years) so that the risk for breast cancer would be similar to that in women who receive routine mammographic screening. Methods Data Collection Initially, we included data on women 40 to 89 years of age who underwent screening mammography between 1996 and 1998, as submitted by seven registries in the BCSC (North Carolina; New Mexico; New Hampshire; Vermont; Colorado; Seattle, Washington; and San Francisco, California). We included women who reported having previous mammography or who had a previous mammographic examination recorded in a registry within 2 years of the index mammogram. Women with breast implants or a personal history of breast cancer were excluded. In addition, women with missing data for age (<1%), breast density (27%), or HRT use (21%) were excluded (36% of all data). Demographic characteristics, clinical characteristics, and accuracy measures for women missing any of this information were very similar to those for women with complete data. All registries obtained institutional review board approval for data collection and linkage procedures, and careful data management, processing, and security procedures were followed (27). Consortium mammography registries and data collection procedures are described elsewhere (26). Briefly, seven institutions in seven states receive funding from the National Cancer Institute to maintain mammography registries that cover complete or contiguous portions of each state. Data are collected similarly at each registry. Demographic and history information is collected from women at the time of mammography by using a self-administered survey or face-to-face interview methods. Variables include date of birth, history of previous mammography, race or ethnicity, current use of HRT (prescription medication used to treat perimenopausal and postmenopausal symptoms), and menopausal status. We assumed that women 55 years of age and older were perimenopausal or postmenopausal. For women 40 to 54 years of age, premenopausal status was defined as having regular menstrual periods with no HRT use; perimenopausal or postmenopausal status was defined as either removal of both ovaries or uncertainty about whether periods had stopped permanently. This latter category was further classified into HRT users and nonusers. These definitions recognize that HRT users with intact uteri may have menstrual-like bleeding. Additional data, including mammographic breast density, mammographic assessment, and recommended follow-up (based on the American College of Radiology Breast Imaging Reporting and Data System [BI-RADS]), are collected from the technologist and radiologist at the time of mammography (25). Pathology data are collected from one or more sources: regional Surveillance, Epidemiology, and End Results (SEER) programs, state cancer registries, or pathology laboratories. Design We included all screening examinations for women who met the described criteria and who had at least one screening mammogram in 1996, 1997, or 1998. These years were chosen to ensure 1-year follow-up for cancer reporting and to account for routine reporting schedules in obtaining data from SEER and state cancer registries. We classified mammography as screening if a radiologist indicated that the examination was a bilateral, two-view (craniocaudal and mediolateral) examination. To avoid including diagnostic examinations, we excluded any breast imaging study performed within the previous 9 months. Because our goal was to study routine screening, mammographic accuracy was calculated on the basis of the initial assessment of the screening views alone (only 6% required supplemental imaging). Interpretation codes included BI-RADS assessments of 0 (incomplete), 1 (negative), 2 (negative, benign), 3 (probably benign), 4 (suspicious abnormality), or 5 (highly suggestive of malignancy). In cases in which the initial screening visit included both a screening examination and additional imaging to determine an assessment, the initial screening assessment was assigned a 0 (incomplete assessment) for analysis. When a woman had different assessments by breast, we chose the highest-level assessment for the woman as a whole (woman-level assessment) on the basis of the following hierarchy of overall level of radiologic concern: 1 < 2 < 3 < 0 < 4 < 5. We defined a screening examination as positive if it was assigned a BI-RADS assessment code of 0, 4, or 5. An assessment code of 3 associated with a recommendation for immediate additional imaging, biopsy, or surgical evaluation was also classified as positive. Although the BI-RADS recommendation for a code 3 (probably benign) is short-interval follow-up, immediate work-up was recommended in 37% of code 3s in the pooled BCSC data; therefore, this assessment is more consistent with a BI-RADS code of 0 (incomplete assessment) (28). We defined a screening examination as negative if it received a BI-RADS assessment code of 1, 2, or 3 when associated with short-interval follow-up only or routine follow-up. We classified breast pathology outcomes as cancer if pathology or cancer registry data identified a diagnosis of invasive or ductal carcinoma in situ. Lobular carcinoma in situ (<0.01% of cancer cases in our pooled data) was not considered a diagnosis of cancer in our analyses because it cannot be detected by mammography and is not treated. Examinations were classified as false-positive when the assessment was positive and breast cancer was not diagnosed within the follow-up period (365 days after the index screening examination or until the next examination, whichever occurred first). Examinations were classified as true-positive when the assessment was positive and cancer was diagnosed. A false-negative examination was a negative assessment with a diagnosis of cancer within the follow-up period. A true-negative examination was a negative assessment with no subsequent diagnosis of cancer within the follow-up period. Radiographic breast density was defined according to BI-RADS as follows: 1) almost entirely fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, and 4) extremely dense (25). We excluded one registry that collects two categories of breast density (dense or not dense) at some facilities. Statistical Analysis For age, breast density, and HRT groups, we calculated rates of incident breast cancer, rates of breast cancer detected by mammography, and rates of missed cancer. To examine the nonlinear effects of age, we categorized age into 10-year groups, except for ages 40 to 59, which were divided into 5-year groups to explore changes around menopause. Accuracy indices included sensitivity and specificity. Sensitivity was calculated as true-positive/(true-positive + false-negative). Specificity was calculated as true-negative/(true-negative + false

