tbuckley/cabot-search huggingface dataset:
Interventions to Prevent Falls in Community-Dwelling Older Adults
Authors: Wanda K. Nicholson, Michael Silverstein, John B. Wong, Michael J. Barry, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Carlos Roberto Jaén, Marie Krousel-Wood, Sei Lee, Li Li, Goutham Rao, John M. Ruiz, James Stevermer, Joel Tsevat, Sandra Millon Underwood, Sarah Wiehe
Journal: JAMA (2024)

Importance Falls are the leading cause of injury-related morbidity and mortality among older adults in the US. In 2018, 27.5% of community-dwelling adults 65 years or older reported at least 1 fall in the past year and 10.2% reported a fall-related injury. In 2021, an estimated 38 742 deaths resulted from fall-related injuries. Objective The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the effectiveness and harms of primary care–relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling adults 65 years or older. Population Community-dwelling adults 65 years or older at increased risk of falls. Evidence Assessment The USPSTF concludes with moderate certainty that exercise interventions provide a moderate net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. The USPSTF concludes with moderate certainty that multifactorial interventions provide a small net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. Recommendation The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians individualize the decision to offer multifactorial interventions to prevent falls to community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences. (C recommendation)
Ipsilateral recurrence and breast cancer outcomes in carriers of<i> BRCA1/2</i> pathogenic variants according to locoregional treatments.
Authors: Rinat Bernstein-Molho, Ory Haisraely, Shira Galper, Einav Nili Gal-Yam, Orit Kaidar-Person
Journal: Journal of Clinical Oncology (2024)

e12584 Background: Our previous study of 255 breast cancer (BC) patients, carriers of BRCA1/2 pathogenic variants (PV), showed that patients who underwent mastectomy without post-mastectomy radiotherapy (PMRT) had higher rates of local recurrence (LR) than those who underwent PMRT or breast-conserving therapy (BCT). Our aim was to verify our previous findings in a larger cohort. Methods: Clinical data was extracted from the medical records of BRCA1/2 mutation carriers with BC, treated at a single institution between 1/2006-12/2022. Data extracted included demographics, tumor characteristics, disease stage, surgical and oncological treatment, use of RT and disease outcomes. Results: Overall, 481 BC patients with BRCA1/2 germline mutations were identified, 20 of them presented with synchronous bilateral disease. Median follow-up time was 75.3 months (range 12.5-211). After excluding 16 patients with metastatic de novo disease and 1 patient not operated for medical reasons, 464 patients with 484 primary tumors were analyzed. Of these, 234 (48.3%) mastectomies (84% were skin- or nipple-sparing, SSM/NSM, 16% total mastectomy) and 250 (51.7%) BCT were performed. In the non-PMRT group (n=153) there was earlier disease stage at diagnosis (77.6% of tumors were Tis and T1N0) compared to the PMRT group (n=81) and BCT group (4.9% and 45%, respectively, p&lt;0.001). All had free surgical margins. LR rate in the study cohorts was 20/153 breasts (13.1%) in the non-PMRT group compared with 1/81 breasts (1.2%) in the PMRT group (p=0.003), and 16/250 (6.4%) in the BCS group (p=0.024). All but one recurrence were invasive. Cumulative incidence of LR at 5 and 10 years was 14.1% and 15.9% in the non-PMRT, compared to 4.4% and 9.4% in BCT group, respectively (p=0.034). No significant difference in overall survival was observed (p=0.39). Conclusions: BRCA1/2 PV carriers treated with mastectomy without PMRT had higher rates of LR than those who underwent mastectomy and PMRT or BCT, despite earlier stage disease. Further studies are needed to compare these outcomes to non- BRCA1/2 carriers and find means to improve local control in these patients.
Sequential use of PI3K/AKT/mTOR pathway inhibitors alpelisib and everolimus in patients with hormone receptor-positive (HR+) metastatic breast cancer.
Authors: Sherry Shen, Anton Safonov, Maria Bromberg, Yuan Chen, Mehnaj Ahmed, Pedram Razavi, Komal L. Jhaveri
Journal: Journal of Clinical Oncology (2024)

