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Background Although breast cancer survivors are at risk for cardiovascular disease (CVD) from treatment late effects, evidence to inform long-term and age-specific cardiovascular surveillance recommendations is lacking. Methods We conducted a retrospective cohort study of 10 211 women diagnosed with first primary unilateral breast cancer in Kaiser Permanente Washington or Colorado (aged 20 years and older, survived ≥1 year). We estimated multivariable adjusted hazard ratios (HRs) for associations between initial chemotherapy regimen type (anthracycline and/or trastuzumab, other chemotherapies, no chemotherapy [referent]) and CVD risk, adjusted for patient characteristics, other treatments, and CVD risk factors. Cumulative incidence was calculated considering competing events. Results After 5.79 median years, 14.67% of women developed CVD (cardiomyopathy and/or heart failure [HF], ischemic heart disease, stroke). Women treated with anthracyclines and/or trastuzumab had a higher risk of CVD compared with no chemotherapy (adjusted HR = 1.53, 95% confidence interval [CI] = 1.31 to 1.79), persisting at least 5 years postdiagnosis (adjusted HR5-<10 years = 1.85, 95% CI = 1.44 to 2.39; adjusted HR≥10 years = 1.83, 95% CI = 1.34 to 2.49). Cardiomyopathy and/or HF risks were elevated among women treated with anthracyclines and/or trastuzumab compared with no chemotherapy, especially for those aged younger than 65 years (adjusted HR20-54years = 2.97, 95% CI = 1.72 to 5.12; adjusted HR55-64years = 2.21, 95% CI = 1.52 to 3.21), differing for older women (adjusted HR≥65 years = 1.32, 95% CI = 0.97 to 1.78), and at least 5 years postdiagnosis (adjusted HR5-<10years = 1.89, 95% CI = 1.35 to 2.64; adjusted HR≥10 years = 2.21, 95% CI = 1.52 to 3.20). Anthracyclines and/or trastuzumab receipt was associated with increased ischemic heart disease risks after 5 or more years (adjusted HR5-<10years = 1.51, 95% CI = 1.06 to 2.14; adjusted HR≥10 years = 1.86, 95% CI = 1.18 to 2.93) with no clear age effects, and stroke risk (adjusted HR = 1.33, 95% CI = 1.05 to 1.69), which did not vary by time or age. There was some evidence of long-term cardiomyopathy and/or HF and ischemic heart disease risks with other chemotherapies. Among women aged younger than 65 treated with anthracyclines and/or trastuzumab, up to 16% developed CVD by 10 years (20-54 years = 6.91%; 55-64 years = 16.00%), driven by cardiomyopathy and/or HF (20-54 years = 3.90%; 55-64 years = 9.78%). Conclusions We found increased long-term risks of cardiomyopathy and/or HF and ischemic heart disease among breast cancer survivors treated with anthracyclines and/or trastuzumab and increased cardiomyopathy and/or HF risk among women aged younger than 65 years. [ABSTRACT FROM AUTHOR]

