Eribulin can represent a therapeutic alternative for patients with advanced breast cancer who have received at least one or two lines of anthracyclines-based chemotherapy and taxane therapy. In this observational study, we focused on long-responder patients, i.e. with an objective response or stability ≥ 6 months under eribulin to better characterize them.

Metastatic breast cancer (MBC) patients treated by eribulin in 2nd, 3rd or 4th line between September 2011 and June-2018 were included. The following parameters were assessed: primary tumor and metastasis characteristics, type of response and duration, disease progression, treatment received, toxicities, progression free survival (PFS), overall survival (OS), and prognostic factors of OS and PFS. Special attention was paid to patients with hepatic disease (HD).

Among the 98 patients included, an analysis was conducted on 84 patients (median age 62). Median duration of response was 25.6 weeks (95 IC 22-27.7) with a median number of infusions of 6. Response was similar, irrespective of ERI line number. HD was observed in 70.2 % of patients. Median PFS was 9 months (95 %CI 8-10). Subgroup analysis showed similar PFS, irrespective of HD (p = 0.21) and treatment line (p = 0.46). Median OS was 24 months. (95 % IC 20-31). The main prognostic factors of OS were duration of response (p < 0.001) and, progesterone receptor positiveness was associated to PFS (p = 0.006).

This multicentric, retrospective study highlights eribulin as a potential second-line therapy for MBC with a median response duration of 25 weeks after 6 infusions. The safety and efficacy profiles align with previous studies, supporting its role as a viable treatment option. Notably, the response and PFS were independent of hepatic metastasis, suggesting benefit across various MBC subtypes, including those with liver involvement. However, the retrospective design warrants cautious interpretation, and further prospective studies are needed to confirm these findings and optimize eribulin's use, potentially through molecular profiling for personalized treatment strategies.

In recent decades, the potentiality of marine natural products (MNPs) in the medical field has been increasingly recognized. Natural compounds derived from marine microorganisms, algae, and invertebrates have shown significant promise for treating inflammation-related diseases. In this review, we cover the three primary sources of MNPs and their diverse and unique chemical structures and bioactivities. This review aims to summarize the progress of MNPs in combating inflammation-related diseases. Moreover, we cover the functions and mechanisms of MNPs in diseases, highlighting their functions in regulating inflammatory signaling pathways, cellular stress responses, and gut microbiota, among others. Meanwhile, we focus on key technologies and scientific methods to address the current limitations and challenges in MNPs.

Metastatic triple-negative breast cancer has a poor prognosis and poses significant therapeutic challenges. Until recently, limited therapeutic options have been available for patients with advanced disease after failure of first-line chemotherapy. The aim of this review is to assess the current evidence supporting second-line treatment options in patients with metastatic triple-negative breast cancer. Evidence was reviewed from controlled clinical trials in which eribulin, vinorelbine, capecitabine, gemcitabine, gemcitabine plus carboplatin, fam-trastuzumab-deruxtecan, sacituzumab govitecan, olaparib, and talazoparib were used in the second-line treatment for metastatic breast cancer, either as study drugs or as comparators. The benefit of treatment was evaluated using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale. Based on the evidence review, sacituzumab govitecan was identified as the preferred second-line treatment option for patients with metastatic triple-negative breast cancer, supported by clinical evidence and consensus across international clinical guidelines. Olaparib and talazoparib are of use in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer and germline BRCA1/2 mutations. Exploratory data for fam-trastuzumab-deruxtecan suggest a survival benefit in human epidermal growth factor receptor 2-low, hormone-receptor-negative patients, but further solid evidence is required. Other chemotherapies with lower European Society for Medical Oncology-Magnitude of Clinical Benefit Scale scores may continue to be useful in highly selected patients.

This study aimed to evaluate the efficacy and safety of docetaxel rechallenge in HER2-negative metastatic breast cancer (MBC) patients who discontinued docetaxel for reasons other than disease progression.

We retrospectively analyzed HER2-negative MBC patients treated with docetaxel-based therapy (DBT) at our institution from 2010 to 2020. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were assessed. Multivariate Cox regression and propensity score matching analysis (PSMA) were used to minimize bias.

Among 600 patients, 369 only received docetaxel once (control group), while 231 (38.5%) received docetaxel rechallenge as second or later-line therapy (rechallenge group). In the second-line rechallenge subset (143 patients), ORR was 51.0%, and PFS was 6.7 months. Multivariate analysis showed that a response to initial DBT (stable disease [SD] vs. complete response/partial response [CR/PR]: odds ratio [OR] 2.615, 95% confidence interval [CI] 1.373-4.981; p = 0.03) independently predicted the ORR. Beyond second-line rechallenge, the ORR and PFS were 37.5% and 5.6 months, respectively. After PSMA, the rechallenge group demonstrated significantly improved OS compared to the control group: 50.5 months vs. 46.0 months (Hazard Ratio [HR] 0.632; 95% CI 0.455-0.878; p = 0.006). The toxicities reported were manageable, primarily hematologic, with grade 3-4 events occurring in 19.5% of cases.