1057 Background: Alpelisib (A), a PI3K inhibitor, is FDA-approved with fulvestrant for patients with PIK3CA-mutated HR+/HER2- MBC. Everolimus (E), an mTOR inhibitor, is FDA-approved with endocrine therapy (ET) regardless of PI3K/AKT/mTOR pathway mutation status. The efficacy and safety of sequential treatment with these pathway inhibitors is not well described. Methods: This single-center retrospective cohort study identified patients with HR+/HER2- MBC treated with both A and E sequentially, each in combination with ET, in either order from 2012-2023. We collected information on patient demographics, clinical and pathologic characteristics, treatment history, treatment adverse effects, and dates of disease progression (defined as radiographic or clinical progression leading to treatment change) from medical records. Patients treated first with E then A were categorized as Group 1 and those first with A then E as Group 2. Rates of prior CDK4/6i use were compared between groups with the chi-square test; differences in prior lines of therapy were assessed with the Wilcoxon rank sum test. Median PFS1 (PFS on 1 st pathway inhibitor) and PFS2 (PFS on 2 nd pathway inhibitor) were computed using the Kaplan-Meier method and the impact of prior treatment on PFS2 between groups was compared using Cox proportional hazards analysis. Results: 115 patients with HR+/HER2- MBC were included in this study. There were 62 (54%) patients in Group 1 and 53 (46%) patients in Group 2. Median prior lines of therapy in the metastatic setting for Group 1 was 4 (range 1-13) and for Group 2 was 3 (range 1-8; p=0.08). Median number of intervening therapies between E and A in Group 1 was 2 (range 0-8) and between A and E in Group 2 was 0 (range 0-4; p&lt;0.001). 34/62 (55%) patients in Group 1 and 45/53 (85%) in Group 2 received prior CDK4/6i ( p&lt;0.001). In Group 1, 49/62 (79%) of patients discontinued E for progression and 13 (21%) discontinued for toxicity. Median PFS1 was 9.2 months (95%CI 5.5-13.0) and PFS2 was 5.0 months (95%CI 4.6-7.9). In Group 2, 34/53 (64%) of patients discontinued A for progression and 19 (36%) discontinued for toxicity. Median PFS1 was 9.3 months (95%CI 7.0-14.0) and PFS2 was 3.5 months (95%CI 3.0-4.1). After adjusting for prior CDK4/6i use and prior lines of therapy (total and intervening), PFS2 was not significantly different between the groups. Genomic information will be included at the time of presentation. Conclusions: This is the largest retrospective study to-date of patients treated sequentially with PI3K/AKT/mTOR pathway inhibitors. PFS was longer with the 1st pathway inhibitor than with the 2nd regardless of sequence. This has implications for optimal integration of capivasertib, an AKT inhibitor, into HR+ MBC treatment. Prospective studies testing optimal sequencing are needed.
Preventing Falls in Older Persons
Authors: David B. Reuben, David A. Ganz
Journal: JAMA (2024)

US Preventive Services Task Force; Wanda K. Nicholson, MD, MPH, MBA; Michael Silverstein, MD, MPH; John B. Wong, MD; Michael J. Barry, MD; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Esa M. Davis, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Marie Krousel-Wood, MD, MSPH; Sei Lee, MD, MAS; Li Li, MD, PhD, MPH; Goutham Rao, MD; John M. Ruiz, PhD; James Stevermer, MD, MSPH; Joel Tsevat, MD, MPH; Sandra Millon Underwood, PhD, RN; Sarah Wiehe, MD, MPH
Single institution retrospective review of patients with metastatic hormone receptor positive breast cancer receiving first line therapy of CDK4/6 inhibitors.
Authors: Anika Bhargava, Michelle Tavcar, Brian Dong
Journal: Journal of Clinical Oncology (2024)

