Predicting drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors and forward planning.

INTRODUCTION: Cyclin-dependent kinase (CDK) 4/6 inhibitors are cornerstones in the treatment of Hormone Receptor (HR) positive and Human Epidermal Growth factor (HER2) negative metastatic breast cancer. Given their widespread use in the metastatic setting and emerging use in the adjuvant setting, studying drug-drug interactions (DDI) of these medications is of utmost importance. AREAS COVERED: This review provides key background information on the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. We discuss drug-drug interactions including those with proton pump inhibitors as well as CYP3A substrates, inhibitors, and inducers. We describe the effect of these drugs on membrane transporters and their substrates as well as those drugs that increase risk of CDK4/6 toxicities. Finally, we explore future directions for strategies to minimize drug-drug interactions. EXPERT OPINION: It is crucial to be mindful of medications that may interfere with drug absorption, such as proton pump inhibitors, as well as those that interfere with drug metabolism, such as CYP3A4 inhibitors and inducers. Additionally, special consideration should be given to populations at higher risk for polypharmacy, such as older patients with greater comorbidities. These interactions and patient characteristics should be considered when developing individual treatment plans with CDK4/6 inhibitors.

Barriers and facilitators to effective cervical cancer screening in Belize: a qualitative analysis.

PURPOSE: Belize has among the highest cervical cancer incidence and mortality rates of Latin American and Caribbean countries. This study evaluates the perspectives of key stakeholders for cervical cancer screening in Belize and identifies the barriers and facilitators for providing equitable access to prevention services. METHODS: Semi-structured interviews discussing cervical cancer screening were conducted with key stakeholders across the six districts of Belize in 2018. Interviews were transcribed, coded, and analyzed thematically; themes were organized by levels of the social-ecological model. RESULTS: We conducted 47 interviews with health care providers (45%), administrators (17%), government officials (25%), and other stakeholders (13%). Majority (78%) of interviews were from the public sector. Perceived barriers to cervical cancer screening were identified across multiple levels: (1) Individual Patient: potential delays in Pap smear results and fear of a cancer diagnosis; (2) Provider: competing clinician responsibilities; (3) Organizational: insufficient space and training; (4) Community: reduced accessibility in rural areas; and (5) Policy: equipment and staffing budget limitations. The main facilitators we identified included the following: (1) at the Community level: resource-sharing between public and private sectors and dedicated rural outreach personnel; (2) at the Policy level: free public screening services and the establishment of population-based screening. CONCLUSION: Despite free, publicly available cervical cancer screening in Belize, complex barriers affect access and completion of management when abnormal screening tests are identified. Provider workload, education outreach, and additional funding for training and facilities are potential areas for strengthening this program and increasing detection and management for cervical cancer control.

Racial Disparity Among Patients Undergoing Surgical Aortic Valve Replacement and Transcatheter Aortic Valve Replacement in the United States.

Transcatheter aortic valve replacement (TAVR) has emerged as a minimally invasive alternative to surgical aortic valve replacement (SAVR). However, racial disparities in the utilization of TAVR persist. This meta-analysis attempts to determine whether the prevalence of adverse outcomes (procedure-related complications) represent barriers to the use of TAVR among African Americans (AA). The TAVR cohort consisted of 89.6% Caucasian (C) and 4.7% AA, while the SAVR cohort included 86.9% C and 6.4% AA. The utilization rate (UR) of TAVR was 1.48 and .35 among C and AA, respectively, while the UR of SAVR was 1.44 and .48 among C and AA, respectively. Following TAVR, for AA the odds ratio (OR) was greater for stroke (OR = 1.22, P = .02) and transient ischemic attack (TIA) (OR = 1.57, P < .001) and lower for undergoing the insertion of a permanent pacemaker (OR = .81, P < .001). While there was a significant difference between C and AA in TAVR and SAVR utilization, outcomes between groups following TAVR are comparable; therefore, adverse outcomes do not appear to be a barrier to the use of TAVR among eligible AA.

Assessment of Cervical Cancer Prevention and Treatment Infrastructure in Belize.