This study suggests that docetaxel rechallenge may be an effective and tolerable later-line treatment option for patients with HER2-negative MBC, particularly those who responded to initial DBT. However, further prospective, randomized controlled research is needed to fully evaluate its impact on disease response in this patient population.

Triple-negative breast cancer (TNBC) is traditionally treated with systemic chemotherapy, often resulting in significant off-target toxicity. In this study, we assess the efficacy of intraductal chemotherapeutic delivery, aimed at reducing systemic side effects. Using an in situ TNBC model, created by intraductal injection of 4T1-luc cells, we identified day 3 post-tumor implantation as an optimal early intervention point. Echocardiographic analysis confirmed that intraductal administration of eribulin (ERI) or doxorubicin (DOX) did not cause cardiac dysfunction or apoptosis. Our results demonstrate that intraductal delivery of ERI and DOX significantly enhances anti-tumor and anti-metastatic effects. Mechanistically, ERI followed by DOX increased intratumoral perfusion, improved drug concentration, reversed epithelial-mesenchymal transition, and inhibited tumor cell invasion and metastasis. Additionally, this approach triggered immunogenic cell death and activated a systemic anti-tumor immune response. These findings underscore the potential of intraductal chemotherapy as a safe, highly effective approach, offering a preclinical foundation for minimally invasive TNBC therapies.

Metastatic breast cancer (mBC) remains an incurable disease, and most patients will experience disease progression during their treatment course. Although endocrine therapy remains the mainstay of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative mBC, significant progress has been and continues to be made in the treatment of this BC subtype. The discovery of molecular markers, mutations in key cellular pathways, and genomic signatures have led to the development of novel and targeted agents, such as antibody-drug conjugates, oral selective estrogen receptor downregulators, and inhibitors of the PI3K/AKT/mTOR pathway. This has resulted in significant improvements in the survival and quality of life of patients. With the increasing number of treatment options for patients, appropriate drug sequencing remains a challenge. Treatment discussions should involve patient-physician shared decision making, with consideration of genomic data, previous lines of therapy, side effect profiles, and clinical trial enrollment.

Effective later-line chemotherapy treatment options are scarce for patients with metastatic breast cancer (MBC). Trifluridine-tipiracil has shown survival benefit in heavily pre-treated patients with metastatic colorectal and in gastric cancer refractory to a fluoropyrimidine. This study aimed to investigate the efficacy of trifluridine-tipiracil in a Western population of previously treated patients with oestrogen receptor (ER+), HER2- MBC to facilitate further optimization of this treatment strategy.

Adult patients at least 18 years old diagnosed with hormone receptor positive, HER2- receptor negative MBC with a performance status of 0 or 1 who have been treated with capecitabine in the metastatic setting and up to two other lines of chemotherapy, including a taxane, were enrolled in this single-arm, multicentre, phase 2 study in the Netherlands. The participants received trifluridine-tipiracil 35 mg/m2 orally twice a day on days 1-5 and days 8-12 during a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the disease control rate (DCR) at 8 weeks, defined as the percentage of patients that had stable disease, partial response or complete response according to RECIST 1.1, in all patients that received at least one dose of trifluridine-tipiracil and met the key eligibility criteria defined a priori. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life and were performed in all patients that received at least one dose of trifluridine-tipiracil. The primary endpoint was considered met, justifying further research of this treatment regimen, if the lower boundary of the 80% confidence interval (CI) exceeded 30%. The study was registered within ClinicalTrials.gov (NCT04489173) and is closed for inclusion.

Fifty female patients were enrolled from September 2020 to July 2023, with a median of 3 (IQR, 2-3) previous endocrine therapy lines and 2 (IQR, 2-3) chemotherapy lines for MBC. The DCR rate at 8 weeks was 64.0% (n = 32, 95% CI: 50.1-75.9%; 80% CI: 55.0-72.1%), thereby meeting the primary endpoint of this study. At data cutoff (January 8, 2024), the median follow-up time was 18.2 months (IQR, 13.1-25.1 months). The median PFS was 5.4 months (95% CI: 2.0-7.2 months) and the median OS 14.0 months (95% CI: 8.8-17.8 months). The safety profile of trifluridine-tipiracil aligned with expected toxicities and included leukopenia (n = 36, 69%), neutropenia (n = 43, 83%), and fatigue (n = 43, 83%). The most common grade 3-4 AEs were primarily haematological disorders and included neutropenia (n = 38, 73%), leukopenia (n = 15, 29%) and anaemia (n = 6, 12%). The most common SAEs (any grade) with a possible relationship with trifluridine-tipiracil included anaemia (n = 2) and vomiting (n = 2). No treatment-related deaths occurred. Quality of life scores remained stable throughout the treatment.

Trifluridine-tipiracil demonstrated promising efficacy in heavily pre-treated patients with MBC, despite prior exposure to a fluoropyrimidine. Clinically, this suggests that trifluridine-tipiracil holds potential as a viable oral later-line treatment option with a manageable toxicity profile while maintaining quality of life. Preparations for a phase 3 trial are underway.

