Citations

Abstract Context Single-tier newborn screening (NBS) for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone (17OHP) measured by fluoroimmunoassay (FIA) in samples collected at 24 to 48 hours produces a high false-positive rate (FPR). Second-tier steroid testing can reduce the FPR and has been widely implemented. Objective We investigated the accuracy of an alternative multitier CAH NBS protocol that incorporates molecular testing of the CYP21A2 gene and reduces the first-tier 17OHP cutoff to minimize missed cases. Methods We create a Minnesota-specific CYP21A2 pathogenic variants panel; developed a rapid, high-throughput multiplex, allele-specific-primer-extension assay; and performed a 1-year retrospective analysis of Minnesota NBS results comparing metrics between a conventional steroid-based 2-tier protocol and a molecular-based multitier NBS protocol, applied post hoc. Results CYP21A2 gene sequencing of 103 Minnesota families resulted in a Minnesota-specific panel of 21 pathogenic variants. The Centers for Disease Control and Prevention created a molecular assay with 100% accuracy and reproducibility. Two-tier steroid-based screening of 68 659 live births during 2015 resulted in 2 false negatives (FNs), 91 FPs, and 1 true positive (TP). A 3-tier protocol with a lower first-tier steroid cutoff, second-tier 21-variant CYP21A2 panel, and third-tier CYP21A2 sequencing would have resulted in 0 FNs, 52 FPs, and 3 TPs. Conclusion Incorporation of molecular testing could improve the accuracy of CAH NBS, although some distinct challenges of molecular testing may need to be considered before implementation by NBS programs.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Objective: The purpose of this study was to implement a 2-phase approach to rapidly increase the number of annual wellness visits (AWVs) and build a sustainable model at 3 study units (Mayo Clinic in Rochester, Minnesota, and clinics in 2 regions of Mayo Clinic Health System), which collectively serve approximately 80 000 patients who qualify for an AWV annually. Methods: In the rapid improvement phase, beginning in July 2022, goals at the facilities were reoriented to prioritize AWVs, educate staff on existing AWV resources, and create low-effort workflows so that AWVs could be incorporated into existing patient appointments. Staff at all 3 study units worked independently and iterated quickly. In the second phase, all study units collaborated to design and implement a best-practice solution while they leveraged the engagement and lessons learned from the first phase and invested in additional system elements and change management to codify long-term success. Results: The number of AWVs completed monthly increased in each study unit. In the rapid improvement phase, the number of AWVs increased but then plateaued (or decreased at some study units). In April 2023, the final scheduled outreach automation and visit tools were implemented, and the number of AWVs was sustained or increased, while outreach and scheduling times were decreased. The number of completed AWVs increased from 1148 across all study units in the first 6 months of 2022 to 14 061 during the first 6 months of 2023. Conclusions: The lessons learned from this project can be applied to other health systems that want to provide more patients with AWVs while improving operational efficiency. The keys are to have a clear vision of a successful outcome, engage all stakeholders, and iterate quickly to find what works best for the organization.

Abstract Objectives: Carriers of pathogenic variants in high penetrance mutations, including BRCA 1 or BRCA 2 face higher lifetime risks of developing breast and tubo-ovarian cancers, and possibly endometrial cancers, than non-carriers. In particular, relative risks are higher among carriers than non-carriers at younger ages, suggesting the value of early initiation of breast cancer screening and the use of sensitive imaging methods, such as magnetic resonance imaging (MRI). Further, breastfeeding appears protective for these three cancers in the general population, and potentially among mutation carriers, albeit based on limited evidence. Given that data related to knowledge and perspectives of carriers about these issues are limited, we surveyed mutation carriers regarding breastfeeding, cancer risk, and the deferral of breast cancer screening coinciding with reproductive events. These data may guide future cancer prevention research and developing of targeted communication campaigns. Methods: Researchers at Mayo Clinic, in collaboration with Facing Our Risk of Cancer Empowered (FORCE) – a large, national