PURPOSE: Belize has one of the highest cervical cancer burdens among Latin American and Caribbean countries, despite the implementation of national policies to increase access to prevention and treatment services. This study evaluates the policies, infrastructure, and workforce of the cervical cancer management system in Belize to inform capacity building efforts. METHODS: In 2018, health facility assessments were conducted across all six districts of Belize at the national pathology facility and 12 public facilities identified as critical to cervical cancer control. Human and infrastructure resource availability and existing policies related to cervical cancer screening and treatment services were assessed through a structured instrument. RESULTS: The public cervical cancer screening workforce in Belize consists of 75 primary care nurses and physicians-one per 1,076 screening-eligible women, with 44% conducting rural outreach. All districts have at least one screening facility, but 50% perform screening services only once per week. Colposcopy and loop electrical excision procedures are available in three and four districts, respectively; radical hysterectomy and chemotherapy are available in two districts; and radiation therapy is unavailable. Of essential pathology equipment, 38.5% were present and functional, 23% were present but nonfunctional, and 38.5% were unavailable. Additionally, 35% of supplies were unavailable at the time of assessment, and 75% were unavailable at least once in the 12 months before assessment. CONCLUSION: Public-sector cervical cancer management services differ among districts of Belize, with tertiary service availability concentrated in the largest district. Screening, outreach, and pathology are limited mostly by resource availability. This study characterizes the current capacity of services in Belize and pinpoints health system components for future investment and capacity-building efforts.

Mutation Rates in Cancer Susceptibility Genes in Patients With Breast Cancer With Multiple Primary Cancers.

PURPOSE: Women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. Whether mutations in genes other than BRCA1/2 are enriched in patients with breast and another primary cancer over those with a single breast cancer (S-BC) is unknown. PATIENTS AND METHODS: We identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in 2 different cohorts: cohort 1, high-risk breast cancer program (multiple primary breast cancer [MP-BC], n = 551; S-BC, n = 449) and cohort 2, familial breast cancer research study (MP-BC, n = 340; S-BC, n = 1,464). Mutation rates in these 2 cohorts were compared with a control data set (Exome Aggregation Consortium [ExAC]). RESULTS: Overall, pathogenic mutation rates for autosomal, dominantly inherited genes were higher in patients with MP-BC versus S-BC in both cohorts (8.5% v 4.9% [P = .02] and 7.1% v 4.2% [P = .03]). There were differences in individual gene mutation rates between cohorts. In both cohorts, younger age at first breast cancer was associated with higher mutation rates; the age of non-breast cancers was unrelated to mutation rate. TP53 and MSH6 mutations were significantly enriched in patients with MP-BC but not S-BC, whereas ATM and PALB2 mutations were significantly enriched in both groups compared with ExAC. CONCLUSION: Mutation rates are at least 7% in all patients with BRCA1/2 mutation-negative MP-BC, regardless of age at diagnosis of breast cancer, with mutation rates up to 25% in patients with a first breast cancer diagnosed at age < 30 years. Our results suggest that all patients with breast cancer with a second primary cancer, regardless of age of onset, should undergo multigene panel testing.

Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing.

PURPOSE: The risks, benefits, and utilities of multiplex panels for breast cancer susceptibility are unknown, and new counseling and informed consent models are needed. We sought to obtain patient feedback and early outcome data with a novel tiered-binned model for multiplex testing. METHODS: BRCA1/2-negative and untested patients completed pre- and posttest counseling and surveys evaluating testing experiences and cognitive and affective responses to multiplex testing. RESULTS: Of 73 patients, 49 (67%) completed pretest counseling. BRCA1/2-negative patients were more likely to proceed with multiplex testing (86%) than those untested for BRCA1/2 (43%; P < 0.01). Many patients declining testing reported concern for uncertainty and distress. Most patients would not change anything about their pre- (76%) or posttest (89%) counseling sessions. Thirty-three patients (72%) were classified as making an informed choice, including 81% of those who proceeded with multiplex testing. Knowledge increased significantly. Anxiety, depression, uncertainty, and cancer worry did not significantly increase with multiplex testing. CONCLUSION: Some patients, particularly those without prior BRCA1/2 testing, decline multiplex testing. Most patients who proceeded with testing did not experience negative psychological responses, but larger studies are needed. The tiered-binned approach is an innovative genetic counseling and informed consent model for further study in the era of multiplex testing.Genet Med 18 1, 25-33.