e13090 Background: Breast cancer continues to be the most commonly diagnosed cancer in women. The majority of these cancers are estrogen positive (ER+) and about 6% of new cases are stage 4 at time of diagnosis. The current standard of care for postmenopausal women with stage 4 ER+ breast cancer is a combination of an aromatase inhibitor (AI) with a cyclin-dependent kinase (CDK) 4/6 inhibitor. Based on Medicare data claim analysis from IQVIA, CDK 4/6 inhibitors are being used nationally in the first line setting in 56% of cases where 24% of cases were treated with AI monotherapy. The state of Kentucky currently lies below this national average by using this treatment regimen in 38% of cases where 47% of cases are treated with AI monotherapy. The reason for this discrepancy between the national average and Kentucky is currently unknown. To further understanding, we have conducted an internal review of adherence to the guidelines. Methods: This is a single center retrospective study done at University of Louisville, Brown Cancer Center. Data was collected on patients who had biopsy proven metastatic hormone positive breast cancer from July 2021 until May 2023 (n=41). Collected characteristics include age on diagnosis, tumor grade, sites of metastatic disease, first line treatment received, choice of CDK4/6 inhibitor if received, and prior exposure to chemotherapy or anti-estrogen therapy. Results: In our cohort of 41 patients, we found that 63.4% (n=26) of patients received an AI and CDK4/6 inhibitor in the first line. There were 4.88% (n=2) of patients who received AI monotherapy, 21.9% (n=9) received Fulvestrant and CDK4/6 inhibitor, 4.88 % (n=2) received AI and Fulvestrant and 4.88% (n=2) received Fulvestrant alone. In total, patients who received estrogen therapy plus CDK4/6 inhibitor totaled 85% of new patients (n=35). Conclusions: This internal review showed our institution to be compliant with endocrine therapy and CDK 4/6 inhibitor in front-line treatment for the majority of metastatic ER+ patients. Given the supportive data for use of CDK 4/6 inhibitors in front-line treatment, the compliance is expected to be much higher. We recommend continued discussion amongst oncology providers to help identify barriers to treatment and determine the causes for poor compliance in the state of Kentucky.
Clinical features of breast cancer in Ashkenazi Jewish carriers of the two founder BRCA1 pathogenic variants.
Authors: Rachel Michaelson-Cohen, Lee Sarah Lenz, Luna Kadouri, Tamar Yablonski-Peretz, Ephrat Levy-Lahad, Shani Paluch-Shimon
Journal: Journal of Clinical Oncology (2024)

e12557 Background: Germline pathogenic variants (PVs) in BRCA1 and BRCA2 are the most common cause of hereditary breast and ovarian cancer. Carriers have a significantly elevated risk of developing breast cancer (BC) and ovarian cancer (OC) compared to the general female population. Two prevalent PVs in Ashkenazi Jews (AJ) in the BRCA1 gene are 185delAG and 5382insC. This study aims to compare clinical features of disease between the PV carrier groups. Methods: Data was collected retrospectively on 282 BC patients who were carriers of 5382insC or 185delAG, treated in Hadassah and Shaare Zedek Medical Centers between the years 1978 and 2021. Data collected included features such as age at disease onset, staging at diagnosis, additional malignancies or recurrence of disease, pathological features such as hormone receptor status and HER2 status (tumor subtype), and treatments. Disease characteristics and outcomes were compared. Results: There were 207 carriers of the 185delAG PV, while 75 carried the 5382insC PV. Amongst carriers of 185delAG, vs. 5382InsC, 58.1% vs. 35.8% (p&lt;0.01) had triple negative BC (TNBC), while 28.2% vs. 52.6% (p&lt;0.01) had hormone positive BC, respectively (Table). There was no significant difference in disease-free or overall survival, even after adjusting for age, stage and other potential confounders. Although it appeared that 5382insC carriers suffered a higher rate of OC (14% vs. 9.6%), and that 185delAG had a higher rate of non-OC malignancies (8.2% vs. 4%), these differences did not reach statistical significance. Conclusions: Our study suggests that 5382insC and 185delAG differ in their patterns of disease. Despite the lower rates of TNBC, 5382insC carriers had similar survival to 185delAG carriers. This could suggest that the hormone receptor positive disease amongst 5382InsC carriers had a less favorable course of disease, with a similar outcome as in those with TNBC. Further studies are warranted to better understand this pattern of disease aggression. [Table: see text]
Real-world treatment outcomes in patients with HR+ HER2- advanced breast cancer treated with CDK4/6 inhibitors and endocrine therapy.
Authors: Renata Duchnowska, Katarzyna Soter, Jolanta Smok-Kalwat, Aleksandra Grela-Wojewoda, Karolina Winsko-Szczęsnowicz, Katarzyna Pogoda, Grzegorz Kade, Iwona Danielewicz, Bartosz Szymanowski, Joanna Kiszka, Joanna Streb, Ewa Kalinka, Aleksandra Łacko, Justyna Żubrowska, Marek Ziobro, Bogumila Czartoryska-Arlukowicz, Michał Jurczyk, Tomasz Lewandowski, Jacek Jassem, Michał Bieńkowski
Journal: Journal of Clinical Oncology (2024)

