Diana L. Miglioretti

Radiation Dose Associated With Common Computed Tomography Examinations and the Associated Lifetime Attributable Risk of Cancer

BACKGROUND Use of computed tomography (CT) for diagnostic evaluation has increased dramatically over the past 2 decades. Even though CT is associated with substantially higher radiation exposure than conventional radiography, typical doses are not known. We sought to estimate the radiation dose associated with common CT studies in clinical practice and quantify the potential cancer risk associated with these examinations. METHODS We conducted a retrospective cross-sectional study describing radiation dose associated with the 11 most common types of diagnostic CT studies performed on 1119 consecutive adult patients at 4 San Francisco Bay Area institutions in California between January 1 and May 30, 2008. We estimated lifetime attributable risks of cancer by study type from these measured doses. RESULTS Radiation doses varied significantly between the different types of CT studies. The overall median effective doses ranged from 2 millisieverts (mSv) for a routine head CT scan to 31 mSv for a multiphase abdomen and pelvis CT scan. Within each type of CT study, effective dose varied significantly within and across institutions, with a mean 13-fold variation between the highest and lowest dose for each study type. The estimated number of CT scans that will lead to the development of a cancer varied widely depending on the specific type of CT examination and the patients age and sex. An estimated 1 in 270 women who underwent CT coronary angiography at age 40 years will develop cancer from that CT scan (1 in 600 men), compared with an estimated 1 in 8100 women who had a routine head CT scan at the same age (1 in 11 080 men). For 20-year-old patients, the risks were approximately doubled, and for 60-year-old patients, they were approximately 50% lower. CONCLUSION Radiation doses from commonly performed diagnostic CT examinations are higher and more variable than generally quoted, highlighting the need for greater standardization across institutions.

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

The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk

IMPORTANCE Increased use of computed tomography (CT) in pediatrics raises concerns about cancer risk from exposure to ionizing radiation. OBJECTIVES To quantify trends in the use of CT in pediatrics and the associated radiation exposure and cancer risk. DESIGN Retrospective observational study. SETTING Seven US health care systems. PARTICIPANTS The use of CT was evaluated for children younger than 15 years of age from 1996 to 2010, including 4 857 736 child-years of observation. Radiation doses were calculated for 744 CT scans performed between 2001 and 2011. MAIN OUTCOMES AND MEASURES Rates of CT use, organ and effective doses, and projected lifetime attributable risks of cancer. RESULTS The use of CT doubled for children younger than 5 years of age and tripled for children 5 to 14 years of age between 1996 and 2005, remained stable between 2006 and 2007, and then began to decline. Effective doses varied from 0.03 to 69.2 mSv per scan. An effective dose of 20 mSv or higher was delivered by 14% to 25% of abdomen/pelvis scans, 6% to 14% of spine scans, and 3% to 8% of chest scans. Projected lifetime attributable risks of solid cancer were higher for younger patients and girls than for older patients and boys, and they were also higher for patients who underwent CT scans of the abdomen/pelvis or spine than for patients who underwent other types of CT scans. For girls, a radiation-induced solid cancer is projected to result from every 300 to 390 abdomen/pelvis scans, 330 to 480 chest scans, and 270 to 800 spine scans, depending on age. The risk of leukemia was highest from head scans for children younger than 5 years of age at a rate of 1.9 cases per 10 000 CT scans. Nationally, 4 million pediatric CT scans of the head, abdomen/pelvis, chest, or spine performed each year are projected to cause 4870 future cancers. Reducing the highest 25% of doses to the median might prevent 43% of these cancers. CONCLUSIONS AND RELEVANCE The increased use of CT in pediatrics, combined with the wide variability in radiation doses, has resulted in many children receiving a high-dose examination. Dose-reduction strategies targeted to the highest quartile of doses could dramatically reduce the number of radiation-induced cancers.

Chronic spinal pain and physical-mental comorbidity in the United States: Results from the national comorbidity survey replication