Servier, France.

Eribulin is a preferred treatment for patients with advanced breast cancer (BC) following anthracyclines and taxanes. The final analysis of the IRENE study assessed the incidence and resolution of eribulin-induced peripheral neuropathy (EIPN), along with safety and quality of life (QoL), in patients with advanced/metastatic BC. IRENE was an observational, single-arm, prospective, multicenter cohort study. Patients aged ≥18 years with locally advanced/metastatic BC that progressed after 1-3 prior chemotherapeutic regimens received eribulin and were monitored for new-onset or worsening EIPN. Secondary endpoints included time to disease progression, safety, and health-related QoL. In total, 108 (32.2%) out of 335 patients experienced EIPN; 18 (5.4%) experienced grade ≥3 EIPN. Median time to EIPN resolution (EIPN ended or returned to baseline) was 78.7 weeks (95% CI 77.1-not estimable). Median time to disease progression was 4.5 months (95% CI 3.9-5.5). Treatment-emergent adverse events (TEAEs) occurred in 322 (96.1%) patients; serious TEAEs occurred in 185 (55.2%) patients. Incidence and resolution rates of EIPN were comparable with existing evidence from previous trials. TEAEs were consistent with the established eribulin safety profile, with no new safety signals. Eribulin treatment did not appear to affect QoL, as measured by EQ-5D-3L and EQ-VAS, or patient-reported neuropathy symptoms, as measured by the PNQ.

This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m2). In part 2, patients were enrolled in two cohorts (mTNBC and HER2-negative breast cancer brain metastasis [BCBM]), and received HE072 70 mg/m2 every two weeks (Q2W). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and treatment emergent adverse events (TEAEs). The secondary endpoints were pharmacokinetic profiles and efficacy including objective response rate (ORR) and disease control rate (DCR) (all patients) and Central Nervous System ORR and clinical benefit rate (CBR, for patients with HER2-negative BCBM), duration of response, progression free survival (PFS), overall survival (OS). A total of 119 patients were enrolled, including 101 mTNBC and 18 HER2-negative BCBM. One dose limiting toxicity (grade 3 nausea and vomiting) occurred at 70 mg/m2, and the MTD was not reached. The most common ≥ grade 3 TEAEs related to HE072 included neutropenia (21.0%), leukopenia (18.5%), diarrhea (10.1%). Among 87 evaluable patients with mTNBC, 22 patients (25.3%) achieved overall response. The DCR was 67.8% (59/87). The median PFS and OS were 4.8 months and 14.1 months, respectively. The RP2D was 70 mg/m2 Q2W. Promising antitumor activity in heavily pre-treated patients with mTNBC was observed, which warrants further validation.

The objective of this study was to compare the efficacy and safety of subsequent chemotherapy with single eribulin or utidelone combined with a capecitabine regimen in patients with advanced breast cancer who had previously been treated with anthracyclines and paclitaxel.

This work was a retrospective analysis of 85 patients from July 2018 to July 2023. Forty-two and 43 patients were treated with the eribulin regimen and the utidelone/capecitabine regimen, respectively. The endpoints included progression-free survival, overall survival, the objective remission rate and safety. Survival analyses and multifactorial analyses were performed via the Kaplan‒Meier method, log-rank test and Cox regression models.

As of 15 April 2024, the mPFS durations of the patients in the utidelone/capecitabine and eribulin treatment groups were 7.7 and 5.2 months, respectively, and the mOS durations were 22.0 and 18.2 months, respectively. Subgroup analyses revealed that in advanced first-line therapy, the mPFS durations of the utidelone/capecitabine group and the eribulin group were 11.8 and 7.0 months, respectively, and this difference was significant. In the eribulin treatment arm, the mPFS of first-line therapy was 7.0, whereas it was 3.3 months for posterior-line therapy, and this difference was significant. The most common adverse reactions were neurotoxicity, hand‒foot syndrome, hematological toxicity, gastrointestinal toxicity, and abnormalities in hepatic and renal functions.

In conclusion, either utidelone/capecitabine or eribulin chemotherapy may result in a survival benefit with a tolerable adverse effect profile and favorable safety profile in patients with metastatic breast cancer. The first-line use of eribulin resulted in better PFS and ORR than posterior-line use, and the combination of utidelone/capecitabine represents a more efficacious approach in the advanced first-line therapy of breast cancer.

We conducted a meta-analysis of published randomized controlled trials to compare the effectiveness and safety of eribulin versus paclitaxel for patients with breast cancer.

We systematically searched multiple databases including Cochrane, PubMed, Medline, and Embase. The primary outcomes analyzed were overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), and adverse events (AEs). These outcomes were evaluated using RevMan5.3 software.

A total of 5 studies were included in the analysis. Compared to paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs not only extended the overall survival of patients but also improved the disease control rate (DCR) [risk ratio (RR) 0.98, (95% confidence intervals (CI): 0.70, 1.38), p = 0.92]. Hematological system diseases [RR 1.18 (95% CI: 1.07, 1.31), p = 0.002] were the most frequently observed adverse event with eribulin, while paclitaxel was more likely to cause nervous system lesion [RR 0.66 (95% CI: 0.54, 0.80), p < 0.0001].

