Universal genetic counseling in breast cancer patients significantly improves overall testing rates and improves completion rates in subpopulations.

PURPOSE: The NCCN guidelines recommend genetic testing in those patients at increased risk of breast cancer in order to identify candidates for increased frequency of screening or prophylactic mastectomy. However, genetic testing may now identify patients who may benefit from recently developed targeted breast cancer therapy. In order to more widely identify these patients, we implemented genetic counseling for all patients diagnosed with breast cancer. METHODS: In 2021, all patients evaluated within a Midwestern community hospital system diagnosed with breast cancer were offered genetic counseling. This group of patients was compared to a cohort of patients in 2021 who were offered genetic counseling based on NCCN guidelines. With Pearson's chi square, Fisher's Exact test, Mann-Whitney U, and multivariate regression as appropriate, individual demographic data and genetic testing completion between 2019 and 2021 were evaluated. RESULTS: A total of 973 patients were reviewed. 439 were diagnosed with breast cancer in 2019 and 534 in 2021. Demographics and stage at diagnosis (p = 0.194) were similar between years. Completion of genetic testing increased from 204 (46.5%) in 2019 to 338 (63.3%) in 2021 (p < 0.01) with the universal counseling protocol. Specifically, genetic testing completion increased significantly in older patients (p = 0.041) and patients receiving Medicare benefits (p = 0.005). The overall pathogenic variants found increased from 32 to 39 with the most common including BRCA2 (n = 11), CFTR (n = 9), CHEK2 (n = 8), BRCA1 (n = 6). CONCLUSION: Universal genetic counseling was related to a significant increase in genetic testing completion and an increase in pathogenic variants found among breast cancer patients, specifically in subpopulations which may have been previously excluded by traditional NCCN genetic testing screening guidelines.

Impact of Implementing B-RSTTM to Screen for Hereditary Breast and Ovarian Cancer on Risk Perception and Genetic Counseling Uptake Among Women in an Academic Safety Net Hospital.

BACKGROUND: Lower socioeconomic status is strongly associated with decreased perception of cancer risk. Fewer low socioeconomic status women than expected currently access cancer genetic services from which they may benefit. PATIENTS AND METHODS: We screened women presenting for a screening mammogram at a safety net academic hospital using the Breast Cancer Genetics Referral Screening Tool Version 3.0 (B-RSTTM), an online tool designed to identify individuals potentially at risk for hereditary breast and ovarian cancer. Participants screening either positive (high risk) or negative (moderate risk) were offered genetic counseling appointments. We used a brief survey to evaluate change in risk perception before and after using B-RSTTM, and after a genetic counseling appointment, if applicable. Barriers to accepting appointments were assessed when participants declined. RESULTS: Of the 126 participants, 91 (72.2%) screened negative-average risk, 13 (10.3%) screened negative-moderate risk, and 22 (17.5%) screened positive. Of those who screened positive or negative-moderate, 24 (68.6%) expressed interested in a genetic counseling appointment, of which 19 (79.2%) scheduled. Four of the 19 scheduled (21.1%) completed the appointment. We found a significant difference in the number who rated their breast cancer risk correctly on the post-test between the groups who self-rated as low, moderate, or high risk. Those who perceived themselves as high risk were the most likely to rate their risk correctly on the post-test (P < .001). CONCLUSION: We showed that using B-RSTTM in a safety net academic hospital was effective at identifying women at increased risk for hereditary breast and ovarian cancer.

Counselees' Perspectives of Genomic Counseling Following Online Receipt of Multiple Actionable Complex Disease and Pharmacogenomic Results: a Qualitative Research Study.

Genomic applications raise multiple challenges including the optimization of genomic counseling (GC) services as part of the results delivery process. More information on patients' motivations, preferences, and informational needs are essential to guide the development of new, more efficient practice delivery models that capitalize on the existing strengths of a limited genetic counseling workforce. Semi-structured telephone interviews were conducted with a subset of counselees from the Coriell Personalized Medicine Collaborative following online receipt of multiple personalized genomic test reports. Participants previously had either in-person GC (chronic disease cohort, n = 20; mean age 60 years) or telephone GC (community cohort, n = 31; mean age 46.8 years). Transcripts were analyzed using a Grounded Theory framework. Major themes that emerged from the interviews include 1) primary reasons for seeking GC were to clarify results, put results into perspective relative to other health-related concerns, and to receive personalized recommendations; 2) there is need for a more participant driven approach in terms of mode of GC communication (in-person, phone, video), and refining the counseling agenda pre-session; and 3) there was strong interest in the option of follow up GC. By clarifying counselees' expectations, views and desired outcomes, we have uncovered a need for a more participant-driven GC model when potentially actionable genomic results are received online.

Sustained reprogramming of the estrogen response after chronic exposure to endocrine disruptors.

The pervasive nature of estrogenic industrial and dietary compounds is a growing health concern linked to cancer, obesity, and neurological disorders. Prior analyses of endocrine disruptor action have focused primarily on the short-term consequences of exposure. However, these studies are unlikely to reflect the consequences of constant exposures common to industrialized countries. Here we examined the global effects of long-term endocrine disruption on gene transcription and estrogen signaling. Estrogen-dependent breast cancer cell lines were chronically treated with physiologically relevant levels of bisphenol A or genistein for more than 70 passages. Microarray analysis demonstrated global reprogramming of the transcriptome when compared with a similarly cultured control cell line. Estrogen-responsive targets showed diminished expression in both the presence and absence of estrogen. Estrogen receptor recruitment, H3K4 monomethylation, and deoxyribonuclease accessibility were reduced at nearby response elements. Based on these observations, we investigated the potential of long-term endocrine disruptor exposure to initiate persistent transcriptional reprogramming. Culture of chronically exposed cell lines in the absence of the endocrine disruptors did not reverse many of the signaling defects that accumulated during treatment. Taken together, these data demonstrate that chronic exposure to endocrine disrupting compounds can permanently alter physiological hormone signaling.