Patient Experience of Women With Dense Breasts Undergoing Screening Contrast-Enhanced Mammography.

OBJECTIVE: We investigated patient experience with screening contrast-enhanced mammography (CEM) to determine whether a general population of women with dense breasts would accept CEM in a screening setting. METHODS: In this institutional review board-approved prospective study, patients with heterogeneous and extremely dense breasts on their mammogram were invited to undergo screening CEM and complete pre-CEM and post-CEM surveys. On the pre-CEM survey, patients were asked about their attitudes regarding supplemental screening in general. On the post-CEM survey, patients were asked about their experience undergoing screening CEM, including causes and severity of any discomfort and whether they would consider undergoing screening CEM again in the future or recommend it to a friend. RESULTS: One hundred sixty-three women were surveyed before and after screening CEM. Most patients, 97.5% (159/163), reported minimal or no unpleasantness associated with undergoing screening CEM. In addition, 91.4% (149/163) said they would probably or very likely undergo screening CEM in the future if it cost the same as a traditional screening mammogram, and 95.1% (155/163) said they would probably or very likely recommend screening CEM to a friend. Patients in this study, who were all willing to undergo CEM, more frequently reported a family history of breast cancer than a comparison cohort of women with dense breasts (58.2% vs 47.1%, P = .027). CONCLUSION: Patients from a general population of women with dense breasts reported a positive experience undergoing screening CEM, suggesting screening CEM might be well received by this patient population, particularly if the cost was comparable with traditional screening mammography.

The Breast-Imaging Operations, Practices and Systems Inventory: A framework to examine mammography facility effects on screening in rural communities.

PURPOSE: Develop and test a measurement framework of mammogram facility resources, policies, and practices in Appalachia. METHODS: Survey items describing 7 domains of imaging facility qualities were developed and tested in the Appalachian regions of Kentucky, Ohio, Pennsylvania, Virginia, and West Virginia. Medicare claims data (2016-2018) were obtained on catchment area mammogram services. Construct validity was examined from associations with facility affiliation, community characteristics, mammogram screening uptake, and market reach. Analyses were performed with t-tests and ANOVA. RESULTS: A total of 192 (of 377) sites completed the survey. Five factors were initially selected in exploratory factor analysis (FA) and refined in confirmatory FA: capacity, outreach & marketing, operational support, radiology review (NNFI = .94, GFI = 0.93), and diagnostic services (NNFI = 1.00, GFI = 0.99). Imaging capacity and diagnostic services were associated with screening uptake, with capacity strongly associated with catchment area demographic and economic characteristics. Imaging facilities in economically affluent versus poorer areas belong to larger health systems and have significantly more resources (P < .001). Facilities in economically distressed locations in Appalachia rely more heavily on outreach activities (P < .001). Higher facility capacity was significantly associated (P < .05) with larger catchment area size (median split: 48.5 vs 51.6), mammogram market share (47.4 vs 52.7), and screening uptake (47.6 vs 52.4). CONCLUSIONS: A set of 18 items assessing breast imaging services and facility characteristics was obtained, representing policies and practices related to a facility's catchment area size, market share, and mammogram screening uptake.

Factors associated with perceived personal risk for breast cancer among women with dense breasts.

PURPOSE: To determine what patient factors are associated with a high or an accurate perceived personal risk (PPR) for breast cancer. METHODS: An IRB-approved survey study of women with dense breasts presenting for annual screening mammography was previously conducted from March 2017 to February 2018. Patients were asked to estimate their personal risk for breast cancer and to answer questions about prior breast care-related medical interactions. Survey data were combined post hoc with demographic and clinical data, including breast cancer risk status, and socioeconomic data imputed for each patient from census data. Logistic regression was used to determine which patient factors were associated with a high or accurate PPR. RESULTS: Surveys were completed by 508 women with dense breasts (median age 59.0 years). A high PPR was independently associated with younger age (AOR, 1.71 [95% CI, 1.13, 2.60]), family history of breast cancer (AOR 4.27 [95% CI, 2.81-7.34]), having a clinical "high-risk" designation (AOR, 3.43 [95% CI, 1.13-10.39], and having been called back from screening (AOR, 1.94 [95% CI, 1.14-3.32]). A lower accuracy of PPR was independently associated with a family history of breast cancer (AOR, 0.25 [95% CI, 0.14-0.42]) and having been called back from screening (AOR, 0.58 [95% CI, 0.35-0.98]). CONCLUSION: Women with dense breasts who had a family history of breast cancer or who had been called back from screening had a higher but less accurate PPR. Women with a "high-risk" clinical designation had a higher PPR, even when controlling for family history.

Factors Associated With Breast Cancer Screening Behaviors Among Women With Dense Breasts.