Compared with paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs can also prolong the PFS and OS of BC patients. Our recommendation is to use eribulin plus other chemotherapy drugs to treat advanced BC and to continuously monitor and manage the drug-related adverse events.

Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown.

This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m2 twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status.

Eighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR+ breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m2 twice daily. DLTs included hyperglycemia, QTc prolongation, fatigue, and chest pain. The most common grade 3 adverse event (AE) was hyperglycemia (28%). No grade 4 AEs were observed. Three patients discontinued therapy due to an AE. One-third of patients required dose reduction of both alpelisib and capecitabine. Four patients experienced a partial response and 8 patients experienced stable disease. The median progression-free survival was 9.7 months (95% CI 2.8-13.5 months) and median overall survival was 18.2 months (95% CI 7.2-35.2 months). Twelve patients had PIK3CA mutation testing completed, of these 2 had known or likely deleterious PIK3CA mutation.

This study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study.

HER2-low populations constitute a heterogeneous group, and the cytotoxic anticancer agent efficacy based on HER2 status remains unclear. This study evaluated the clinicopathological features and outcomes of patients with advanced breast cancer showing HER2-low expression treated with eribulin or capecitabine, two treatment options after anthracycline and taxane treatment.

We retrospectively evaluated patients who were treated with eribulin or capecitabine between 2011 and 2015. HER2 status was evaluated according to the ASCO/CAP guidelines.

No significant difference was observed in overall survival (OS; eribulin: hazard ratio [HR], 0.66; 95% CI 0.40-1.10; capecitabine: HR, 0.76; 95% CI 0.45-1.30) or progression-free survival (PFS; eribulin: HR, 1.13; 95% CI 0.72-1.78; capecitabine: HR, 0.90; 95% CI 0.56-1.44) between patients receiving eribulin (HER2-null: 35, HER2-low: 44) and those receiving capecitabine (HER2-null: 41, HER2-low: 33). Subgroup analysis revealed no significant differences in OS between the two groups in the hormone-positive and -negative populations for eribulin and capecitabine. HER2-null and HER2-low patients showed objective response rates (ORRs) of 22.5% and 9.1% (p = 0.09) overall, and 32.0% and 10.5% (p = 0.03), respectively, in hormone-positive cases among eribulin-treated patients. No response was observed in hormone-negative patients. Capecitabine treatment in HER2-null and HER2-low patients had overall ORRs of 26.8% and 15.2% (p = 0.23), respectively, with 27.3% and 16.1% (p = 0.28) for hormone-positive cases; and 25.0% and 0% (p = 1.0), respectively, for hormone-negative cases.

Eribulin and capecitabine sensitivity may vary based on HER2 expression in patients with HER2-low and HER2-null breast cancer. Prognosis was similar between the HER2-low and the HER2-null groups.

Pre-clinical data suggests a potential synergistic effect of eribulin and platinum. However, clinical data on the combination for metastatic breast cancer (mBC) is lacking. We evaluated the efficacy and safety of eribulin plus carboplatin (ErCb) in patients with mBC.

This multicenter, real-world cohort study included patients with pre-treated metastatic triple negative breast cancer (TNBC) or endocrine-refractory hormone receptor (HR) positive, HER2-negative mBC who received ErCb. Eribulin (1.4 mg/m2) and carboplatin (target AUC = 2) were administered intravenously on day 1 and 8 of 21-day cycle. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.

From March 2022 to December 2023, a cohort of 37 patients were recruited to the study. Among them, 22 patients have TNBC and 15 have HR + HER2 - mBC. Of the 22 patients with TNBC, 8 had an initial diagnosis of the HR + HER2 - subtype. The median treatment was 6 cycles (range, 2 - 8 cycles). In the full cohort, TNBC, and HR + HER2 - subgroup, the ORR were 51.4%, 54.5% and 46.7%, the DCR were 81.1%, 81.8% and 80%, and the median PFS were 5 months, 5 months, and 5.2 months, respectively. The median OS was 12.7 months in the entire cohort and 12.8 months in TNBC subgroup. The most common grade 3/4 hematological AEs were neutropenia (37.8%), leukopenia (35.1%), febrile neutropenia (10.8%), thrombocytopenia (5.4%), and anemia (2.7%). No grade 3/4 non-hematological AEs were observed.

ErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.

The Dutch Committee for the Evaluation of Oncological Agents (cieBOM) assesses the clinical benefit of systemic anti-cancer treatments (SACTs). For SACTs tested in non-randomized trials (NRTs), cieBOM primarily utilizes response-related thresholds as assessment criteria. As sufficiency of NRT-based evidence for benefit assessments is questionable, this study investigated whether and how NRTs can be used to assess the clinical benefit of new SACTs initially appraised by cieBOM based on randomized controlled trials (RCTs).

