Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a ...retrospective multicentre study focusing on breast cancer-related MAHA.
Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records.
Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2-, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0-1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 1.6; 31.8), elevated bilirubin (OR = 6.9 1.1; 42.6), haemoglobin < 8.0 g/dL (OR = 3.7 0.9; 16.7) and prothrombin time < 50% (OR = 9.1 1.2; 50.0). A score to predict early death displayed a sensitivity of 86% (95% CI 0.67; 0.96), a specificity of 73% (95% CI 0.52; 0.88) and an area under the curve of 0.90 (95% CI 0.83; 0.97).
Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.
Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an ...intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor HR expression and HER2 protein expression/gene amplification).
We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype.
20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies.
Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.
Few data are available concerning the safety of bevacizumab (B) in combination with locoregional radiation therapy (RT). The objective of this study was to evaluate the 5-year late toxicity of ...concurrent B and RT in non-metastatic breast cancer.
This multicentre prospective study included non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT versus RT alone. All patients received neoadjuvant or adjuvant chemotherapy and normofractionated breast or chest wall RT, with or without regional lymph node RT. B was administered at an equivalent dose of 5 mg/kg once a week for 1 year. The safety profile was evaluated 1, 3 and 5 years after completion of radiotherapy.
A total of 64 patients were included between November 2007 and April 2010. Median follow-up was 60 months (12-73) and 5-year late toxicity data were available for 46 patients. The majority of tumours were triple-negative (68.8%), tumour size <2cm (41.3%) with negative nodal status (50.8%). Median total dose of B was 15,000mg and median duration was 11.2 months. No grade ≥3 toxicity was observed. Only 8 patients experienced grade 1-2 toxicities: n = 3 (6.5%) grade 1 lymphedema, n = 2 (4.3%) grade 1 pain, n = 1 (2.2%) grade 2 lymphedema, n = 1 (2.2%) grade 1 fibrosis. Five-year overall survival was 93.8%, disease-free survival was 89% and locoregional recurrence-free survival was 93.1%.
Concurrent B and locoregional RT are associated with acceptable 5-year toxicity in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed.
The phosphatidylinositol‐3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in HER2‐negative breast cancer and may play a role in taxane resistance. The phase ...IB/II TAKTIC trial (NCT01980277) has shown that combining a dual AKT and p70 ribosomal protein S6 kinase (p70S6K) inhibitor (LY2780301) taken orally with weekly paclitaxel in HER2‐negative advanced breast cancer is feasible, with preliminary evidence of efficacy. We wanted to explore whether circulating tumor DNA (ctDNA) may be a surrogate marker of treatment efficacy in this setting. Serial plasma samples were collected and cell‐free DNA was sequenced using low‐coverage whole‐genome sequencing, and analysis was completed with droplet digital polymerase chain reaction (PCR) for some patients with driver mutations. Baseline tumor fraction (TF) and TF after 7 weeks on treatment were compared to progression‐free survival (PFS) and the overall response rate. We also explored circulating copy number alterations associated with treatment failure. Of the 51 patients enrolled in the TAKTIC trial, at least one plasma sample was available for 44 cases (96 timepoints). All patients with tumor TP53, PI3KCA, or AKT1 mutations harbored at least one of these alterations in plasma. TF at inclusion was correlated with PFS (6m‐PFS was 92% for ctDNAneg patients vs 68% for ctDNApos cases; hazard ratio HR = 3.45, 95% confidence interval CI 1.34–8.90, P = 0.007). ctDNA status at week 7 was not correlated with prognosis. Even though most circulating copy number alterations were conserved at disease progression, some genomic regions of interest were altered in post‐progression samples. In conclusion, ctDNA detection at baseline was associated with shorter PFS in patients included in the TAKTIC trial. Plasma‐based copy number analysis may help to identify alterations involved in resistance to treatment.
We used whole‐genome sequencing of circulating tumor DNA (ctDNA) to obtain copy number alteration profiles from the plasma of patients with metastatic breast cancer receiving a combination of paclitaxel and LY2780301 (dual AKT/p70S6H inhibitor). ctDNA detection at baseline predicted shorter progression‐free survival. Post‐progression plasma copy number alteration analysis may identify genomic alterations involved in resistance to treatment.
Taxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously ...treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies.
We analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3–24 months after previous (neo)adjuvant taxanes treatment.
Of 23,501 female patients with MBC in ESME, 1057 met the selection criteria. 58.4% received a taxane-based regimen (75.4% concomitant bevacizumab) and 41.6% received other CT.
