scholarly journals Average duration of prior treatment lines predicts clinical benefit to eribulin chemotherapy in patients with metastatic breast cancer

2021 ◽  
Author(s):  
Faye Coe ◽  
Vivek Misra ◽  
Yamini McCabe ◽  
Helen Adderley ◽  
Laura Woodhouse ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Average Duration ◽  
Metastatic Breast ◽  
Previous Treatment ◽  
Cox Proportional Hazards ◽  
Electronic Prescribing ◽  
Prognostic Impact ◽  
Full Cohort ◽  
Metastatic Setting

Abstract Purpose The aim of this study was to identify factors associated with progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC) treated with eribulin in a real-world setting, to improve information provision in those considering treatment. Methods Patients treated with eribulin for MBC at The Christie NHS Foundation Trust, Manchester, UK, between August 2011 and December 2018 were included (n = 439). Data were collected by retrospective review of medical records and electronic prescribing systems. Factors such as biological subtype, distant recurrence-free interval, previous lines of chemotherapy and the ‘average duration of previous treatment lines’ (ADPT) (calculated as: (date of initiation of eribulin–date of MBC) / the number of previous treatment lines in the metastatic setting) were evaluated for prognostic impact using Cox proportional hazards regression. Results In the full cohort, the median PFS and OS were 4.1 months (95% CI 3.7–4.4) and 8.6 months (95% CI 7.4–9.8), respectively. Outcomes were significantly inferior for those with triple-negative breast cancer (TNBC) (n = 92); PFSTNBC: 2.4 months (95% CI 2.1–3.0), p =  < 0.001 and OSTNBC: 5.4 months (95% CI 4.6–6.6), p =  < 0.001. ADPT was the only factor other than subtype significantly associated with PFS and OS. Longer ADPT was also significantly associated with PFS and OS in those with TNBC. For example, women in the lowest ADPT tertile (< 5.0 months) achieved a median OS of only 4.3 months, whereas those in the upper ADPT tertile (> 8.7 months) had a median OS of 12.1 months (p = 0.004). Conclusion Our results indicate that the ADPT lines is an important factor when predicting the outcome with eribulin chemotherapy in a palliative setting and that quantitative guidance on the likely PFS and OS with treatment can be provided using ADPT. Validation in additional cohorts is warranted.

scholarly journals CATCH: A Prospective Precision Oncology Trial in Metastatic Breast Cancer

2021 ◽  
pp. 676-686
Author(s):  
Mario Hlevnjak ◽  
Markus Schulze ◽  
Shaymaa Elgaafary ◽  
Carlo Fremd ◽  
Laura Michel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Management ◽  
Metastatic Breast ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Precision Oncology ◽  
Whole Genome ◽  
Free Survival

PURPOSE CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial. METHODS From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations. RESULTS Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. CONCLUSION The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients.

scholarly journals Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Lauren Darrigues ◽  
Jean-Yves Pierga ◽  
Alice Bernard-Tessier ◽  
Ivan Bièche ◽  
Amanda Bartolini Silveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Somatic Mutations ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Prognostic Impact ◽  
Radiological Evaluation ◽  
Tumor Dna

Abstract Background Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2−) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency. Methods ER+ HER2− MBC patients were included in a prospective observational cohort before treatment initiation. Tumor response was assessed by radiological evaluation (RECIST v1.1) every 3 months. Plasma samples were collected before treatment (baseline), at day 15 (D15), at day 30 (D30), and at disease progression. We searched for somatic mutations from archived tumor tissues by targeted deep sequencing. For patients with somatic mutations identified, circulating tumor DNA (ctDNA) was tracked using digital droplet PCR. Ratios of ctDNA levels ([D15/baseline] and [D30/baseline]) were then correlated with prospectively registered patient characteristics and outcomes. Results Twenty-five of the 61 patients enrolled had a somatic mutation testable in plasma (NPIK3CA = 21, NTP53 = 2, NAKT1 = 2). At baseline, 84% of patients had detectable ctDNA levels but ctDNA levels had no prognostic impact on PFS (p = 0.10). Among those patients, ctDNA was still detected in 82% at D15 and 68% at D30. ctDNA clearance observed at day 30 was associated with longer PFS (HR = 7.2, 95% CI = 1.5–32.6, p = 0.004). On the contrary, a [D30/baseline] ctDNA ratio > 1 was associated with a shorter PFS (HR = 5.1, 95% CI = 1.4–18.3, p = 0.02) and all 5 patients with increased ctDNA levels at D30 showed disease progression after 3 months under palbociclib-fulvestrant. Finally, at the time of radiological tumor progression, ctDNA was detected in all patients tested. Conclusion Our study demonstrates that the efficiency of palbociclib and fulvestrant can be monitored by serial analyses of ctDNA before radiological evaluation and that early ctDNA variation is a prognostic factor of PFS.