Using the RCTs underpinning cieBOM recommendations issued between 2015 and 2017, we searched for matching NRTs and applied the NRT-related assessment criteria by cieBOM to them. We then compared the assessment outcomes to the respective RCT-based cieBOM recommendations. Further, we investigated how the assessments would change when applying different response-related thresholds and adding a progression-free survival (PFS) threshold.

For 13 of the 37 eligible recommendations, a matching NRT was found. Two treatments were assessed positively and six negatively; five treatments were non-assessable. Two positive recommendations matched a positive NRT-based assessment; one matching negative assessment was found, and one treatment could not be assessed based on either trial results. Adding a > 6 months PFS threshold decreased the number of non-assessable NRTs (five to two).

Limited publications and inconsistent data reporting hampered the viability of NRTs for clinical benefit assessments of SACTs beyond the scope of rare indications. Further, response-related assessment criteria alone might not fully grasp the clinical benefit of novel SACTs. NRT-based assessments should be considered with caution due to uncertainty of the trial results.

In the global phase 3 DESTINY-Breast04 study (NCT03734029), the anti-human epidermal growth factor 2 (HER2) antibody-drug conjugate trastuzumab deruxtecan (T-DXd) demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS), with manageable safety compared with treatment of physician's choice (TPC) in patients with HER2-low metastatic breast cancer (mBC) who had received 1-2 prior lines of chemotherapy.

This subgroup analysis examined the efficacy and safety of T-DXd versus TPC in 213 patients from Asian countries and regions who were enrolled in the DESTINY-Breast04 trial and randomized to T-DXd (n = 147) or TPC (n = 66).

Median PFS with T-DXd and TPC was 10.9 and 5.3 months, respectively, in Asian patients with hormone receptor-positive mBC, and 10.9 and 4.6 months, respectively, in the overall Asian population. In both populations, median OS was not reached with T-DXd and was 19.9 months with TPC. The objective response rate was higher with T-DXd versus TPC in all Asian patients. Median treatment duration was 8.4 months with T-DXd and 3.5 months with TPC. The most common grade ≥ 3 drug-related treatment-emergent adverse events in Asian patients treated with T-DXd were neutropenia (16.3%), anemia (12.9%), and leukopenia (11.6%); the incidences of neutropenia and leukopenia were higher with TPC versus T-DXd. Adjudicated drug-related interstitial lung disease or pneumonitis with T-DXd was 14.3%; the majority of events were grade 1-2.

T-DXd demonstrated clinically meaningful survival benefits versus TPC in Asian HER2-low mBC patients, regardless of hormone receptor status, with no new safety signals.

ClinicalTrials.gov, NCT03734029.

Human epidermal growth factor receptor 2 (HER2) expression is an important biomarker in breast cancer (BC). Most BC cases categorised as HER2-negative (HER2-) express low levels of HER2 [immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridisation not amplified (ISH-)] and represent a clinically relevant therapeutic category that is amenable to targeted therapy using a recently approved HER2-directed antibody-drug conjugate. A group of practising pathologists, with expertise in breast pathology and BC biomarker testing, outline best practices and guidance for achieving consensus in HER2 IHC scoring for BC.

The authors describe current knowledge and challenges of IHC testing and scoring of HER2-low expressing BC and provide best practices and guidance for accurate identification of BCs expressing low levels of HER2. These expert pathologists propose an algorithm for assessing HER2 expression with validated IHC assays and incorporate the 2023 American Society of Clinical Oncology and College of American Pathologist guideline update. The authors also provide guidance on when to seek consensus for HER2 IHC scoring, how to incorporate HER2-low into IHC reporting and present examples of HER2 IHC staining, including challenging cases.

Awareness of BC cases that are negative for HER protein overexpression/gene amplification and the related clinical relevance for targeted therapy highlight the importance of accurate HER2 IHC scoring for optimal treatment selection.

Disitamab vedotin (DV; RC48-ADC) is an antibody-drug conjugate comprising a human epidermal growth factor receptor 2 (HER2)-directed antibody, linker and monomethyl auristatin E. Preclinical studies have shown that DV demonstrated potent antitumor activity in preclinical models of breast, gastric, and ovarian cancers with different levels of HER2 expression. In this pooled analysis, we report the safety and efficacy of DV in patients with HER2-overexpression and HER2-low advanced breast cancer (ABC).

In the phase I dose-escalation study (C001 CANCER), HER2-overexpression ABC patients received DV at doses of 0.5-2.5 mg/kg once every two weeks (Q2W) until unacceptable toxicity or progressive disease. The dose range, safety, and pharmacokinetics (PK) were determined. The phase Ib dose-range and expansion study (C003 CANCER) enrolled two cohorts: HER2-overexpression ABC patients receiving DV at doses of 1.5-2.5 mg/kg Q2W, with the recommended phase 2 dose (RP2D) determined, and HER2-low ABC patients receiving DV at doses of 2.0 mg/kg Q2W to explore the efficacy and safety of DV in HER2-low ABC.