Does Utilization of Screening Mammography Explain Racial and Ethnic Differences in Breast Cancer

Context Breast cancer mortality rates have fallen but still differ by race and ethnicity. One explanation might be differences in mammography use. Content These investigators linked data from mammography registries to tumor registries and showed that African-American and Hispanic women have longer intervals between mammography and are more likely to have advanced-stage tumors at diagnosis and to die of breast cancer than white women. However, in women with similar screening histories, these rates were similar regardless of race or ethnicity. Implications Differences in mammography use may explain ethnic disparities in the incidence of advanced-stage breast cancer and in mortality rates. The Editors Breast cancer mortality rates in the United States began to decrease in the 1990s (1) because of increased use of screening mammography and improved breast cancer treatment (2, 3). However, these decreases have primarily benefited non-Hispanic white women, whereas the mortality rate for breast cancer in African-American women changed little (1). Although racial and ethnic differences in breast cancer mortality rates have been consistently documented (1, 4-9), reasons for the persistence of these differences have been difficult to ascertain (10). Possible explanations include differences in biological characteristics of tumors (11-13); patient characteristics, such as obesity, that may affect prognosis; mammography use (14, 15); timeliness and completeness of breast cancer diagnosis and treatment (16, 17); social factors, such as education, literacy, and cultural beliefs; and economic factors, such as income level and health insurance coverage, that might affect a patients access to and choices for breast cancer screening and treatment (18-22). Stage at diagnosis, the strongest predictor of breast cancer survival (23), is proportionally higher in all non-Asian minority groups than in white women (8). Although minority women have historically undergone less mammography than white women (14), several recent surveys have found only small differences in mammography use between white and nonwhite women (24, 25). These observations raised doubt that tumors go undiagnosed until later stages in minority women because of infrequent breast cancer screening (26). However, the 2 most widely cited surveys of mammography use are based on self-report and only inquire about recent use, not adherence over time (24, 25). We explored stage of disease at diagnosis, tumor characteristics (including size and grade), and lymph node involvement among women of different races and ethnicities whose patterns of mammography use were similar. We hypothesized that differences in tumor characteristics may result primarily from differences in mammography use and that women with similar patterns of mammography use may have similar tumor characteristics. We had sufficient sample sizes within each racial and ethnic group and obtained sufficiently detailed data regarding mammography use to permit stratification of the cohort by pattern of mammography use; this technique enabled us to compare tumor characteristics among women with similar screening histories. Methods Data Source We pooled data from facilities that participate in 7 mammography registries that form the National Cancer Institutefunded Breast Cancer Surveillance Consortium: San Francisco Mammography Registry, San Francisco, California; Group Health Cooperative, Seattle, Washington; Colorado Mammography Project, Denver, Colorado; Vermont Breast Cancer Surveillance System, Burlington, Vermont; New Hampshire Mammography Network, Lebanon, New Hampshire; Carolina Mammography Registry, Chapel Hill, North Carolina; and New Mexico Mammography Project, Albuquerque, New Mexico. The data consisted of information sent to the registries regarding all mammographic evaluations performed at these facilities, including radiology reports and breast health surveys. The surveys, which were completed by patients at each mammography examination, included questions regarding race, ethnicity, presence of breast symptoms, and previous mammography use. Breast cancer diagnoses and tumor characteristics were obtained through linkage with state tumor registries; regional Surveillance, Epidemiology, and End Results programs; and hospital-based pathology services. Previous research has shown that at least 94% of cancer cases are identified through these linkages (27). Each surveillance registry captures most mammography case reports within its respective geographic area, and mammograms in these registries include approximately 2% of mammographic examinations performed in the United States. Each registry obtains annual approval from its institutional review board to collect mammography-related information and to link with tumor registries. Participants This study included women without a history of breast cancer who were 40 years of age and older who had undergone