bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost consequence model of the MammaPrint (70-gene signature) and 21-gene signature in patients with primary HR+HER2-, N1 early-stage breast cancer in Germany.
Authors: Lux Michael Patrick , Sandor Mariana Felicia , Hofman Viktoria , Fischer Lotta Ada , Kuemmel Sherko , Pronin Darina , Klinkhamer Jelle , Mueller-Huesmann Harald 
Published: May 2024

534 Background: The MammaPrint 70-gene and Oncotype DX 21-gene signatures serve to stratify breast cancer tumors, distinguishing between those with low or high risk of distant metastasis. Patients with a low genomic risk tumor have the option to avoid overtreatment by omitting chemotherapy and minimize associated toxicities. This analysis evaluates the economic impact of implementing MammaPrint, Oncotype DX (ODx), or no gene signature testing for patients with HR+ HER2- early breast cancer with 1 to 3 positive lymph nodes (N1) in Germany. Methods: We constructed a cost-consequence model to assess the budget implications of MammaPrint, ODx, and not employing a gene signature, considering both the healthcare payers and societal perspective. The model focuses on patients with HR+/HER2-/N1 breast tumors who, in the absence of a gene expression analysis, would receive chemotherapy in 63% of cases according to the data of the certified breast cancers in Germany. Input data were sourced from MINDACT, RxPONDER, literature, the EBM, the DRG system. The healthcare payer perspective covers testing, direct/indirect costs of chemotherapy, and disease recurrence costs. The societal perspective adds transport costs and productivity losses to these. Results: A projected 9,207 HR+/HER2-/N1 breast cancer patients were candidates for genomic testing. In MINDACT, patients were classified as MammaPrint Low Risk in 73% of cases, and in RxPONDER 83% of patients were categorized as ODx Low Risk (RS 0-25). The model demonstrated per patient savings from a healthcare payer perspective of €3.766 for MammaPrint and €900 for ODx compared to not using any gene signature for N1 breast cancer patients in Germany. Importantly, the savings are even more substantial from a societal perspective, reaching €11.815 for MammaPrint and €11.243 for ODx. When limiting the population to women >50 years, similar results were observed with per patient savings from a payer perspective of €3.766 and €1.549, and from a societal perspective of €9.826 and €9.349, for MammaPrint and ODx, respectively. Conclusions: These data demonstrate that personalized treatment planning with genomic testing for breast cancer with HR+/HER2-/LN1 breast cancer, leads to a reduction in chemotherapy use and associated costs in Germany. Although MammaPrint designates a smaller proportion of genomically high risk patients compared to ODx, MammaPrint Low Risk patients without chemotherapy demonstrate higher survival outcomes. Consequently, any increased chemotherapy costs are offset by lower testing and distant recurrence expenses, making MammaPrint a cost-conscious option.
Impact of CYP2D6 polymorphisms on adverse events in patients with breast cancer treated with tamoxifen: Insights from an early dose escalation trial in CYP2D6 poor metabolizers.
Authors: Blancas Isabel , Martínez-De Dueñas Eduardo , Rodríguez-Serrano Fernando 
Published: May 2024

547 Background: Tamoxifen is widely used in treating hormone receptor-positive breast cancer. It is primarily metabolized by the CYP2D6 enzyme to yield active metabolites. However, CYP2D6 polymorphisms have been associated with a differential response to tamoxifen. In a clinical trial involving an early dose escalation of tamoxifen in poor metabolizers, we found endoxifen concentration levels similar to those of patients with extensive phenotype, and no long-term survival differences among CYP2D6 phenotypes. However, the impact of that dose escalation on side effect incidence was not addressed. Methods: In this study, we analyzed the incidence of specific side effects - osteoarticular pain, hot flashes, asthenia, and uterine alterations - in 86 breast cancer patients, differentiated by their CYP2D6 phenotype estimated according to the Clinical Pharmacogenetics Implementation Consortium. In poor metabolizers, the tamoxifen standard dose of 20 mg/day was escalated to 40 mg/day and 60 mg/day for 4 months each, and then treated with 20 mg/day until completing the treatment. Kaplan-Meier analysis and Cox proportional hazards regression model were employed to assess the relationship between the CYP2D6 phenotype and the incidence of these side effects. Results: The median follow-up time was 139.5 months. The analyses revealed that only uterine changes showed significant differences between CYP2D6 phenotypes, with a lower incidence in extensive metabolizers (P-value < 0.001 in Kaplan-Meier; HR in Cox of 0.195, 95% CI 0.073 - 0.521, P = 0.001). This finding persisted after adjustment for the covariates tumor grade, size, nodal status, chemotherapy, and radiotherapy in multivariate Cox regression (HR 0.098, 95% CI 0.020 - 0.466, P = 0.004). Selection of a subgroup through Propensity Score Matching (21 vs 21) corroborated these results. The spectrum of uterine changes and pathologies included endometrial hyperplasia, polyps, adenocarcinoma, myometrial or endometrial thickening, and the presence of multiple myomas. Conclusions: Our study indicates that an early increase in tamoxifen dose in poor metabolizer patients according to CYP2D6 polymorphisms may significantly affect the incidence of uterine changes, but not the incidence of osteoarticular pain, hot flashes, or asthenia. Clinical trial information: 2007-002942-40/ES .