non-profit organization that addresses the needs of people and families affected by inherited mutations linked to cancer – designed and conducted a survey using the Mayo Clinic’s external RedCap system. The survey covered genetic testing and results, history of live births and breastfeeding history for mothers, history of risk-reducing surgery, personal cancer history, sources of information about cancer screening, breastfeeding knowledge, and breast cancer screening at various times, including during pregnancy, while breastfeeding, and after weaning. The survey was disseminated through FORCE’s electronic newsletter, website, social media pages, and advocacy partners. Survey responses were collected anonymously and analyzed descriptively using standard descriptive statistics, including frequency and percentages for categorical responses and means (SD) or medians (IQR) for continuously scaled responses. The open-ended responses were analyzed qualitatively using standard qualitative methodology. Results: Respondents included 253 women, of whom 88.7% were U.S. residents and 92.9% were white. The mean age + SD was 47(13) years, 61.7% were parous, with a mean age at first birth of 22.58 (13.16) years. Approximately 60% of women were carriers of mutations in BRCA1 or BRCA2 or both genes and all but two of the remaining women reported mutations in other genes linked to increased cancer risk. At the time of the survey, 92% of women had undergone a mammogram, with first screen at a mean age of 35 (6.49) years, and 85.3% had undergone breast MRI, with first screen at a mean age of 43 (12.39) years. Among 34.3% of participants, their 1st postpartum mammogram occurred >3 years after the birth of their last child and 57% had 1st MRI 3 years postpartum. Preliminarily, our analysis shows that nearly 90% of women were unaware of their mutation status prior to pregnancy and approximately 1/3 did not undergo radiologic screening until 3 years postpartum. While 62.6% of respondents believed that breastfeeding lowers breast cancer risk, 74.2% of participants responded that nursing had no effect on tubo-ovarian cancer risk, and 78.2% considered that nursing did not impact endometrial cancer risk. Discussion and Conclusions: Preliminarily, we conclude that most women in the surveyed population were unaware of their mutation status when pregnant years earlier and many had not undergone screening until years after delivery. Many participants did not consider breastfeeding a potentially protective factor for women’s cancers. These data raise issues about the potential value of discussing genetic testing with women when considering family planning and mutation carriers, addressing complex issues about breast cancer screening while pregnant and breastfeeding. Citation Format: Laura Pacheco-Spann, Mark Sherman, Susan Friedman, Diane Rose, Miriam Levi, Alex Hochwald, Jennifer Ridgeway, Sophia Blumenfeld. Breastfeeding and Breast Cancer Screening Among Carriers of Pathogenic Variants in BRCA 1 and BRCA 2 and Other High Penetrance Genes: Knowledge and Perspectives [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-03.

Abstract Background Current American Joint Committee on Cancer (AJCC) breast cancer staging considers contralateral axillary metastasis (CAM) stage IV disease (M1). Retrospective studies suggest that women with CAM have improved overall survival (OS) compared to those with distant metastasis (M1) and/or comparable OS to locally advanced breast cancer (LABC). These studies support consideration of curative intent treatment; however, they contain heterogeneous cohorts with highly variable treatment strategies. We sought to evaluate treatment and outcomes in a well-defined CAM cohort treated with contemporary systemic and locoregional therapy. Methods We performed a retrospective multi-institution cohort study to compare OS of patients with CAM matched 1:3 on age +/- 5 years to LABC (defined as cN2-3 and/or pN2-3), and to non-CAM M1. CAM patients classified as type 1) de novo CAM, synchronous with the contralateral primary, 2) metachronous isolated CAM in the setting of prior surgical and/or radiation treatment to primary index cancer, 3) synchronous with, or 4) metachronous after an in-breast or axillary nodal recurrence of the primary index cancer. The M1 cohort included de novo and recurrent metastasis with varied sites and number of metastasis. OS was defined as time from CAM diagnosis to death or last follow-up for CAM patients; time from primary diagnosis to death or last follow-up for LABC; and time from metastatic diagnosis to death or last follow-up for M1. Unadjusted OS was estimated