mammography at least once for screening or diagnostic purposes between 1996 and 2002 (n= 1010515). We categorized the race and ethnicity of the participating women (the mammography registry cohort) as non-Hispanic white (n= 789997), non-Hispanic African American/black (n= 62408), Hispanic (n= 90642), Asian/Pacific Islander (n= 49867), or Native American/Native Alaskan (n= 17601). We excluded women who did not report their race or ethnicity (n= 133235 [12%]) or reported mixed or other race (n= 6003 [<1%]). Breast cancer was diagnosed in a subset of the women in the mammography registry cohort (Table 1). Table 1. General Categorization of Study Participants Characterization of Mammography Use We included all mammographic evaluations in eligible women that were performed during the study period. We characterized each mammogram that was included in the study by the time interval between that mammogram and the one most recently preceding it. We determined these intervals by using examination dates that were recorded in the database (data were available for 85% of patients) and self-reported dates that the remaining women provided at the time of their examination. The mammography screening intervals were categorized into the following groups: within 1 year (4 to 17 months); 2 years (18 to 29 months); 3 years (30 to 41 months); and 4 years or longer (>41 months). At the time of each mammogram, women completed a breast health survey and provided the date of their last mammogram. We created 2 classifications for first mammograms. Mammography was classified as a first screening if the radiologist coded the examination as screening and the woman reported no breast symptoms. The mammogram was classified as diagnostic if the radiologist coded the examination as diagnostic or if the woman reported a breast mass or nipple discharge. Women whose first mammogram was diagnostic were assigned to the never screened group. Of note, a woman could have had mammography more than once during the study period and therefore could contribute more than 1 observation to the analyses. A woman could have observations that were categorized into different mammography screening intervals. For example, a woman could have had her first mammographic evaluation in 1998 and had subsequent mammography in 1999 and 2001. Her first mammogram would have been categorized as a first screening or as diagnostic, depending on the radiologists indication for that examination and whether the patient reported symptoms. Her second mammogram would have been categorized in the 1 year group, and her third mammography would have been categorized in the 2 year group. Breast Cancer To determine breast cancer status, we tracked each participants mammogram for 365 days following the date it had been obtained or until the patient underwent her next mammographic examination (whichever came first). Consequently, each tumor was associated with a single mammogramthat obtained closest to the date of diagnosis. We characterized breast cancer as either invasive or ductal carcinoma in situ. Large tumors were defined as invasive tumors that were 15 mm or larger in diameter. We used the TNM (tumor, node, metastasis) system (which is based on the criteria of the American Joint Committee on Cancer) to classify stage at diagnosis as 0 (ductal carcinoma in situ), 1, 2, 3, or 4 (28); advanced-stage tumors were defined as invasive lesions of stage 2 or higher. High-grade tumors were defined as invasive lesions of grades 3 and 4. Lymph node status was defined as positive, negative, or unknown. Advanced disease was defined as the presence of a large, advanced-stage, high-grade tumor or lymph nodepositive tumor at the time of diagnosis. Statistical Analysis We calculated the frequency distributions of various risk factors for all women in the mammography registry cohort. Among the subset of women with breast cancer (n= 17558), we calculated the proportion of tumors that were invasive and, among invasive tumors, the proportion that were advanced-stage or high-grade tumors; we then calculated the distribution by race and ethnicity. For all women in the cohort, we evaluated whether overall and advanced cancer rates per 1000 mammograms were similar across racial and ethnic groups after we adjusted for age and registry by using Poisson regression. We then calculated whether adjusted overall and advanced cancer rates per 1000 mammograms were similar across mammography screening interval groups. Because overall and advanced cancer rates varied across racial and ethnic groups (P< 0.001) and by previous mammography use (P< 0.001), and because mammography use potentially varied by race and ethnicity, we modeled cancer rates among similarly screened women in each ethnic group. We used Poisson regression to adjust for age and registry; an interaction term between race and ethnicity and previous mammography use was included in the Poisson model to allow for possible differences in the association between ethnicity and cancer rates by mammography group

