Breast cancer (BC) is the most frequent cancer in women with more than 70% of BC patients being treated with hormonal therapy (HT). Among these patients, some report difficulties in remembering what ...they are supposed to do at the right moment, referring to prospective memory (PM). PM is essential for autonomy and medical adherence of patients, and requires an ecological assessment. Virtual reality, that recreates naturalistic environment, seems to be a promising method to evaluate PM. Several BC patients also report sleep disturbances. Given the role of sleep on memory consolidation, it is imperative to explore the influence of sleep quality on PM in BC patients treated with HT. The purpose of PROSOM-K study is to assess PM functioning using virtual reality and sleep quality in BC treated or not with HT.
PROSOM-K is a prospective study including post-menopausal BC patients ≤70 years old treated with radiotherapy (n = 25) or with radiotherapy and HT (n = 25), and healthy post-menopausal women (n = 25) matched for age and education. PM will be assessed using a virtual reality based task. Other cognitive functions and psychosocial factors will be assessed with validated questionnaires and neuropsychological tests. The study is divided in 3 sessions: a session of familiarisation with the virtual environment and the PM task: a day-time session during which participants learn intentions during the morning and recall them in the evening; and a night-time session during which participants learn intentions in the evening and recall them the following morning. Women will be monitored by wrist actigraphy; during the night-time session, objective sleep quality and quantity will be measured by polysomnography.
This is a novel study aiming to assess PM using virtual reality, coupled with the evaluation of other cognitive functions. Polysomnographic study of sleep will provide further information about architectural sleep disturbances in BC. Association between sleep architecture parameters and PM mechanism in BC women treated with HT will be described in detail. We expect our results will provide knowledge for patients and clinicians and further help to improve patient care and cognitive therapy.
NCT03420105 , registered: January 10, 2018.
The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy ...included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg
every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00-1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54-1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30-0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12-1.13) for patients with PD-L1
TNBC (n = 32) and 0.49 (95% CI: 0.18-1.34) for those with PD-L1
TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05-0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42-2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.
ERRB2 (formerly HER2)-positive advanced breast cancer (ABC) remains typically incurable with optimal treatment undefined in later lines of therapy. The chimeric antibody margetuximab shares ERBB2 ...specificity with trastuzumab but incorporates an engineered Fc region to increase immune activation.
To compare the clinical efficacy of margetuximab vs trastuzumab, each with chemotherapy, in patients with pretreated ERBB2-positive ABC.
The SOPHIA phase 3 randomized open-label trial of margetuximab plus chemotherapy vs trastuzumab plus chemotherapy enrolled 536 patients from August 26, 2015, to October 10, 2018, at 166 sites in 17 countries. Eligible patients had disease progression on 2 or more prior anti-ERBB2 therapies and 1 to 3 lines of therapy for metastatic disease. Data were analyzed from February 2019 to October 2019.
Investigators selected chemotherapy before 1:1 randomization to margetuximab, 15 mg/kg, or trastuzumab, 6 mg/kg (loading dose, 8 mg/kg), each in 3-week cycles. Stratification factors were metastatic sites (≤2, >2), lines of therapy (≤2, >2), and chemotherapy choice.
Sequential primary end points were progression-free survival (PFS) by central blinded analysis and overall survival (OS). All α was allocated to PFS, followed by OS. Secondary end points were investigator-assessed PFS and objective response rate by central blinded analysis.
A total of 536 patients were randomized to receive margetuximab (n = 266) or trastuzumab (n = 270). The median age was 56 (27-86) years; 266 (100%) women were in the margetuximab group, while 267 (98.9%) women were in the trastuzumab group. Groups were balanced. All but 1 patient had received prior pertuzumab, and 489 (91.2%) had received prior ado-trastuzumab emtansine. Margetuximab improved primary PFS over trastuzumab with 24% relative risk reduction (hazard ratio HR, 0.76; 95% CI, 0.59-0.98; P = .03; median, 5.8 95% CI, 5.5-7.0 months vs 4.9 95% CI, 4.2-5.6 months; October 10, 2018). After the second planned interim analysis of 270 deaths, median OS was 21.6 months with margetuximab vs 19.8 months with trastuzumab (HR, 0.89; 95% CI, 0.69-1.13; P = .33; September 10, 2019), and investigator-assessed PFS showed 29% relative risk reduction favoring margetuximab (HR, 0.71; 95% CI, 0.58-0.86; P < .001; median, 5.7 vs 4.4 months; September 10, 2019). Margetuximab improved objective response rate over trastuzumab: 22% vs 16% (P = .06; October 10, 2018), and 25% vs 14% (P < .001; September 10, 2019). Incidence of infusion-related reactions, mostly in cycle 1, was higher with margetuximab (35 13.3% vs 9 3.4%); otherwise, safety was comparable.
