bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIK3CA testing and treatment patterns among patients with metastatic breast cancer in US community clinical practice.
Authors: Kim Eunice , Dhillon Preet Kaur , Lambert Peter , Cheng Anna , Basho Reva K. 
Published: June 2024

e13059 Background: PIK3CA mutations are present in ~35-40% of HR+/HER2- breast cancer patients. Targeted treatments are approved and in development for patients with advanced disease, and clinical guidelines recommend biomarker testing. This retrospective cohort study characterized PIK3CA mutation testing and treatment patterns among HR+/HER2- metastatic breast cancer (mBC) patients in United States (US) community clinical practices. Methods: We used the nationwide Flatiron Health electronic health record-derived de-identified database to select patients diagnosed with HR+/HER2- mBC from January 2011 to May 2023. We described baseline characteristics of patients tested and not tested for PIK3CA mutation. We captured rates of PIK3CA mutation testing (anytime and ≤1 year) prior to starting first-line (1L), second-line (2L), and third-line (3L) treatment; test and sample types; secular trends over time; and test turnaround time (TAT). Treatment patterns for patients with a PIK3CA-mutated tumor were also described from 2019 onwards. Results: Among 14,246 HR+/HER2- mBC patients treated at community sites, 4,537 had a PIK3CA mutation test result during the study period. 25% of patients had more than one PIK3CA mutation test. Test rates increased from 2011 to 2023 for all patients starting 1L, 2L, or 3L during the study period (Table). In 2023, the percentage of patients tested anytime prior to 1L, 2L, and 3L start dates were 11% (37 of 324 patients), 52% (140 of 271 patients), and 65% (133 of 204 patients), respectively. Among tested patients, those who were tested between 1L and 2L increased from 32% in 2018 to 45% in 2023. Median time from mBC diagnosis date to first test was variable across years: 8, 10, and 3 months in 2018, 2020, and 2022, respectively. During the study period, most PIK3CA mutation tests were next-generation sequencing (NGS) (88%) and used tumor tissue (72%). Median TAT decreased from 12 days in 2018 to 7 days in 2023. Among patients with a PIK3CA-mutated tumor in 2019 and onwards who received treatment, 36% of patients received alpelisib-containing regimens. Conclusions: PIK3CA mutation testing in HR+/HER2- mBC patients has increased over time in community clinical practice, and timing has shifted to earlier lines of therapy among tested patients. However, overall testing and subsequent treatment with pathway-directed therapy are still low despite clinical guidelines, which may reflect potential gaps in access to PIK3CA mutation testing and the continued unmet need regarding available targeted agents within the current treatment landscape. [Table: see text]
Use of Oncotype vs. Breast Cancer Index (BCI) for extended endocrine therapy decisions: A single center analysis in stage IA hormone receptor positive breast cancer.
Authors: Kovalenko Iuliia , Seltun Faith , He Alice , Garg Chandi , Azhar Maha , Proskuriakova Ekaterina , Wert Yijin , Lu Kit Yu 
Published: June 2024

e13083 Background: Extended Endocrine Therapy (EET) for hormone receptor positive HER-2 negative early-stage breast cancer reduces late recurrence risks but raises concerns about toxicity. Biomarker tests like the Breast Cancer Index (BCI) are vital for identifying patients who could benefit from continued ET, reassuring others against unnecessary extension. This study evaluates prognostic implications for both Oncotype Dx (Recurrence score, RS) and BCI amidst concerns about added testing costs in patients with early stage, estrogen receptor (ER) positive breast cancer. Methods: This is a single institution retrospective review of Stage IA ER positive HER-2 negative breast cancer patients who underwent both Oncotype Dx and BCI testing from January 2021 to December 2023. Pearson's correlation coefficient (r) was used to assess the linear relationship between the assays (p<0.05 for significance), analysis was performed with SAS software, version 9.4. Results: Fifty-eight patients with Stage IA ER positive HER-2 negative breast cancer who had both Oncotype and BCI results were identified (100% female; mean age 72.2 years [54-87]). After a median followed up of 72 months (63-75), no systemic or locoregional recurrences were reported. A low positive correlation between Oncotype