Cervical Cancer Prevention: New Tools and Old Barriers

Cervical cancer is the second most common female tumor worldwide, and its incidence is disproportionately high (>80%) in the developing world. In the United States, in which Papanicolaou (Pap) tests have reduced the annual incidence to approximately 11,000 cervical cancers, >60% of cases are reported to occur in medically underserved populations as part of a complex of diseases linked to poverty, race/ethnicity, and/or health disparities. Because carcinogenic human papillomavirus (HPV) infections cause virtually all cervical cancer, 2 new approaches for cervical cancer prevention have emerged: 1) HPV vaccination to prevent infections in younger women (aged ≤18 years) and 2) carcinogenic HPV detection in older women (aged ≥30 years). Together, HPV vaccination and testing, if used in an age‐appropriate manner, have the potential to transform cervical cancer prevention, particularly among underserved populations. Nevertheless, significant barriers of access, acceptability, and adoption to any cervical cancer prevention strategy remain. Without understanding and addressing these obstacles, these promising new tools for cervical cancer prevention may be futile. In the current study, the delivery of cervical cancer prevention strategies to these US populations that experience a high cervical cancer burden (African‐American women in South Carolina, Alabama, and Mississippi; Haitian immigrant women in Miami; Hispanic women in the US‐Mexico Border; Sioux/Native American women in the Northern Plains; white women in the Appalachia; and Vietnamese‐American women in Pennsylvania and New Jersey) is reviewed. The goal was to inform future research and outreach efforts to reduce the burden of cervical cancer in underserved populations. Cancer 2010.

Randomized, Controlled Trial of an Easy-to-Read Informed Consent Statement for Clinical Trial Participation: A Study of the Eastern Cooperative Oncology Group

PURPOSE Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population. This study hypothesized that use of an easy-to-read consent statement, when compared with a standard consent statement, will result in higher patient comprehension of the clinical treatment protocol, lower patient anxiety, higher patient satisfaction, and higher patient accrual. METHODS A randomized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups. Institutions were randomly assigned to administer either an easy-to-read consent statement or the standard consent statement to patients being recruited to participate in selected cancer treatment trials. Telephone interviews were conducted with a total of 207 patients to assess study outcomes. RESULTS Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm. Patient comprehension and state anxiety were not affected by the intervention. Accrual rates into the parent studies also did not differ significantly between the two study groups. CONCLUSION Clinical trial informed consent statements can be modified to be easier to read without omitting critical information. Patient anxiety and satisfaction can be affected by the consent document. The generalizability of these study results is limited by the characteristics of the patient sample. Ninety percent of the sample were white women, and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64, indicating a literacy level at or above the ninth grade.

The use of illustrations and narrative text style to improve readability of a health education brochure.

Research suggests that much of the available health education literature requires a level of reading ability that makes it inaccessible to a large proportion of the population in greatest need of health information. The present study tested the value of illustrations and a narrative text style as means of improving the readability of a brochure designed to provide information on cervical cancer and condyloma. Two versions of the brochure were designed, one that had only text presented as simple sentences in bullet-type format (SMOG reading level score of 7.7), and a second version that had somewhat more difficult text formatted in a narrative style (SMOG grade level score of 8.4) together with drawings designed to complement the text. A randomized study design was used to test for comprehension, perceived ease of understanding, and overall rating of the two brochures. Women selected from one private and three public health primary-care clinics were randomly assigned to read one of the two brochures. The brochure with illustrations and narrative text was given a significantly higher overall rating than the one with bullet-type text and no illustrations, while no difference was found in perceived ease of reading. Among poor readers, comprehension was significantly greater for women who read the brochure with illustrations and narrative text, with no difference in comprehension of the two brochures for better readers. The results suggest that the use of aids such as illustrations and text style can make health education literature more accessible to high-risk populations, while remaining interesting enough to appeal to individuals at all levels of reading ability.

Evaluation of Health Education Programs: Current Assessment and Future Directions

Recently there has been an increase in the different types of strategies used in health education interventions, including an emphasis on broadening programs focused on individual behavior change to include larger units of practice. There has also been an increasing critique of the traditional physical science paradigm for evaluating the multiple dimensions inherent in many interventions. Additionally, there is a growing recognition of the importance of involving multiple stakeholders in designing, implementing, and evaluating interventions. Each of these factors carries specific evaluation challenges. With the overall aim of strengthening the evaluation of health education programs, this article aims to (a) present conceptual and technical design issues and options, (b) describe different approaches to evaluation, (c) highlight evaluation approaches that have been effective, (d) critique the limitations of traditional evaluation approaches, (e) examine promising approaches and implications for future evaluations, and (f) provide recommendations for evaluation designs, data collection methods, roles, responsibilities, and principles for evaluating interventions.