with the Kaplan-Meier method, and Cox proportional hazards models were used to estimate the association of group with OS after adjustment for covariates Results We identified 57 CAM and 155 LABC from 8 institutions (2016-2022), and 632 M1 from a single institution. The median age was similar between groups (CAM=59 years, LABC=58, M1=57, p=0.44), and there were no statistically significant differences in hormone receptor status (p=0.25). There were more Non-Hispanic Black patients in the M1 cohort compared to CAM or LABC (p< 0.001). The majority of CAM cases were delayed metachronous from the index cancer (type 2, 35.1%), or synchronous with a recurrence (type 3, 33.3%). Type 1 (de novo, 14%) and type 4 (delayed metachronous after breast cancer recurrence, 17.5%) were less frequent. Among CAM patients, 49.1% were hormone receptor positive (HR+)/HER2-negative (HER2-), 22.8% HR-/HER2-, 10.5% HR+/HER2+, and 5.3% HR-/HER2+. Comparing CAM versus LABC, invasive ductal carcinoma (IDC) was more commonly seen in CAM (82.5% vs 66.5%), as was grade 3 (45.6% vs 35.5%), and triple negative (22.8% vs 13.5%). Conversely, in LABC, treatment of the primary index cancer more frequently included chemotherapy (CAM=71.9%, LABC=92.3%), mastectomy (CAM=54.4%, LABC 74.2%), and adjuvant radiation (CAM=73.7%, LABC=90.3%). On multivariable analysis adjusting for age, race/ethnicity, and hormone receptor status, both CAM and M1 had inferior survival to LABC (Table 1), but with a 2.4-fold difference for CAM (95% CI 1.42-4.07, p=0.001) versus a 6.3-fold difference for M1 (95% CI 4.29-9.23, p=< 0.001). Discussion In this contemporary, multi-institution study, we demonstrated that CAM patients selected for presumed curative intent treatment experienced improved OS when compared to stage IV (M1) patients. Our data adds additional support for re-evaluating the current stage IV designation, in favor of N3, and consideration of curative intent treatment in this disease. Table. Adjusted* Overall Survival Comparing Patients with Breast Cancer Contralateral Axillary Metastasis (CAM) to those with Locally Advanced Breast Cancer (LABC) and Metastatic Disease (M1) *Adjusted for age, race/ethnicity, hormone receptors. Citation Format: Meghan R. Flanagan, Stephanie Downs-Canner, Samantha Thomas, Astrid Botty van de bruele, Margaret Lillie, Kristalyn Gallagher, Tammeza Gibson, James Jakub, Alexandra Verosky, Sarah Tevis, Malia Brennan, Francys Verdial, Jennifer Q. Zhang, Leisha Elmore, Jennifer Plichta, Laura Rosenberger. A Multi-Institutional Review of Contralateral Axillary Metastases: Time for Reclassification as Local-Regional Event? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-13.

Background Self-scheduling of medical visits is becoming available at many medical institutions. We aimed to examine the self-scheduled visit counts and rate of growth of self-scheduled visits in a multispecialty practice. Methods For 85 weeks extending from January 1, 2022 through August 24, 2023, we examined self-scheduled visit counts for over 1500 self-scheduled visit types. We compared completed self-scheduled visit counts to all scheduled completed visit counts for the same visit types. We collected counts of the most frequently self-scheduled visit types for each week and examined the change over time. We also determined the proportion that each visit type was self-scheduled. Results There were 20,769 699 completed visits during the course of the study that met the criteria for inclusion. Self-scheduled visits accounted for 4.0% of all completed visits (838 592/20,769 699). Over the 85-week span, self-scheduled visits rose from 3.0% to 5.3% of the total. There were 1887 unique visit types that were associated with completed visits. There were just 6 appointment visit types of the total 1887 self-scheduled visit types that accounted for 50.7% of the total 838 592 self-scheduled visits. Those 6 visit types were a lab blood test visit (19.5%, 163 K visits), two Family Medicine office visit types (13.0%, 109 K visits), a screening mammogram visit type (6.6%, 55 K visits), a scheduled express care visit type (6%, 50 K visits) and a COVID immunization visit type (5.7%, 48 K visits). Twenty-one visit types that were self-scheduled accounted for 75% of the total self-scheduled visits. Four seasonal visits, accounting for 10.6% of the total self-scheduled visits, were responsible for almost all the non-linear change in self-scheduling. Conclusion Self-scheduling accounted for a small but growing percent of all outpatient scheduled visits in a multispecialty, multisite practice. A wide range of visit types can be successfully self-scheduled.

