For poorly understood reasons, Black non‐Hispanic (BNH) women meeting National Comprehensive Cancer Network (NCCN) criteria for genetic testing for breast cancer risk are less likely than White non‐Hispanic (WNH) women to undergo testing (Armstrong, Micco, Carney, Stopfer, & Putt, JAMA, 293, 1729 and 2005). We compared physician referral rates and uptake for genetic testing of BNH and WNH women meeting select NCCN criteria (breast cancer under age 50, two primary breast cancers, triple‐negative disease under age 60) in the Cancer Center at George Washington University (GWCC) between 2015 and 2018. Of the 723 BNH and WNH patients treated for breast cancer at GWCC, 28% met study criteria for genetic counseling referral (n = 252; BNH n = 115, WNH n = 137). Physician referral rates to genetic counseling differed significantly by race (BNH 75.7%, n = 87 and WNH 92.7%; n = 127; χ2 = 14.19, p‐value < .01). Once referred, though, there was no significant difference in uptake of genetic counseling by race (BNH 95.4%, n = 83; WNH 97.6%, n = 124, χ2 = 1.33, p‐value = .25) for patients appropriately referred.

Annual MRI screening is recommended as an adjunct to mammography for BRCA1 and BRCA2 mutation carriers. Prophylactic oophorectomy has been shown to decrease breast cancer risk in BRCA1/2 mutation carriers. Here, we aimed to examine the combined effects of MRI and oophorectomy. For this purpose, 93 BRCA1/2 mutation carriers were screened with yearly mammograms and yearly MRI scans. Study endpoints were defined as date of breast cancer diagnosis, date of prophylactic mastectomy, or date of most recent contact. Of 93 women, with a median age of 47, 80 (86%) had prophylactic oophorectomy. Fifty-one women (55%) had BRCA1 mutations. A total of 283 MRI scans were performed. Eleven breast cancers (9 invasive, 2 ductal carcinoma in situ) were detected in 93 women (12%) with a median follow-up of 3.2 years (incidence 40 per 1,000 person-years). Six cancers were first detected on MRI, three were first detected by mammogram, and two were “interval cancers.” All breast cancers occurred in BRCA1 mutation carriers (incidence 67 per 1,000 person-years). Apart from BRCA1 vs. BRCA2 mutation status, there were no other significant predictors of breast cancer incidence. Most invasive breast cancers were estrogen receptor negative (7 of 9) and lymph node negative (7 of 9). There have been no systemic recurrences with a median follow-up of 19 months after cancer diagnosis. Finally, it was concluded that all breast cancers occurred in BRCA1 mutation carriers, in most cases despite oophorectomy. These data suggest that surveillance and prevention strategies may have different outcomes in BRCA1 and BRCA2 mutation carriers.

PurposeTriple negative breast cancer (TNBC) is characterized by the presence of immune cells in the tumor microenvironment, however, the response to single-agent immune checkpoint inhibitor (ICI) therapy is modest. Preclinical models have demonstrated that intratumoral regulatory T cells (Tregs) dampen the antitumor response to ICI. We performed a single-arm phase II trial to evaluate the efficacy of a single low dose of cyclophosphamide (Cy) to deplete Tregs administered before initiating pembrolizumab.Patients and methods40 patients with pretreated metastatic TNBC were enrolled. The primary endpoints were progression-free survival (PFS) and change in peripheral blood Tregs after Cy. Secondary endpoints included overall response rate (ORR), duration of response, overall survival, treatment-related adverse events (AEs), and correlative evaluations.ResultsMedian PFS was 1.8 months, and the ORR was 21%. Tregs were not significantly decreased after Cy prior to ICI (−3.3%, p=0.19), and increased significantly after the first cycle of therapy (+21% between cycles 1 and 2, p=0.005). Immune-related AEs were similar to historical pembrolizumab monotherapy, and were associated with response to therapy (p=0.02). Patients with pretreatment tumors harboring increased expression of B cell metagene signatures and increased circulating B cell receptor repertoire diversity were associated with clinical response and immune-related toxicity (IRT).ConclusionsAmong patients with heavily pretreated TNBC, Cy prior to pembrolizumab did not significantly deplete Tregs, and in those with decreased numbers there was rapid recovery following therapy. Increased B cell gene expression in baseline samples was associated with clinical response and IRT.

Background Breast cancer survivors (BCSs) are a growing population with a higher prevalence of insomnia than women of the same age without a history of cancer. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to be effective in this population, but it is not widely available to those who need it. Objective This study aimed to better understand BCSs’ experiences with insomnia and to explore the feasibility and acceptability of delivering CBT-I using a virtual assistant (Amazon Alexa). Methods We first conducted a formative phase with 2 focus groups and 3 in-depth interviews to understand BCSs’ perceptions of insomnia as well as their interest in and comfort with using a virtual assistant to learn about CBT-I. We then developed a prototype incorporating participant preferences and CBT-I components and demonstrated it in group and individual settings to BCSs to evaluate acceptability, interest, perceived feasibility, educational potential, and usability of the prototype. We also collected open-ended feedback on the content and used frequencies to describe the quantitative data. Results We recruited 11 BCSs with insomnia in the formative phase and 14 BCSs in the prototype demonstration. In formative work, anxiety, fear, and hot flashes were identified as causes of insomnia. After prototype demonstration, nearly 79% (11/14) of participants reported an interest in and perceived feasibility of using the virtual assistant to record sleep patterns. Approximately two-thirds of the participants thought lifestyle modification (9/14, 64%) and sleep restriction (9/14, 64%) would be feasible and were interested in this feature of the program (10/14, 71% and 9/14, 64%, respectively). Relaxation exercises were rated as interesting and feasible using the virtual assistant by 71% (10/14) of the participants. Usability was rated as better than average, and all women reported that they would recommend the program to friends and family. Conclusions This virtual assistant prototype delivering CBT-I components by using a smart speaker was rated as feasible and acceptable, suggesting that this prototype should be fully developed and tested for efficacy in the BCS population. If efficacy is shown in this population, the prototype should also be adapted for other high-risk populations.