Twenty-four patients with HER2-overexpression ABC in C001 CANCER, 46 patients with HER2-overexpression ABC and 66 patients with HER2-low ABC in C003 CANCER were enrolled. At 2.0 mg/kg RP2D Q2W, the confirmed objective response rates were 42.9% (9/21; 95% confidence interval [CI]: 21.8%-66.0%) and 33.3% (22/66; 95% CI: 22.2%-46.0%), with median progression-free survival (PFS) of 5.7 months (95% CI: 5.3-8.4 months) and 5.1 months (95% CI: 4.1-6.6 months) for HER2-overexpression and HER2-low ABC, respectively. Common (≥5%) grade 3 or higher treatment-emergent adverse events included neutrophil count decreased (17.6%), gamma-glutamyl transferase increased (13.2%), asthenia (11.0%), white blood cell count decreased (9.6%), peripheral neuropathy such as hypoesthesia (5.9%) and neurotoxicity (0.7%), and pain (5.9%).

DV demonstrated promising efficacy in HER2-overexpression and HER2-low ABC, with a favorable safety profile at 2.0 mg/kg Q2W.

Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with oestrogen receptor-positive metastatic breast cancer.

Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression-free survival (PFS), was monitored at 3, 6 and 9 months; secondary endpoints, clinical benefit rate (CBR), safety and tolerability profiles, were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics.

The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months, respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and, critically, appear informative of acquired resistance in real time.

Changes in ctDNA can occur rapidly and reflect changes in patients' clinical tumour responses (NCT02681523).

Several HER2-targeting antibody-drug conjugates (ADC) have gained market approval for the treatment of HER2-expressing metastasis. Promising responses have been reported with the new generation of ADCs in patients who do not respond well to other HER2-targeting therapeutics. However, these ADCs still face challenges of resistance and/or severe adverse effects associated with their particular payload toxins. Eribulin, a therapeutic agent for the treatment of metastatic breast cancer and liposarcoma, is a new choice of ADC payload with a distinct mechanism of action and safety profile.

We've generated a novel HER2-tageting eribulin-containing ADC, BB-1701. The potency of BB-1701 was tested in vitro and in vivo against cancer cells where HER2-expressing levels vary in a large range. Bystander killing effect and toxin-induced immunogenic cell death (ICD) of BB-1701 were also tested.

In comparison with HER2-targeting ADCs with DM1 and Dxd payload, eribulin-containing ADC demonstrated higher in vitro cytotoxicity in HER2-low cancer cell lines. BB-1701 also effectively suppressed tumors in models resistant to DM1 or Dxd containing ADCs. Mode of action studies showed that BB-1701 had a significant bystander effect on HER2-null cells adjacent to HER2-high cells. In addition, BB-1701 treatment induced ICD. Repeated doses of BB-1701 in nonhuman primates showed favorable pharmacokinetics and safety profiles at the intended clinical dosage, route of administration, and schedule.

The preclinical data support the test of BB-1701 in patients with various HER2-expressing cancers, including those resistant to other HER2-targeting ADCs. A phase I clinical trial of BB-1701 (NCT04257110) in patients is currently underway.

This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan.

The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines.

In this study, 2236 patients with mTNBC (median age 66.0 years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2 months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively.

This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.

Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse. The purpose of the study is to evaluate outcomes of patients with Human Epidermal Growth Factor Receptor (HER2)-normal advanced breast cancer treated with capecitabine monotherapy as first-line treatment.

The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS).

A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5-18.0), and median PFS was 6.0 months (95% CI: 5.3-6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45-70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01).

 In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies.

Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions.

The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials.

We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC.

We selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group. We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone. Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p < 0.001.

We confirmed that gender minorities are severely underrepresented among BC registration trials. We observed a lower rate of men in trials envisaging endocrine manipulation or in less contemporary trials. This work sought to urge the scientific community to increase the awareness level towards the issue of gender minorities and to endorse more inclusive criteria in clinical trials.

Aim: This systematic literature review aims to summarize the efficacy/effectiveness of treatments, including eribulin (ERI)-based and anti-human epidermal growth factor receptor 2 (HER2) treatments in advanced/metastatic HER2+ breast cancer. Methods: Three databases from 2016 to September 2021 were searched for clinical trials and observational studies in patients receiving first-line (1L) standard of care (SOC), second-line (2L) SOC or third-line or subsequent lines (3L+). Results: 2692 citations were screened, and 38 studies were included. Eleven studies were randomized-controlled trials (RCTs; 5 in 1L, 6 in 3L+), 6 were single-arm trials (5 in 1L, 1 in 3L+) and 21 were observational studies (13 in 1L, 6 in 2L, 4 in 3L+ [note that studies with subgroups for 1L, 2L, 3L+ are double-counted]). Longer overall survival (OS) was associated with 1L and 2L treatment, and for 3L+ studies that included ERI, ERI or trastuzumab (Tmab) + ERI led to longer OS than treatments of physician's choice (median OS of 11, 10 and 8.9 months, respectively). Progression-free survival was 9 months in Tmab + pertuzumab (Pmab) + ERI, 4 months in Tmab + ERI and 3.3 months in ERI. Conclusion: Available treatments provide a wide range of efficacy. However, later lines lack standardization and conclusions on comparative effectiveness are limited by differing trial designs. Thus, the chance of prolonged survival with new agents warrants further research.