and BCI was observed across the entire cohort (r=0.4058; p=0.0016). However, subgroup analysis showed no significant correlations: Oncotype <11 (n=17; r=0.2415; p=0.3504), Oncotype ≤18 (n=43; r=0.0914; p=0.5600), Oncotype <26 (n=51; r=0.2530; p=0.0733); Oncotype ≥26 (n=7; r=-0.5634; p=0.1878). Correlation was also not found in patients with Grade 1 tumor (n=16; r=0.3138; p=0.2365). Thirty-nine patients (67.24%) had their treatment recommendation changed based on BCI results. Side effects from ET affected 15 patients (25.86%) and included arthralgias (60%, n=9), hot flashes (26.67%, n=4), depression (13.33%, n=2), insomnia (6.67%, n=1), and others (53.3%, n=8). Twenty-two patients (37.93%) developed new osteopenia, and 6 (10.34%) new osteoporosis while on EET. Eight patients (13.79%) had ET interruption during their treatment course. Conclusions: Despite inclination towards cost-saving measures, Oncotype DX may be more useful to give prognosis in the early adjuvant period whereas BCI is more useful to evaluate late recurrence risk. Low or high Oncotype scores and tumor grade may not align with BCI findings. Considering the importance of managing toxicity against the risk of late recurrence, incorporating BCI testing can enhance EET recommendations, even for Stage I, node-negative, ER positive patients.
A phase II trial combining SHR-1316, bevacizumab, and cisplatin/carboplatin in patients with TNBC with active brain metastases.
Authors: Li Ting , Zhao Mingchuan , Cao Jun , Wang Jianfei , Tao Zhonghua , Wang Biyun , Hu Xichun , Zhang Jian 
Published: June 2024

e13133 Background: Triple-negative breast cancer (TNBC) has a high risk of brain metastases (BM), leading to poor survival. Treatment options for BMs are limited, and the combination of chemotherapy and immune checkpoint inhibitor is the standard-of-care for PD-L1 positive metastatic TNBC. Platinum-based systematic therapy is the mainstay of TNBC treatment and the addition of bevacizumab has shown improvement in the progression-free survival (PFS) of patients with BM. Therefore, this study aims to investigate the efficacy and safety of SHR-1316 (anti-PD-L1) in combination with bevacizumab and cisplatin/carboplatin in TNBC patients with BMs. Methods: In this single-center phase II trial, TNBC patients with active BM received SHR-1316, bevacizumab, and cisplatin/carboplatin. Prior treatment with bevacizumab or anti-PD-1/PD-L1 were not allowed. Prior platinum was allowed only in cases of previous platinum-sensitive response. The primary endpoint was objective response rate (ORR) of central nervous system (CNS), as assessed according to the response assessment in neuro-oncology brain metastases. The secondary endpoint included clinical benefit rate (CBR) of CNS, PFS, overall survival (OS), first progression site and safety. Results: As of January 12th, 2024, a total of 23 female patients with ECOG PS≥1(100%) were enrolled. The median number of previous lines of therapy for metastatic disease was 1 (0-3). All patients had active BM, of which 87% (20/23) were BM treatment-naïve and 13% (3/23) had BM progression after previous local therapy, 26.1% (6/23) had received a prior platinum agent. Of the 23 evaluable patients, the confirmed CNS ORR was 65.2% (95%CI: 42.7%-83.6%), with 3 complete response (CR), 12 partial response (PR), 7 stable disease (SD), and 1 progressive disease (PD). The median CNS-PFS was 11.2 months (95%CI, 5.8 to not reached), median PFS was 7.6 months (95%CI, 5.7-11.9), and median OS was 13.2 months (95%CI, 9.5 to not reached). Treatment-related adverse events (TRAEs) were reported in all 23 patients, and the most common TRAEs were neutrophil count decreased (69.6%, 16/23), anemia (65.2%, 15/23), asthenia (60.9%, 14/23), Hypomagnesaemia (56.5%, 13/23), leukopenia (52.2%, 12/23) and electrocardiogram T wave abnormal (52.2%, 12/23). The incidence of grade ≥3 TRAEs was 43.5% (10/23), including neutropenia (13%, 3/23), platelet count decreased (8.7%, 2/23), and hypertension (8.7%, 2/23). Only one patient had a grade 4 TRAE (lymphocytopenia), and SHR-1316 related serious adverse event (facial nerve disorder) occurred in only one patient. No grade 5 AEs were noted. Conclusions: SHR-1316 plus bevacizumab and cisplatin/carboplatin achieves a significant improvement in CNS ORR and brings PFS and OS benefits in TNBC patients with active BMs. As an effective and safe treatment, this triple-combination warrants further investigation. Clinical trial information: NCT04303988 .