Patient-reported outcomes in N1 breast cancer: A phase III trial comparing whole-breast to whole-breast plus regional irradiation after taxane-based chemotherapy (KROG 1701).
Authors: Kim Nalee , Park Won , Kim Haeyoung , Cho Won Kyung , Park Yeon Hee , Ahn Sung Ja , Jung Jinhong , Jo In Young , Lee Kyu Chan , Kim Tae Hyun , Kim Tae Gyu , Shin Kyung Hwan , Kim Jin Hee , Lee Jong Hoon , Lee Hyung-Sik , Park Hae Jin , Lee Ju Hye , Koh Minji , Kim Yong Bae , Lee Ik Jae ,   Korean Radiation Oncology Group 17-01 Study Committee
Published: May 2024

577 Background: Recent randomized trials have highlighted the benefits of regional node irradiation (RNI) in high-risk node-positive or pN1 breast cancer, yet its impact in the context of modern taxane-based adjuvant chemotherapy remains unclear. In this multi-center phase III trial, we study to prove the hypothesis that there is no difference in terms of disease-free survival between standard whole-breast irradiation (WBI) with RNI and WBI alone in pN1 breast cancer patients receiving taxane-based adjuvant chemotherapy. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are now reported. Methods: The KROG 17-01 trial (NCT03269981), a prospective, multicenter, non-inferiority study, randomized patients with pN1 breast cancer after breast-conserving surgery and adjuvant taxane-containing chemotherapy to WBI or WBI+RNI. Both conventional and hypofractionated radiotherapy (RT) were allowed. PROs were assessed using the EORTC QLQ-C30 and QLQ-BR23 modules. All data were collected at baseline, during RT, and at follow-up intervals of 3-6 months, 1, 2, 3, 4, and 5 years post-treatment. Linear mixed models were used to compare PROs between treatment arms. Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI). Overall, PRO domains improved over time (p<0.001). During RT, the WBI+RNI group experienced more fatigue, nausea, and vomiting (p<0.05), and reported lower global health (p=0.090) and physical functioning (p=0.049) with borderline significance compared to the WBI group. At 3-6 months post-RT, WBI+RNI group also showed higher arm symptom scores (p=0.030). Apart from these specific timepoints, no significant differences were observed in other PRO domain scores, including arm and breast symptoms, between treatment arms. In addition, there was no significant differences in PRO domains according to RT techniques and fractionation, except for breast symptoms during RT, favoring hypofractionation and intensity-modulated RT. Conclusions: In patients with pN1 breast cancer treated with taxane-based adjuvant chemotherapy, adding RNI was associated with minor, transient declines in specific PRO domains. However, these differences were not clinically significant, indicating comparable overall patient experiences between the two treatment arms. Clinical trial information: NCT03269981 .
A retrospective look: Industry partnership and transparency in phase III randomized clinical trials of breast cancer targeted therapies across two decades.