In this phase 3 randomized clinical trial, margetuximab plus chemotherapy had acceptable safety and a statistically significant improvement in PFS compared with trastuzumab plus chemotherapy in ERBB2-positive ABC after progression on 2 or more prior anti-ERBB2 therapies. Final OS analysis is expected in 2021.
ClinicalTrials.gov Identifier: NCT02492711.
The CPS+EG scoring system was initially described in unselected early breast cancer (eBC) patients treated with neoadjuvant chemotherapy (NAC), leading to refined prognostic stratification, and thus ...helping to select patients for additional post-NAC treatments. It remains unknown whether the performance is the same in new biological breast cancer entities such as the HER2-low subtype.
Outcomes (disease-free (DFS) and overall survival OS)) of 608 patients with HER2-non amplified eBC and treated with NAC were retrospectively analyzed according to CPS-EG score. We compared the prognostic stratification abilities of the CPS+EG in HER2-low and HER2–0 eBC, analyzing ER+ and ER- tumors separately.
In ER+ eBC, the CPS+EG scoring system seems to retain a prognostic value, both in HER2-low and HER2–0 tumors, by distinguishing populations with significantly different outcomes (good: score 0–1, poor: score 2–3, and very poor: score 4–5). Using C-indices for DFS and OS, CPS+EG provided the highest prognostic information in ER+ eBC, especially in HER2–0 tumors. In contrast, in ER- eBC, the CPS+EG does not appear to be able to distinguish different outcome groups, either in HER2-low or HER2–0 tumors. In ER- eBC, C-indices for DFS and OS were highest for pathological stage, reflecting the predominant prognostic importance of residual disease in this subtype.
HER2-low status does not influence the prognostic performance of the CPS+EG score. Our results confirm the usefulness of the CPS+EG score in stratifying the prognosis of ER+ eBC after NAC, for both HER2–0 and HER2-low tumors. For ER- eBC, HER2-low status does not influence the performance of the CPS+EG score, which was lower than that of the pathological stage alone.
•HER2-low status does not influence the prognostic performance of the CPS+EG score.•For ER+ eBC, the CPS+EG score properly stratifies both HER2-0 and HER2-low tumors.•For ER- eBC, the performance of the CPS+EG score is lower than that of the PS alone.
Abstract
Gamma-ray astronomy has become one of the main experimental ways to test the modified dispersion relations (MDRs) of photons in vacuum, obtained in some attempts to formulate a theory of ...quantum gravity. The MDRs in use imply time delays that depend on the energy and that increase with distance following some function of redshift. The use of transient, or variable, distant and highly energetic sources already allows us to set stringent limits on the energy scale related to this phenomenon, usually thought to be of the order of the Planck energy, but robust conclusions on the existence of MDR-related propagation effects still require the analysis of a large population of sources. In order to gather the biggest sample of sources possible for MDR searches at teraelectronvolt energies, the H.E.S.S., MAGIC, and VERITAS collaborations enacted a joint task force to combine all their relevant data to constrain the quantum gravity energy scale. In the present article, the likelihood method used to combine the data and provide a common limit is described in detail and tested through simulations of recorded data sets for a gamma-ray burst, three flaring active galactic nuclei, and two pulsars. Statistical and systematic errors are assessed and included in the likelihood as nuisance parameters. In addition, a comparison of two different formalisms for distance dependence of the time lags is performed for the first time. In a second article, to appear later, the method will be applied to all relevant data from the three experiments.
Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with ...high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes.
Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy.
Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months 0–56.6, 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; 95%CI 0.36–2.90, p = 0.98) and iDFS (HR = 0.83; 95%CI 0.31–2.23, p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% 95%CI 78.0–96.4 and 89.9% 95%CI 81.8–98.7 in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it.
NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed.
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•First CDK4/6 neoadjuvant randomised trial to report survival outcomes.•NEOPAL trial compared neoadjuvant Letrozole Palbociclib versus chemotherapy.•Pathological complete response rates were identically low (3.8% and 5.9%, respectively).•Progression-free survival (HR = 1.01; 95%CI 0.36–2.90, p = 0.98) did not differ between both arms.•Invasive disease-free survival (HR = 0.83; 95%CI 0.31–2.23, p = 0.71) did not differ between both arms.
Background and Aims:
Because of its low prevalence, metastatic breast cancer (MBC) in males is managed based on clinical experience with women. Using a real-life database, we aim to provide a ...comprehensive analysis of male MBC characteristics, management and outcome.
Methods:
The Epidemiological Strategy and Medical Economics Data Platform collected data for all men and women ⩾18 years with MBC in 18 participating French Comprehensive Cancer Centers from January 2008 to November 2016. Demographic, clinical, and pathological characteristics were retrieved, as was treatment modality. Men were matched 1:1 to women with similar characteristics.
