Karen J. Wernli

Outcomes of Screening Mammography by Frequency, Breast Density, and Postmenopausal Hormone Therapy

IMPORTANCE Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age. OBJECTIVE To compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use. DESIGN Prospective cohort. SETTING Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries. PARTICIPANTS Data were collected prospectively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC. MAIN OUTCOMES AND MEASURES We used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (>20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval. RESULTS Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of womens breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively). CONCLUSIONS AND RELEVANCE Women aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high.

Patterns of Breast Magnetic Resonance Imaging Use in Community Practice

IMPORTANCE Breast magnetic resonance imaging (MRI) is increasingly used for breast cancer screening, diagnostic evaluation, and surveillance. However, we lack data on national patterns of breast MRI use in community practice. OBJECTIVE To describe patterns of breast MRI use in US community practice during the period 2005 through 2009. DESIGN, SETTING, AND PARTICIPANTS Observational cohort study using data collected from 2005 through 2009 on breast MRI and mammography from 5 national Breast Cancer Surveillance Consortium registries. Data included 8931 breast MRI examinations and 1,288,924 screening mammograms from women aged 18 to 79 years. MAIN OUTCOMES AND MEASURES We calculated the rate of breast MRI examinations per 1000 women with breast imaging within the same year and described the clinical indications for the breast MRI examinations by year and age. We compared women screened with breast MRI to women screened with mammography alone for patient characteristics and lifetime breast cancer risk. RESULTS The overall rate of breast MRI from 2005 through 2009 nearly tripled from 4.2 to 11.5 examinations per 1000 women, with the most rapid increase from 2005 to 2007 (P = .02). The most common clinical indication was diagnostic evaluation (40.3%), followed by screening (31.7%). Compared with women who received screening mammography alone, women who underwent screening breast MRI were more likely to be younger than 50 years, white non-Hispanic, and nulliparous and to have a personal history of breast cancer, a family history of breast cancer, and extremely dense breast tissue (all P < .001). The proportion of women screened using breast MRI at high lifetime risk for breast cancer (>20%) increased during the study period from 9% in 2005 to 29% in 2009. CONCLUSIONS AND RELEVANCE Use of breast MRI for screening in high-risk women is increasing. However, our findings suggest that there is a need to improve appropriate use, including among women who may benefit from screening breast MRI.

Screening Outcomes in Older US Women Undergoing Multiple Mammograms in Community Practice: Does Interval, Age, or Comorbidity Score Affect Tumor Characteristics or False Positive Rates?

Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risk of adverse tumor characteristics and false positive rates according to screening interval, age, and comorbidity. Methods From January 1999 to December 2006, data were collected prospectively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims. Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses. We used logistic regression analyses to calculate the odds of advanced (IIb, III, IV) stage, large (>20 millimeters) tumors, and 10-year cumulative probability of false-positive mammography by screening frequency (1 vs 2 years), age, and comorbidity score. The comorbidity score was derived using the Klabunde approximation of the Charlson score. All statistical tests were two-sided. Results Adverse tumor characteristics did not differ statistically significantly by comorbidity, age, or interval. Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48.0% (95% confidence interval [CI] = 46.1% to 49.9%) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0% (95% CI = 28.1% to 29.9%) of biennial screeners. Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity.

Inverse association of NSAID use and ovarian cancer in relation to oral contraceptive use and parity

We examined the association between non-steroidal anti-inflammatory drug (NSAID) use and ovarian cancer by potential effect modifiers, parity and oral contraceptive use, in a population-based case–control study conducted in Wisconsin and Massachusetts. Women reported prior use of NSAIDs and information on risk factors in a telephone interview. A total of 487 invasive ovarian cancer cases and 2653 control women aged 20–74 years were included in the analysis. After adjustment for age, state of residence and other covariates, ever use of NSAIDs was inversely associated with ovarian cancer in never users of oral contraceptives (odds ratio (OR)=0.58, 95% confidence interval (CI) 0.42–0.80) but not for ever users (OR=0.98, 95% CI 0.71–1.35) (P-interaction=0.03). A reduced risk with NSAID use was also noted in nulliparous women (OR=0.47, 95% CI 0.27–0.82) but not among parous women (OR=0.81, 95% CI 0.64–1.04) (P-interaction=0.05). These results suggest that use of NSAIDs were beneficial to women at greatest risk for ovarian cancer.

Occupational risk factors for nasopharyngeal cancer among female textile workers in Shanghai, China

Aims: To investigate whether occupational exposure to dusts and chemicals in the Chinese textile industry are associated with risk of nasopharyngeal cancer. Methods: Sixty seven nasopharyngeal carcinoma (NPC) cases identified during 1989–98 and a random sample (n = 3188) of women were included in a case cohort study nested in a cohort of 267 400 women textile workers in Shanghai, China. A complete occupational history of work in the textile industry was obtained for each woman. A job exposure matrix developed by experienced industrial hygienists was used to assess exposures to specific dusts and chemicals. Results: Risk of NPC is associated with cumulative exposure to cotton dust. The hazard ratio for women cumulatively exposed to >143.4 mg/m3 × years of cotton dust was 3.6 (95% CI 1.8 to 7.2) compared with unexposed women. Trends of increasing risk were also found with increasing duration of exposure to acids and caustics (p = 0.05), and with years worked in dyeing processes (p = 0.06). Women who worked at least 10 years in dyeing processes had a 3.6-fold excess risk of NPC (95% CI 1.0 to 12.1). Conclusions: Occupational exposure to cotton dust, acids, and caustics, and work in dyeing and printing jobs in the textile industry may have increased risk of NPC in this cohort.

