bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effectiveness of palbociclib plus aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: A real-world study.
Authors: Yue Jian , Yuan Peng , Wang Xue , Ju Jie , Gao Song-lin , Yang Zixuan , Kang Yikun , Lei Zixuan , Shuai You , Wei Tong 
Published: June 2023

e13057 Background: In the real world, there are still a large number of HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy with fulvestrant monotherapy in China, especially patients with bone metastases only. It is due to lack of data comparing the effective between Palbociclib combined with AI and fulvestrant monotherapy as initial endocrine therapy. On the other hand, there are economic factors and access issues. According to the National Cancer Center's previous clinical experience, Palbociclib combined with AI is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. Therefore, we collected and summarized the previous clinical data in our center to compare the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/ HER2-advanced breast cancer patients receiving initial endocrine therapy in China. Methods: This is a retrospective real-world experience aimed at verifying the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/ HER2-advanced breast cancer patients receiving initial endocrine therapy in China. The primary aim was rwPFS; secondary aims were overall survival, and objective response rate. Patients received Palbociclib combined with AI or fulvsetrant monotherapy. Results: In total, 346 patients were enrolled, 193 to Palbociclib plus AI and 153 to fulvestrant monotherapy. Median age was 55 years (range 28-88); 191 had visceral involvement (116 in Palbociclib plus AI group and 75 in fulvestrant group). At a median follow up of 38 months (range 4-78). The median PFS was 20.0 months (95% CI 17.3–22.7) in the Palbociclib plus AI group and 12 months (95% CI 9.6–14.3) in the fulvestrant group (hazard ratio 0.593, 95% CI 0.470–0.749, p<0·0001). The 6-month progression-free rate was 83.9% in the Palbociclib plus AI group and 75.8% in fulvestrant group. The 6-month progression-free rate was 83.9% in the Palbociclib plus AI group and 75.8% in fulvestrant group. The 12-month progression-free rate was 65.8% in the Palbociclib plus AI group and 46.4% in fulvestrant monotherapy group. The over survival was not reached in the Palbociclib plus AI group and it was 65 months (95% CI 55.6–75.4) in the fulvestrant group. Grade 3-4 adverse events occurred in Palbociclib plus AI group. The most common grade 3 or 4 adverse events were neutropenia (47.7%) and leucopenia (27.5%) in the Palbociclib plus AI group. Conclusions: The efficacy of palbociclib plus AI is worthy of recognition and the toxicity was acceptable. Compared with fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy, Palbociclib plus AI might have a better survival. Clinical trial information: NCT05000736 .
Clinicopathological characteristics, evolution, treatment patterns and outcomes of hormone-receptor-positive/HER2-low-positive metastatic breast cancer: A retrospective analysis.
Authors: Wang Biyun , You Shuhui , Zhao Yannan 
Published: June 2023

e13058 Background: HER2-low positivity is more prevalent in breast cancers with positive hormone receptor (HR). Patients with HR-positive and low HER2 expression may have different prognosis and characteristics. Nevertheless, research focusing on HR-positive/HER2-low-positive breast cancer remains scarce. Methods: This study included 458 patients with HR-positive/HER2-negative metastatic breast cancer (HR+/HER2- MBC) who received first- or second-line endocrine therapy at the Fudan University Shanghai Cancer Center (FUSCC) between July 2010 and October 2022. Results: Clinicopathological characteristics, HER2 expression in primary and metastatic lesions, treatment patterns, and clinical outcomes of various therapies were compared between the HER2-low-positive and HER2-zero groups. 54.37% (249/458) of the HR+/HER2- MBC patients were HER2-low-positive. Comparable clinicopathological characteristics were observed in the HER2-low-positive and HER2-zero groups. PFS of first- and second-line endocrine treatment was comparable for HER2-low-positive and HER2-zero patients. When taking chemotherapy, the HER2-low-positive group had a shorter PFS than the HER2-zero group (median PFS: 8.64 vs. 9.03 months, p = 0.03). 41.79% (28/67) of HER2-zero primary tumors increased their HER2 score on biopsy, while 41.67% (35/84) of HER2-low-positive tumors became HER2-zero. Patients with an elevated HER2 IHC score from the primary tumor to the metastatic tumor had a longer PFS than those with constant HER2-low-positive status (median PFS: 11.99 months vs. 8.84 months, p = 0.02). Conclusions: HR-positive MBC patients with HER2-low and HER2-zero expression responded similarly to endocrine therapy. But HER2-low-positivity in HR-positive MBC may reduce chemotherapeutic effectiveness and HER2 heterogeneity should be taken into consideration.