Authors: Ruan Qiao , Mann-Grewal Amandeep Kaur , Johnson Caitlin Ruth , Behler Caroline , Kapp Daniel Stuart , Chan John K 
Published: May 2024

580 Background: To unveil industry involvement with respect to sponsorship, authorship, and demographic shifts in the trends of randomized clinical trials for breast cancer targeted therapies over the past two decades. Methods: All randomized phase III clinical trials focusing on targeted therapies for breast cancer were systematically identified from clinicaltrials.gov and reviewed using peer-reviewed publications. Trials that focused solely on chemotherapy and hormonal therapy were excluded. SAS Enterprise Guide v7.1 was used to analyze trial characteristics, authorship, and demographic details with Chi-square and Fisher’s exact tests. Results: From 2005-2023, 998 breast cancer treatment clinical trials were identified; 110 trials were included in the final analysis. Overall, 8.2% were limited to the U.S. and Canada while 67.3% were carried out internationally. 34.5% were led by cooperative (Co-op) groups vs 65.5% by pharmaceutical industries. 19.1% of trials were published in the New England Journal of Medicine (NEJM); all NEJM published trials reported positive results and 76.2% of were industry led. In contrast, of the 4.5% of trials featured in The Lancet, only 60% showed positive findings and 60% had major industry sponsorship. The most common industry partnerships were with Roche (27.3%), Novartis (12.7%), and Pfizer (7.3%) while the most common leading Co-op group was the National Cancer Institute (7.3%). To evaluate trends, trials were split into 3 time periods based on publication dates: 2005-2011, 2012-2017, and 2018-2023. The number of trial publications increased from 13 to 43 to 54. Of the 70% of trials that reported race/ethnicity data, the proportion of White patients decreased (84.5%, 78.8%, 79.3%; p<0.001) and the proportion of Asian patients increased (8.9%, 18.4%, 16.7%; p<0.001). However, enrollment of Black (6.6%, 2.8%, 4.0%; p<0.001) and Hispanic (7.0%, 2.8%, 5.0%; p<0.001) patients remained low. There were no statistically significant changes in international participation (46.2%, 69.8%, 70.4%; p=0.22), the proportion of exclusively industry-led (46.2%, 74.4%, 63.0%; p=0.15) or Co-op group-designed trials (61.5%, 35.7%, 26.4%; p=0.10). Industry-involved data collection increased from 23.1% to 64.2% to 73.6% (p=0.01) while industry sponsored data analysis (38.5%, 61.9%, 66.0%; p=0.49) and manuscript drafting (38.5%, 66.7%, 71.7%; p=0.09) did not significantly change. Conclusions: Over time, there was a notable rise in the number of phase III clinical trials for breast cancer targeted therapies. More than 70% of these trials now engage in international collaboration. Despite this progress, there remains an underrepresentation of Black and Hispanic participants in trial enrollment. Today, nearly 70% of trials have major industry sponsorship in study design, data analysis, and manuscript preparation.
Comparing 18F-FDG positron emission tomography (PET) and breast magnetic resonance imaging (MRI) to predict pathological complete response (pCR) and 3-year invasive disease-free survival (3-y iDFS) in patients (pts) with HER2+ early breast cancer (EBC): An unplanned exploratory analysis of PHERGain trial.
Authors: Pérez García José Manuel , Cortes Javier , Ruiz-Borrego Manuel , Stradella Agostina , Bermejo Begoña , Escrivá-de-Romaní Santiago , Calvo Lourdes , Gebhart Geraldine , Kerrou Khaldoun , García-Mosquera Juan José , Gion Maria , Antonarelli Gabriele , López-Montero Laura , Rodríguez-Morató José , Mina Leonardo , Sampayo-Cordero Miguel , Llombart-Cussac Antonio 
Published: May 2024

586 Background: The PHERGain phase II trial (1) (NCT03161353) demonstrated the feasibility of chemotherapy (CT)-free treatment using a PET-based, pCR-adapted strategy in HER2+ EBC pts treated with dual HER2 blockade (trastuzumab pertuzumab; HP). Due to limited PET availability, breast MRI is warranted as an alternative tool for assessing early treatment response. Methods: Briefly, group B pts in PHERGain were initially treated with HP, and CT was subsequently introduced according to on-treatment PET results. Adjuvant therapy was determined based on prior neoadjuvant treatment (NAT) and pCR. All pts completed up to 18 HP cycles. PET and MRI were performed before randomization and after 2 treatment cycles, with an additional MRI performed before surgery. PET response was centrally assessed per EORTC criteria. Locally assessed MRI response was defined as a ≥30% decrease in the sum of diameters of the target lesions. MRI reduction was defined ad hoc as any shrinkage in the diameter of target lesions after 2 cycles without new lesions or progressive disease in non-target lesions. Results: After 2 HP cycles, 79.6% (227/285) of group B pts were PET responders, 47% (134/285) had an MRI response, and 82.5% (235/285) achieved an MRI reduction. A high association was observed between PET response and MRI reduction. Similar rates of pCR and 3-y iDFS were observed between pts with a PET response or an MRI reduction. PET-nonresponders without MRI reduction had the worst 3-y iDFS despite receiving standard NAT with CT and HP (Table). Conclusions: The complex design of this study does not allow a direct comparison between PET and MRI. Although PET is the recommended imaging technique for early treatment response, these data suggest that MRI-assessed tumor shrinkage could alternatively guide NAT after the first 2 HP cycles in HER2+ EBC pts following the PHERGain strategy when PET is not available. 1. Pérez-García JM, Lancet Oncol 2021. Clinical trial information: NCT03161353 . [Table: see text]
Impact of extent of disease at presentation on oncologic outcomes according to pathologic response to neoadjuvant systemic therapy among participants of the I-SPY2 clinical trial.
