tbuckley/cabot-search huggingface dataset:
Co-occurrence of <i>ESR1</i> and<i> PIK3CA</i> mutations in HR+/HER2- metastatic breast cancer: Incidence and outcomes with targeted therapy.
Authors: Naomi Dempsey, Priya Bhatt, Courtney Lewis, Dana Tolman, Yolcar Chamorro, Muni Rubens, Lauren Carcas, Ana Cristina Sandoval-Leon, Manmeet Singh Ahluwalia, Reshma L. Mahtani, Natasha Harpalani
Journal: Journal of Clinical Oncology (2024)

e13097 Background: ESR1 and PIK3CA mutations inform the use of targeted agents such as alpelisib (A), elacestrant (E), and capivasertib in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). These mutations predict a worse prognosis and shorter response to endocrine therapy (ET). The prevalence of PIK3CA and ESR1 mutations detected via circulating tumor DNA (ctDNA) in mBC is about 35% and 33%, respectively, and the co-occurrence rate is 10-15%. Treatment outcomes with these targeted agents in pts with both mutations can inform sequencing decisions. Methods: We retrospectively analyzed pts treated at Miami Cancer Institute with HR+/HER2- mBC who underwent ctDNA testing (performed by Guardant360) between March 2019 and Jan 2024. The rate of co-occurring pathogenic ESR1 and PIK3CA mutations on a single sample was quantified. We report pt demographics, disease characteristics, and real world outcomes on A + ET and E in the co-mutated cohort. Results: Of the 626 pts who underwent ctDNA testing, 31.6% (n=198) had at least one PIK3CA mutation and 23.8% (n=149) had at least one ESR1 mutation. Co-mutations in both ESR1 and PIK3CA were found in 10.4% (n=65). In the co-mutated cohort, median age was 63, 84.6% were post-menopausal, and 58.5% were Hispanic. Most pts received prior CDK4/6 inhibitor (90.7%). A + ET was administered to 27 pts (41.5%) with a median of 2 prior lines of therapy (range 1-8). In these pts, 33.3% (n=9) achieved stable disease, 25.9% (n=7) partial response, 14.8% (n=4) progression, and 18.5% (n=5) discontinued due to toxicity prior to re-staging. E was administered to 12 pts (18.5%) with a median of 4 prior lines of therapy (range 1-13), with 4 pts still on treatment. None achieved stable disease or objective response, 66.7% (n=8) developed progression of disease as best response, and 33.3% (n=4) currently remain on treatment pending response evaluation. In the co-mutated cohort, only 4 received both A + ET and E, (3 received A first, 1 received E first). Pts treated with A + ET only (n=23) had a median time to next treatment (mTTNT) of 120 days (range 5-566) and those who received E only (n=8) had a mTTNT of 86 days (range 13-106) (Chi square=4.289, df = 1, p&lt;0.05). The 4 pts who received both therapies were excluded from this mTNNT analysis. Conclusions: The rate of ESR1 and PIK3CA co-mutation in this cohort was consistent with the reported literature. mTTNT was significantly longer with A + ET compared to E, but real world outcomes on E remain immature with one-third of pts still on E at the time of analysis. A limitation of this study was the small sample size. Further analyses are warranted to clarify the optimal sequencing of these targeted therapies such as A, E, and capivasertib in pts with co-mutations in ESR1 and PIK3CA.
Trends over time in liquid biopsy testing in patients with metastatic breast cancer (MBC) across the Mayo Clinic enterprise.