Background: Women with dense breasts have an increased risk of breast cancer. However, breast density is measured with variability, which may reduce the reliability and accuracy of its association with breast cancer risk. This is particularly relevant when visually assessing breast density due to variation in inter- and intra-reader assessments. To address this issue, we developed a longitudinal breast density measure which uses an individual woman's entire history of mammographic density, and we evaluated its association with breast cancer risk as well as its predictive ability. Methods: In total, 132,439 women, aged 40–73 yr, who were enrolled in Kaiser Permanente Washington and had multiple screening mammograms taken between 1996 and 2013 were followed up for invasive breast cancer through 2014. Breast Imaging Reporting and Data System (BI-RADS) density was assessed at each screen. Continuous and derived categorical longitudinal density measures were developed using a linear mixed model that allowed for longitudinal density to be updated at each screen. Predictive ability was assessed using (1) age and body mass index-adjusted hazard ratios (HR) for breast density (time-varying covariate), (2) likelihood-ratio statistics (ΔLR-χ2) and (3) concordance indices. Results: In total, 2704 invasive breast cancers were diagnosed during follow-up (median = 5.2 yr; median mammograms per woman = 3). When compared with an age- and body mass index-only model, the gain in statistical information provided by the continuous longitudinal density measure was 23% greater than that provided by BI-RADS density (follow-up after baseline mammogram: ΔLR-χ2 = 379.6 (degrees of freedom (df) = 2) vs. 307.7 (df = 3)), which increased to 35% (ΔLR-χ2 = 251.2 vs. 186.7) for follow-up after three mammograms (n = 76,313, 2169 cancers). There was a sixfold difference in observed risk between densest and fattiest eight-category longitudinal density (HR = 6.3, 95% CI 4.7–8.7), versus a fourfold difference with BI-RADS density (HR = 4.3, 95% CI 3.4–5.5). Discriminatory accuracy was marginally greater for longitudinal versus BI-RADS density (c-index = 0.64 vs. 0.63, mean difference = 0.008, 95% CI 0.003–0.012). Conclusions: Estimating mammographic density using a woman's history of breast density is likely to be more reliable than using the most recent observation only, which may lead to more reliable and accurate estimates of individual breast cancer risk. Longitudinal breast density has the potential to improve personal breast cancer risk estimation in women attending mammography screening. [ABSTRACT FROM AUTHOR]

Background: In women with previously treated breast cancer, occurrence and timing of second breast cancers have implications for surveillance. The authors examined the timing of second breast cancers by primary cancer estrogen receptor (ER) status in the Breast Cancer Surveillance Consortium. Methods: Women who were diagnosed with American Joint Commission on Cancer stage I–III breast cancer were identified within six Breast Cancer Surveillance Consortium registries from 2000 to 2017. Characteristics collected at primary breast cancer diagnosis included demographics, ER status, and treatment. Second breast cancer events included subsequent ipsilateral or contralateral breast cancers diagnosed >6 months after primary diagnosis. The authors examined cumulative incidence and second breast cancer rates by primary cancer ER status during 1–5 versus 6–10 years after diagnosis. Results: At 10 years, the cumulative second breast cancer incidence was 11.8% (95% confidence interval [CI], 10.7%–13.1%) for women with ER‐negative disease and 7.5% (95% CI, 7.0%–8.0%) for those with ER‐positive disease. Women with ER‐negative cancer had higher second breast cancer rates than those with ER‐positive cancer during the first 5 years of follow‐up (16.0 per 1000 person‐years [PY]; 95% CI, 14.2–17.9 per 1000 PY; vs. 7.8 per 1000 PY; 95% CI, 7.3–8.4 per 1000 PY, respectively). After 5 years, second breast cancer rates were similar for women with ER‐negative versus ER‐positive breast cancer (12.1 per 1000 PY; 95% CI, 9.9–14.7; vs. 9.3 per 1000 PY; 95% CI, 8.4–10.3 per 1000 PY, respectively). Conclusions: ER‐negative primary breast cancers are associated with a higher risk of second breast cancers than ER‐positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period. Women with estrogen receptor‐negative primary breast cancers are at higher risk of second breast cancers than women with estrogen receptor‐positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period. [ABSTRACT FROM AUTHOR]