Effects of a smoke-free law on hair nicotine and respiratory symptoms of restaurant and bar workers

Objective: Bar and restaurant workers’ exposure to secondhand smoke (SHS) was compared before and 3 and 6 months after implementation of a smoke-free ordinance. Methods: Hair nicotine, self-reported exposure to SHS, and respiratory symptoms were assessed on 105 smoking and nonsmoking workers from randomly selected establishments in Lexington, Kentucky. Thirty-eight percent were current smokers with more than half smoking 10 or fewer cigarettes per day. Workers provided a hair sample at baseline and at the 3-month interview. Results: There was a significant decline in hair nicotine 3 months postlaw when controlling for cigarettes smoked per day. Bar workers showed a significantly larger decline in hair nicotine compared with restaurant workers. The only significant decline in SHS exposure was in the workplace and other public places. Regardless of smoking status, respiratory symptoms declined significantly postlaw. Conclusions: Hospitality workers demonstrated significant declines in hair nicotine and respiratory symptoms after the law. Comprehensive smoke-free laws can provide the greatest protection to bar workers who are the most vulnerable to SHS exposure at work.

Does Distance Matter? Distance to Mammography Facilities and Stage at Diagnosis of Breast Cancer in Kentucky.

BACKGROUND National and regional data indicate that breast cancer early detection is low in Kentucky, especially rural regions, perhaps because access to mammography services can be problematic. OBJECTIVE This study examined the distance between residences of women diagnosed with breast cancer and the nearest mammography facility, as a risk factor for advanced stage diagnosis in rural populations. METHODS 1999-2003 Kentucky Cancer Registry data were used for this study. A total of 12,322 women, aged 40 and older at diagnosis, with no previous history of cancer, and with known cancer stage were included. Travel distance was obtained using a geographic information system (GIS). Hierarchical logistic regression models were used to analyze the relationship between travel distance and advanced stage diagnosis. RESULTS Advanced diagnoses had longer average travel distances than early stage diagnoses (P < 0.01). After adjusting for age, race, insurance, and education at census tract level, the odds of advanced diagnosis were significantly greater for women residing over 15 miles from a facility, compared to those living within 5 miles (adjusted OR = 1.50, 95% CI = 1.25-1.80). CONCLUSION Although socioeconomic status, race, and age may help explain advanced diagnoses, longer travel distance also adversely affects early detection for rural populations. Accurate measurement of spatial accessibility indicators, such as travel distance, facilitates identification of at-risk groups so that interventions can be developed to reduce this disease.

A Comparison of Two Native American Navigator Formats: Face-to-Face and Telephone

The study was designed to test the relative effectiveness of a Navigator intervention delivered face-to-face or by telephone to urban Native American women. The effectiveness of the intervention was evaluated using a design that included a pretest, random assignment to face-to-face or telephone group, and posttest. The Social Cognitive Theory-based intervention was a tailored education program developed to address individual risk factors for breast cancer. At posttest, self-reported mammograms in the past year increased from 29% to 41.3% in the telephone group and from 34.4% to 45.2% in the face-to-face group. There was no difference in change from pretest to posttest between the telephone and face-to-face groups. Navigators can be effective in increasing adherence to recommendations for screening mammography among urban American Indian women.

Testing the risk compensation hypothesis for safety helmets in alpine skiing and snowboarding

Objective: The prevalence of helmet use by alpine skiers and snowboarders was estimated and self-reports on risk taking were assessed to test for potential risk compensation when using helmets in these sports. Setting: Skiers and snowboarders were observed and interviewed at 34 resorts in the western United States and Canada. Subjects: Respondents were 1779 adult skiers and snowboarders in the 2003 ski season. Outcome measures: Observations of helmet use and questions about perceived speed and degree of challenge when not wearing a helmet (helmet wearers) or in previous ski seasons (non-helmet wearers). Results: Helmet wearers reported that they skied/snowboarded at slower speeds (OR = 0.64, p<0.05) and challenged themselves less (OR = 0.76, p<0.05) than non-helmet wearers. Adoption of safety helmets in 2003 (23%) continued to increase over 2002 (OR = 0.46, p<0.05) and 2001 (OR = 0.84, p<0.05). Conclusions: No evidence of risk compensation among helmet wearers was found. Decisions to wear helmets may be part of a risk reduction orientation. Helmet use continues to trend upwards but adoption may be slowing.