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Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer. Materials and Methods This prospective case-control study included patients who underwent a bilateral breast MRI examination and were receiving care at one of three centers in the United States from November 2010 to July 2017. Breast volume, fibroglandular tissue (FGT) volume, and BPE were quantified using fully automated software. Fat volume was defined as breast volume minus FGT volume. BPE extent was defined as the proportion of FGT voxels with enhancement of 20% or more. Spearman rank correlation between quantitative BPE extent and Breast Imaging Reporting and Data System (BI-RADS) BPE categories assigned by an experienced board-certified breast radiologist was estimated. With use of multivariable logistic regression, breast cancer case-control status was regressed on tertiles (low, moderate, and high) of BPE, FGT volume, and fat volume, with adjustment for covariates. Results In total, 536 case participants with breast cancer (median age, 48 years [IQR, 43-55 years]) and 940 cancer-free controls (median age, 46 years [IQR, 38-55 years]) were included. BPE extent was positively associated with BI-RADS BPE (rs = 0.54; P < .001). Compared with low BPE extent (range, 2.9%-34.2%), high BPE extent (range, 50.7%-97.3%) was associated with increased odds of breast cancer (odds ratio [OR], 1.74 [95% CI: 1.23, 2.46]; P for trend = .002) in a multivariable model also including FGT volume (OR, 1.39 [95% CI: 0.97, 1.98]) and fat volume (OR, 1.46 [95% CI: 1.04, 2.06]). The association of high BPE extent with increased odds of breast cancer was similar for premenopausal and postmenopausal women (ORs, 1.75 and 1.83, respectively; interaction P = .73). Conclusion Objectively measured BPE at breast MRI is associated with increased breast cancer odds for both premenopausal and postmenopausal women. Clinical trial registration no. NCT02301767 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bokacheva in this issue.

BACKGROUND: Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be associated with breast cancer risk, but previous studies of the association are equivocal and limited by incomplete blinding of BPE assessment. In this study, we evaluated the association between BPE and breast cancer based on fully blinded assessments of BPE in the unaffected breast. METHODS: The Imaging and Epidemiology (IMAGINE) study is a multicenter breast cancer case-control study of women receiving diagnostic, screening, or follow-up breast MRI, recruited from three comprehensive cancer centers in the USA. Cases had a first diagnosis of unilateral breast cancer and controls had no history of or current breast cancer. A single board-certified breast radiologist with 12 years experience, blinded to case-control status and clinical information, assessed the unaffected breast for BPE without view of the affected breast of cases (or the corresponding breast laterality of controls). The association between BPE and breast cancer was estimated by multivariable logistic regression separately for premenopausal and postmenopausal women. RESULTS: The analytic dataset included 835 cases and 963 controls. Adjusting for fibroglandular tissue (breast density), age, race/ethnicity, BMI, parity, family history of breast cancer, BRCA1/BRCA2 mutations, and other confounders, moderate/marked BPE (vs minimal/mild BPE) was associated with breast cancer among premenopausal women [odds ratio (OR) 1.49, 95% CI 1.05-2.11; p = 0.02]. Among postmenopausal women, mild/moderate/marked vs minimal BPE had a similar, but statistically non-significant, association with breast cancer (OR 1.45, 95% CI 0.92-2.27; p = 0.1). CONCLUSIONS: BPE is associated with breast cancer in premenopausal women, and possibly postmenopausal women, after adjustment for breast density and confounders. Our results suggest that BPE should be evaluated alongside breast density for inclusion in models predicting breast cancer risk.

BackgroundDespite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT), HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC) services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma.Methodology/principal findingsA prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic) or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment). During June 2009- March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines.Conclusions/significanceThis is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery strategy, with important implications for programs striving to eliminate vertical transmission of HIV and improve maternal health.Trial registrationClinicalTrials.gov NCT00931216 http://clinicaltrials.gov/ct2/show/NCT00931216.

The article responds to criticisms of a study on the agreement between medical record abstraction (MRA) and self-reported breast cancer treatment data. The authors defend their use of MRA as the gold standard and explain their methodology, which included obtaining information from multiple healthcare providers. They address suggestions to consider a wider age range at breast cancer diagnosis and analyze recall bias, concluding that self-reported treatment information in younger women with breast cancer can be reliably ascertained even 2 decades post-diagnosis. The study was funded by the US National Institutes of Health and the authors declared no conflicts of interest. [Extracted from the article]