Background: Advanced breast cancer is an outcome used to evaluate screening effectiveness. The advanced cancer definition resulting in the best discrimination of breast cancer death has not been studied in a breast imaging population.Methods: A total of 52 496 women aged 40-79 years participating in the Breast Cancer Surveillance Consortium diagnosed with invasive cancer were staged using the 8th edition of American Joint Committee on Cancer (AJCC) anatomic and prognostic pathologic systems and Tomosynthesis Mammographic Imaging Screening Trial (TMIST) tumor categories. We calculated the area under the receiver operating characteristic curve for predicting 5-year breast cancer death and the sensitivity and specificity for predicting 5-year breast cancer death for 3 advanced cancer classifications: anatomic stage IIB or higher, prognostic pathologic stage IIA or higher, and TMIST advanced cancer.Results: The area under the receiver operating characteristic curves for predicting 5-year breast cancer death for AJCC anatomic stage, AJCC prognostic pathologic stage, and TMIST tumor categories were 0.826 (95% confidence interval [CI] = 0.817 to 0.835), 0.856 (95% CI = 0.846 to 0.866), and 0.789 (95% CI = 0.780 to 0.797), respectively. AJCC prognostic pathologic stage had statistically significantly better discrimination than AJCC anatomic stage (difference = 0.030, bootstrap 95% CI = 0.024 to 0.037) and TMIST tumor categories (difference = 0.067, bootstrap 95% CI = 0.059 to 0.075). The sensitivity and specificity for predicting 5-year breast cancer death for AJCC anatomic stage IIB or higher, AJCC prognostic pathologic stage IIA or higher, and TMIST advanced cancer were 72.6%, 76.7%, and 96.1%; and 78.9%, 81.6%, and 41.1%, respectively.Conclusions: Defining advanced cancer as AJCC prognostic pathologic stage IIA or higher most accurately predicts breast cancer death. Use of this definition by investigators will facilitate comparing breast cancer screening effectiveness studies. [ABSTRACT FROM AUTHOR]

Background: Potential benefits of screening mammography among women ages 75 years and older remain unclear.Methods: We evaluated 10-year cumulative incidence of breast cancer and death from breast cancer and other causes by Charlson Comorbidity Index (CCI) and age in the Medicare-linked Breast Cancer Surveillance Consortium (1999-2010) cohort of 222 088 women with no less than 1 screening mammogram between ages 66 and 94 years.Results: During median follow-up of 107 months, 7583 were diagnosed with invasive breast cancer and 1742 with ductal carcinoma in situ; 471 died from breast cancer and 42 229 from other causes. The 10-year cumulative incidence of invasive breast cancer did not change with increasing CCI but decreased slightly with age: ages 66-74 years (CCI0 = 4.0% [95% CI = 3.9% to 4.2%] vs CCI  ≥ 2 = 3.9% [95% CI = 3.5% to 4.3%]); ages 75-84 years (CCI0 = 3.7% [95% CI = 3.5% to 3.9%] vs CCI  ≥ 2 = 3.4% [95% CI = 2.9% to 3.9%]); and ages 85-94 years (CCI0 = 2.7% [95% CI = 2.3% to 3.1%] vs CCI  ≥ 2 = 2.1% [95% CI = 1.3% to 3.0%]). The 10-year cumulative incidence of other-cause death increased with increasing CCI and age: ages 66-74 years (CCI0 = 10.4% [95% CI = 10.3 to 10.7%] vs CCI ≥ 2 = 43.4% [95% CI = 42.2% to 44.4%]), ages 75-84 years (CCI0 = 29.8% [95% CI = 29.3% to 30.2%] vs CCI ≥ 2 = 61.7% [95% CI = 60.2% to 63.3%]), and ages 85 to 94 years (CCI0 = 60.3% [95% CI = 59.1% to 61.5%] vs CCI  ≥ 2 = 84.8% [95% CI = 82.5% to 86.9%]). The 10-year cumulative incidence of breast cancer death was small and did not vary by age: ages 66-74 years = 0.2% (95% CI = 0.2% to 0.3%), ages 75-84 years = 0.29% (95% CI = 0.25% to 0.34%), and ages 85 to 94 years = 0.3% (95% CI = 0.2% to 0.4%).Conclusions: Cumulative incidence of other-cause death was many times higher than breast cancer incidence and death, depending on comorbidity and age. Hence, older women with increased comorbidity may experience diminished benefit from continued screening. [ABSTRACT FROM AUTHOR]