Authors: Sumeet Kumar Yadav, Sanjna Rajput, Thoshik Samineni, Kevin Thompson, Xiaojia Tang, Roberto Antonio Leon-Ferre, Ciara Catherine O'Sullivan, Prema P. Peethambaram, Pooja Prem Advani, Kostandinos Sideras, Saranya Chumsri, Paula Gill, Jonathan Ticku, Karen S. Anderson, Brenda Ernst, Donald W. Northfelt, Tufia C. Haddad, Matthew P. Goetz, Krishna Rani Kalari, Karthik Giridhar
Journal: Journal of Clinical Oncology (2024)

e13036 Background: In January 2023, the FDA approved elacestrant for ESR1-mutated, ER+/HER2- MBC based on a companion diagnostic cell free (cf)DNA test (Guardant Health). In this study, we analyze the trends of liquid biopsy utilization at Mayo Clinic (MC) over a 3 year period to understand the impact of this drug approval on testing patterns and identify emergent alterations in patients (pts) with MBC. Methods: We extracted clinically performed Guardant 360 and Guardant 360 CDx ordered at MC sites in Rochester (MN), Florida (FL), Arizona (AZ), and across 9 additional Mayo Clinic Health System (MCHS) sites. Pts with MBC were identified using the EMR and analyzing visit diagnosis codes and staging information. Shifts in testing patterns were analyzed over a 3 year period from January 1, 2021 - December 31, 2023. Data was collected on the number of tests, serial testing, frequency of pathogenic mutations, and emergent mutations in ESR1 and PIK3CA. Chi-square test was used to compare the categorical values. Results: Between 2021-2023, 2,741 pts with MBC were seen across all sites. A total of 408 cfDNA tests were performed in 370 unique patients with MBC. Most pts (90%) had 1 test performed. The proportion of pts with MBC tested was 85/1350 (6.3%) in 2021, 77/1495 (5.2%) in 2022, and 208/1558 (13.4%) in 2023. The increased proportion of pts tested in 2023 was statistically significant compared to prior years (p&lt;0.0001), while no difference was observed between 2021 and 2022 (p 0.19). Testing patterns varied by site, with FL ordering the highest number of tests, followed by MN and AZ. Of the 34 providers practicing during the entire period seeing more than 10 MBC pts, the number of providers ordering Guardant testing increased from 15/34 (2021) and 14/34 (2022) to 20/34 (2023), though not statistically significant (p 0.15). Of the 41% with EMR-documented staging available, testing was highest in the ER+/HER2- (81.3%) subtype, followed by TNBC (13.6%) and then HER2+ (5.2%). The most commonly identified mutations identified in the first testing were PIK3CA (41.1%), TP53 (40.5%), ESR1 (30.5%), and ATM (13.2%). D538G (8.0%), Y537N (4.4%), and Y537S (3.5%) were frequent emergent mutations seen in ESR1. Conclusions: We observed an increase in cfDNA testing at the start of 2023 which aligns with the FDA approval of elacestrant. We observed variation by site and individual providers that warrants further exploration to improve cfDNA testing in MBC pts at Mayo Clinic.
Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: A single-centre retrospective study.
Authors: Lili Wang, Weiwei Huang, Chenxi Wang, Qi Chen, Yangkun Shen, Zhijian Huang, Jian Liu, Xiaoyan Lin, Fan Wu, Xinhua Chen, Nani Li, Yi Hong, Mulan Chen, Jieyu Li, Chuanzhong Huang, Suhong Yu
Journal: Journal of Clinical Oncology (2024)

e13135 Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Methods: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n=45) and platinum-based therapy (n=51). The follow-up period for all patients ended on December 31st, 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median PFS compared to platinum-based (hazard ratio (HR)=0.41, p=0.006), nab-paclitaxel-based (HR=0.36, p=0.001) and other chemotherapy (HR=0.39, p&lt;0.001). Also, eribulin induced a remarkable prolongation of the median OS duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusions: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted. Clinical trial information: NCT05953909 .
Prevalence of “HER2 ultra-low” among patients with advanced breast cancer with historical IHC0 status.
