Jennifer M. Gierisch

Benefits and Harms of Breast Cancer Screening A Systematic Review

IMPORTANCE Patients need to consider both benefits and harms of breast cancer screening. OBJECTIVE To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy. EVIDENCE REVIEW We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO (to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, as well as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes among women at average risk of breast cancer (no known genetic susceptibility, family history, previous breast neoplasia, or chest irradiation). We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews. FINDINGS Across all ages of women at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95% CI, 0.73-0.89]; Canadian Task Force: RR, 0.82 [95% CI, 0.74-0.94]; Cochrane: RR, 0.81 [95% CI, 0.74-0.87]); were greater in a meta-analysis of cohort studies (RR, 0.75 [95% CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, among women 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. For women with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy result was higher (7.0% [95% CI, 6.1%-7.8%]) for annual compared with biennial (4.8% [95% CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive results were lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was low in quality. There was no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE. CONCLUSIONS AND RELEVANCE For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.

Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review

Oral contraceptives may influence the risk of certain cancers. As part of the AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, we conducted a systematic review to estimate associations between oral contraceptive use and breast, cervical, colorectal, and endometrial cancer incidence. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews. Study inclusion criteria were women taking oral contraceptives for contraception or ovarian cancer prevention; includes comparison group with no oral contraceptive use; study reports quantitative associations between oral contraceptive exposure and relevant cancers; controlled study or pooled patient-level meta-analyses; sample size for nonrandomized studies ≥100; peer-reviewed, English-language; published from January 1, 2000 forward. Random-effects meta-analyses were conducted by estimating pooled ORs with 95% confidence intervals (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial cancers studies. Breast cancer incidence was slightly but significantly increased in users (OR, 1.08; CI, 1.00–1.17); results show a higher risk associated with more recent use of oral contraceptives. Risk of cervical cancer was increased with duration of oral contraceptive use in women with human papillomavirus infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86; CI, 0.79–0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43–0.77) were significantly reduced by oral contraceptive use. Compared with never use, ever use of oral contraceptives is significantly associated with decreases in colorectal and endometrial cancers and increases in breast cancers. Although elevated breast cancer risk was small, relatively high incidence of breast cancers means that oral contraceptives may contribute to a substantial number of cases. Cancer Epidemiol Biomarkers Prev; 22(11); 1931–43. ©2013 AACR.

Oral Contraceptives and Risk of Ovarian Cancer and Breast Cancer Among High-Risk Women: A Systematic Review and Meta-Analysis

PURPOSE To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. METHODS We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. RESULTS From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. CONCLUSION Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To estimate the overall reduction in ovarian cancer risk associated with the use of oral contraceptive pills (OCPs) and whether reduction in risk is affected by specifics of OCP use, such as formulation or duration of use. DATA SOURCES: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published from January 1990 to June 2012, with primary analysis of studies published since January 2000. METHODS OF STUDY SELECTION: We reviewed 6,476 citations. We included English-language controlled studies with human participants reporting a quantitative association between exposure to OCPs (in which the explicit or implicit indication for OCP use was prevention of pregnancy or ovarian cancer) compared with no use of OCPs. Two investigators independently reviewed the title and abstract and full-text of articles for inclusion or exclusion decision; discordant decisions were resolved by team review and consensus. TABULATION, INTEGRATION, AND RESULTS: Fifty-five studies met inclusion criteria. A random-effects meta-analysis of 24 case-control and cohort studies showed significant reduction in ovarian cancer incidence in ever-users compared with never-users (odds ratio 0.73, 95% confidence interval 0.66–0.81). There was a significant duration–response relationship, with reduction in incidence of more than 50% among women using OCPs for 10 or more years. The lifetime reduction in ovarian cancer attributable to the use of OCPs is approximately 0.54% for a number-needed-to-treat of approximately 185 for a use period of 5 years. CONCLUSION: Significant duration-dependent reductions in ovarian cancer incidence in the general population are associated with OCP use.