Background: Genetic testing to determine BRCA status has been available for over two decades, but there are few population-based studies of test diffusion. We report 10-year trends in BRCAtesting in an integrated health-care system with long-standing access to genetic services.Methods: A cohort of women aged 18 years and older was created to ascertain BRCA testing (n = 295 087). Annual testing rates between 2005 and 2015 were calculated in all women with and without incident (ie, newly diagnosed) breast and ovarian cancers and in clinically eligible subgroups by family cancer history, personal cancer history, and age at diagnosis. Secular trends were assessed using Poisson regression. Women tested early (2005-2008), midway (2009-2012), and late (2013-2015) in the study period were compared in cross-sectional analyses.Results: Between 2005 and 2015, annual testing rates increased from 0.6/1000 person-years (pys) (95% confidence interval [CI] = 0.4 to 0.7/1000 pys) to 0.8/1000 pys (95% CI = 0.6 to 1.0/1000 pys) in women without incident breast or ovarian cancers. Rates decreased from 71.5/1000 pys (95% CI = 42.4 to 120.8/1000 pys) to 44.4/1000 pys (95% CI = 35.5 to 55.6/1000 pys) in women with incident diagnoses, despite improvements in provision of timely BRCA testing during this time frame. We found no evidence of secular trends in clinically eligible subgroups including women with family history indicating increased hereditary cancer risk, but no personal cancer history. At the end of the study period, 97.0% (95% CI = 96.6% to 97.3%) of these women remained untested.Conclusion: Many eligible women did not receive BRCA testing despite having insurance coverage and access to specialty genetic services, underscoring challenges to primary and secondary hereditary cancer prevention. [ABSTRACT FROM AUTHOR]

In previous studies, we found modestly decreased and increased risks of second breast cancer events with the use of statins and antibiotics, respectively, after adjustment for surveillance mammography. We evaluated detection bias by comparing receipt of surveillance mammography among users of these 2 disparate classes of medication. Adult women diagnosed with early-stage breast cancer during 1990-2008 (n = 3,965) while enrolled in an integrated health-care plan (Group Health Cooperative; Washington State) were followed for up to 10 years in the Commonly Used Medications and Breast Cancer Outcomes (COMBO) Study. Categories of antibiotic use included infrequent (1-3 dispensings/12 months) and frequent (≥4 dispensings/12 months) use, and categories of statin use included less adherent (1 dispensing/6 months) and adherent (≥2 dispensings/6 months). We examined associations between medication use and surveillance mammography using multivariable generalized estimating equations and evaluated the impact of adjusting for surveillance within Cox proportional hazard models. Frequent antibiotic users were less likely to receive surveillance mammography (odds ratio (OR) = 0.90, 95% confidence interval (CI): 0.82, 0.99) than were nonusers; no association was found among infrequent users (OR = 0.96, 95% CI: 0.90, 1.03). Adherent statin use was associated with more surveillance compared with nonuse (OR = 1.11, 95% CI: 1.01,1.25), but less adherent statin use was not (OR = 1.03, 95% CI: 0.81,1.31). Nodifference in associations between medications of interest and second breast cancer events was observed when surveillance was removed from otherwise adjusted models. The influence of detection bias by medication use warrants further exploration. [ABSTRACT FROM AUTHOR]

We describe the relationship between preoperative magnetic resonance imaging ( MRI) and the utilization of additional imaging, biopsy, and primary surgical treatment for subgroups of women with interval versus screen-detected breast cancer. We determined the proportion of women receiving additional breast imaging or biopsy and type of primary surgical treatment, stratified by use of preoperative MRI, separately for both groups. Using Breast Cancer Surveillance Consortium ( BCSC) data, we identified a cohort of women age 66 and older with an interval or screen-detected breast cancer diagnosis between 2005 and 2010. Using logistic regression, we explored associations between primary surgical treatment type and preoperative MRI use for interval and screen-detected cancers. There were 204 women with an interval cancer and 1,254 with a screen-detected cancer. The interval cancer group was more likely to receive preoperative MRI (21% versus 13%). In both groups, women receiving MRI were more likely to receive additional imaging and/or biopsy. Receipt of MRI was not associated with increased odds of mastectomy ( OR = 0.99, 95% CI: 0.67-1.50), while interval cancer diagnosis was associated with significantly higher odds of mastectomy ( OR = 1.64, 95% CI: 1.11-2.42). Older women with interval cancer were more likely than women with a screen-detected cancer to have preoperative MRI, however, those with an interval cancer had 64% higher odds of mastectomy regardless of receipt of MRI. Given women with interval cancer are reported to have a worse prognosis, more research is needed to understand effectiveness of imaging modalities and treatment consequences within this group. [ABSTRACT FROM AUTHOR]