Screening for Skin Cancer in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

IMPORTANCE Skin cancer, primarily melanoma, is a leading cause of morbidity and mortality in the United States. OBJECTIVE To provide an updated systematic review for the US Preventive Services Task Force regarding clinical skin cancer screening among adults. DATA SOURCES MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published from January 1, 1995, through June 1, 2015, with surveillance through February 16, 2016. STUDY SELECTION English-language studies conducted in asymptomatic populations 15 years and older at general risk for skin cancer. DATA EXTRACTION AND SYNTHESIS Relevant data were abstracted, and study quality was rated. MAIN OUTCOMES AND MEASURES Melanoma incidence and mortality, harms from cancer screening, diagnostic accuracy, and stage distribution. RESULTS No randomized clinical trials were identified. There was limited evidence on the association between skin cancer screening and mortality. A German ecologic study (n = 360,288) found a decrease of 0.8 per 100,000 melanoma deaths in a region with population-based skin cancer screening compared with no change or slight increases in comparison regions. The number of excisions needed to detect 1 skin cancer from clinical visual skin examinations varied by age and sex; for example, 22 for women 65 years or older compared with 41 for women aged 20 to 34 years. In 2 studies of performing visual skin examination, sensitivity to detect melanoma was 40.2% and specificity was 86.1% when conducted by primary care physicians (n = 16,383). Sensitivity was 49.0% and specificity was 97.6% when skin examinations were performed by dermatologists (n = 7436). In a case-control study of melanoma (n = 7586), cases diagnosed with thicker lesions (>0.75 mm) had an odds ratio of 0.86 (95% CI, 0.75-0.98) for receipt of a physician skin examination in the prior 3 years compared with controls. Eight cohort studies (n = 236,485) demonstrated a statistically significant relationship between the degree of disease involvement at diagnosis and melanoma mortality, regardless of the characterization of the stage or lesion thickness. Tumor thickness greater than 4.0 mm was associated with increased melanoma mortality compared with thinner lesions, and late stage at diagnosis was associated with increased all-cause mortality. CONCLUSIONS AND RELEVANCE Only limited evidence was identified for skin cancer screening, particularly regarding potential benefit of skin cancer screening on melanoma mortality. Future research on skin cancer screening should focus on evaluating the effectiveness of targeted screening in those considered to be at higher risk for skin cancer.

Occupational exposures and breast cancer among women textile workers in Shanghai

Background: Breast cancer incidence rates have been increasing in China over the past 2 decades. Most studies have focused on reproductive, dietary, and genetic risk factors. Little is known about the contribution of occupational exposures. Methods: We conducted a case-cohort study within a cohort of female textile workers who had participated in a randomized trial of breast self-examination in Shanghai, China. We compared 1709 incident breast cancer cases with an age-stratified reference subcohort (n = 3155 noncases). Cox proportional hazards modeling, adapted for the case-cohort design, was used to estimate hazard ratios for breast cancer in relation to duration of employment in various job processes and duration of exposure to several agents. We also evaluated the associations of cotton dust and endotoxin with breast cancer. Results: Cumulative exposures to cotton dust and endotoxin demonstrated strong inverse gradients with breast cancer risk when exposures were lagged by 20 years (trend P-values <0.001). We did not observe consistent associations with exposures to electromagnetic fields, solvents, or other chemicals. Conclusion: Endotoxin or other components of cotton dust exposures may have reduced risks for breast cancer in this cohort, perhaps acting at early stages of carcinogenesis. Replication of these findings in other occupational settings with similar exposures will be needed to confirm or refute any hypothesis regarding protection against breast cancer.

Development of a job exposure matrix (JEM) for the textile industry in Shanghai, China

We developed a job exposure matrix (JEM) for the Shanghai textile industry constructed along three axes: industry sector, textile process, and hazardous agent. We assessed 35 different categories of dust, chemical, and physical agents for 149 textile processes within nine industry sectors: cotton, cotton/synthetic, cotton/other (nonsynthetic), wool, silk, synthetic, mineral, other mixed (e.g., wool and synthetic), and nonproduction. The JEM was constructed from two components: a priori assessment of the textile process by a team of U.S. industrial hygienists, and the prevalence of exposures reported by Chinese industrial hygienists in specific textile processes within the factory. The JEM was applied to an ongoing case-cohort study of cancer in women textile workers. The JEM assessed only dichotomous exposure (ever/never), and could be coupled with cumulative exposure by years of employment. The most common exposures in cotton mills were cotton dust and solvent exposures. Dyeing processes had the highest frequency of exposures, including solvents, acids, bases and caustics, bleaching agents, dyes, dye chemicals and intermediates, and formaldehyde. Only two processes were identified with formaldehyde exposure, beck dyeing and resin finishing. The most prevalent exposures among the subcohort, occurring in more than 60% of the women, were electromagnetic fields, lubricants, and cotton dust. More than one-third of subcohort subjects were also exposed to synthetic fiber dust, and slightly less than one-third of women were exposed to endotoxin. This JEM could be applicable for epidemiologic research in other textile industries.

Use of antidepressants and NSAIDs in relation to mortality in long-term breast cancer survivors.

The aim of this study was to assess the post‐diagnosis use of antidepressants and non‐steroidal anti‐inflammatory drugs (NSAIDs) in relation to all‐cause, breast cancer, and cardiovascular disease (CVD) mortality among long‐term breast cancer survivors.

Antidepressant medication use and breast cancer risk

Most epidemiologic studies have detected no association between prior use of antidepressant medications and breast cancer risk. Despite the uniform conclusion, there is a continuous rise in the proportion of women using antidepressants, lending support to further monitoring of disease effects.