scholarly journals Locoregional Surgery in Metastatic Breast Cancer: Do Concomitant Metabolic Aspects Have a Role on the Management and Prognosis in this Setting?

2020 ◽  
Vol 10 (4) ◽  
pp. 227
Author(s):  
Maria Ida Amabile ◽  
Federico Frusone ◽  
Alessandro De Luca ◽  
Domenico Tripodi ◽  
Giovanni Imbimbo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Medical Treatment ◽  
Cancer Progression ◽  
Metastatic Breast ◽  
Treatment Decision ◽  
Careful Consideration ◽  
Level Of Evidence ◽  
Systemic Treatments ◽  
Metastatic Setting

Although they cannot be considered curative, the new therapeutic integrated advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. Traditionally, surgery was confined to palliation of symptomatic or ulcerating lumps. Data suggest, in some cases, a possible additive role for more aggressive locoregional surgical therapy in combination with systemic treatments in the metastatic setting, although a low level of evidence has been shown in terms of improvement in overall survival in MBC patients treated with surgery and medical treatment compared to medical treatment alone. In this light, tumor heterogeneity remains a challenge. To effectively reshape the therapeutic approach to MBC, careful consideration of who is a good candidate for locoregional resection is paramount. The patient’s global health condition, impacting on cancer progression and morbidity and their associated molecular targets, have to be considered in treatment decision-making. In particular, more recently, research has been focused on the role of metabolic derangements, including the presence of metabolic syndrome, which represent well-known conditions related to breast cancer recurrence and distant metastasis and are, therefore, involved in the prognosis. In the present article, we focus on locoregional surgical strategies in MBC and whether concomitant metabolic derangements may have a role in prognosis.

scholarly journals Neutrophil-lymphocyte ratio in metastatic breast cancer is not an independent predictor of survival, but depends on other variables

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alejandra Ivars Rubio ◽  
Juan Carlos Yufera ◽  
Pilar de la Morena ◽  
Ana Fernández Sánchez ◽  
Esther Navarro Manzano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Univariate Analysis ◽  
Metastatic Breast ◽  
Prognostic Impact ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio

AbstractThe prognostic impact of neutrophil-lymphocyte ratio (NLR) in metastatic breast cancer (MBC) has been previously evaluated in early and metastatic mixed breast cancer cohorts or without considering other relevant prognostic factors. Our aim was to determine whether NLR prognostic and predictive value in MBC was dependent on other clinical variables. We studied a consecutive retrospective cohort of patients with MBC from a single centre, with any type of first line systemic treatment. The association of NLR at diagnosis of metastasis with progression free survival (PFS) and overall survival (OS) was evaluated using Cox univariate and multivariate proportional hazard models. In the full cohort, that included 263 MBC patients, a higher than the median (>2.32) NLR was significantly associated with OS in the univariate analysis (HR 1.36, 95% CI 1.00–1.83), but the association was non-significant (HR 1.12, 95% CI 0.80–1.56) when other clinical covariates (performance status, stage at diagnosis, CNS involvement, visceral disease and visceral crisis) were included in the multivariate analysis. No significant association was observed for PFS. In conclusion, MBC patients with higher baseline NLR had worse overall survival, but the prognostic impact of NLR is likely derived from its association with other relevant clinical prognostic factors.

scholarly journals Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for A Cost-Effective and Dynamic Biomarker

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1243 ◽  
Author(s):  
Giacomo Pelizzari ◽  
Debora Basile ◽  
Silvia Zago ◽  
Camilla Lisanti ◽  
Michele Bartoletti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lactate Dehydrogenase ◽  
Prognostic Factor ◽  
Metastatic Breast ◽  
Prognostic Impact ◽  
Line Treatment ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Treatment

Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40–5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16–5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00–7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

scholarly journals Prognostic Impact of Src, CDKN1B, and JAK2 Expression in Metastatic Breast Cancer Patients Treated with Trastuzumab

2019 ◽  
Vol 12 (5) ◽  
pp. 739-748
Author(s):  
Panagiota Economopoulou ◽  
Vassiliki Kotoula ◽  
Georgia-Angeliki Koliou ◽  
Kyriaki Papadopoulou ◽  
Christos Christodoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Prognostic Impact ◽  
Breast Cancer Patients

scholarly journals Oncology Nursing Support for Safe and Effective Use of Eribulin in Metastatic Breast Cancer

2014 ◽  
Vol 8 ◽  
pp. CMO.S14038 ◽  
Author(s):  
Diana Donovan ◽  
Laura Urquhart ◽  
Una Hopkins ◽  
Sandra Knight ◽  
Laura Moore
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Nurse Practitioners ◽  
Nurse Practitioner ◽  
Core Competencies ◽  
Clinical Signs ◽  
Metastatic Breast ◽  
Proactive Management ◽  
Metastatic Setting

Nurse practitioners play important roles in breast cancer prevention, early detection, therapeutic efficacy, and surveillance. Assessment of a patient's health status is part of the nine nurse practitioner core competencies updated in 2012 by the National Organization of Nurse Practitioner Faculties. Although adverse events are common in treatment for metastatic breast cancer (MBC), proactive management strategies can limit the number and/or severity of adverse events. Additionally, knowledge of common metastatic sites and clinical signs/symptoms of recurrence provides one of the first-line strategies for successful treatment. We review five case studies of women with MBC who were managed successfully with eribulin mesylate in late lines of therapy after at least two chemotherapeutic regimens for advanced breast cancer that included both an anthracycline and a taxane in either the adjuvant or metastatic setting.

Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2:HER2 dimerization in a clinic-based cohort of patients with metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1025-1025 ◽  
Author(s):  
M. Toi ◽  
J. Sperinde ◽  
W. Huang ◽  
S. Saji ◽  
S. Ohno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Cox Proportional Hazards ◽  
Her2 Expression ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Differential Survival ◽  
Term Survival ◽  
Trastuzumab Treatment

1025 Background: Women with metastatic breast cancer (MBC) that overexpress HER2 experience improved overall survival (OS) when treated with trastuzumab. Immunohistochemistry (IHC) for HER2 protein expression and fluorescence in situ hybridization (FISH) for HER2 gene amplification are the preferred methods of determining HER2 positivity. However, not all HER2 positive patients respond equally well to trastuzumab. We describe the identification of subgroups of HER2+ patients with distinct clinical outcomes based on their quantitative levels of HER2 expression and HER2:HER2 dimerization. Methods: 75 patients with MBC drawn from six oncology clinics in Japan were assayed for HER2 expression and HER2:HER2 dimerization using FFPE specimens by the eTag assay, a proximity-based assay designed to detect and quantify protein-protein dimers. All patients had MBC, were treated with at least one chemotherapy (CT) regimen prior to receiving trastuzumab, and had FFPE specimens available for testing. 33% had at least 3 metastatic sites. 88% were selected for treatment based on IHC and 12% based on FISH. 16% were treated with trastuzumab alone and 84% with trastuzumab plus CT. Median clinical follow-up was 26 months. Cox proportional hazards and Kaplan-Meier (KM) analyses were performed. Results: The most significant variables associated with OS were the presence of brain metastases and the total number of metastases. In the overall population, correcting for the confounding influence of number of metastases, KM analyses demonstrated that patients with higher HER2 expression survived significantly longer than patients with lower HER2 expression (HR for death = 0.36, p = 0.0036). This relationship was even more significant for HER2:HER2 dimers (HR = 0.29, p = 0.0003). Conclusions: In a clinic-based population of Japanese women with MBC treated with heterogeneous prior and concomitant (with trastuzumab) CT regimens, the quantitative levels of HER2 expression and HER2:HER2 dimerization identified subsets of patients within a population of pre-selected HER2+ patients with different probabilities of long-term survival following trastuzumab treatment. No significant financial relationships to disclose.

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