Preoperative breast magnetic resonance imaging (MRI) use among Medicare beneficiaries with breast cancer has substantially increased from 2005 to 2009. We sought to identify factors associated with preoperative breast MRI use among women diagnosed with ductal carcinoma in situ (DCIS) or stage I-III invasive breast cancer (IBC). Using Surveillance, Epidemiology, and End Results and Medicare data from 2005 to 2009 we identified women ages 66 and older with DCIS or stage I-III IBC who underwent breast-conserving surgery or mastectomy. We compared preoperative breast MRI use by patient, tumor and hospital characteristics stratified by DCIS and IBC using multivariable logistic regression. From 2005 to 2009, preoperative breast MRI use increased from 5.9% to 22.4% of women diagnosed with DCIS and 7.0% to 24.3% of women diagnosed with IBC. Preoperative breast MRI use was more common among women who were younger, married, lived in higher median income zip codes and had no comorbidities. Among women with IBC, those with lobular disease, smaller tumors (<1 cm) and those with estrogen receptor negative tumors were more likely to receive preoperative breast MRI. Women with DCIS were more likely to receive preoperative MRI if tumors were larger (>2 cm). The likelihood of receiving preoperative breast MRI is similar for women diagnosed with DCIS and IBC. Use of MRI is more common in women with IBC for tumors that are lobular and smaller while for DCIS MRI is used for evaluation of larger lesions. [ABSTRACT FROM AUTHOR]

Introduction: Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk). Methods: We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method. Results: Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; Ptrend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; Ptrend= 0.07). No other chemicals demonstrated associations with percentage breast density. Conclusions: Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥65 years and are at risk for developing subsequent malignancies. METHODS: Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk. RESULTS: Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥73% had a body mass index ≤30 kg/m2. Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47). CONCLUSIONS: Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Few data have been published on mammography performance in women who are younger than 40 years. [ABSTRACT FROM PUBLISHER]

Background: Being overweight or obese is associated with increased breast cancer risk and disease severity among postmenopausal women, but whether extent of mammography use and accuracy modify this association and further contribute to increases in disease severity at diagnosis among overweight and obese women is unclear. Methods: We prospectively collected data during 1996-2005 on 287115 postmenopausal women not using hormone therapy (HT) who underwent 614562 mammography examinations; 4446 women were diagnosed with breast cancer within 12 months of a mammography examination. We calculated rates per 1000 mammography examinations of large (> 15 mm), advanced-stage (IIb, III, or IV), high-grade (3 or 4), estrogen receptor (ER)-positive and -negative, and screen-detected and non-screen-detected breast cancer across body mass index (BMI, kg/m2) groups defined as normal (18.5-24.9), overweight (25.0-29.9), obese class I (30.0-34.9), and obese class II/III (⩾35.0), adjusting for age, race/ethnicity, and mammography registry and use. All statistical tests were two-sided. Results: Adjusted rates per 1000 mammography examinations of overall breast cancer increased across BMI groups (6.6 normal, 7.4 overweight, 7.9 obese I, 8.5 obese II/III; Ptrend < .001), as did rates of advanced disease, including large invasive (2.3 normal, 2.6 overweight, 2.9 obese I, 3.2 obese II/III; Ptrend < .001), advanced-stage (0.8 normal, 0.9 overweight, 1.3 obese I, 1.5 obese II/III; Ptrend < .001), and high nuclear grade (1.5 normal, 1.7 overweight, 1.7 obese I, 1.9 obese II/III; Ptrend = .10) tumors. Rates of ER-positive tumors increased across BMI groups (Ptrend < .001); rates of ER-negative tumors did not. Rates of screen-detected cancers were higher among overweight and obese women than normal and underweight women, but rates of non-screen-detected (false-negative) cancers were similar. Rates of advanced breast cancer increased across BMI groups regardless of extent of mammography use. Conclusions: Patterns of mammography use and mammography accuracy are not the primary reasons for higher rates of advanced breast cancer among overweight and obese postmenopausal women not using HT; thus, biologic differences in breast tumor development and/or progression may be important. [ABSTRACT FROM AUTHOR]