This paper investigates comorbidity between chronic back and neck pain and other physical and mental disorders in the US population, and assesses the contributions of chronic spinal pain and comorbid conditions to role disability. A probability sample of US adults (n=5692) was interviewed. Chronic spinal pain, other chronic pain conditions and selected chronic physical conditions were ascertained by self‐report. Mood, anxiety and substance use disorders were ascertained with the Composite International Diagnostic Interview (CIDI). Role disability was assessed with questions about days out of role and with impaired role functioning. The 1 year prevalence of chronic spinal pain was 19.0%. The vast majority (87.1%) of people with chronic spinal pain reported at least one other comorbid condition, including other chronic pain conditions (68.6%), chronic physical conditions (55.3%), and mental disorders (35.0%). Anxiety disorders showed as strong an association with chronic spinal pain as did mood disorders. Common conditions not significantly comorbid with chronic spinal pain were diabetes, heart disease, cancer, and drug abuse. Chronic spinal pain was significantly associated with role disability after controlling for demographic variables and for comorbidities. However, comorbid conditions explained about one‐third of the gross association of chronic spinal pain with role disability. We conclude that chronic spinal pain is highly comorbid with other pain conditions, chronic diseases, and mental disorders, and that comorbidity plays a significant role in role disability associated with chronic spinal pain. The societal burdens of chronic spinal pain need to be understood and managed within the context of comorbid conditions.

Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010

CONTEXT Use of diagnostic imaging has increased significantly within fee-for-service models of care. Little is known about patterns of imaging among members of integrated health care systems. OBJECTIVE To estimate trends in imaging utilization and associated radiation exposure among members of integrated health care systems. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of electronic records of members of 6 large integrated health systems from different regions of the United States. Review of medical records allowed direct estimation of radiation exposure from selected tests. Between 1 million and 2 million member-patients were included each year from 1996 to 2010. MAIN OUTCOME MEASURE Advanced diagnostic imaging rates and cumulative annual radiation exposure from medical imaging. RESULTS During the 15-year study period, enrollees underwent a total of 30.9 million imaging examinations (25.8 million person-years), reflecting 1.18 tests (95% CI, 1.17-1.19) per person per year, of which 35% were for advanced diagnostic imaging (computed tomography [CT], magnetic resonance imaging [MRI], nuclear medicine, and ultrasound). Use of advanced diagnostic imaging increased from 1996 to 2010; CT examinations increased from 52 per 1000 enrollees in 1996 to 149 per 1000 in 2010, 7.8% annual increase (95% CI, 5.8%-9.8%); MRI use increased from 17 to 65 per 1000 enrollees, 10% annual growth (95% CI, 3.3%-16.5%); and ultrasound rates increased from 134 to 230 per 1000 enrollees, 3.9% annual growth (95% CI, 3.0%-4.9%). Although nuclear medicine use decreased from 32 to 21 per 1000 enrollees, 3% annual decline (95% CI, 7.7% decline to 1.3% increase), PET imaging rates increased after 2004 from 0.24 to 3.6 per 1000 enrollees, 57% annual growth. Although imaging use increased within all health systems, the adoption of different modalities for anatomic area assessment varied. Increased use of CT between 1996 and 2010 resulted in increased radiation exposure for enrollees, with a doubling in the mean per capita effective dose (1.2 mSv vs 2.3 mSv) and the proportion of enrollees who received high (>20-50 mSv) exposure (1.2% vs 2.5%) and very high (>50 mSv) annual radiation exposure (0.6% vs 1.4%). By 2010, 6.8% of enrollees who underwent imaging received high annual radiation exposure (>20-50 mSv) and 3.9% received very high annual exposure (>50 mSv). CONCLUSION Within integrated health care systems, there was a large increase in the rate of advanced diagnostic imaging and associated radiation exposure between 1996 and 2010.

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

Rising Use Of Diagnostic Medical Imaging In A Large Integrated Health System

Little has been published characterizing specific patterns of the dramatic rise in diagnostic imaging during the past decade. In a large health plan, 377,048 patients underwent 4.9 million diagnostic tests from 1997 through 2006. Cross-sectional imaging nearly doubled over those years, rising from 260 to 478 examinations per thousand enrollees per year. Imaging with computed tomography (CT) doubled, and imaging with magnetic resonance imaging (MRI) tripled. Cross-sectional studies added to existing studies instead of replacing them, and the annual per enrollee cost of radiology imaging more than doubled. The dramatic rise in imaging raises both costs and radiation exposure.

Cumulative Probability of False-Positive Recall or Biopsy Recommendation After 10 Years of Screening Mammography: A Cohort Study