In hormone-receptor positive (HR+)/HER2- MBC, multivariate analysis showed no difference in OS between taxanes without bevacizumab compared to other CT (HZR = 1.3 0.97; 1.74, but taxanes was significantly associated with worse PFS (HZR = 1.48 1.14; 1.93).
In TNBC, taxanes without bevacizumab and carboplatin/gemcitabine were not superior to other CT for OS (HZR = 1.07 0.79; 1.44 and HZR = 0.81 0.58; 1.13, respectively), while for PFS, taxanes was inferior (HZR = 1.33 1.06–1.67) and carboplatin plus gemcitabine was superior to other CT (HZR = 0.63 0.46; 0.87).
For both subtypes, the worse outcome observed with paclitaxel was no longer observed with the addition of bevacizumab.
With the limitation of retrospective design, taxanes rechallenge in early metastatic relapse of BC may result in a worse PFS in TNBC and HR+/HER2- MBC, which was not observed with the addition of bevacizumab.
•Patients with HER2-advanced breast cancer (ABC) have often previously received taxanes in the (neo)adjuvant setting.•Current guidelines suggest a rechallenge by taxanes in ABC with DFI≥12 months, few data are available for DFI ≤24 months.•Taxane rechallenge in early metastatic relapse of BC (DFI ≤24 months) may result in a worse PFS in TNBC and HR+/HER2- ABC.•In TNBC, the addition of bevacizumab to taxanes improves PFS and OS for DFI ≤24 months.
Purpose
This study assessed sustainable return to work (SRTW) of breast cancer survivors (BCS).
Methods
We used data from the prospective French cohort, CANTO. We included 1811 stage I–III BCS who ...were <57 years old and employed at the moment of diagnosis and working 2 years after diagnosis. Using logistic regression, we investigated the role of clinical, health and socio‐economic factors, and the work environment on SRTW 3 years after diagnosis. We compared having any sick leave with having worked continuously and being unemployed to having worked continuously between 2 and 3 years after diagnosis.
Results
Overall, 77% (n = 1395) worked continuously after return to work (RTW). Out of the other 416 BCS, 66% had any sick leave period, 33% had been unemployed, 4% had an early retirement, 2% a disability and 1% another status (multiple situations possible). Being on sick leave was associated with age > 50 (OR = 0.59; 95%CI = 0.43–0.82), stage III (2.56; 1.70–3.85), tumour subtype HR+/HER2+ (0.61; 0.39–0.95), severe fatigue (1.45; 1.06–1.98), workplace accommodations (1.63; 1.14–2.33) and life priorities (0.71; 0.53–0.95). Unemployment was associated with age > 50 (0.45; 0.29–0.72), working in the public sector (0.31; 0.19–0.51), for a small company (3.00; 1.74–5.20) and having a fixed‐term contract (7.50; 4.74–11.86).
Conclusions
A high number of BCS have periods of sick leave or unemployment after RTW. The determinants differ between sick leave and unemployment.
Implications for cancer survivors
BCS need to be supported even after RTW, which should be regarded as a process.
Inflammatory breast cancer (IBC) is a rare entity with a poor prognosis. We analysed the survival outcomes of patients with nonmetastatic IBC and the prognostic value of tumour or nodal responses to ...assess their individual prognostic impact across IBC subtypes. This retrospective multicentre study included patients diagnosed with IBC between 2010 and 2017 to account for advances in neoadjuvant systemic therapies and modern radiotherapy at seven oncology centres in France. Three hundred and seventeen patients were included and analysed. After a median follow-up of 52 months, the 5-year DFS was lower for triple-negative (TN) (50.1% vs. 63.6%; p < 0.0001). After multivariate analyses, incomplete nodal response was the only significant prognostic factor in the triple-negative group (HR:6.06). The poor prognosis of TN-IBC was reversed in the case of nodal response after neoadjuvant chemotherapy. Breast response does not appear to be a decisive prognostic factor in patients with TN-IBC compared to lymph node response. Despite improvements in neoadjuvant treatments, IBC remains associated with a poor prognosis. In TN-IBC patients, lack of pathological complete node response was associated with poorer survival than any other group. Treatment intensification strategies are worth investigating.
Background
The aim of this study is to determine if the choice of the
18
F-FDG-PET protocol, especially matrix size and reconstruction algorithm, is of importance to discriminate between ...immunohistochemical subtypes (luminal versus non-luminal) in breast cancer with textural features (TFs).