Breast cancer is the most common cancer type in women. The vast majority of breast cancer patients have hormone receptor-positive (HR+) tumors. In advanced HR+ breast cancer, the combination of endocrine therapy with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors is considered the standard of care in the front-line setting. Nevertheless, resistance to hormonal therapy and CDK4/6 inhibitors eventually occurs, leading to progression of the disease. Antibody-drug conjugates (ADCs) comprise a promising therapeutic choice with significant efficacy in patients with HR+ breast cancer, which is resistant to endocrine treatment. ADCs typically consist of a cytotoxic payload attached by a linker to a monoclonal antibody that targets a specific tumor-associated antigen, offering the advantage of a more selective delivery of chemotherapy to cancer cells. In this review, we focus on the ADC mechanisms of action, their toxicity profile and therapeutic uses as well as on related biomarkers and future perspectives in advanced HR+ breast cancer.

In the Netherlands, the clinical benefit of systemic anti-cancer treatments (SACTs) is assessed by the Committee for the Evaluation of Oncological Agents (cieBOM). For non-curative SACTs, the assessment is based on the hazard ratio (HR) for progression-free survival and/or overall survival (OS), and the difference in median survival. We evaluated the impact of different thresholds for effectiveness by reassessing the clinical benefit of SACTs.

We reassessed SACTs that were initially assessed by cieBOM between 2015 and 2017. Four scenarios were formulated: replacing an "OR" approach (initial assessment) by an "AND" approach (used in all scenarios), changing the HR threshold from < 0.70 (initial assessment) to < 0.60, changing the threshold for the difference in median survival from > 12 weeks (initial assessment) to > 16 weeks, and including thresholds for OS rates. The outcomes of these scenarios were compared to the outcomes of the initial assessment.

Reassessments were conducted for 41 treatments. Replacing the "OR" approach by an "AND" approach substantially decreased the number of positive assessments (from 33 to 22), predominantly affecting immunotherapies. This number further decreased (to 21 and 19, respectively) in case more restrictive thresholds for the HR and difference in median survival were used. Including thresholds for OS rates slightly mitigated the impact of applying an "AND" approach.

The scenario-specific thresholds had a substantial impact; the number of negative assessments more than doubled. Since this was not limited to treatments with marginal survival benefits, understanding the potential challenges that may arise from applying more restrictive thresholds is essential.

This prospective real-world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China.

In this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo-/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed.

One hundred and thirty-four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3-15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first- or second-line treatment was significantly better than those who received eribulin as ≥3-line treatment (6.9 months [95% CI: 3.2-8.8] vs. 4.0 months [95% CI: 3.4-4.6], p = 0.006). The mPFS of patients with triple-negative, HER2-positive, and HER2(-)/HR(+) was 3.4 (95% CI: 2.7-4.1), 6.2 (95% CI: 2.3-10.1) and 5.0 months (95% CI: 4.1-5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6-6.3] vs. 4.0 months [95% CI: 3.3-4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non-TNBC receiving eribulin as ≤2-line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment-related adverse events.

Eribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real-world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

Taxanes are the basic components of breast cancer chemotherapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows improved antitumor effects because of more targeted delivery. However, the effects of nab-paclitaxel have not been systematically studied in patients with metastatic breast cancer (MBC) pretreated with taxanes. Considering the limited treatment options for MBC, this study retrospectively evaluated the clinical efficacy and adverse effects of nab-paclitaxel in patients with taxane-pretreated MBC.

Patients who had previously received taxanes and subsequently received nab-paclitaxel chemotherapy for MBC at Jiangsu Cancer Hospital between October 2014 and April 2022 were included for analysis. The primary end point was progression-free survival (PFS), and the secondary end points were the objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and side effects.

A total of 236 female patients with MBC were included. The median PFS was 7.20 months (95% confidence interval [CI], 6.63-7.80 months), and the ORR, DCR, and CBR were 29.55% (95% CI, 23.50%-35.60%), 83.64% (95% CI, 78.70%-88.60%), and 56.36% (95% CI, 49.80%-63.00%), respectively. Following nab-paclitaxel treatment, the median PFS of patients who were sensitive to taxanes during previous treatments was significantly longer than that of patients who were resistant to taxanes (7.57 months vs. 4.43 months, p < .001). The most common adverse events were sensory neuropathy (89.83%), neutropenia (48.73%), leukopenia (46.61%), and anemia (35.59%).

Nab-paclitaxel demonstrated clinical activity in taxane-pretreated patients with MBC. This beneficial effect was observed both in patients who were sensitive and resistant to taxanes during previous treatments. These results suggest nab-paclitaxel as the preferred chemotherapy regimen in patients with MBC, regardless of their sensitivity to taxanes during previous treatments.