OBJECTIVE: We sought to identify patient factors associated with patient-reported screening behaviors in women with dense breasts. METHODS: An IRB-approved survey study of women with dense breasts presenting for annual screening mammography at an outpatient imaging center was previously conducted from March 2017 to February 2018. The survey included questions regarding mammographic screening frequency and recent participation in supplemental screening. These survey data were combined post hoc with clinical and demographic data and socioeconomic data imputed from census data. Logistic regression was used to identify patient factors associated with reported screening behaviors. RESULTS: Surveys were completed by 508 women (median age, 59.0 years; range, 31.0-86.0 years) with dense breasts. Multivariable analysis demonstrated an independent association of undergoing mammographic screening annually with a history of discussing breast density with a doctor (adjusted odds ratio [AOR], 2.60; P = 0.019). Undergoing supplemental screening in the previous three years was independently associated with younger age (AOR, 1.59; P = 0.004), strong family history of breast cancer (AOR, 3.84; P = 0.027), higher perceived personal risk for breast cancer (AOR, 3.47; P = 0.004), and increased concern about radiation associated with screening examinations (AOR, 3.31; P = 0.006). CONCLUSION: Women with dense breasts who had discussed breast density with a doctor were more likely to report undergoing annual screening mammography, while younger women and women with a strong family history of breast cancer, higher perceived personal risk for breast cancer, or greater concern about radiation were more likely to report recently undergoing supplemental screening.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Implementation of Abbreviated Breast MRI for Screening: AJR Expert Panel Narrative Review.

Abbreviated breast MRI (AB-MRI) is being rapidly adopted to harness the high sensitivity of screening MRI while addressing issues related to access, cost, and workflow. The successful implementation of an AB-MRI program requires collaboration across administrative, operational, financial, technical, and clinical providers. Institutions must be thoughtful in defining patient eligibility for AB-MRI and providing recommendations for screening intervals, as existing practices are heterogeneous. Similarly, there is no universally accepted AB-MRI protocol, though guiding principles should harmonize abbreviated and full protocols while being mindful of scan duration and amount of time patients spend on the MRI table. The interpretation of AB-MRI will be a new experience for many radiologists and may require a phased rollout and a careful audit of performance metrics over time to ensure benchmark metrics are achieved. AB-MRI finances, which are driven by patient self-payment, will require buy-in from hospital administration with the recognition that downstream revenues will be needed to support initial costs. Finally, successful startup of an AB-MRI program requires active engagement with the larger community of patients and referring providers. As AB-MRI becomes more widely accepted and available, best practices and community standards will continue to evolve to ensure high-quality patient care.

Advantages and Challenges of Using Breast Biopsy Markers.

Percutaneous image-guided biopsy procedures are the standard of care for histologic assessment of suspicious breast lesions. Post-biopsy tissue markers (clips) optimize patient management by allowing for assessment on follow-up imaging and precise lesion localization. Markers are used to ensure accurate correlation between imaging modalities, guide preoperative localization for malignant and high-risk lesions, and facilitate accurate identification of benign lesions at follow-up. Local practices differ widely, and there are no data detailing the exact frequency of use of clips for different breast biopsies. There are many indications for biopsy marker deployment, and some difficulties may be encountered after placement. The placement of biopsy markers has many advantages and few disadvantages, such that deployment should be routinely used after percutaneous biopsy procedures with rare exception.

Pan-Cancer Drivers Are Recurrent Transcriptional Regulatory Heterogeneities in Early-Stage Luminal Breast Cancer.

The heterogeneous composition of solid tumors is known to impact disease progression and response to therapy. Malignant cells coexist in different regulatory states that can be accessed transcriptomically by single-cell RNA sequencing, but these methods have many caveats related to sensitivity, noise, and sample handling. We revised a statistical fluctuation analysis called stochastic profiling to combine with 10-cell RNA sequencing, which was designed for laser-capture microdissection (LCM) and extended here for immuno-LCM. When applied to a cohort of late-onset, early-stage luminal breast cancers, the integrated approach identified thousands of candidate regulatory heterogeneities. Intersecting the candidates from different tumors yielded a relatively stable set of 710 recurrent heterogeneously expressed genes (RHEG), which were significantly variable in >50% of patients. RHEGs were not strongly confounded by dissociation artifacts, cell-cycle oscillations, or driving mutations for breast cancer. Rather, RHEGs were enriched for epithelial-to-mesenchymal transition genes and, unexpectedly, the latest pan-cancer assembly of driver genes across cancer types other than breast. These findings indicate that heterogeneous transcriptional regulation conceivably provides a faster, reversible mechanism for malignant cells to evaluate the effects of potential oncogenes or tumor suppressors on cancer hallmarks. SIGNIFICANCE: Profiling intratumor heterogeneity of luminal breast carcinoma cells identifies a recurrent set of genes, suggesting sporadic activation of pathways known to drive other types of cancer.See related articles by Schaff and colleagues, p. 1853 and Sutcliffe and colleagues, p. 1868.