1067 Background: The addition of cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) to endocrine therapy (ET) improves progression-free (PFS) and overall survival (OS) in hormone receptor-positive, HER2-negative advanced breast cancer (HR+/HER2- ABC) in 1 st and 2 nd line setting. The international guidelines advise using 1 st line CDK4/6i; however, its superiority over 2 nd line use is debatable. Methods: We retrospectively analyzed clinical data of HR+/HER2- ABC pts administered palbociclib (PAL), ribociclib (RIB) or abemaciclib (ABM) added to either 1 st or 2 nd line ET. Results: A total of 1511 pts (PAL=507; RIB=724; ABM=280) from 11 cancer Polish centers treated between Sep 2017 and Dec 2023. Median follow-up was 29.6 (95%CI 28.2 to 30.9) months (m). Mean age was 62.6±11.9, 58.9±12.2 and 61.4±10.8 years in PAL, RIB and ABM, respectively. 815 patients (53.9%) had visceral and 1109 (73.4%) bone metastases. 1254 pts (83%) received 1 st line CDK4/6i, in 841 (67%) combined with aromatase inhibitor (AI) and in 413 (33%) with fulvestrant (FUL). Second-line CDK4/6i was used in 257 pts (17%); 59 (23%) and 198 (67%) with AI and FUL, respectively. There was no difference in PFS, PFS2, and OS between three CDK4/6i in combination with AIs in 1 st and 2 nd line setting. Median PFS (95%CI) for 1 st line AI with PAL, RIB, ABM were 29.0 (21.6-37.0), 32.0 (24.5-36.9), not reached (N/R) (21.9-N/R) m; PFS2: 37.0 (28.8-N/R), 33.0 (29.5-40.2), N/R (28.9-N/R); OS: 48.9 (42.9-N/R), 48.6 (41.9-N/R), N/R (36.7-N/R). Median PFS (95%CI) for 2 nd line AI with PAL, RIB, ABM were 11.9 (9.49-N/R), 10.8 (8.27-N/R), 11.0 (6.43-N/R); PFS2: 22.7 (16.8-N/R), 32.3 (24.9-N/R), 31.0 (13.2-N/R); OS: 27.4 (24.4-N/R), 36.7 (30.1-N/R), 45.5 (29.0-N/R) (no statistical significance). In contrast, RIB+FUL was superior to PAL+FUL and ABM+FUL in both lines (Table). The safety profile was concordant with the reported data for ET + CDK4/6i. Conclusions: Identifying predictive factors of response is essential for the rational use of CDK4/6i and ET in HR+/HER2- ABC. [Table: see text]
Outcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer.
Authors: Paolo Tarantino, Do Lee, Julia Foldi, Pamela R. Soulos, Cary Philip Gross, Thomas Grinda, Eric P. Winer, Nancy U. Lin, Ian E. Krop, Sara M. Tolaney, Maryam B. Lustberg, Sarah L Sammons
Journal: Journal of Clinical Oncology (2024)