The association between baseline patient characteristics and alpelisib-induced hyperglycaemia in patients with HR+, HER2-, PIK3CA-mutated metastatic breast cancer.
Authors: Godina Eva , Borstnar Simona 
Published: June 2023

e13059 Background: Alpelisib (A) is a PI3Kα-selective inhibitor and degrader which, in combination with fulvestrant, has been approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC). Hyperglycemia is the most commonly observed adverse event of A. A pooled analysis of X2101 AND SOLAR-1 trials showed the association between five baseline patient characteristics (age, fasting plasma glucose (FPG), glycated haemoglobin, body mass index (BMI) and blood monocyte count (BMC)) and the development of A-induced hyperglycaemia (HG). We examined the association between baseline factors and the A-induced HG grade (G) ≥2 in a real-world setting. Methods: We performed the retrospective observational study and included patients (pts) with HR+, HER2-, PIK3CA-mutated metastatic breast cancer who received A + fulvestrant between Oct 18, 2019, and Oct 13, 2022, at the Institute of Oncology Ljubljana. Electronic records were reviewed. Baseline age, FPG, glycated haemoglobin, BMI and BMC before the start of A therapy and glucose levels during treatment with A were collected. Random plasma glucose values (RPG) were used for HG grading according to CTCAE V. The chi-square test was used to determine the association between the baseline characteristics and A-induced HG G ≥2. Results: Thirty-one female pts were included in the analysis. The median follow-up was 21 months, and the median duration of A treatment was 5.4 months. The baseline pts characteristics were as follows: median age 58 years (range 33–80), median FPG 5.6 mmol/L (range 3.10–8.6), median BMI 21.7 kg/m² (range 18.7–30.4), and median BMC was 10.3% (range 5.3–16.6). Baseline glycated haemoglobin values were only known for 58.1% of patients, so we did not further analyse them. The highest HG grades during treatment with A were as follows: G0 in 14 pts (45.2%), G1 in 5 pts (16.1%), G2 in 6 pts (19.4%), G3 in 6 pts (19.4 %). The calculated cut-off values associated with A-induced HG ≥2 were: age above 65 years, FPG above 5.9 mmol/L and BMC more than 11.5. None of the BMI cut-off values was associated with HG G≥2. Association between the baseline age, FPG and BMC and A-induced HG G≥2. Conclusions: Age over 65 years, FPG more than 5.9 mmol/L and BMC more than 11.5% have a statistically significant higher probability for A-induced HG G≥2. Therefore, these patients need more frequent blood glucose measurements, lifestyle adjustments and early treatment with metformin and/or other oral glucose-lowering agents. [Table: see text]
Treatment patterns and clinical outcomes following endocrine resistance among with HER2-low metastatic breast cancer: Retrospective observational study.
Authors: Mehta Sandhya , Savill Kristin M. Zimmerman , Wang Peng , Pathak Prathamesh , Lam Clara , Kwong Jackie , Feinberg Bruce A. 