Authors: Sandhya Mehta, Anushree Iyengar, Hannah Barman, Nivedita Rangarajan, Michele Sue-Ann Woo, Simone T. Sredni, Rosemarie Di Donato, Safak Simsek, Erinn P. Downs, Aziza Nassar, Darren M. Wilson, Katherine Krieser, Elise Bieri Patzke, Natalie Kyek, Jason Hipp, Tyler Wagner
Journal: Journal of Clinical Oncology (2024)

e13156 Background: Breast Cancer (BC) patients are classified as HER2-positive (IHC3+ or IHC2+/ISH+) or HER2-negative (IHC0, IHC1+ and 2+/ISH-). Within the HER2-negative category, patients who meet HER2-low (IHC1+ or IHC2+/ISH-) criteria can benefit from HER2 targeted therapy like trastuzumab deruxtecan. Patients who meet IHC0 criteria with incomplete and faint membrane staining in &gt;0 but ≤10% of tumor cells — defined as “HER2 Ultra-low”, may also benefit from HER2 targeted therapy. This study aimed to assess the prevalence of “HER2 Ultra-Low” expression based on re-scored HER2 IHC biopsy slides. Methods: This study utilized EHR data from all three US Mayo Clinic campuses. A total of 300 patients with advanced BC (stages III-IV), and clinically documented HER2 IHC0 status between Jan 2017 and Jan 2023, were identified. One biopsy slide per patient (IHC assay: VENTANA Pathway anti-HER2/neu (4B5) rabbit monoclonal primary antibody) was digitized and scanned at 40x magnification. Two Mayo Clinic pathologists independently scored and reported HER2 status according to 2023 ASCO-CAP guidelines and included tumor stain percentage for each slide. Patients were considered “HER2 Ultra-Low” if their slide was scored as IHC0 with &gt;0% but ≤10% staining. Cohen’s κ was used to quantify agreement between pathologists. Results: The re-scored patients (n=300) had a mean age of 57.8 years (SD=13.5), with ~97% having IHC0 documentation within 30 days of the reviewed biopsy slide. A total of 285 (95%) patients remained classified as IHC0 by at least one pathologist. Of these, 60% (n=171) were determined as “HER2 Ultra-low” by at least one pathologist. The rate of “HER2 Ultra-Low” per pathologist ranged from 43% (n=121) to 45% (n=104). The overall inter-pathologist concordance was 57%; patients with no observable HER2 IHC staining accounted for majority of the concordant patients (Table). Conclusions: About 3 in 5 advanced BC patients originally classified as HER2 IHC0 met the “HER2 Ultra-Low” criteria by at least one pathologist, implying that significant number of additional patients may benefit from HER2 targeted therapy. The relatively low concordance between HER2 expert pathologists in identifying lower levels of HER2 expression suggests the need for increased precision enabled by digital tools, leveraging AI, training for community practice pathologists, and continuing to follow best practice recommendations in determining HER2 IHC status. [Table: see text]
A phase II trial of anlotinib combined chemotherapy as second-line and above therapy in HER2-negative advanced breast cancer.