Endocrine therapy (ET) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is currently the first-line standard treatment for most patients with hormone receptor-positive (HR+) and human epidermal growth receptor 2-negative (HER2-) metastatic or advanced breast cancer. However, the majority of tumors response to and eventually develop resistance to CDK4/6is. The mechanisms of resistance are poorly understood, and the optimal postprogression treatment regimens and their sequences continue to evolve in the rapidly changing treatment landscape. In this review, we generally summarize the mechanisms of resistance to CDK4/6is and ET, and describe the findings from clinical trials using small molecule inhibitors, antibody-drug conjugates and immunotherapy, providing insights into how these novel strategies may reverse treatment resistance, and discussing how some have not translated into clinical benefit. Finally, we provide rational treatment strategies based on the current emerging evidence.

Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.

Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients.

CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P < .001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P = .241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P = .001).

In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.

Precision oncology programs using next-generation sequencing to detect predictive biomarkers are extending therapeutic options for patients with metastatic breast cancer (mBC). Regularly, based on the recommendations of the interdisciplinary molecular tumor board (iMTB), an inclusion in a clinical trial is not possible. In this case, the German health insurance system allows for the application of reimbursement for an off-label drug use. Here, we describe the current challenges and our experience with reimbursement of molecular therapies in mBC.

A total of 100 applications for reimbursement of off-label therapies recommended by an iMTB were filed for patients with mBC, of which 89 were evaluable for this analysis. The approval rate was correlated with the molecular level of evidence of the respective therapy according to the National Center for Tumor Diseases (NCT) and European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) classification as well as with pretreatment therapy lines.

Overall, 53.9% (48/89) of reimbursement applications were approved. Applications for therapies based on level of evidence m1 (NCT classification), tier I and II (ESCAT classification) had a significantly and clinically relevant increased chance of reimbursement, while a greater number of previous treatment lines had no significantly increased chance of approval, though a trend of approval toward higher treatment lines was detectable.

Currently, the German jurisdiction seems to aggravate the clinical implementation of clinically urgently needed molecular therapies.

Metastatic triple-negative breast cancer (mTNBC) is an invasive histologic subtype with a poor prognosis and rapid progression. Currently, there is no standard therapy for the third-line treatment of mTNBC. In this study, we conducted a network meta-analysis to compare regimens and determine treatment outcomes.

We performed a systematic search of PubMed, EMBASE, the Cochrane Central Register of Controlled Bases, and the minutes of major conferences. Progression-free survival, overall survival, and objective response rate were analyzed through network meta-analysis using the R software (R Core Team). The efficacy of the treatment regimens was compared using hazard ratios, odds ratios, and 95% CIs.

We evaluated 15 randomized controlled trials involving 6,010 patients. Compared with the physician's choice treatment, sacituzumab govitecan showed significant advantages in progression-free survival and overall survival, with hazard ratio values of 0.41 (95% CI: 0.32-0.52) and 0.48 (95% CI, 0.39-0.60). In terms of objective response rate, sacituzumab govitecan is the best-performing therapy (odds ratio: 10.82; 95% CI: 5.58-20.97). Adverse events among grades 3 to 5 adverse reactions, the incidence of neutropenia and leukopenia in each regimen was higher, whereas the incidence of fever, headache, hypertension, and rash was lower.

Compared with the treatment of the physician's choice, sacituzumab govitecan appears more efficacious and is the preferred third-line treatment for mTNBC.

Eribulin is widely used to treat metastatic breast cancer (BC). Higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in several cancer types. However, the association between BC prognosis and peripheral immune status remains controversial. In the present study, the relative effects of NLR and PLR on survival in patients with metastatic BC were quantified and their clinical prognostic value was evaluated. This retrospective study included 156 patients with metastatic BC who received eribulin monotherapy at Saitama Medical University International Medical Center. Clinicopathological features were examined (peripheral blood findings and biochemical liver and kidney function test results) and univariate and multivariate analyses were conducted of the overall survival (OS). The 156 patients treated with eribulin had a median follow-up duration of 18.3 months. Before eribulin treatment, patients with absolute lymphocyte counts (ALC) >1,500/µl, NLR <3.0, and PLR <150 had significantly longer OS than those with lower ALC, and higher NLR and PLR (median OS, 25.5 vs. 15.5 months; P<0.01; 20.3 vs. 13.6 months, P<0.01; and 29.2 vs. 14.8 months; P<0.001, respectively). Patients with anemia [hemoglobin (Hb) <10 g/dl] or liver dysfunction [albumin-bilirubin (ALBI) grade 2/3] had significantly shorter OS than those without (P<0.001, respectively). Multivariate analysis revealed low ALBI grade (P<0.001), high Hb (P<0.01) and low PLR (P<0.05) as independent factors of longer OS after eribulin administration. Low PLR, anemia and liver dysfunction might be factors associated with prolonged OS in patients with metastatic BC on eribulin therapy, which could be clinically useful, as their evaluation requires neither new equipment nor invasive testing.