Authors: Leon-Ferre Roberto Antonio , Dimitroff Katrina , Yau Christina , Giridhar Karthik , Mukhtar Rita A. , Hirst Gillian L. , Hylton Nola , Symmans W. Fraser Fraser , Goetz Matthew P. , Esserman Laura , Boughey Judy Caroline 
Published: May 2024

594 Background: Recent analyses in HER2+ and triple negative (TN) breast cancer (BC) treated with neoadjuvant systemic therapy (NAST) suggest that extent of disease at presentation (tumor [T] size and nodal [N] involvement) influences outcomes independently of response to NAST, even in the context of pathologic complete response (pCR). Given this, we evaluated the association of clinical T and N status prior to NAST with long-term outcomes in I-SPY2. Methods: We identified patients (pts) with TN and HER2+ BC who received NAST on the I-SPY2 trial with available clinical T size and N status prior to NAST, pathologic response after NAST, and follow up for recurrence and survival. We conducted univariable and multivariable (MV) Cox proportional models for Event Free (EFS), Distant Recurrence Free (DRFS), and Overall Survival (OS) in TN and HER2+ BC according to response after NAST, adjusting for residual cancer burden (RCB) category. Results: Of 1,170 pts with TN or HER2+ BC, 1,013 were eligible (TN: 623 and HER2+: 390), after 157 pts were excluded due to missing critical variables. Median follow up was 4.4 years (range 0.3-10.2). Median age was 48 for TN and 49 for HER2+ BC. Following NAST, pCR was achieved in 277 (45%) pts with TN and 197 (51%) pts with HER2+ BC. Among pts with pCR, separate MV analyses for TN and HER2+ BC showed no independent association between clinical T and N category with EFS, DRFS or OS (p values all > 0.05). However, among pts with residual disease, clinical T category (but not clinical N status) prior to NAST retained independent prognostic information in both TN and HER2+ BC in a MV model adjusting for age, RCB class, and hormone receptor status (for HER2+ BC). Compared to cT1-2, cT3-4 stage at diagnosis was associated with worse EFS, DRFS, and OS in TNBC, and with worse EFS, DRFS (but not OS) in HER2+ BC (Table). Additionally, hormone receptor status was independently associated with outcomes in HER2+ BC with residual disease (data not shown). The 5y EFS for cT1-2 vs cT3-4 according to RCB class in TNBC were: RCB0: 94% vs 95%, RCB1: 90% vs 65%, RCB2: 74% vs 44% and RCB3: 45% vs 20%. The 5y EFS for cT1-2 vs cT3-4 according to RCB class in HER2+ were: RCB0: 95% vs 88%, RCB1: 89% vs 84%, RCB2: 85% vs 64% and RCB3: 56% vs 50%. Conclusions: Tumor size (but not N involvement) prior to NAST was independently associated with outcomes in TN and HER2+ BC with residual disease, independently of RCB class. TN and HER2+ BC achieving pCR exhibited favorable outcomes regardless of extent of disease prior to NAST. These data are consistent with prior findings of the Neobioscore contributing only in the context of residual disease. Clinical trial information: NCT01042379 . [Table: see text]
Risk of VTE in TNBC treated with neoadjuvant immunotherapy.