Authors: Yuan Yuan, Lili Zhang, Ting Xu, Weili Xiong, Sainan Hu, Jiayuan Huang, Min Dong, Xinyu Xu, Kexin Lou
Journal: Journal of Clinical Oncology (2024)

e13140 Background: The group of HER2-negative accounts for about 75% of breast cancer and has limited response to chemotherapy. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. In this study, we assessed the efficacy and safety of anlotinib plus chemotherapy in second-line and above treatment of HER-2 negative advanced breast cancer. Methods: This open-label, single-arm, phase II study enrolled women aged 18-75 years with HER2-negative breast cancer who underwent at least one-line chemotherapy. All patients were treated with anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle) in combination with investigator-selected chemotherapy. The primary endpoint evaluated in this study was the median progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety. Results: From August 2022 to August 2023, 33 patients were enrolled in this study including 22(66.7%) HR+/HER2- patients and 11(33.3%) TNBC patients. After a median follow-up time of 11 months (95% CI, 5.8-16.2), the median PFS (mPFS) of the all patients was 8.6 months (95% CI 7.3-NA). In the HR+ and HR- populations, mPFS was 7.6 months versus 9.5 months (HR,0.376 [95%CI 0.12-1.13], p=0.072), respectively. All the patients had the confirmed best overall response assessments, no patient achieved complete response (CR); 11(33.3%) patients got partial response (PR) and 19(57.6%) patients achieved stable disease (SD). ORR was 33.3% (95% CI 18.0-51.8), DCR was 90.9% (95% CI 75.7-98.1) and CBR was 60.6% (95% CI 42.1-77.1). The most frequently observed adverse events were elevated triglycerides (78.8%), elevated blood sugar (63.6%), anemia (60.6%), elevated cholesterol (51.5%), elevated alanine aminotransferase (48.5%), and leukopenia (48.5%). Dose reductions due to adverse events occurred in 7 (21.2%) patients. Conclusions: Anlotinib combined with chemotherapy showed a promising efficacy with an acceptable safety profile for second-line and above patients with HER2-negative metastatic breast cancer. Further studies enrolling more patients are still needed.
Landscape of HER2-low breast cancer: Insights from a six-year study on incidence and clinicopathological characteristics.
Authors: Michel Abou Khalil, Lea Habibian, Christine Martin, Karl Semaan, Abir Khaddage, Nadine EL Kassis, Carole Kesrouani, Hampig Raphael Kourie, David M. Atallah
Journal: Journal of Clinical Oncology (2024)

e13148 Background: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+ or 2+ in immunohistochemistry (IHC) and the absence of the ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2 breast cancer to novel anti-HER2 antibody-drug conjugates, rising interest in the HER2-low subtype. To date, data on characteristics of HER2-low breast cancer subtype is limited. Herein, we describe the clinicopathological characteristics of HER2-low breast cancer subtype compared HER2-zero/negative breast cancer. Methods: Real-world data from the Anatomic Pathology Division of Hotel Dieu de France, spanning 2017-2022, was retrospectively collected. Patients with HER2-IHC 3+ and HER2-IHC 2+ with ISH-amplified (HER2-positive) were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Patients were then categorized based on their hormone receptor (HR) status. Clinicopathological characteristics between the groups were compared using a Chi-Square and Mann–Whitney U tests. Results: Out of 1195 patients, we observed 341 (28.5%) HER2-low breast cancers cases. HER2-positive breast cancer cases (n=178; 14.9%) were subsequently excluded. There was no significant difference in age and sex between the HER2-low and the HER2-zero group (p=0.3 and 0.8, respectively). HER2-low breast cancer was associated with positive estrogen receptor (ER) status and positive progesterone receptor (PR) status (p&lt;0.001 and p=0.01, respectively). Ductal adenocarcinomas were more frequently observed in the HER2-low group, whereas lobular and metaplastic adenocarcinomas were especially prevalent in the HER2-zero group (all p&lt;0.001). When stratified by HR status, 87.4% of patients had HR-positive status and 12.6% were HR-negative. Furthermore, the occurrence rate of tumors with a low Ki-67 labeling index was comparable between the two groups (p=0.9). However, among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (p = 0.04; Table). Conclusions: In conclusion, this study showed that HER2-low is a distinct from HER2-zero and is frequently present among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Our findings suggest that, within HR-negative breast cancer, breast cancer with low HER2 expression exhibits a less aggressive profile when compared to HER2-zero tumors. [Table: see text]
Real-world experience with CDK4/6 inhibitors in the first-line palliative setting for HR+/HER2- advanced breast cancer.
