Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer ...patients receiving EM as second, third and fourth line in a national real‐life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression‐free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti‐HER2 targeted therapies use, we thus performed a subanalysis in HER2− patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to “Other chemotherapies” patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth‐line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth‐line). No significant difference was reported in second‐line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2− patients, a significant difference was seen for all lines, including 2nd‐line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real‐world database, HER2‐negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2‐targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti‐HER2 therapies addition in this setting still needs to be defined.
What's new?
An emerging therapy for metastatic breast cancer may extend survival over other chemotherapies. Eribulin mesylate (EM), a microtubule‐dynamics inhibitor, was approved by the FDA in 2010 as a later‐line therapy for metastatic breast cancer. Here, the authors evaluated EM effectiveness by analyzing data from 16,703 MBC patients. Treatment with EM as a third or fourth line therapy improved survival compared to other chemotherapy, but as a second line therapy, EM only benefited patients with HER2‐ disease. Since this trial was retrospective, not randomized, different proportions of patients in the two treatment groups received HER‐targeting therapies, which may have influenced the result.
Twenty to 30% of patients with breast cancer have cognitive impairment after surgery and before adjuvant treatment, but very few studies have focused on cognition before any treatment. This study ...used a subgroup of women with newly diagnosed breast cancer from the French cancer and toxicities (CANTO) cohort to describe cognition before any treatment in comparison with a group of healthy controls (HC).
Cognitive assessment was performed before any breast cancer treatment (surgery or neoadjuvant treatment) on women with newly diagnosed invasive stage I-III breast cancer and HCs. Objective cognitive performance, cognitive complaints, anxiety, depression, and fatigue were assessed. Objective cognitive impairment was defined according to International Cognition and Cancer Task Force recommendations.
Of the 264 included patients with breast cancer (54 ± 11 years) and 132 age-matched HCs (53 ± 9 years), overall objective cognitive impairment was observed in 28% of patients with breast cancer and 8% of HCs (
< 0.001). Cognitive complaints were reported by 24% of patients versus 12% of HCs (
< 0.01). Patients reported significantly more anxiety and emotional and cognitive fatigue than HCs (
< 0.01). After adjustment, significantly more patients with breast cancer had overall objective cognitive impairment than HCs OR = 3.01; 95% confidence interval (CI): 1.31-6.88 without significant difference between groups for cognitive complaints (OR = 1.38; 95% CI: 0.65-2.92). Cognitive complaints were positively associated with fatigue (OR = 1.03; 95% CI: 1.02-1.05).
In this prospective study, compared with HCs, patients with localized breast cancer had more objective cognitive impairment before any treatment. Cognitive complaints were mostly related to fatigue.
Baseline assessment before treatment is important to assess the impact of each cancer treatment on cognition.
Abstract Purpose Cognitive deficits (CD) are reported among cancer patients receiving chemotherapy, but may also be observed before treatment. Though elderly patients are expected to be more prone to ...present age-related CD, poor information is available regarding the impact of cancer and chemotherapy on this population. This study assessed baseline cognitive functions (before adjuvant treatment) in elderly early stage breast cancer (EBC) patients. Methods Women >65 years-old with newly diagnosed EBC were included in this prospective study. Episodic memory, working memory, executive functions and information processing speed were assessed by neuropsychological tests. Questionnaires were used to assess subjective CD, anxiety, depression, fatigue, quality of life and geriatric profile. Objective CD were defined using International Cognition and Cancer Task Force criteria. A group of elderly women without cancer coupled with published data related to healthy women were used for comparison (respectively to subjective and objective CD). Results Among the 123 elderly EBC patients (70 ± 4 years) included, 41% presented objective CD, which is greater than expected in healthy population norms (binomial test P < .0001). Verbal episodic memory was mainly impaired (21% of patients). No correlation was observed between objective CD and cancer stage or geriatric assessment. Subjective CD only correlated with verbal episodic memory ( P = .01). Conclusions This is the first large series assessing baseline cognitive functions in elderly EBC patients. More than 40% presented objective CD before any adjuvant therapy, which is higher than what is reported among younger patients. Our results reinforce the hypothesis that age is a risk factor for CD in EBC patients.