Prevalence of “HER2 ultra-low” among patients with advanced breast cancer with historical IHC0 status.
Authors: Mehta Sandhya , Iyengar Anushree , Barman Hannah , Rangarajan Nivedita , Woo Michele Sue-Ann , Sredni Simone T. , Di Donato Rosemarie , Simsek Safak , Downs Erinn P. , Nassar Aziza , Wilson Darren M. , Krieser Katherine , Patzke Elise Bieri , Kyek Natalie , Hipp Jason , Wagner Tyler 
Published: June 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 >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 >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]
Mutations and mortality in very young patients with breast cancer.
Authors: Saxena Raina , Chung Victoria , Peeples James , Yang Yanming , Song William , Olet Susan , Sheen Melanie Anne 
Published: June 2024

e13157 Background: Breast cancer diagnoses in young women have increased over the last 10 years. Despite decreasing mortality rates for breast cancer, disparities continue to exist for specific populations including Black women and premenopausal women. Recent studies observe a 41% increased death rate in Black women compared to White women, and a two-fold increased mortality in women younger than 50 years. Many biological and societal factors can affect breast cancer mortality. We sought to evaluate the relationship between germline mutations (GM), breast cancer subtype, and mortality based on race in a unique, young breast cancer patient population. Methods: We assembled a 10-year retrospective chart review (2012 to 2022) of 773 women diagnosed with breast cancer under the age of 40 in a regional health network. Data was collected from electronic medical records. Associations were assessed using the chi-square test using SAS version 9.4. Results: Out of the 773 patient information collected, 60% of patients were White, 36% Black, and 3% Other. A total of 675 patients had genetic results and 124 patients with documented GM. Of patients with GM, 48 were Black and 74 were White. 13 patients with germline mutations had documented deaths. There was no statistical link between germline mutations and mortality. Of the 13 patients, 4 (30%) were Black and 9 (70%) were White. There was no statistical difference amongst area deprivation index (ADI) quintiles for mortality in patients with GM. Of the 675 patients with genetics data, 72 patients without GM died which includes 31 Black patients, 38 White patients, 3 Other. Based on our data, there is a higher prevalence of germline mutations (60%) in White patients over Black patients and a descriptive predominance of mortality despite absence of statistical significance. More patients who resided in areas of higher ADI (2-4) with GM died than in areas of lower ADI. Conclusions: Our data demonstrates a descriptive prevalence in mortality among young White patients compared to young Black patients. Across the USA, the Black population is 13% and in Louisiana, that population is 33%. Given that our cohort population was 36% Black, it is noteworthy that we were unable to demonstrate a statistical mortality predominance among these young patients. [Table: see text]
A phase Ia/b trial of ARX788 combined with toripalimab for HER2-low advanced breast cancer (ABC) and other HER2-expressing solid tumors.