Published: June 2023

e13069 Background: Endocrine therapy (ET) ± CDK 4/6 inhibitors is a common initial treatment for HR+/HER2-low (IHC 1+ or IHC2+/ISH-) metastatic breast cancer (mBC). However, many patients eventually progress on ET-based regimen and receive subsequent chemotherapy (CT). This study aimed to describe treatment patterns and outcomes following endocrine resistance among HR+/HER2-low mBC patients in U.S community oncology practices. Methods: Participating oncologists from Cardinal Health’s Oncology Provider Extended Network (OPEN) provided data from the medical charts of adult patients with HR+/HER2-low mBC who received at least two lines (2L) of systemic therapy, with first line (1L) initiated between Feb 19, 2016, and Dec 31, 2018. Analysis was performed among patients who received a subsequent chemotherapy (CT) after progression on their last observed line of ET-based regimen. Patient characteristics and treatment history were summarized descriptively. Kaplan-Meier analyses of treatment outcomes, including physician-reported real-world progression free survival (rwPFS), time to treatment response (TTR) and time to treatment discontinuation (TTD) were performed. Results: 150 HR+/HER2-low mBC patients who received subsequent chemotherapy after ET resistance were included [mean age: 61±11 years, 57.3% were white and 32.7% were black]. The proportion of patients who stopped ET after 1L, 2L and ≥3L of ET were 23.3% (n=35), 70.7% (n=106) and 6.0% (n=9), respectively. The mean duration of ET-based regimens was 29.7 (SD: 13.12) months. Among patients who stopped ET after 1L (n=35), most patients received fulvestrant + palbociclib (48.6%) in 1L prior to switching to CT. Among those who stopped ET after 2 or more lines (n=115), most patients received letrozole + palbociclib (57.4%) in 1L and fulvestrant (46.1%) in 2L. The most common CT regimen utilized was capecitabine (47.0%) followed by paclitaxel (28.0%). The median rwPFS on CT was 8.12 months (95% CI 7.36-9.24), with slightly shorter median rwPFS among those who stopped ET after 1L (7.82 months, 95% CI 7.07-9.53) vs. 2L+ (8.19 months, 95% CI 6.97-9.99). The median TTD of CT was 7.82 months (95% CI 7.07-8.61) and TTR was 4.96 months (95% CI 4.24-5.72), with similar estimates observed between patients who stopped ET after 1L and 2L+. Conclusions: In this small sample of HR+/HER2-low mBC patients, most patients switched to CT after receiving two lines of ET based regimens. Following ET resistance, durability of response with subsequent CT was short and similar irrespective of number of prior lines of ET based regimens. This preliminary chart review study highlights the unmet need for a more effective therapeutic alternative to CT after ET for HR+/HER2-low mBC patients. Further research using larger sample and more robust clinical data is warranted to confirm the study findings.
A quality improvement initiative on the utility of the Oncotype DX breast cancer assay in a community hospital.
Authors: Iqbal Sabah , Desai Krishna , Baralo Bohdan , Jain Akhil , Pereira Kristal , Renzu Mahvish , Mehta Vidhi , Singh Vartika , Ramesh Nithya , Deshpande Sohiel , Edlukudige Keshava Vinay , Thirumaran Rajesh 
Published: June 2023

e13072 Background: Since the advent of Oncotype DX (ODX) breast recurrence score (RS) assay, the use of adjuvant chemotherapy (CT) in the treatment of breast cancer has significantly reduced. This test not only estimates the benefit of CT, but also determines the risk of distant recurrence in patients with early-stage breast cancer with hormone-receptor (ER/PR) positive, human epidermal growth factor receptor (HER) 2-negative, and axillary lymph node negative or positive (1-3 positive nodes) disease. All patients are categorized based on their scores ranging from 0-100 as follows: low (RS≤10), intermediate (RS11-25) and high risk (RS≥26). Further studies proved that adjuvant CT is beneficial in pre-menopausal women with RS 0-25, however offered no benefit to post-menopausal women in the same category. The aim of our study was to assess the implementation of these guidelines in a community hospital in an underserved area. Methods: At Mercy Catholic Medical Center, we performed a retrospective analysis on 303 female patients with newly diagnosed breast cancer, identified between January 2017 – October 2022. We included patients with ER/PR+, HER2-, lymph node negative or positive, who had undergone surgery and were to receive endocrine therapy with or without adjuvant CT. Patients who were lost to follow-up or did not undergo the genetic testing were excluded from the study. We then analyzed the treatment strategies based on RS categories. All patients who did not receive CT was either because it was not indicated (old age, post-menopausal) or patients refused. Results: 81 patients underwent ODX testing among whom, 60.5%, 35.8%, and 3.7% patients were Black, White and Hispanic/Asian, respectively. 1.2%, 9.8%, 18.51%, 34.56%, 35.08% were aged ≤40, 41-50, 51-60, 61-70 and ≥71 years, respectively. Based on the RS, we identified 29.62% in low risk, 56.79% in intermediate risk, and 13.5% in high-risk categories. 100% patients in the high-risk category were prescribed CT and only 7.4% patients with RS 0-25 received CT. 12 patients were found to be lymph node positive, among whom, 3 had RS≥26 and 2 were pre-menopausal, all of whom were prescribed CT. Out of these, 7 were post-menopausal with RS 0-25 and only 1 received CT. Conclusions: Our hospital data suggests that implementation of ODX and adherence to its guidelines has significantly helped avoid CT and its related side effects in the low and intermediate risk categories. Implementation of this cost-effective test has consistently increased in the last two decades and is now an imperative tool in clinical decision-making specially in community hospitals serving underprivileged populations. [Table: see text]
Is HER2 expression related to CDKi efficacy in HER2-negative luminal metastatic breast cancer?