Background
Proof of concept studies has reported that circulating endothelial cell (CEC) count may be associated with the outcome of HER2-negative metastatic breast cancer (mBC) patients treated by ...chemotherapy and the anti-VEGF antibody bevacizumab. We report the results obtained in an independent prospective validation cohort (COMET study, NCT01745757).
Methods
The main baseline criteria were HER2-negative mBC, performance status 0–2 and no prior chemotherapy for metastatic disease. CECs were detected by CellSearch® from 4 ml of blood at baseline and after 4 weeks of weekly paclitaxel and bevacizumab therapy. CEC counts (considered both as a continuous variable and using the previously described 20 CEC/4 ml cutoff) were associated with clinical characteristics and progression-free survival (PFS).
Results
CEC count was obtained in 251 patients at baseline and in 207 patients at 4 weeks. Median baseline CEC count was 22 CEC/4 ml (range 0–2231). Baseline CEC counts were associated with performance status (
p
= 0.02). No statistically significant change in CEC counts was observed between baseline and 4 weeks of therapy. High baseline CEC count was associated with shorter PFS in univariate and multivariate analyses (continuous:
p
< 0.001; dichotomized: HR 1.52, 95% CI 1.15–2.02,
p
= 0.004). CEC counts at 4 weeks had no prognostic impact.
Conclusion
This study confirms that CEC count may be associated with the outcome of mBC patients treated with chemotherapy and bevacizumab. However, discrepancies with previous reports in terms of both the timing of CEC count and the direction of the prognostic impact warrant further clinical investigation.
Background
Previous studies have revealed both sleep alterations and prospective memory (PM) impairments in breast cancer (BC) patients. PM refers to memory of intended actions and is crucial for ...daily living tasks and treatment compliance. As sleep is known to favor memory consolidation, one may expect that changes in sleep quality related to BC would have an impact on PM performance. This study aimed at assessing sleep-dependent consolidation of intentions using an ecological, virtual reality-based PM task in BC patients not treated with chemotherapy.
Materials and methods
Thirty-seven early stages BC patients and 21 healthy controls (HC) participated in this study. PM was assessed using a virtual reality task, during which participants learnt a list of intentions and recalled them after a retention interval filled with a day awake or a night of sleep monitored by polysomnography. Sleep spindles and slow waves, brain oscillations involved in sleep-dependent memory consolidation, were quantified automatically using the Aseega software (Physip). Subjective sleep disturbances and markers of quality of life (psychological distress, fatigue, and well-being) were assessed by questionnaires.
Results
Greater PM performance was observed after sleep than after an equivalent period of daytime wakefulness for both groups (HC and BC). PM performance after sleep did not differ significantly between groups. Yet, BC patients reported greater sleep disturbances than HC which were related with poorer intentions retrieval, greater psychological distress, fatigue and poorer well-being. The frequency of spindles was higher and the amplitude of slow waves lower in BC patients compared to HC. However, no significant association was observed between polysomnography parameters and PM scores in the whole sample of participants.
Conclusion
Although subtle changes in brain oscillations involved in sleep-dependent memory consolidation were observed, these changes did not significantly impair overnight PM consolidation in BC patients. Nevertheless, poorer PM performance was associated with greater sleep complaints which in turn were related to poorer quality of life. Overall, these data suggest that sleep-dependent PM consolidation mechanisms are not altered in early stages BC patients not treated with chemotherapy. Further investigations are needed to understand the association between markers of quality of life and sleep-dependent memory consolidation.
Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses.
The kinetics of central nervous system (CNS) ...metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method).
CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2-/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR- (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triple-negative and HER2-/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR-, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2-/HR+ patients (p <0.0001).
Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients.
NCT03275311.
Adverse effects of breast cancer treatment can negatively affect survivors' work ability. Previous reports lacked detailed clinical data or health-related patient-reported outcomes (PROs) and did not ...prospectively assess the combined impact of treatment and related sequelae on employment.
We used a French prospective clinical cohort of patients with stage I-III breast cancer including 1,874 women who were working and ≥ 5 years younger than legal retirement age (≤ 57 years) at breast cancer diagnosis. Our outcome was nonreturn to work (non-RTW) 2 years after diagnosis. Independent variables included treatment characteristics as well as toxicities (Common Toxicity Criteria Adverse Events CTCAE v4) and PROs (European Organization for Research and Treatment of Cancer EORTC Quality of life Questionnaires, Breast cancer module QLQ-BR23 and Fatigue module QLQ-FA12, Hospital Anxiety and Depression Scale) collected 1 year after diagnosis. Logistic regression models assessed correlates of non-RTW, adjusting for age, stage, comorbidities, and socioeconomic covariates.