Abstract Background: In patients with micro- and macrometastases in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC), additional positive nodes are found in >60% of cases and axillary lymph node dissection (ALND) is currently considered standard of care. The likelihood of finding additional positive lymph nodes in patients with residual isolated tumor cells (ITCs) is unknown, and the benefit of ALND is unclear. As a consequence, surgical management of the axilla in these patients is not standardized. We sought to evaluate how often additional positive lymph nodes are found, to determine factors associated with ALND, and to compare oncological outcomes in patients treated with and without ALND after identification of residual ITCs in the SLN. Methods: Data were collected from 42 centers: 20 in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks, and 22 in North and South America. We included patients with cT1-4 N0-3 breast cancer at diagnosis who underwent NAC followed by axillary staging with either SLN biopsy (SLNB) or targeted axillary dissection (TAD) and were found to have residual ITCs [ypN0(i+)]. Single-tracer mapping was allowed for cN0 patients, while dual mapping or TAD was required for cN+ cases. Axillary treatment included completion ALND and/or nodal radiotherapy (RT). Competing risk analysis was performed to assess the cumulative incidence rates of any axillary recurrence (AR), locoregional recurrence (LRR), and any invasive (locoregional or distant) recurrence. Five-year cumulative incidence rates were compared between patients who underwent ALND and those who did not using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 412 patients treated with NAC followed by surgery from 01/2009-05/2022. 146 (35.4%) had completion ALND and 266 (64.6%%) did not. Median patient age was 48 years. The majority (57%) of patients had clinical T2 tumors, and 68% had biopsy-proven N1 disease. Most were HR+/HER2- (41%) or HER2+ (39%). Most patients (80%) received anthracycline and taxane-based chemotherapy regimens. Nodal RT was administered to 83% of patients. The median number of SLNs with ITCs was 1. Patients treated with ALND were more likely to have ITCs detected on frozen section (61% v 6.7%, p< 0.001), to have N2/3 disease at presentation (15.1% v 5.6%, p=0.001) and to have LVI (40% v 26%, p=0.004) (Table 1). There was no significant trend over time in the proportion of patients undergoing completion ALND during the study period (p=0.5). In the ALND group, additional positive nodes were found in 43/146 (29.5%) of cases, and consisted of macrometastases in 11/146 (7.5%), micrometastases in 9/146 (6.2%), and ITCs in 23/146 (15.8%). 5-year rates of any AR, LRR, and any invasive recurrence in the entire cohort were 2.7% (95% CI 1.2-5.4), 2.8% (95% CI 1.2-5.4) and 16% (95% CI 11-21), respectively. There was no statistical difference between patients who underwent ALND and those who did not in any of the 3 endpoints (2.2% v 3.1%, p=0.6), (2.6% v 3.0%, p=0.4) and (14% v 18%, p=0.12), respectively. Conclusion: The likelihood of finding additional positive lymph nodes in patients with ITCs after NAC is lower than in patients with residual micro- and macrometastases, and in the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population. Overall, these results do not support routine ALND in patients with residual ITCs. Table 1. Clinicopathological Features of the Study Cohort, Stratified by Type of Axillary Surgery Frequency (row percent) reported for categorical variables, and median (IQR) reported for continuous variables. SLNB sentinel lymph node biopsy; TAD targeted axillary dissection; SLNs sentinel lymph nodes; LNs lymph nodes; pCR pathologic complete response; ACT anthracycline and taxane; AC anthracycline; H Herceptin, HP, Herceptin and Perjeta; TC taxol (or Taxotere) and carboplatinum; LVI lymphovascular invasion; BCS breast-conserving surgery. ^ Applied to HER2- tumors only (n=252). ^^ Applies to HER2+ tumors only (n=160). # LVI was present on core biopsy or final pathology. * Applies to BCS patients only (n=175). ** Applies to mastectomy patients only (n=237). Citation Format: Giacomo Montagna, Alison Laws, Massimo Ferrucci, Mary Mrdutt, Natália Polidorio, Varadan Sevilimedu, Tracy-Ann Moo, Andrea Barrio, Marissa K. Boyle, Flavia Vidal Cabero, Daniela Cocco, Fabio Corsi, Angelena Crown, Meghan R. Flanagan, Mehmet Ali Gulcelik, Callie Hlavin, Justyna Jelinska, Hasan Karanlik, Susan Kesmodel, Henry Kuerer, Sherko Küemmel, Cornelia Leo, Tehillah Menes, Melissa Pilewskie, Nina Pislar, Nicola Rocco, Jai Min Ryu, Leonardo Soares, Christoph Tausch, M. Umit Ugurlu, CICERO URBAN, Astrid Botty van de Bruele, Denise Vorburger, Fredrik Wärnberg, Anna Weiss, Austin Williams, Stephanie Wong, Steven G. Woodward, Susie X. Sun, Jennifer Q. Zhang, M. Firdos Ziauddin, Guldeniz Karadeniz Cakmak, Nuran Bese, Thorsten Kühn, Judy Boughey, Tari King, Nina Ditsch, Maggie Banys-Paluchowski, Monica Morrow, Walter Weber. Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-02.