Authors: Garcés María Yeray Rodríguez , Fernández Madrigal Laura , Morales Pancorbo David , Bayo Juan L. 
Published: June 2023

e13073 Background: Cyclin kinase inhibitors (CDKi) are the standard of care in the first line of luminal (Lum) metastatic breast cancer (MBC). HER2 overexpression is a classic risk factor in BC, however, the use of targeted therapy has changed the prognosis of this disease, even with anti-HER2 efficacy data in cases of low HER2 expression. We wonder if the level of HER2 expression can be a predictor of efficacy in treatment with CDKi. Methods: Descriptive, observational, retrospective and analytical study of patients with MBC treated with CDKi, in the period 2018-2022. Descriptive and analytical statistical analysis (IBM SPSS Statistics 22) using logistic regression and Kaplan-Meier with long-rank test to analyze the relationship between CKi efficacy and HER2 expression (negative = 0+; HER2 low = 1+ and 2 + with SISH negative). Results: We analyzed 152 patients (p) with Lum MBC under treatment with CDKi (median 58 years), in first and successive lines. HER2 expression: 31% 46p (0+), 54% 81p (1+) and 14% 21p (2+ and SISH negative). 41% were treated with palbociclib, 34% with ribociclib, and 26% with abemaciclib. Radiological response (RR) to CDKi was achieved by 34.1% (CRR 2.4%, PRR 31.7), and the rest stable disease (SD) or progressive disease (PD): SD 42% and PD 22%. In the overall OR, there was no evidence of a risk association between the response to CDKi and the level of HER2 expression. We obtained similar results in the analysis stratified by type of CDKi. In the multivariate study, for the variables CDKi type and HER2 expression, the logistic regression model was not statistically significant either. Regarding the Kaplan-Meier analysis, we compared the median PFS and OS using the Long-rank test, based on the expression of HER2. In the complete series we did not find statistically significant differences between the curves. In the palbociclib subgroup the curves split in favor of HER2 0+ vs. HER2 low: 44 months 95%CI (7.6-80) vs 16 months 95%CI (7.9-24); p = 0.01. Regarding OS, we found no significant differences. With ribociclib, the curves separate in favor of HER2 low versus HER2 0+: 33 months 95%CI (7.2-18) vs. 13 months 95%CI (23-42); p = 0.03. In OS we did not find significant differences either. In the subgroup with abemaciclib, we observed a trend towards greater survival in HER2 0+ patients, but with no significant difference between the PFS or OS curves. Conclusions: Based on our study, the expression of HER2 could be considered a predictor of efficacy depending on the CDKi used. We assume greater survival with palbociclib in HER2 negative patients (0+) and with ribociclib in HER2 low patients. We consider it essential to develop studies with a larger sample size and clinical trials that allow us to demonstrate the hypothesis of our work with scientific evidence.
Inhibition of FASN as a potential treatment of advanced endocrine therapy-resistant breast cancer.
Authors: Gunuganti Avani , Balinda Henriette , Brenner Andrew J. 