Authors: Farooqui Ayesha , Kao Jeremy , Farooqui Marwah Wafa , Danciu Oana Cristina 
Published: May 2024

e12658 Background: Triple-negative breast cancer (TNBC) has limited treatment options. KEYNOTE 522 led to the approval of neoadjuvant (NT) Pembrolizumab in July 2021 changing the treatment paradigm for early stage TNBC. While improving pathologic complete response it also slightly increased treatment related adverse events. Some studies show increased risk of venous thromboembolism (VTE) with Pembrolizumab; however, it is unclear if immunotherapy (IO) increases the risk of VTE in a NT setting. Breast cancer is not classically associated with high risk for VTE. Here, we assess the incidence of VTE in TNBC patients receiving NT Pembrolizumab. Methods: All women diagnosed with TNBC and treated with NT Pembrolizumab between August 2021-December 2023 (t = 29 months) at our institution were included (N = 26). Stage 4 disease at time of diagnosis was excluded. The study endpoint was the development of VTE at any time following the initiation of Pembrolizumab as identified by CT chest angiography or venous duplex ultrasound. Risk factors and protective factors for VTE including body mass index, prior VTE, concurrent chest port, illicit drug use, smoking, hypertension, diabetes, kidney disease, hyperlipidemia, and prior antiplatelet/anticoagulant use were assessed for each patient. Results: In our study population, 1 patient developed VTE following initiation of Pembrolizumab (3.8%). This patient developed a pulmonary embolism 13 days after the 2nd dose of Pembrolizumab (179 days after 1st dose). Risk factors for this patient were obesity (BMI = 52.9), concurrent chest port, and hypertension. Protective factors included no prior history of VTE, illicit drug use, smoking, diabetes, kidney disease, or hyperlipidemia. A comparison of the risk factors is summarized (Table). Conclusions: The cumulative VTE incidence for all immune therapies is reported as 7-10% in the 1st year. Patients with breast cancer have a 6% incidence of VTE in the 1st year. This rate does not account for cancer subtype, stage, or treatment type. Our exploratory study is novel in looking at incidence of VTE in the NT immunotherapy use setting. These results suggest a lower incidence compared to the cumulative studies previously mentioned. There is a possible synergistic interaction between Pembrolizumab therapy and other traditional risk factors in the development of VTE in TNBC. Further analysis will seek to stratify the individual risk of Pembrolizumab in VTE compared to other risk factors. Future work will include expanding our study population to additional solid tumors utilizing NT Pembrolizumab including melanoma and non-small cell lung carcinoma. Once risk is definitively established, it will be important to take measures to mitigate the risks to improve cancer related outcomes. [Table: see text]
Comparative analysis of Keynote522 treatment outcomes in Hispanic versus non-Hispanic patients with breast cancer: A single tertiary center experience.
Authors: Banwait Ranjit Singh , Shaker Sarah , Sharma Aditi , Parekh Jay , Mazo- Canola Marcela 
Published: May 2024

e12661 Background: The addition of pembrolizumab to neoadjuvant chemotherapy on the Keynote522 (KN522) clinical trial, changed the standard of care for early stage triple negative breast cancer (TNBC). This regimen demonstrated longer event free survival and higher percentage of patients with pathologic complete responses (pCR). However, limited data exist on the comparative outcomes between Hispanic and non-Hispanic patients in real-world settings as this patient population was likely underrepresented on the original trial. Methods: We conducted a retrospective analysis of patients with early stage TNBC treated on KN522 regimen and undergoing surgery at a single tertiary center from July 2021 to present. Patients were stratified into Hispanic and non-Hispanic ethnicity cohorts. The primary endpoint was pCR rate, and secondary endpoints was incidence of adverse effects (AEs). Results: Among a cohort of 41 patients identified, 26 (63%) were of Hispanic and 15 (37%) were non-Hispanic. The pCR rate was 50% among Hispanic and 53% among non-Hispanic patients (p=0.83). Hispanic patients experienced higher rates of anemia (88% vs. 67%, p=0.06), fatigue (85% vs. 60%, p=0.07), skin rash (46% vs. 27%, p=0.21), and endocrine toxicities (23% vs. 13%, p=0.21). However, Hispanic patient also had fewer hospitalizations (35% vs. 47%, p=0.44), dose-modifications (12% vs. 40%, p=0.53), dose omissions (19% vs. 33%, p=0.31), and showed higher KN522 completion rates (81% vs. 53%, p=0.06). Conclusions: Our findings indicate a comparable pCR rate between Hispanic and non-Hispanic patients with early-stage TNBC receiving KN522 therapy. While Hispanic patients exhibited higher incidences of certain adverse effects, they demonstrated lower rates of hospitalizations, dose modifications, and omissions, alongside a notably higher completion rate of the KN522 regimen. These trends may be attributed to various factors such as genetic predispositions, and potentially differential physiological responses to therapy within this ethnic group. These findings underscore the importance of including minorities, such as Hispanic patients, in clinical trial populations to ensure that treatment outcomes are representative of diverse patient demographics. [Table: see text]