Two years after diagnosis, 21% of patients had not returned to work. Odds of non-RTW were significantly increased among patients treated with combinations of chemotherapy and trastuzumab (odds ratio OR
chemotherapy-hormonotherapy: for chemotherapy-trastuzumab, 2.01; 95% CI, 1.18 to 3.44; for chemotherapy-trastuzumab-hormonotherapy, 1.62; 95% CI, 1.10 to 2.41). Other significant associations with non-RTW included grade ≥ 3 CTCAE toxicities (OR
no, 1.59; 95% CI, 1.15 to 2.18), arm morbidity (OR
no, 1.59; 95% CI, 1.19 to 2.13), anxiety (OR
no, 1.47; 95% CI, 1.02 to 2.11), and depression (OR
no, 2.29; 95% CI, 1.34 to 3.91).
Receipt of systemic therapy combinations including trastuzumab was associated with increased odds of non-RTW. Likelihood of unemployment was also higher among patients who reported severe physical and psychological symptoms. This comprehensive study identifies potentially vulnerable patients and warrants supportive interventional strategies to facilitate their RTW.
Background
Group‐based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored ...cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early‐stage breast cancer (EBC) after adjuvant treatment compared with healthy controls.
Patients and Methods
Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age‐, sex‐, and education‐matched). The pretreatment assessment was conducted before adjuvant therapy, and the post‐treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status.
Results
The sample consisted of women newly diagnosed with EBC (n = 118) and healthy controls (n = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant (p = .0001). Thirty‐six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline.
Conclusion
This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer‐term remote follow‐up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC.
Implications for Practice
After the end of adjuvant treatment, 31% of older adults with early‐stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow‐up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients’ autonomy.
Cancer and cancer treatments could accelerate the cognitive aging process. This article describes pre‐ and post‐treatment objective cognitive changes in older adults with early stage breast cancer after adjuvant treatment compared with matched healthy controls.
The BEVERLY-2 single-arm phase II trial assessed the efficacy and safety of combining neoadjuvant chemotherapy with bevacizumab and trastuzumab for the treatment of HER2-positive inflammatory breast ...cancer (IBC). Here, we report the results of a preplanned survival analysis at 3 years of follow-up, along with the association between outcome and circulating biomarkers and pathologic complete response (pCR).
Patients received fluorouracil, epirubicin, cyclophosphamide, and bevacizumab (cycles 1-4) and docetaxel, trastuzumab, and bevacizumab (cycles 5-8) before surgery, followed by trastuzumab and bevacizumab for 30 weeks after surgery. Circulating tumor cell (CTC) and endothelial cell (CEC) counts were assessed at baseline, cycle 5, preoperative, postoperative, and at 1 year.
Fifty-two patients were included. The 3-year disease-free survival (DFS) rate was 68% and overall survival (OS) rate was 90%. pCR (centrally reviewed) was strongly associated with 3-year DFS 80% and 53% in patients with/without pCR, respectively (P = 0.03). CTC detection also independently predicted 3-year DFS 81% vs. 43% for patients with <1 vs. ≥1 CTC/7.5 mL at baseline (P = 0.01). Patients with no CTCs detected at baseline and with pCR had a high 3-year DFS (95%). CEC changes during treatment had no prognostic value.
Our study suggests that the prognosis of IBC relies on more than the achievement of pCR and highlights the role of early hematogenous tumor dissemination as assessed by CTCs. Combining these two prognostic factors isolates a subgroup of IBC with excellent survival when treated with bevacizumab- and trastuzumab-containing regimens.
For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a ...real-life study.
The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation.
The ESME research programme included 9921 patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval CI, 10.8–12.1), 5.8 (95% CI, 5.3–6.1) and 5.5 (95% CI, 4.6–6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P < 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P < 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months.
Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET.
•Contrary to guidelines, endocrine therapy was prescribed to a minority of patients.•In our real-life cohort, median PFS compared favourably with clinical trial results.•Patients with a low tumour burden may achieve prolonged response.
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