The National Council on Radiation Protection and Measurements (NCRP) is coordinating an expansive epidemiologic effort entitled the Million Person Study of Low-Dose Radiation Health Effects (MPS). Medical workers constitute the largest occupational radiation-exposed group whose doses are typically received gradually over time. A unique opportunity exists to establish an Institutional Review Board/Privacy Board (IRB/PB) approved, retrospective feasibility sub-cohort of diseased Memorial Sloan Kettering Cancer Center (MSK) medical radiation workers to reconstruct occupational/work history, estimate organ-specific radiation absorbed doses, and review existing publicly available records for mortality from cancer (including leukemia) and other diseases. Special emphasis will be placed on dose reconstruction approaches as a means to provide valid organ dose estimates that are as accurate and precise as possible based on the available data, and to allow proper evaluation of accompanying uncertainties. Such a study that includes validated dose measurements and information on radiation exposure conditions would significantly reduce dose uncertainties and provided greatly improved information on chronic low-dose risks. The feasibility sub-cohort will include deceased radiation workers from MSK who worked during the nearly seventy-year timeframe from 1946 through 2010 and were provided individual personal radiation dosimetry monitors. A feasibility assessment focused on obtaining records for about 25–30,000 workers, with over 124,000 annual doses, including personnel/work histories, specific dosimetry data, and appropriate information for epidemiologic mortality tracing will be conducted. MSK radiation dosimetry measurements have followed stringent protocols complying with strict worker protection standards in order to provide accurate dose information for radiation workers that include detailed records of work practices (including specific task exposure conditions, radiation type, energy, geometry, personal protective equipment usage, badge position, and missed doses), as well as recorded measurements. These dose measurements have been ascertained through a variety of techniques that have evolved over the years, from film badges to thermoluminescent dosimetry technology to optically stimulated luminescent methodologies. It is expected that individual total doses for the sub-cohort will have a broad range from <10 mSv to > =1000 mSv. MSK has pioneered the use of novel radiation diagnostic and therapeutic approaches over time (including initial work with x-rays, radium, and radon), with workplace safety in mind, resulting in a variety of radiation worker exposure scenarios. The results of this feasibility sub-cohort of deceased radiation workers, and associated lessons learned may potentially be applied to an expanded multicenter study of about 170,000 medical radiation worker component of the MPS. [ABSTRACT FROM AUTHOR]

Evidence is mounting that cigarette smoking contributes to second primary contralateral breast cancer (CBC) risk. Whether radiation therapy (RT) interacts with smoking to modify this risk is unknown. In this multicenter, individually matched, case-control study, we examined the association between RT, smoking, and CBC risk. The study included 1521 CBC cases and 2212 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2008 aged younger than 55 years. Absorbed radiation doses to contralateral breast regions were estimated with thermoluminescent dosimeters in tissue-equivalent anthropomorphic phantoms, and smoking history was collected by interview. Rate ratios (RRs) and 95% confidence intervals (CIs) for CBC risk were estimated by multivariable conditional logistic regression. There was no interaction between any measure of smoking with RT to increase CBC risk (eg, the interaction of continuous RT dose with smoking at first breast cancer diagnosis [ever/never]: RR = 1.00, 95% CI = 0.89 to 1.14; continuous RT dose with years smoked: RR = 1.00, 95% CI = 0.99 to 1.01; and continuous RT dose with lifetime pack-years: RR = 1.00, 95% CI = 0.99 to 1.01). There was no evidence that RT further increased CBC risk in young women with first primary breast cancer who were current smokers or had smoking history. [ABSTRACT FROM AUTHOR]

Whether radiation therapy (RT) affects contralateral breast cancer (CBC) risk in women with pathogenic germline variants in moderate- to high-penetrance breast cancer-associated genes is unknown. In a population-based case-control study, we examined the association between RT; variants in ATM, BRCA1/2, or CHEK2*1100delC; and CBC risk. We analyzed 708 cases of women with CBC and 1399 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2000 and aged younger than 55 years at diagnosis and screened for variants in breast cancer-associated genes. Rate ratios (RR) and 95% confidence intervals (CIs) were estimated using multivariable conditional logistic regression. RT did not modify the association between known pathogenic variants and CBC risk (eg, BRCA1/2 pathogenic variant carriers without RT: RR = 3.52, 95% CI = 1.76 to 7.01; BRCA1/2 pathogenic variant carriers with RT: RR = 4.46, 95% CI = 2.96 to 6.71), suggesting that modifying RT plans for young women with breast cancer is unwarranted. Rare ATM missense variants, not currently identified as pathogenic, were associated with increased risk of RT-associated CBC (carriers of ATM rare missense variants of uncertain significance without RT: RR = 0.38, 95% CI = 0.09 to 1.55; carriers of ATM rare missense variants of uncertain significance with RT: RR = 2.98, 95% CI = 1.31 to 6.80). Further mechanistic studies will aid clinical decision-making related to RT. [ABSTRACT FROM AUTHOR]

