A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer.

BACKGROUND: The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. METHODS: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival. RESULTS: The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported. CONCLUSIONS: The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed.

Does Breast Density Increase the Risk of Re-excision for Women with Breast Cancer Having Breast-Conservation Therapy?

BACKGROUND: Women with dense breasts may have less-accurate preoperative evaluation of extent of disease, potentially affecting the achievement of negative margins. The goal of this study is to examine the association between breast density and re-excision rates in women having breast-conserving surgery for invasive breast cancer. PATIENTS AND METHODS: Women with stage I/II invasive breast cancer treated with breast-conserving surgery between 1/1/2014 and 10/31/2014 were included. Breast density was assessed by two radiologists. The association between breast density and re-excision was examined using logistic regression. RESULTS: Seven hundred and one women were included. Overall, 106 (15.1%) women had at least one re-excision. Younger age at diagnosis was associated with increased breast density (p < 0.001). On univariable analysis, increased breast density was associated with significantly increased odds of re-excision (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.04-1.83), as was multifocal disease, human epidermal growth factor receptor 2 (HER2) positive status, and extensive intraductal component (EIC) (all p < 0.05). On multivariable analysis, breast density remained significantly associated with increased odds of re-excision (OR 1.37, 95% CI 1.00-1.86), as did multifocality and EIC. HER2 positive status was not significantly associated with re-excision on multivariable analysis. CONCLUSIONS: Women with dense breasts are more likely to need additional surgery (re-excision after breast-conserving surgery), but increased breast density did not adversely affect disease-free survival in our study. Our findings support the need for further study in developing techniques that can help decrease re-excisions for women with dense breasts who undergo breast-conserving surgery.

Breast cancer screening in transgender patients: findings from the 2014 BRFSS survey.

PURPOSE: Transgender patients undergoing transitions often receive cross-sex hormonal therapies, placing them at uncertain risk for developing breast cancer. There is limited population-based information about the extent to which transgender patients undergo mammography screening. Our purpose was to determine the extent to which transgender patients undergo mammography screening using nationally representative survey data. METHODS: Transgender participants between ages 40-74 in the 2014 Behavioral Risk Factor Surveillance System survey were included. Proportions undergoing mammography screening in the last year or two years were calculated stratified by age category and transition status [male to female(MtF), female to male(FtM), non-conforming]. For each transition status, predictors of mammography screening were calculated using logistic regression. RESULTS: 220 transgender patients were within 40-74 years old(35% were MtF, 51% were FtM, 14% were non-conforming). 60.0% underwent mammography screening within the last year (MtF-54.5%, FtM-64.3%, non-conforming-58.1%). 74.1% underwent screening within the last two years(MtF-70.1%, FtM-75.9%, non-conforming-77.4%). For all transgender patients, income category (OR 1.16, 0.82-1.64), higher education category (OR 1.09, 0.31-3.86) and health insurance (OR 0.38, 0.10-1.41) were not associated with increased adherence to mammography screening. Transgender patients were comparably likely to undergo mammography screening compared with non-transgender patients (Adjusted OR 0.97, 0.58-1.62). CONCLUSIONS: High proportions of transgender survey respondents undergo mammography screening (57.9-66.1% within the last year, 71.9-74.4% within the last two years) in our sample, proportions comparable to non-transgender survey respondents.

Breast Imaging for Transgender Individuals: Assessment of Current Practice and Needs.

PURPOSE: The aim of this study was to investigate breast radiologists' practices related to recording sex and gender in the electronic medical record, knowledge and attitudes about breast cancer screening recommendations for transgender individuals, and experience and willingness to enter screening mammography data from transgender patients into databases that document service provision and outcomes of cancer detection protocols. METHODS: A 19-question anonymous survey was distributed by e-mail to all active physician members of the Society of Breast Imaging. Response characteristics were assessed as frequencies and percentages and compared between groups using the Fisher exact test or χ2 test. The degree of agreement between questions was assessed using the McNemar test. RESULTS: Four hundred one radiologists across the United States and Canada responded (response rate 18%). Recording birth-assigned sex distinct from gender identity was reported by 44 of 352 respondents (13%). Depending on geographic region, 38% to 62% of breast radiologists followed screening guidelines for transgender women, and 226 of 349 (65%) did not provide screening recommendations for transgender men. Of 400, 324 (81%) believed that the evidence base for screening transgender individuals is incomplete, and 247 of 352 (70%) were either unsure of or had no Lesbian, Gay, Bisexual, Transgender, Queer competency training. A majority (247 of 401 [62%]) of respondents reported that they would enroll transgender patients in existing or novel national databases. CONCLUSIONS: In the practice of breast imaging, there is a substantial need to record transgender and other gender-nonconforming information. Breast radiologists differ in their practice and knowledge regarding screening of transgender women and men but expressed interest in contributing data to facilitate longitudinal databases needed to inform cancer screening guidelines.

Overview of Breast Cancer Screening and Diagnosis.

Screening mammography saves lives. The mainstay of screening has been mammography. Multiple alternative options, however, for supplemental imaging are now available. Some are just improved anatomic delineation whereas others include physiology added to anatomy. A third group (molecular imaging) is purely physiologic. This article describes and compares the available options and for which patient populations they should be used.

Inter-observer agreement on the assessment of relative liver lesion signal intensity on hepatobiliary phase imaging with gadoxetate (Gd-EOB-DTPA).

PURPOSE: The purpose of the study was to assess the inter-observer agreement on the qualitative and quantitative evaluation of relative signal intensity of liver lesions on delayed hepatobiliary phase (HBP) MRI with gadoxetate (Gd-EOB-DTPA). METHODS: 105 patients with liver lesions, who had delayed HPB MRI using gadoxetate were reviewed retrospectively. For each patient, four readers (two fellows in training and two attending radiologists) qualitatively assessed the relative SI of the largest representative lesion on a five point scale, and quantitatively measured the relative SI of the lesion to adjacent liver parenchyma using region of interests (ROI). Intra-class correlation (ICC) and kappa statistics with quadratic weights (k) analysis, and maximally selected rank statistic were performed. RESULTS: Substantial agreement between fellows (k = 0.719; ICC = 0.705) and almost perfect agreement between attending radiologists (k = 0.853; ICC = 0.849) were found for both qualitative and quantitative assessments of relative SI on delayed HPB imaging. A cut-off ratio to differentiate between hypointense and iso- to hyperintense lesions by ROI was calculated to be 0.90. CONCLUSION: Inter-observer agreement of liver lesion relative SI on delayed HBP imaging is high and may improve with radiologist experience. A cut-off ratio of relative SI at 0.90 may be useful to quantitatively distinguish hypointense from iso- to hyperintense liver lesions.