Smoking Cessation Interventions for Patients with Depression: A Systematic Review and Meta-analysis

OBJECTIVESWe conducted a systematic literature review of smoking cessation interventions for patients with histories of depressive disorders or current significant depressive symptoms. We examined the comparative effectiveness of smoking cessation strategies on abstinence rates, differential effects of cessation strategies by depression status (i.e., history positive vs. current depression), and differential effects by gender.DATA SOURCESPeer-reviewed literature in MEDLINE, Embase, PsycINFO, and Cochrane Library.Study eligibility criteria, participants, and interventionsRandomized controlled trials or secondary analysis of RCT data comparing two or more smoking cessation interventions or intervention to control, and reporting cessation outcomes in adults with depression.STUDY APPRAISAL AND SYNTHESIS METHODSTwo trained researchers screened articles for inclusion. When possible, we estimated pooled risk ratios with 95% confidence intervals by using a random effects model with the Mantel–Haenszel method. We synthesized other studies qualitatively. We classified each intervention as antidepressants, nicotine replacement therapy (NRT), brief smoking cessation counseling, smoking cessation behavioral counseling, or behavioral mood management.RESULTSWe identified 16 unique RCTs, of which, only three trials recruited participants with current depression. Meta-analysis demonstrated a small, positive effect of adding behavioral mood management (RR = 1.41, 95% CI 1.01–1.96). All included antidepressant trials showed small, positive effects, but risk ratio summary was not significant (RR = 1.31, 95% CI 0.73–2.34). Three NRT trials demonstrated small, positive effects on smoking cessation rates. We found insufficient evidence to examine gender and depression status moderator effects.LIMITATIONSFew RCTs exist that test smoking cessation interventions among adults with depression. To make meaningful comparisons, we created broad intervention categories that contained heterogeneity.CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGSFew trials enrolled smokers with current depression. Most of data identified were from subgroup analyses of patients history-positive for depression. However, several promising interventions exist. Healthcare providers should consider encouraging their patients with significant depressive symptoms or depression histories to seek smoking cessation services that include NRT and behavioral mood management.

Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis.

OBJECTIVE: To estimate the risk of venous thromboembolism, stroke, or myocardial infarction (MI) associated with the use of oral contraceptive pills (OCPs) and to describe how these risks vary by dose or formulation. DATA SOURCES: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published from January 1995 through June 2012 that evaluated the association between OCP use and risk of venous thromboembolism, stroke, or MI. METHODS OF STUDY SELECTION: We reviewed 6,476 citations. We included English-language, controlled studies with human participants reporting a quantitative association between exposure to OCPs and outcomes of venous thromboembolism, stroke, or MI. Two investigators independently reviewed articles for inclusion or exclusion; discordant decisions were resolved by team review and consensus. Random-effects meta-analysis was used to generate summary odds ratios (ORs). TABULATION, INTEGRATION, AND RESULTS: Fifty studies met inclusion criteria. There were no randomized clinical trials. We found threefold increased odds of venous thromboembolism among current compared with noncurrent OCP users (14 studies; OR 2.97, 95% confidence interval [CI] 2.46–3.59). We found twofold increased odds of ischemic stroke (seven studies; OR 1.90, 95% CI 1.24–2.91). There was no evidence of increased risk of hemorrhagic stroke (four studies; OR 1.03, 95% CI 0.71–1.49) or MI (eight studies; OR 1.34, 95% CI 0.87–2.08). CONCLUSION: Current use of combined OCPs is associated with increased odds of venous thromboembolism and ischemic stroke but not hemorrhagic stroke or MI.

Longitudinal Predictors of Nonadherence to Maintenance of Mammography

Background: Regular adherence to screening mammography, also known as maintenance of mammography, reduces breast cancer morbidity and mortality. However, mammography maintenance is uncommon and little is know about why women do not maintain regular screening schedules. We investigated longitudinal predictors of women not maintaining adherence. Methods: Participants were insured women enrolled in an intervention trial who had screening mammograms 8 to 9 months before study enrollment (n = 1,493). Data were collected from 2003 to 2008. We used discrete event history analysis to model nonadherence to mammography maintenance over three successive annual screening intervals (+ 2 months). Results: Most (54%) women did not maintain screening adherence over 3 years. Women who did not maintain adherence were more likely to be ages 40 to 49 years, rate their health fair or poor, be less satisfied with their last mammography experiences, report one or more barriers to getting mammograms, be less than completely confident about getting their next mammograms (lower self-efficacy), or have weaker behavioral intentions. The odds of not maintaining adherence decreased over time. Discussion: Although great strides have been achieved in increasing the proportion of women who have received mammograms, most women still are not maintaining regular mammography use over time. Our findings provide insights into targets for future mammography maintenance interventions. Cancer Epidemiol Biomarkers Prev; 19(4); 1103–11. ©2010 AACR.