Whether a recent large decline in use of postmenopausal hormone therapy after the release of the Women's Health Initiative findings in July 2002 and/or a decline in screening mammography use is related to a recently reported decline in breast cancer incidence in the United States is controversial. We prospectively collected data from four screening mammography registries from January 1997 through December 2003 for 603411 screening mammography examinations performed on women aged 50-69 years. Of these women, 3238 were diagnosed with breast cancer within 12 months of a screening examination. We calculated quarterly rates of self-reported current postmenopausal hormone therapy use and of invasive breast cancer, ductal carcinoma in situ (DCIS), and estrogen receptor (ER)-positive invasive breast cancer adjusted for age, registry, and time between screening examinations. All statistical tests were two-sided. Between 2000 and 2002 and between 2002 and 2003, annual rates of postmenopausal hormone therapy use declined by 7% and 34%, respectively (Ptrend<.001 for both). Between 2000 and 2003, annual rates of invasive cancer declined by 5% (Ptrend =.003). Between 2001 and 2003, annual rates of ER-positive invasive breast cancer declined by 13% (Ptrend =.002). Rates of DCIS were stable during the study period. Our finding of a statistically significant decline in the rate of ER-positive invasive breast cancer in a screening mammography population after the start of a concomitant substantial decline in postmenopausal hormone therapy use suggests that a decline in screening mammography rates is unlikely to account for the recent decline in US breast cancer incidence. [ABSTRACT FROM AUTHOR]

Background Whether a change over time in clinically measured mammographic breast density influences breast cancer risk is unknown. Methods From January 1993 to December 2003, data that included American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density categories (1-4 in order of increasing density) were collected prospectively on 301 955 women aged 30 and older who were not using postmenopausal hormone replacement therapy and underwent at least two screening mammography examinations; 2639 of the women were diagnosed with breast cancer within 1 year of the last examination. Women's first and last BI-RADS breast density (average 3.2 years apart) and logistic regression were used to model the odds of having invasive breast cancer or ductal carcinoma in situ diagnosed within 12 months of the last examination by change in BI-RADS category. Rates of breast cancer adjusted for age, mammography registry, and time between screening examinations were estimated from this model. All statistical tests were two-sided. Results The rate (breast cancers per 1000 women) of breast cancer was higher if BI-RADS breast density category increased from 1 to 2 (5.6, 95% confidence interval (CI) = 4.7 to 6.9) or 1 to 3 (9.9, 95% CI = 6.4 to 15.5) compared to when it remained at BI-RADS density of 1 (3.0, 95% CI = 2.3 to 3.9; P<.001 for trend). Similar and statistically significant trends between increased or decreased density and increased or decreased risk of breast cancer, respectively, were observed for women whose breast density category was initially 2 or 3 and changed categories. BI-RADS density of 4 on the first examination was associated with a high rate of breast cancer (range 9.1-13.4) that remained high even if breast density decreased. Conclusion An increase in BI-RADS breast density category within 3 years may be associated with an increase in breast cancer risk and a decrease in density category with a decrease in risk compared to breast cancer risk in women in whom breast density category remains unchanged. Two longitudinal measures of BI-RADS breast density may better predict a woman's risk of breast cancer than a single measure. [ABSTRACT FROM AUTHOR]