BACKGROUND False-positive mammography results are common. Biennial screening may decrease the cumulative probability of false-positive results across many years of repeated screening but could also delay cancer diagnosis. OBJECTIVE To compare the cumulative probability of false-positive results and the stage distribution of incident breast cancer after 10 years of annual or biennial screening mammography. DESIGN Prospective cohort study. SETTING 7 mammography registries in the National Cancer Institute-funded Breast Cancer Surveillance Consortium. PARTICIPANTS 169,456 women who underwent first screening mammography at age 40 to 59 years between 1994 and 2006 and 4492 women with incident invasive breast cancer diagnosed between 1996 and 2006. MEASUREMENTS False-positive recalls and biopsy recommendations stage distribution of incident breast cancer. RESULTS False-positive recall probability was 16.3% at first and 9.6% at subsequent mammography. Probability of false-positive biopsy recommendation was 2.5% at first and 1.0% at subsequent examinations. Availability of comparison mammograms halved the odds of a false-positive recall (adjusted odds ratio, 0.50 [95% CI, 0.45 to 0.56]). When screening began at age 40 years, the cumulative probability of a woman receiving at least 1 false-positive recall after 10 years was 61.3% (CI, 59.4% to 63.1%) with annual and 41.6% (CI, 40.6% to 42.5%) with biennial screening. Cumulative probability of false-positive biopsy recommendation was 7.0% (CI, 6.1% to 7.8%) with annual and 4.8% (CI, 4.4% to 5.2%) with biennial screening. Estimates were similar when screening began at age 50 years. A non-statistically significant increase in the proportion of late-stage cancers was observed with biennial compared with annual screening (absolute increases, 3.3 percentage points [CI, -1.1 to 7.8 percentage points] for women age 40 to 49 years and 2.3 percentage points [CI, -1.0 to 5.7 percentage points] for women age 50 to 59 years) among women with incident breast cancer. LIMITATIONS Few women underwent screening over the entire 10-year period. Radiologist characteristics influence recall rates and were unavailable. Most mammograms were film rather than digital. Incident cancer was analyzed in a small sample of women who developed cancer. CONCLUSION After 10 years of annual screening, more than half of women will receive at least 1 false-positive recall, and 7% to 9% will receive a false-positive biopsy recommendation. Biennial screening appears to reduce the cumulative probability of false-positive results after 10 years but may be associated with a small absolute increase in the probability of late-stage cancer diagnosis. PRIMARY FUNDING SOURCE National Cancer Institute.

Risk Factors for Breast Cancer for Women Aged 40 to 49 Years: A Systematic Review and Meta-analysis

BACKGROUND Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions. PURPOSE To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor. DATA SOURCES MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium. STUDY SELECTION English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor. DATA EXTRACTION Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when sufficient studies were available or from the best evidence based on study quality, size, and applicability when meta-analysis was not possible. Data from the Breast Cancer Surveillance Consortium were analyzed with proportional hazards models by using partly conditional Cox regression. Reference groups for comparisons were set at U.S. population means. DATA SYNTHESIS Sixty-six studies provided data for estimates. Extremely dense breasts on mammography or first-degree relatives with breast cancer were associated with at least a 2-fold increase in risk for breast cancer. Prior breast biopsy, second-degree relatives with breast cancer, or heterogeneously dense breasts were associated with a 1.5- to 2.0-fold increased risk; current use of oral contraceptives, nulliparity, and age 30 years or older at first birth were associated with a 1.0- to 1.5-fold increased risk. LIMITATIONS Studies varied by measures, reference groups, and adjustment for confounders, which could bias combined estimates. Effects of multiple risk factors were not considered. CONCLUSION Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening. PRIMARY FUNDING SOURCE National Cancer Institute.

Hormone therapy prescribing patterns in the United States.

OBJECTIVE: We sought to examine prescribing patterns (prevalence and rates of initiation and discontinuation) for estrogen plus progestin (hormone therapy [HT] and estrogen alone [ET]) in the United States in the 2 years before the published results of Womens Health Initiatives (WHI) HT trials early termination and for 5 months after their release. METHODS: We conducted an observational cohort study of 169,586 women aged 40–80 years who were enrolled in 5 health maintenance organizations in the United States to estimate the prevalence of HT and ET and discontinuation and initiation rates between September 1, 1999, to June 31, 2002 (baseline), and December 31, 2002 (follow-up). We used automated pharmacy data to identify all oral and transdermal estrogen and progestin dispensed during the study period. RESULTS: The prevalence of HT declined 46% from baseline to follow-up (14.6% to 7.9%); ET use declined 28% during the same period (12.6% to 9.1%). The discontinuation of HT increased almost immediately, from 2.5% at baseline to 13.8% in October 2002. We saw an immediate decrease in HT and ET initiation rates, from 0.4% and 0.3% at baseline, respectively, to 0.2% for HT and ET at follow-up. CONCLUSION: The diffusion of the WHI HT trial results had an immediate impact on the discontinuation of HT and ET and is likely responsible for the 46% and 28% decline in the initiation of these respective therapies. Further exploration of why women continue to use HT and identification of methods for addressing reasons for continued use are indicated. LEVEL OF EVIDENCE: II-2