Factors associated with annual-interval mammography for women in their 40s

BACKGROUND Evidence is mounting that annual mammography for women in their 40s may be the optimal schedule to reduce morbidity and mortality from breast cancer. Few studies have assessed predictors of repeat mammography on an annual interval among these women. METHODS We assessed mammography screening status among 596 insured Black and Non-Hispanic white women ages 43-49. Adherence was defined as having a second mammogram 10-14 months after a previous mammogram. We examined socio-demographic, medical and healthcare-related variables on receipt of annual-interval repeat mammograms. We also assessed barriers associated with screening. RESULTS 44.8% of the sample were adherent to annual-interval mammography. A history of self-reported abnormal mammograms, family history of breast cancer and never having smoked were associated with adherence. Saying they had not received mammography reminders and reporting barriers to mammography were associated with non-adherence. Four barrier categories were associated with womens non-adherence: lack of knowledge/not thinking mammograms are needed, cost, being too busy, and forgetting to make/keep appointments. CONCLUSIONS Barriers we identified are similar to those found in other studies. Health professionals may need to take extra care in discussing mammography screening risk and benefits due to ambiguity about screening guidelines for women in their 40s, especially for women without family histories of breast cancer or histories of abnormal mammograms. Reminders are important in promoting mammography and should be coupled with other strategies to help women maintain adherence to regular mammography.

Impact of Mailed and Automated Telephone Reminders on Receipt of Repeat Mammograms. A Randomized Controlled Trial

BACKGROUND This study compares the efficacy of three types of reminders in promoting annual repeat mammography screening. DESIGN RCT. SETTING AND PARTICIPANTS Study recruitment occurred in 2004-2005. Participants were recruited through the North Carolina State Health Plan for Teachers and State Employees. All were aged 40-75 years and had a screening mammogram prior to study enrollment. A total of 3547 women completed baseline telephone interviews. INTERVENTION Prior to study recruitment, women were assigned randomly to one of three reminder groups: (1) printed enhanced usual care reminders (EUCRs); (2) automated telephone reminders (ATRs) identical in content to EUCRs; or (3) enhanced letter reminders that included additional information guided by behavioral theory. Interventions were delivered 2-3 months prior to womens mammography due dates. MAIN OUTCOME MEASURES Repeat mammography adherence, defined as having a mammogram no sooner than 10 months and no later than 14 months after the enrollment mammogram. RESULTS Each intervention produced adherence proportions that ranged from 72% to 76%. Post-intervention adherence rates increased by an absolute 17.8% from baseline. Women assigned to ATRs were significantly more likely to have had mammograms than women assigned to EUCRs (p=0.014). Comparisons of reminder efficacy did not vary across key subgroups. CONCLUSIONS Although all reminders were effective in promoting repeat mammography adherence, ATRs were the most effective and lowest in cost. Health organizations should consider using ATRs to maximize proportions of members who receive mammograms at annual intervals.

Finding the minimal intervention needed for sustained mammography adherence.

BACKGROUND Regular adherence to mammography screening saves lives, yet few women receive regular mammograms. DESIGN RCT. SETTING/PARTICIPANTS Participants were recruited through a state employee health plan. All were women aged 40-75 years and had recent mammograms prior to enrollment (n=3547). Data were collected from 2004 to 2009. INTERVENTION Trial tested efficacy of a two-step adaptively-designed intervention to increase mammography adherence over 4 years. The first intervention step consisted of three reminder types: enhanced usual care reminders (EUCR); enhanced letter reminders (ELR); both delivered by mail, and automated telephone reminders (ATR). After delivery of reminders, women who became off-schedule in any of the 4 years received a second step of supplemental interventions. Three supplemental intervention arms contained priming letters and telephone counseling: barriers only (BarriCall); barriers plus positive consequences of getting mammograms (BarriConCall+); and barriers plus negative consequences of not getting mammograms (BarriConCall-). MAIN OUTCOME MEASURES Average cumulative number of days non-adherent to mammography over 4 years based on annual screening guidelines (analyses conducted in 2009). RESULTS All reminders performed equally well in reducing number of days of non-adherence. Women randomized to receive supplemental interventions had significantly fewer days of non-adherence compared to women who received EUCR (p=0.0003). BarrConCall+ and BarrConCall- conditions did not significantly differ in days non-adherent compared to women in the barriers-only condition (BarriCon). CONCLUSIONS The minimal intervention needed for sustained mammography use is a combination of a reminder followed by a priming letter and barrier-specific telephone counseling for women who become off-schedule. Additional costs associated with supplemental interventions should be considered by organizations deciding which interventions to use. TRIAL REGISTRATION NUMBER NCT01148875.