Background: Risk prediction models for breast cancer can be improved by the addition of recently identified risk factors, including breast density and use of hormone therapy. We used prospective risk information to predict a diagnosis of breast cancer in a cohort of 1 million women undergoing screening mammography. Methods: There were 2 392 998 eligible screening mammograms from women without previously diagnosed breast cancer who had had a prior mammogram in the pre- ceding 5 years. Within 1 year of the screening mammogram, 11 638 women were diagnosed with breast cancer. Separate logistic regression risk models were constructed for premenopausal and postmenopausal examinations by use of a stringent (P<.0001) criterion for the inclusion of risk factors. Risk models were constructed with 75% of the data and validated with the remaining 25%. Concordance of the predicted with the observed outcomes was assessed by a concordance (c) statistic after logistic regression model fit. All statistical tests were two- sided. Results: Statistically significant risk factors for breast cancer diagnosis among premenopausal women included age, breast density, family history of breast cancer, and a prior breast procedure. For postmenopausal women, the statistically significant factors included age, breast density, race, ethnicity, family history of breast cancer, a prior breast procedure, body mass index, natural menopause, hormone therapy, and a prior false-positive mammogram. The model may identify high-risk women better than the Gail model, although predictive accuracy was only moderate. The c statistics were 0.631 (95% confidence interval [CI] = 0.618 to 0.644) for pre- menopausal women and 0.624 (95% CI = 0.619 to 0.630) for postmenopausal women. Conclusion: Breast density is a strong additional risk factor for breast cancer, although it is unknown whether reduction in breast density would reduce risk. Our risk model may be able to identify women at high risk for breast cancer for preventive interventions or more intensive surveillance. [ABSTRACT FROM AUTHOR]

Background: Mammography screening may reduce breast cancer mortality by detecting cancers at an earlier stage. However, certain questions remain, including the ideal interval between mammograms. Methods: We conducted an observational study using information collected by seven mammography registries across the United States to investigate whether women diagnosed with breast cancer after having screening mammograms separated by a 2-year interval (n = 2440) are more likely to be diagnosed with late-stage disease (positive lymph nodes or metastases) than women diagnosed with breast cancer after having screening mammograms separated by a 1-year interval (n = 5400). Analyses were stratified by age and breast density to clarify whether groups that have the poorest mammography sensitivity (i.e., women under age 50 years and those with mammographically dense breasts) would benefit most from annual screening. The subjects were women diagnosed with breast cancer between 1996 and 2001 who were 40–89 years old at their index mammographic examination (i.e., the most recent screen at or before breast cancer diagnosis). Data were analyzed by logistic regression, adjusting for race, ethnicity, family history of breast cancer, and mammography registry. Results: Among women age 40–49 years at the index mammogram, those with a 2-year screening interval were more likely to have late-stage disease at diagnosis than those with a 1-year screening interval (28% versus 21%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.01 to 1.81). There was no increase in late-stage disease for women 50 years or older with a 2-year versus a 1-year screening interval (women age 50–59 years at index mammogram: OR = 0.97, 95% CI = 0.75 to 1.25; women age 60–69 years at index mammogram: OR = 0.99, 95% CI = 0.72 to 1.35; women age 70 years or older at index mammogram: OR = 0.88, 95% CI = 0.64 to 1.19). There was no indication that women with dense breasts would benefit more from a 1-year versus 2-year screening interval than women with fatty breasts. Conclusion: These findings may be useful for policy decisions about appropriate screening intervals and for use in statistical models that estimate the costs and benefits of mammography by age and screening interval. [ABSTRACT FROM AUTHOR]