Authors: Ram Patel, Abdullah Nasser
Journal: Journal of Clinical Oncology (2024)

e13066 Background: CDK4/6 inhibitors paired with aromatase inhibitors (AIs) have redefined the first-line treatment for metastatic breast cancer, as evidenced by several pivotal trials. Although progression-free survival (PFS) has been consistent across these studies, notable differences in overall survival (OS) have been observed. Our study evaluates the real-world efficacy of palbociclib and ribociclib, in combination with AIs, for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer at our institution. Methods: We retrospectively reviewed charts of adult patients with advanced metastatic breast cancer at a single academic center from January 1, 2015, to December 1, 2022. We extracted relevant clinical data to estimate the median PFS and OS associated with palbociclib and ribociclib. Results: Among 75 patients analyzed, the majority were female (98.7%) and postmenopausal (77.3%). Palbociclib was prescribed to 74.7%, while 52.0% presented with de novo stage IV disease. Those on ribociclib were significantly younger (median age 57.6 vs. 67.5 years; p = 0.013) and more likely premenopausal (42.1% vs. 5.4%; p &lt; 0.001). Median PFS for palbociclib was 20.3 months (95% CI: 14.8-46.0), with an OS of 37.2 months (20.3 months to not reached). Median PFS and OS for ribociclib were not reached. The differences in PFS and OS between the drugs were not statistically significant (PFS log-rank p = 0.1; OS log-rank p = 0.2). Conclusions: Our real-world analysis suggests a non-significant trend towards improved PFS and OS for ribociclib over palbociclib when used with AIs for treating HR+/HER2- advanced breast cancer, potentially influenced by the younger age of patients on ribociclib. Further research with larger cohorts and extended follow-up is warranted to substantiate these observations.
Toxicity differences in CDK 4/6 inhibitors seen in Asian and Pacific Islanders.
Authors: Brooke Gushiken, Christa M. Braun-Inglis, Tyler Workman, Jami Aya Fukui
Journal: Journal of Clinical Oncology (2024)

e13086 Background: Cyclin-dependent kinases (CDK) 4/6 inhibitors are the standard of care, first line treatment for hormone receptor positive metastatic breast cancer and adjuvant high-risk hormone receptor positive early stage breast cancer along with endocrine therapy. There have been multiple clinical trials validating the effectiveness, along with toxicities of these agents; however, the majority of these trials lack ethnic diversity. This shortcoming limits the ability to apply these findings in diverse patient populations, especially among Asian and Pacific Islanders in Hawaii. Objective: To determine if the toxicity profile of CDK 4/6 inhibitors in women with breast cancer is different among patients at a community oncology practice in Hawaii, in which the majority of patients are Asian, Pacific Islander or a combination of both when compared to three landmark trials. Methods: A retrospective analysis of thirty-two patients with hormone receptor positive, HER2 negative metastatic or high risk breast cancer who started endocrine therapy and CDK 4/6 inhibitor therapy (abemaciclib, ribociclib, or palbociclib) between 2018-2023. Graded toxicities of each individual patient based on CTCAE criteria V. 5, along with demographic data was reviewed and compared to three main registration trials for these agents (MONARCH-3, MONALEESA-2, PALOMA-2). Results: Combined results from the three large randomized trials reported an average of 75% of participants were Caucasian, as compared to 15% in the Hawaii data. While 19% percent of participants from the combined large randomized trials reported being of Asian descent, none of these trials reported a breakdown of Asians versus Pacific Islanders. In the Hawaii sample, 41% were reported as Pacific Islander and 41% reported as Asian, 15% Caucasian, with the final 3% reported as Hispanic. Collective analysis of the FDA registration trials contained 0% Pacific Islander, 19.8% Asian, 74.3% White, 1.5% Black, and 4.4% Other. The majority of all toxicities of all grades were higher in the Hawaii population as compared to the three national trials, except for neutropenia with ribociclib and diarrhea with palbociclib (Table). Conclusions: The Hawaii analysis that was primarily comprised of Asians and Pacific Islanders revealed an increased incidence of toxicities, despite starting at lower doses rates for all CDK 4/6 inhibitors. This data analysis begins to highlight the importance of representative populations in clinical trials for the most effective and safest care of diverse populations. [Table: see text]