Authors: Shao Xiying , Kuang Ming , Chen Zhanhong , Zheng Yabing , Li Guangliang , Shen Xia-Bo , Huang Ping , Cao Wenming , Xu Lixia , Wang Xiaojia 
Published: June 2024

e13159 Background: ARX788 has been proved with superior PFS compared with a combination of capecitabine and lapatinib in the randomized phase Ⅱ/Ⅲ study for HER2-positive ABC (Ambrx, 2023). Here we report the preliminary safety and efficacy of ARX788 plus toripalimab in HER2-low ABC and other HER2-expressing solid tumors. Methods: This was a phase Ⅰ study conducted in China. Eligible patients were HER2-low (IHC2+ and FISH- or IHC1+) ABC or HER2-expressing (IHC 2+ or 3+) solid tumors. Dose exploration with ARX788 is 1.3, 1.5mg/kg, IV, Q3W plus toripalimab 240mg, IV, Q3W. Primary endpoint was safety and RP2D of Ⅰa and efficacy of Ⅰb. Results: Totally, 12 patients were enrolled in phase Ⅰa, 10 patients were diagnosed with ABC, 1 was diagnosed with BTC and 1 was CRC. 6 patients each were treated with 1.3 and 1.5mg/kg. No DLTs were observed. 12 patients (100%) experienced ≥1 ADRs. The most common (≥20%) ADRs were AST increased (75%), platelet count decreased (75%), alopecia (41.67%), white blood cell count decreased (25%), ALT increased (25%), dry eye (25%), interstitial lung disease (25%) and neutrophil count decreased (25%). 1.5mg/kg dose level showed a slightly higher incidence in hematologic toxicities, interstitial lung disease and alopecia. Grade 3 ADRs occurred in 8 patients (66.67%) with equal incidence of the 2 dose levels, those were ocular events (41.7%, 2 of each level), interstitial lung disease (8.3%, 1 of 1.5mg/kg), platelet count decreased (8.3%, 1 of 1.5mg/kg), jaundice (8.3%, 1 of 1.3mg/kg) and immune-mediated myocarditis (8.3%, 1 of 1.3mg/kg). No grade 4 or 5 ADRs occurred. All ADRs were manageable and have recovered. ORR was 41.7% in 12 patients, with 33.3% and 50% in 1.3 and 1.5mg/kg dose level. In 10 patients with ABC, ORR was 50%, with 40% and 60% in each level. DCR was 83.33% and 100%, respectively. Thus, 1.5mg/kg was determined as RP2D and phase Ⅰb is ongoing with HER2-low ABC patients. Conclusions: ARX788 with 1.5mg/kg combined with toripalimab was shown acceptable safety profile with promising efficacy, no significant increase in adverse reactions or serious unexpected immune-related adverse reactions compared with ARX788 monotherapy, which supports further evaluation for HER2-low ABC in a larger sample in Ⅰb trial. Clinical trial information: CTR20222247.
Frequency of HER2-Low in breast cancer biopsies in Chile.
Authors: Vidal Martín , Rivera Alvaro , Schuler Constanza , Garnham Nicolas , Alcalde Elisa , Ahumada Pablo Pinto , Renner Alex 
Published: June 2024

e13163 Background: In breast cancer (BC), human epidermal growth factor receptor 2 (HER2) is a prognostic and predictive biomarker. Traditionally, the use of HER2-targeted therapies is reserved for BC that overexpress HER2, defined as immunohistochemical (IHC) expression of 3+ or 2+ with amplification of the gene encoding HER2, detected by in situ hybridization (ISH). Recently, the term HER2-Low, defined as the IHC expression of 1+ or 2+ with negative ISH, has gained relevance as a new predictive biomarker for the use of trastuzumab-deruxtecan. The frequency of HER2-Low BC in the Chilean population is unknown. The objective of this study is to show the frequency of HER2-Low BC in a Chilean center. Methods: Descriptive cross-sectional analysis of clinical records and biopsies of localized or metastatic invasive breast carcinoma performed at Clínica Santa María between January 2020 and December 2023. The IHC expression of the estrogen receptor (ER), progesterone receptor (PR), Ki-67, HER2, histological grade (G) and HER2 in situ hybridization (ISH) when appropriate. The frequency and characteristics of HER2-Low cases are described and compared with the surrogate clinicopathological subtypes luminal A, luminal B (HER2-Positive and Negative), HER2-Positive and Triple Negative (TN), according to the St Gallen Consensus Conference 2013. Results: Between January 2020 and December 2023, a total of 339 biopsies with invasive BC were identified, from which 104 (36.0%) met the definition of HER2-Low. The frequency of luminal B and luminal A that met the definition of HER2-Low was 54 (51.9%) and 40 (38.5%), respectively. Of the 253 biopsies classified as luminal, 94 (37.2%) met the definition of HER2-Low, while of the 36 biopsies classified as TN, 10 (27.8%) did. Luminal B HER2-Negative and TN surrogate subtypes that met the definition of HER2-Low had a higher frequency of G3 than their non-HER2-Low counterpart. Conclusions: In the population analyzed, a considerable percentage of cases meet the definition of HER2-Low. This has relevant therapeutic implications. Distribution of biopsies that meet HER2-Low criteria according to surrogate clinicopathological subtype of breast cancer. [Table: see text]
The role of epithelial-mesenchymal transition markers in invasive breast cancer among patients of Arab descent.