Background: Younger women (40–49 years) have lower mammographic sensitivity (i.e., greater proportion of cancers detected after a negative mammogram) than older women (≥50 years). We explored the effect of tumor growth rate, breast density, mammographic image quality, and breast cancer risk factors on mammographic sensitivity in younger and older women. Methods: We studied 576 women (n = 73 aged 40–49 years and n = 503 aged 50 years or older) who were diagnosed with invasive breast cancer between 1988 and 1993. Interval cancers were defined as those diagnosed within 12 or 24 months after a negative screening mammogram and before a subsequent mammogram. Tumor growth rate was assessed by mitotic figure count and Ki-67 positivity. The main outcome measures were percentage of women with interval cancer (1 - mammographic sensitivity) by age, odds ratio (OR) of interval cancer by age, and excess odds (i.e., the percentage of the odds ratio for age that was explained by individual covariates). Results: Interval cancers occurred in 27.7% of younger women and 13.9% of older women within 12 months (OR = 2.36, 95% confidence interval [CI] = 1.14 to 4.77) and in 52.1% of younger women and 24.7% of older women within 24 months (OR = 3.58, 95% CI = 2.15 to 5.97). Greater breast density explained 67.6% of the decreased mammographic sensitivity in younger women at 12 months, whereas rapid tumor growth explained 30.6% and breast density explained 37.6% of the decreased sensitivity in younger women at 24 months. Conclusions: Breast density largely explained decreased mammographic sensitivity at 12 months, whereas rapid tumor growth contributed to decreased mammographic sensitivity at 24 months. A 12-month versus a 24-month mammography screening interval may therefore reduce the adverse impact of faster growing tumors on mammographic sensitivity in younger women. [ABSTRACT FROM AUTHOR]

Background: The purpose of this report is to examine the correlates of quality of life (QOL) of a well-defined group of long-term breast cancer survivors diagnosed between the ages of 40 and 49. Methods: Women were eligible if they were diagnosed with invasive breast cancer or ductal carcinoma in situ 5 to 10 years before June 30, 1998 and were enrolled at Group Health Cooperative, a health maintenance organization in western Washington State. A questionnaire was mailed to 290 women; 216 were included in this analysis. The questionnaire included standardized measures of QOL [e.g., the Cancer Rehabilitation Evaluation System (CARES-SF) and SF-36] as well as general demographic and medical information. ANOVA and logistic regression were used to estimate correlates of self-reported QOL. Results: The mean age at diagnosis was 44.4 years, and the average time since diagnosis was 7.3 years. Women reported high levels of functioning across several standardized QOL scales; mild impairment was found on the CARES-SF Sexual Scale. The presence of breast-related symptoms at survey, use of adjuvant therapy, having lower income, and type of breast surgery were significantly associated with lower QOL 5 to 10 years post-diagnosis on one or more of the scales. Conclusions: Our results emphasize that younger long-term survivors of breast cancer have a high QOL across several standardized measures. However, the long-term consequences of adjuvant therapy and the management of long-term breast-related symptoms are two areas that may be important for clinicians and women with breast cancer in understanding and optimizing long-term QOL. [ABSTRACT FROM AUTHOR]

A response to a letter to the editor is presented about the article "Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population," by K. Kerlikowske, D.L. Miglioretti, D.S.M. Buist, R. Walker and P.A. Carney.

The COVID-19 pandemic disrupted breast cancer screening and diagnostic imaging in the United States. We sought to evaluate how medical facilities prioritized breast imaging services during periods of reduced capacity or upon re-opening after closures. In fall 2020, we surveyed 77 breast imaging facilities within the Breast Cancer Surveillance Consortium in the United States. The survey ascertained the pandemic's impact on clinical practices during March-September 2020. Nearly all facilities (97%) reported closing or operating at reduced capacity at some point during this period. All facilities were open by August 2020, though 14% were still operating at reduced capacity in September 2020. During periods of re-opening or reduced capacity, 93% of facilities reported prioritizing diagnostic breast imaging over breast cancer screening. For diagnostic imaging, facilities prioritized based on rescheduling canceled appointments (89%), specific indication for diagnostic imaging (89%), patient demand (84%), individual characteristics and risk factors (77%), and time since last imaging examination (72%). For screening mammography, facilities prioritized based on rescheduled cancelations (96%), patient demand (83%), individual characteristics and risk factors (73%), and time since last mammogram (71%). For biopsy services, more than 90% of facilities reported prioritization based on rescheduling of canceled exams, patient demand, patient characteristics and risk factors and level of suspicion on imaging. The observed patterns from this large and geographically diverse sample of facilities in the United States indicate that multiple factors were commonly used to prioritize breast imaging services during periods of reduced capacity. [ABSTRACT FROM AUTHOR]