Purpose: We examined the degree of over- and under-reporting of cardiovascular diseases (CVDs) among female breast cancer survivors comparing self-reports to diagnostic codes from the Danish National Patient Register (NPR).Methods: The study comprised 357 Danish breast cancer patients from the WECARE study who completed a telephone interview concerning CVDs. Disease diagnoses for these women were obtained from the NPR. Agreement was calculated as the number of diagnoses that were both self-reported and in the NPR divided by (1) number of self-reported diagnoses (over-reporting) or (2) number of diagnoses in the NPR (under-reporting).Results: In total, 68 women reported 96 specific cardiovascular outcomes of which 56 (58%) were found in the NPR. Ninety cardiovascular diagnoses were found in the NPR of which 56 (62%) were specifically reported at the interview. There was 80% agreement as to the occurrence of a cardiovascular diagnosis overall. Of 289 women reporting no CVD, 273 (94%) had no diagnoses in the NPR.Conclusions: Breast cancer survivors seem to report absence of CVD accurately, but they both over-report and under-report specific cardiovascular diagnoses. Using a broader definition of CVDs improves the agreement between self-reported and NPR data.Implications For Cancer Survivors: Determining how cancer treatments affect the risk of cardiovascular morbidities is essential, and the development of high-quality methods for collecting such data is critical. While self-reported data are adequate for assessing the presence of any CVD condition, medical record review will yield higher quality data on specific CVD conditions. [ABSTRACT FROM AUTHOR]

Background: Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history.Methods: The Women's Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tumors, including estrogen receptor (ER) and progesterone receptor (PR) status, was obtained by telephone interview and medical record abstraction. Multivariable risk ratios (RRs) and 95% confidence intervals (CIs) were estimated in conditional logistic regression models, adjusting for demographics, treatment, and personal medical and family history. A subset of women was screened for BRCA1/2 mutations.Results: Lobular histology of the first tumor was associated with a 30% increase in CBC risk (95% CI 1.0-1.6). Compared to women with ER+/PR+ first tumors, those with ER-/PR- tumors had increased risk of CBC (RR = 1.4, 95% CI 1.1-1.7). Notably, women with ER-/PR- first tumors were more likely to develop CBC with the ER-/PR- phenotype (RR = 5.4, 95% CI 3.0-9.5), and risk remained elevated in multiple subgroups: BRCA1/2 mutation non-carriers, women younger than 45 years of age, women without a breast cancer family history, and women who were not treated with tamoxifen.Conclusions: Having a hormone receptor negative first primary breast cancer is associated with increased risk of CBC. Women with ER-/PR- primary tumors were more likely to develop ER-/PR- CBC, even after excluding BRCA1/2 mutation carriers. Hormone receptor status, which is routinely evaluated in breast tumors, may be used clinically to determine treatment protocols and identify patients who may benefit from increased surveillance for CBC. [ABSTRACT FROM AUTHOR]

Studies examining the relationship between body mass index ( BMI) and risk of contralateral breast cancer ( CBC) have reported mixed findings. We previously showed that obese postmenopausal women with estrogen receptor ( ER)-negative breast cancer have a fivefold higher risk of CBC compared with normal weight women. In the current analysis, we reexamined this relationship in the expanded Women's Environmental Cancer and Radiation Epidemiology ( WECARE) Study, focusing on the impact of menopausal status and ER status of the first breast cancer. The WECARE Study is a population-based case-control study of young women with CBC (cases, N = 1386) and with unilateral breast cancer (controls, N = 2045). Rate ratios ( RR) and 95% confidence intervals ( CI) were calculated to assess the relationship between BMI and risk of CBC stratified by menopausal and ER status. Positive associations with obesity and weight gain were limited to women who became postmenopausal following their first primary breast cancer. Among those with an ER-negative first breast cancer, obesity (vs. normal weight) at first diagnosis was associated with an increased risk of CBC ( RR = 1.9, 95% CI: 1.02, 3.4). Also, weight gain of ≥10 kg after first diagnosis was associated with an almost twofold increased risk of CBC ( RR = 1.9, 95% CI: 0.99, 3.8). These results suggest that women with an ER-negative first primary cancer who are obese at first primary diagnosis or who experience a large weight gain afterward may benefit from heightened surveillance. Future studies are needed to address the impact of weight loss interventions on risk of CBC. [ABSTRACT FROM AUTHOR]

Background: Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics.Methods: The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985-2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models.Results: Compared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55-0.97) and for past users within 3 years of last use (RR = 0.73; 95 % CI = 0.53-1.00). There was no evidence of an increased risk of estrogen receptor-negative CBC associated with ever use of tamoxifen or use for 4.5 or more years. Use of chemotherapy (ever versus never use) was associated with a significantly reduced RR of developing CBC 1-4 years (RR = 0.59; 95 % CI = 0.45-0.77) and 5-9 years (RR = 0.73; 95 % CI = 0.56-0.95) after first breast cancer diagnosis. RRs of CBC associated with tamoxifen or with chemotherapy use were independent of age, family history of breast cancer, body mass index and tumor characteristics of the first breast cancer with the exception that the RR of CBC was lower for lobular histology compared with other histologies.Conclusion: Our findings are consistent with previous studies showing that treatment with tamoxifen or chemotherapy is associated with a lower risk of CBC although the risk reduction appears to last for a limited time period after treatment is completed. [ABSTRACT FROM AUTHOR]