Published: June 2023

e13077 Background: The past decade has seen significant advancement in increasing survival estrogen receptor alpha (ERα) positive breast cancer. The use of selective estrogen receptor down-regulators and modulators (SERMs) and cyclin-dependent kinase inhibitors aided to extend overall survival of breast cancer patients. However, resistance to endocrine therapy is a common occurrence and patients will eventually succumb to their disease. Fatty acid synthase (FASN), a key enzyme in lipid biosynthesis, is overexpressed in more aggressive and therapy-resistant tumors, including breast cancers. FASN inhibitor, TVB-2640, has been evaluated in multiple tumor cell lines and in a phase 1 clinical study, and showed partial responses in 5 patients and multiple patients with prolonged stable disease (≥16 weeks). Methods: We generated therapy-resistant cells by long term exposure to tamoxifen (MCF7/TamR cells), and fulvestrant (MCF7/FR cells). Palbociclib-resistant (MCF7/RB1Crispr and ZR75/RB1Crispr) cells were generated through CRISPR/Cas9 knockout of the retinoblastoma (RB) gene. We assessed the impact of TVB-3166 inhibitor in these cells on proliferation, viability, cell cycle, apoptosis, ERα expression in patient derived explants, and tumor growth in xenografts. RNA sequencing of tamoxifen- and fulvestrant-resistant cells was performed to investigate gene expression. Subcellular localization of ERα was assessed using subcellular fractionations. Palmitoylation and ubiquitination of ERα were assessed by immunoprecipitation. ERα and p-eIF2α protein levels were analyzed by western blot after treatment with TVB with or without the addition of palmitate or BAPTA. Results: TVB treatment leads to a marked inhibition of proliferation in tamoxifen-, fulvestrant- and palbociclib-resistant cells compared to the parental cells. RNA sequencing of explants of patients with ERα positive disease showed down regulation of ESR1 related genes and genes involved in invasiveness. RNA sequencing of fulvestrant-resistant cells showed that treatment with TVB results in down regulation of EMT and E2F target genes, cholesterol homeostasis genes and mTORC1 signaling. Additionally, TVB significantly inhibited tumor growth in mice and decreased proliferation of primary tumor explants compared to untreated controls. FASN inhibition significantly reduced ERα levels most prominently in endocrine resistant cells and altered its subcellular localization. Furthermore, we showed that the reduction of ERα expression upon TVB treatment is mediated through the induction of endoplasmic reticulum stress. Conclusions: Our preclinical data provide evidence that FASN inhibition presents a promising therapeutic strategy for treatment of endocrine-resistant breast cancer. Further clinical development of FASN inhibitors for endocrine resistant breast cancer should be considered.
Clinical characteristics and outcome of PIK3CA mutated hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-), advanced breast cancer (BC) treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i): Real world data.
Authors: Dedic Plavetic Natalija , Čular Katarina , Križić Marija , Popovic Marina , Plestina Stjepko , Silovski Tajana 
Published: June 2023

e13078 Background: BC is the most common malignant disease and leading cancer-related cause of death in women. Despite significant achievements in the treatment, advanced BC (aBC) is still an incurable disease. HR+/HER2- subtype accounts for 70% of all BC. One of the most common mutations in BC is the PIK3CA gene mutation which can induce endocrine and chemo- resistance. In early BC, patients (pts) with PIK3CA mutations mostly have better, but in aBC worse prognosis. Standard first-line treatment for HR+/HER2- aBC is a combination of CDK4/6i and endocrine therapy. PIK3CA status is most often assessed in this group of pts and combination of alpelisib - PIK3CA inhibitor and fulvestrant is second-line treatment option in PIK3CA mutated pts. Methods: Medical records of HR+/HER2- aBC pts who started CDK4/6i therapy between 01.08.2018. and 01.10.2020. were analyzed with prior University Hospital Center Zagreb Ethics Committee approval. Demographics, tumor characteristics, clinical presentation and therapy information were collected. Molecular analysis of PIK3CA mutations was performed on tumor tissue samples. Time to treatment failure (TTF) was analyzed using the Kaplan-Meier method and the data cut-off was 31.12.2022. Results: Of the 103 pts with determined PIK3CA status, 45 (43.7%) had a detectable mutation. Median follow-up was 35 months. CDK4/6i were first line therapy in 31 (68.9%) pts with and 29 (50%) pts without PIK3CA mutation. Endocrine resistance, de novo metastatic disease and bone marrow infiltration were more common in PIK3CA mutated subgroup. The incidence of visceral metastases was similar in both groups, whereas liver metastases were more common in the unmutated group. Disease progression was observed in 69 (67%) pts, 28 (40.6%) of whom were PIK3CA mutated. Median TTF in mutated subgroup was 24 months (95% CI 21-33) and 25 months in unmutated subgroup (95% CI 19-36). During the follow-up period, 35 (34%) pts died, 14 (40%) of whom were PIK3CA mutated. Odds ratios in pts with a PIK3CA mutation. Conclusions: There was no relevant difference in TTF between two groups. However, PIK3CA mutated subgroup had more aggressive clinical features - more often presented with bone marrow infiltration and de novo aBC, statistically relevant OR 5.158 and 2.323 respectively, which is related to lower quality of life and highlights the importance of treatment improvement for this subgroup of pts. [Table: see text]