Patient Characteristics Associated With Patient-Reported Deterrents to Adjunct Breast Cancer Screening of Patients With Dense Breasts.

BACKGROUND. The success of adjunct breast cancer screening of women with dense breasts can be enhanced by identifying and addressing patient concerns regarding adjunct screening modalities. OBJECTIVE. The purpose of this study was to identify patient characteristics associated with patient-reported concerns about adjunct breast cancer screening to facilitate the development of a more effective screening model for women with dense breasts. METHODS. Patients with dense breasts completed surveys between March 2017 and February 2018 regarding factors that might deter them from adjunct screening and about which of three hypothetical screening examinations they might prefer. Additional patient data were extracted from medical records, and socioeconomic data were imputed from federal census data. Logistic regression analyses were conducted to identify associations between patient characteristics and patient attitudes toward adjunct screening. RESULTS. Surveys were completed by 508 women (median age, 59.0 years) with dense breasts. Lower confidence in the sensitivity of mammography of dense breasts was independently associated with lesser concern about adjunct screening examination time (1 divided by adjusted odds ratio [1/AOR], 0.55 [95% CI, 0.34-0.89]), additional imaging that could result (1/AOR, 0.51 [95% CI, 0.31-0.85]), and greater preference for a more sensitive hypothetical screening examination (1/AOR, 1.85 [95% CI, 1.20-2.86]). Concern about examination cost, the most commonly cited deterrent to adjunct screening (66.9%), was independently associated with younger age (1/AOR, 1.45 [95% CI, 1.01-2.08]) but not with imputed socioeconomic variables or other tested variables. Younger age was also associated with lesser concern about pain (1/AOR, 0.69 [95% CI, 0.48-0.99]), additional imaging that could result (1/AOR, 0.48 [95% CI, 0.31-0.76]), and IV contrast administration (1/AOR, 0.56 [95% CI, 0.37-0.83]). CONCLUSION. Younger age and lower confidence in the sensitivity of mammography among women with dense breasts are independently associated with lesser patient concern about common deterrents to adjunct breast cancer screening. Younger age is independently associated with greater concern about the cost of undergoing adjunct breast cancer screening. CLINICAL IMPACT. Concerns about adjunct screening may be reduced by educating patients about the lower sensitivity of mammography of dense breasts and by finding ways to address or mitigate the financial and daily-life impact of adjunct screening, especially for younger patients.

"What Do You Mean It's Not Cancer?" A Review of Autoimmune and Systemic Inflammatory Diseases Involving the Breast.

Autoimmune and systemic inflammatory diseases represent a heterogeneous group of immune-mediated conditions with a wide range of clinical presentations and various affected organs. Autoimmune diseases can present in the breast as localized disease or as part of systemic involvement. Although breast involvement is uncommon, the spectrum of imaging findings can include breast masses, axillary adenopathy, calcifications, and skin changes, the appearance of which can mimic breast cancer. Common etiologies include diabetic mastopathy, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, idiopathic granulomatous mastitis, sarcoidosis, and Immunoglobulin-G4 related mastopathy. This educational review will present multimodality imaging findings of breast manifestations of systemic inflammatory and autoimmune diseases and coexisting complications. It will also review how these disorders may affect breast cancer risk and breast cancer treatment options, including radiation therapy.

External validation of a mammographic texture marker for breast cancer risk in a case-control study.

Purpose: The pattern of dense tissue on a mammogram appears to provide additional information than overall density for risk assessment, but there has been little consistency in measures of texture identified. The purpose of this study is thus to validate a mammographic texture feature developed from a previous study in a new setting. Approach: A case-control study (316 invasive cases and 1339 controls) of women in Virginia, USA was used to validate a mammographic texture feature (MMTEXT) derived in a independent previous study. Analysis of predictive ability was adjusted for age, demographic factors, questionnaire risk factors (combined through the Tyrer-Cuzick model), and optionally BI-RADS breast density. Odds ratios per interquartile range (IQ-OR) in controls were estimated. Subgroup analysis assessed heterogeneity by mode of cancer detection (94 not detected by mammography). Results: MMTEXT was not a significant risk factor at 0.05 level after adjusting for classical risk factors ( IQ - OR = 1.16 , 95%CI 0.92 to 1.46), nor after further adjustment for BI-RADS density ( IQ - OR = 0.92 , 95%CI 0.76 to 1.10). There was weak evidence that MMTEXT was more predictive for cancers that were not detected by mammography (unadjusted for density: IQ - OR = 1.46 , 95%CI 0.99 to 2.15 versus 1.03, 95%CI 0.79 to 1.35, Phet 0.10; adjusted for density: IQ - OR = 1.11 , 95%CI 0.70 to 1.77 versus 0.76, 95%CI 0.55 to 1.05, Phet 0.21). Conclusions: MMTEXT is unlikely to be a useful imaging marker for invasive breast cancer risk assessment in women attending mammography screening. Future studies may benefit from a larger sample size to confirm this as well as developing and validating other measures of risk. This negative finding demonstrates the importance of external validation.

Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection Among Women With Dense Breasts Undergoing Screening.

Importance: Improved screening methods for women with dense breasts are needed because of their increased risk of breast cancer and of failed early diagnosis by screening mammography. Objective: To compare the screening performance of abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT) in women with dense breasts. Design, Setting, and Participants: Cross-sectional study with longitudinal follow-up at 48 academic, community hospital, and private practice sites in the United States and Germany, conducted between December 2016 and November 2017 among average-risk women aged 40 to 75 years with heterogeneously dense or extremely dense breasts undergoing routine screening. Follow-up ascertainment of cancer diagnoses was complete through September 12, 2019. Exposures: All women underwent screening by both DBT and abbreviated breast MRI, performed in randomized order and read independently to avoid interpretation bias. Main Outcomes and Measures: The primary end point was the invasive cancer detection rate. Secondary outcomes included sensitivity, specificity, additional imaging recommendation rate, and positive predictive value (PPV) of biopsy, using invasive cancer and ductal carcinoma in situ (DCIS) to define a positive reference standard. All outcomes are reported at the participant level. Pathology of core or surgical biopsy was the reference standard for cancer detection rate and PPV; interval cancers reported until the next annual screen were included in the reference standard for sensitivity and specificity. Results: Among 1516 enrolled women, 1444 (median age, 54 [range, 40-75] years) completed both examinations and were included in the analysis. The reference standard was positive for invasive cancer with or without DCIS in 17 women and for DCIS alone in another 6. No interval cancers were observed during follow-up. Abbreviated breast MRI detected all 17 women with invasive cancer and 5 of 6 women with DCIS. Digital breast tomosynthesis detected 7 of 17 women with invasive cancer and 2 of 6 women with DCIS. The invasive cancer detection rate was 11.8 (95% CI, 7.4-18.8) per 1000 women for abbreviated breast MRI vs 4.8 (95% CI, 2.4-10.0) per 1000 women for DBT, a difference of 7 (95% CI, 2.2-11.6) per 1000 women (exact McNemar P = .002). For detection of invasive cancer and DCIS, sensitivity was 95.7% (95% CI, 79.0%-99.2%) with abbreviated breast MRI vs 39.1% (95% CI, 22.2%-59.2%) with DBT (P = .001) and specificity was 86.7% (95% CI, 84.8%-88.4%) vs 97.4% (95% CI, 96.5%-98.1%), respectively (P < .001). The additional imaging recommendation rate was 7.5% (95% CI, 6.2%-9.0%) with abbreviated breast MRI vs 10.1% (95% CI, 8.7%-11.8%) with DBT (P = .02) and the PPV was 19.6% (95% CI, 13.2%-28.2%) vs 31.0% (95% CI, 17.0%-49.7%), respectively (P = .15). Conclusions and Relevance: Among women with dense breasts undergoing screening, abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection. Further research is needed to better understand the relationship between screening methods and clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02933489.

Extensive Extramammary Paget's Disease With Underlying Perianal Adenocarcinoma: The Role of Neoadjuvant Radiation Treatment.

Extramammary Paget's disease (EMPD) is an uncommon entity, and secondary EMPD is even rarer. To our knowledge, this report involves one of the only three cases in the literature to date regarding the use of neoadjuvant radiation therapy in the treatment of secondary EMPD. A 65-year-old woman's EMPD had become more widespread over the years to involve buttocks, perineum, anus, vulva, and vagina. Given the knowledge of potential secondary EMPD, suspicious perianal lesions were biopsied. Histology and immunohistochemistry staining confirmed adenocarcinoma. Our patient was treated with neoadjuvant radiation therapy, along with concurrent chemotherapy. This was followed by pelvic exenteration, which confirmed a complete response from the neoadjuvant treatment. We discuss her presentation, investigations, and treatment regimen in detail. In addition, we review the treatment of secondary EMPD as reported in previously published literature.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast.

PURPOSE: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. RESULTS: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). CONCLUSIONS: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.