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.

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.

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.

Preferences and Attitudes Regarding Adjunct Breast Cancer Screening Among Patients with Dense Breasts.

OBJECTIVE: New breast screening modalities are being investigated to address the need for more sensitive breast cancer screening in women with dense breasts. We investigated the preferences and attitudes of these patients regarding adjunct screening modalities to help evaluate the acceptability of these exams. METHODS: In this institutional review board-approved prospective study, patients with dense breasts on their prior mammogram were invited to complete a survey. Patients were asked to estimate their personal breast cancer risk compared with peers, indicate their level of concern related to screening callbacks, radiation exposure, and intravenous (IV) contrast allergies, and identify which factors might deter them from getting adjunct screening exams. RESULTS: Five hundred eight patients with dense breasts presenting for screening mammography completed surveys. While most patients (304/508, 59.9%) felt it was likely or very likely that cancer could be missed on their mammogram, only 8.9% (45/508) had undergone adjunct screening exams in the past 3 years. The most commonly cited deterrents to adjunct screening were cost (340/508, 66.9%), pain (173/508, 34.1%), and concern that adjunct screening could lead to additional procedures (158/508, 31.1%). When asked to select among three hypothetical breast cancer screening modalities, patients strongly preferred the more sensitive examination, even if this involved greater cost (162/508, 31.9%) or IV-contrast administration (315/508, 62.0%). CONCLUSION: Our data suggest that patients with dense breasts prefer adjunct screening exams that are both sensitive and inexpensive, although an increase in sensitivity could outweigh additional cost or even IV-line placement.

Measurement challenge: protocol for international case-control comparison of mammographic measures that predict breast cancer risk.

INTRODUCTION: For women of the same age and body mass index, increased mammographic density is one of the strongest predictors of breast cancer risk. There are multiple methods of measuring mammographic density and other features in a mammogram that could potentially be used in a screening setting to identify and target women at high risk of developing breast cancer. However, it is unclear which measurement method provides the strongest predictor of breast cancer risk. METHODS AND ANALYSIS: The measurement challenge has been established as an international resource to offer a common set of anonymised mammogram images for measurement and analysis. To date, full field digital mammogram images and core data from 1650 cases and 1929 controls from five countries have been collated. The measurement challenge is an ongoing collaboration and we are continuing to expand the resource to include additional image sets across different populations (from contributors) and to compare additional measurement methods (by challengers). The intended use of the measurement challenge resource is for refinement and validation of new and existing mammographic measurement methods. The measurement challenge resource provides a standardised dataset of mammographic images and core data that enables investigators to directly compare methods of measuring mammographic density or other mammographic features in case/control sets of both raw and processed images, for the purposes of the comparing their predictions of breast cancer risk. ETHICS AND DISSEMINATION: Challengers and contributors are required to enter a Research Collaboration Agreement with the University of Melbourne prior to participation in the measurement challenge. The Challenge database of collated data and images are stored in a secure data repository at the University of Melbourne. Ethics approval for the measurement challenge is held at University of Melbourne (HREC ID 0931343.3).