1077 Background: In the clinical trial setting, T-DXd improves survival for patients with HER2+ and HER2-low metastatic breast cancer (MBC), and has also shown preliminary activity in HER2-0 MBC. Little real-world evidence is available on the performance of T-DXd. Methods: We conducted a retrospective observational study using the nationwide Flatiron Health electronic health record (EHR)-derived deidentified database to evaluate the real-world activity of T-DXd. We included patients with MBC who initiated T-DXd between 12/2019 and 1/2023. Tumors were categorized as HER2+ if positive at any timepoint, with HER2- cases further divided into HER2-low (IHC 1+ or 2+ not amplified) and HER2-0 (IHC 0) according to the last biopsy before T-DXd. Real world progression-free survival (rwPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 930 patients were included: 636 with HER2+, 268 with HER2-low and 26 with HER2-0 MBC. Among HER2- patients, 241 (82.0%) were HR+ and 53 (18.0%) were HR- (i.e., triple-negative). A total of 572 (61.5%) patients were White, 101 (10.9%) Black/African American, 88 (9.4%) Hispanic/Latino, 37 (4.0%) Asian and 132 (14.2%) other or missing. Median age was 59 [range 25, 84] and patients received T-DXd in the following lines of therapy (LOT): 54 (5.8%) as 1 st line, 110 (11.8%) as 2 nd line, 179 (19.2%) as 3 rd line, 182 (19.6%) as 4th line and 405 (43.6%) as ≥5 th line. Median number of LOT for advanced disease prior to T-DXd were 3 and 4, respectively, for HER2+ and HER2- patients. In patients with HER2+ MBC, rwPFS and OS were 12.1 and 26 months after initiating T-DXd, respectively. The longest rwPFS, 14.9 months, was observed in the 1st or 2nd LOT, followed by 14.1 months in LOT 3, 12.4 months in LOT 4, and 10.8 months in LOT ≥5. In patients with HER2- MBC, median rwPFS and OS were 6.3 and 15.5 months, respectively. The longest median rwPFS of 8.1 months was observed in the 1st or 2nd LOTs, followed by 6.9 months in LOT 4, 6.2 months in LOTs ≥5, and 6.0 months in LOT 3. Outcomes with T-DXd by HER2 and HR status are provided (Table). Updated data with a larger sample size will be presented. Conclusions: In the largest dataset to date, T-DXd showed favorable real-world activity for treating MBC, although rwPFS appeared shorter than what observed in clinical trials. Encouraging rwPFS was observed in understudied groups, such as patients with triple-negative and HR+/HER2-0 MBC. [Table: see text]
Real-world treatment patterns, healthcare resource utilization and costs of care among newly-diagnosed patients with HR+/HER2- metastatic breast cancer.
Authors: Reva K. Basho, Carmen Ng, Allison Dillon, Lu Chen, Anna Cheng, Yolande Du Toit, Ibrahim M. Abbass
Journal: Journal of Clinical Oncology (2024)

1073 Background: Current literature on the treatment patterns and economic burden among newly diagnosed patients (pts) with HR+/HER2- metastatic breast cancer (mBC) is outdated and may not adequately capture the rapidly evolving treatment landscape. This study addresses this gap by providing a contemporary and comprehensive summary of real-world treatment patterns, healthcare resource utilization (HRU) and cost of care among HR+/HER2- mBC pts, through their first 3 lines of treatment (LOT) following metastatic diagnosis (met dx). Methods: We retrospectively identified adult women with newly diagnosed HR+/HER2- mBC between 10/01/2016 - 06/30/2022 from the IQVIA PharMetrics Plus database. Pts were required to have≥ 6 months of follow up post met dx. The study classified pts hierarchically into mutually exclusive treatment categories across 3 LOTs following met dx: endocrine therapy only (ET), CDK4/6 inhibitor-based therapy (CDKi), alpelisib-based therapy (ALP), mTOR inhibitor-based therapy (mTOR), PARP inhibitor (PARPi), or chemotherapy (CT). Categories with &lt; 30 pts in each line or those with overlapping targeted treatments were grouped into “Others'' (OTH). Baseline characteristics were assessed in the 12 months prior to met dx. HRU and costs of care (in 2022 USD) were measured during the follow-up period and reported in per patient per month (PPPM). Results: The study included 2,449 pts, with 64.6%, 10.5%, 22.8%, 2.1% pts receiving CDKi, CT, ET and OTH in 1LOT, respectively. In 2LOT (n=1,164), 41% of pts received CDKi, 24% CT, 20% ET, 9% mTOR, 4% ALP and 3% OTH. In 3LOT (n=479), 44% of pts received CT, 21% CDKi, 15% ET, 9% mTOR, 6% ALP and 4% OTH. The median treatment duration in 1LOT was longest for pts receiving CDKi (23.5 months) compared to 17.1 months for ET. The PPPM total costs were $15,396, $16,955 and $17,853 in 1, 2 and 3LOT. In 1LOT, CDKi pts had the highest PPPM costs [Table]. In the 2/3 LOT, ALP-treated pts incurred the highest costs followed by CDKi in 2LOT and mTOR-treated pts in 3LOT (Table). CT and ALP had the highest ER visits in 2 (0.18 and 0.13) and 3 LOT (0.20 and 0.27). Conclusions: The majority of patients received CDKi treatment as their 1LOT with a more fragmented treatment landscape in the 2/3LOTs. The incorporation of agents targeting the PI3K pathway (ALP and mTOR) remained low in the 2/3LOTs. Costs associated with the same targeted treatment increased when used in later lines of therapy. Early optimization of targeted therapy and a focus on adverse event management may be associated with economic benefits. [Table: see text]