Authors: Salleh Mais , Alkaram Waed , Zaiem Fadi , Kheil Mira , Jain Deepti , Wahidi Marya , Boerner Julie , Jang Hyejeong , Kim Seongho , Morris Robert , Bandyopadhyay Sudeshna , Ali-Fehmi Rouba 
Published: June 2024

e13166 Background: Epithelial-mesenchymal transition (EMT) is the process wherein polarized and cohesive epithelial cells lose their epithelial characteristics and acquire a mesenchymal phenotype and proceed to the invasive form of the tumor. Numerous regulators play a role in the complex signaling pathways that mediate the EMT process. This study aims to investigate the immunohistochemical (IHC) expression of several EMT-related markers and their implications on the diagnosis and prognosis of breast cancer in a cohort of Arab descent women. Methods: Patients of Arab descent treated surgically for invasive and in-situ breast cancer between 2017-2020 were included in the study. Expressions of Ki-67, Transforming growth factor- β (TGF-β), NF-kappaB (NF-kB), Snail, Vimentin, E-cadherin (E-Cad), and B-catenin (B-Cat) were evaluated by IHC in tissue microarray slides, as per guidelines in the literature. We examined the association between the tumor markers and other clinicopathological variables and prognosis. Fisher's exact tests were utilized to compare categorical variables between groups. Results: One hundred eleven patients were included, 65.8% had invasive ductal carcinoma (IDC); 19.8% had invasive lobular carcinoma (ILC); 13.5% had both ductal and lobular features, and 0.9% had ductal carcinoma in situ. 91 (54.1%) were grade 2 and 303 (41.4%) were grade 3 tumors. Most tumors were ER positive (81.8%), PR positive (75.7%), and HER-2 negative (77.5%). The median age at diagnosis was 52 years. High TGF- β expression was associated with higher frequency of grade 3 tumors (p=0.036), AJCC stage III (p=0.042), and larger tumor size (p=0.036) compared to those with low TGF-B expression. Patients with positive B-Cat expression had a higher risk of death compared to those with negative B-Cat expression (HR, 3.90; 95% CI, 1.19 to 15.93; p=0.024). IDC had a statistically significant increased expression of TGF-B (69.9% vs.45.5%, p=0.045), E-Cad (76.7% vs. 13.6%, p<0.001), and B-Cat (P 39.7% vs. 0%, p<0.001) when compared to ILC. The overall survival at 1 and 5 years were 96.3% (95% CI, 92.7-99.9) and 81.7% (95% CI, 73.8-90.3), respectively. Conclusions: Tumors with high expression for TGF- β and B-Cat exhibit more aggressive clinical behavior, suggesting the potential prognostic and therapeutic value of these markers. Due to the limited research focused on Arab descent women, findings from this study may provide the foundation for more extensive molecular and clinical studies to assess the validity and clinical utility of these biomarkers in breast cancer patients from diverse ethnic backgrounds.