Results:
Of 16,701 evaluable patients, 149 (0.89%) men were identified. These men were older (median age 69 years) and predominantly had hormone receptor HR+/HER2– disease (78.3%). Median overall survival (OS) was 41.8 months 95% confidence interval (CI: 26.9–49.7) and similar to women. Median progression-free survival (PFS) with first-line therapy was 9.3 months 95% CI (7.4–11.5). In the HR+/HER2– subpopulation, endocrine therapy (ET) alone was the frontline treatment for 43% of patients, including antiestrogens (n = 19), aromatase inhibitors (n = 15) with luteinizing hormone-releasing hormone (LHRH) analogs (n = 3), and various sequential treatments. Median PFS achieved by frontline ET alone was similar in men 9.8 months, 95% CI (6.9–17.4) and in women 13 months, 95% CI (8.4–30.9) (p = 0.80). PFS was similar for HR+/HER2– men receiving upfront ET or chemotherapy: 9.8 months 95% CI (6.9–17.4) versus 9.5 months 95% CI (7.4–11.7) (p = 0.22), respectively.
Conclusion:
MBC management in men and women leads to similar outcomes, especially in HR+/HER2– patients for whom ET should also be a cornerstone. Unsolved questions remain and successfully recruiting trials for men are still lacking.
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•Proton therapy in adjuvant breast cancer with nodal involvement allows better sparing of the heart than photon therapy.•Target coverage is better with proton therapy than with ...conventional photon therapy.•No excess of toxicity appears with proton therapy in adjuvant breast cancer with nodal involvement.•Therapeutic trials currently underway will probably demonstrate the full potential of proton therapy in breast cancer.•Systematic cardiac monitoring including echocardiography may be relevant for left breast cancers treated with radiotherapy.
Radiation therapy plays a major role in the management of adjuvant breast cancer with nodal involvement, with an iatrogenic increase of cardio-vascular risk. Photon therapy, even with intensity modulation, has the downsides of high mean heart dose and heterogeneous target coverage, particularly in the case of internal mammary irradiation. This systematic review of the literature aims to evaluate proton therapy in locally advanced breast cancer.
PubMed was searched for original full-text articles with the following search terms: «Proton Therapy» and «Breast Cancer». On-going trials were collected using the words “Breast Cancer” and “Protons”.
13 articles met the criteria: 6 with passive proton therapy (Double Scattering), 5 with Pencil Beam Scanning (PBS) and 2 with a combination of both. Proton therapy offered a better target coverage than photons, even compared with intensity modulation radiation therapy (including static or rotational IMRT or tomotherapy). With proton therapy, volumes receiving 95% of the dose were around 98%, with low volumes receiving 105% of the dose. Proton therapy often decreased mean heart dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with conventional 3D, and 6 Gy for IMRT. Lungs were better spared with proton therapy than with photon therapy. Cutaneous toxicity observed with double scattering is improved with PBS.
Proton therapy reduces mean heart dose in breast cancer irradiation, probably reducing late cardio-vascular toxicity. Large clinical studies will likely confirm a clinical benefit of proton therapy.
Modifications in the processing of information relevant to oneself have been reported in breast cancer (BC) patients. Here, we characterize the longitudinal changes to self‐representations in BC ...patients and how they are related to intrinsic functional brain connectivity. We tested 16 BC patients before (T1) and 1 year after the end of chemotherapy (T2) along with 24 healthy control participants (HC) at similar time points. Participants underwent resting‐state fMRI and completed the Questionnaire of Self‐Representation (QSR), which evaluates self‐assertion and self‐esteem. Resting‐state functional connectivity (RSFC) was calculated for regions implicated in self‐referential processes (dorsomedial prefrontal cortex dmPFC, posterior cingulate cortex PCC, and dorsal anterior cingulate cortex dACC) and correlated with QSR scores. QSR scores were on average larger in patients compared with HC and did not vary over time. RSFC between the dACC and regions supporting body awareness (precentral/postcentral and supramarginal gyri, superior parietal lobule) decreased more between T1 and T2 in BC patients than in HC. BC patients had lower RSFC than HC between the dmPFC and the PCC, and regions supporting mental imagery (precuneus, lingual gyrus), at each time point, and a greater decrease from T1 and T2. QSR scores negatively correlated with RSFC. Patients described themselves as having greater self‐awareness and positive self‐image, reflecting a fighting spirit. In parallel, patients presented a decrease in cortical activity related to body awareness and mental imagery of self‐representations over time that may be related to the positive self‐image patients have and could reflect a temporary adaptive strategy.
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