Procedures
Forty-seven patients referred for breast cancer staging in the framework of a prospective study were reviewed as part of an ancillary study. In addition to standard PET imaging (PSF
WholeBody
), a high-resolution breast acquisition was performed and reconstructed with OSEM and PSF (OSEM
breast
/PSF
breast
). PET standard metrics and TFs were extracted. For each reconstruction protocol, a prediction model for tumour classification was built using a random forests method. Spearman coefficients were used to seek correlation between PET metrics.
Results
PSF
WholeBody
showed lower numbers of voxels within VOIs than OSEM
breast
and PSF
breast
with median (interquartile range) equal to 130 (43–271), 316 (167–1042), 367 (107–1221), respectively (
p
< 0.0001). Therefore, using LifeX software, 28 (59%), 46 (98%) and 42 (89%) patients were exploitable with PSF
WholeBody
, OSEM
breast
and PSF
breast
, respectively.
On matched comparisons, PSF
breast
reconstruction presented better abilities than PSF
wholeBody
and OSEM
breast
for the classification of luminal versus non-luminal breast tumours with an accuracy reaching 85.7% as compared to 67.8% for PSF
wholeBody
and 73.8% for OSEM
breast
. PSF
breast
accuracy, sensitivity, specificity, PPV and NPV were equal to 85.7%, 94.3%, 42.9%, 89.2%, 60.0%, respectively. Coarseness and ZLNU were found to be main variables of importance, appearing in all three prediction models. Coarseness was correlated with SUV
max
on PSF
wholeBody
images (ρ = − 0.526,
p
= 0.005), whereas it was not on OSEM
breast
(ρ = − 0.183,
p
= 0.244) and PSF
breast
(ρ = − 0.244,
p
= 0.119) images. Moreover, the range of its values was higher on PSF
breast
images as compared to OSEM
breast
, especially in small lesions (MTV < 3 ml).
Conclusions
High-resolution breast PET acquisitions, applying both small-voxel matrix and PSF modelling, appeared to improve the characterisation of breast tumours.
Inflammatory breast cancer (IBC) is a highly aggressive entity with a poor outcome and relative resistance to treatment. Despite progresses achieved during the last decades, the survival remains ...significantly lower than non-IBC. Recent clinical trials assessing PD-1/PD-L1 inhibitors showed promising results in non-IBC. Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of different cancers. Several recent studies suggested a potential interest of targeting the immune system in IBC by revealing a more frequent PD-L1 expression and an enriched immune microenvironment when compared with non-IBC. Here, we describe the rationale and design of PELICAN-IPC 2015-016/Oncodistinct-003 trial, an open-label, randomized, non-comparative, phase II study assessing efficacy, and safety of pembrolizumab in combination with anthracycline-containing neoadjuvant chemotherapy in HER2-negative IBC. The trial is ongoing. The primary endpoint is the pCR rate (ypT0/Tis, ypN0) in overall population and the co-primary endpoint is safety profile during a run-in phase. Key secondary objectives include tolerability, invasive disease-free, event-free and overall survivals, as well as collection of tumor and blood samples for translational research.
https://clinicaltrials.gov/ (NCT03515798).
Everolimus is the first oral targeted therapy widely used in advanced HR+/HER2- breast cancer. We sought to evaluate the impact of everolimus-based therapy on overall survival in the ESME-MBC ...database, a national metastatic breast cancer cohort that collects retrospective data using clinical trial-like methodology including quality assessments. We compared 1693 patients having received everolimus to 5928 patients not exposed to everolimus in the same period. Overall survival was evaluated according to treatment line, and a propensity score with the inverse probability of treatment weighting method was built to adjust for differences between groups. Crude and landmark overall survival analyses were all compatible with a benefit from everolimus-based therapy. Adjusted hazard ratios for overall survival were 0.34 (95% CI: 0.16-0.72,
= 0.0054), 0.34 (95% CI: 0.22-0.52,
< 0.0001), and 0.23 (95% CI: 0.14-0.36,
< 0.0001) for patients treated with everolimus in line 1, 2, and 3 and beyond, respectively. No clinically relevant benefit on progression-free survival was observed. Causes for everolimus discontinuation were progressive disease (56.2%), adverse events (27.7%), and other miscellaneous reasons. Despite the limitations inherent to such retrospective studies, these results suggest that adding everolimus-based therapy to the therapeutic sequences in patients with advanced HR+/HER2- breast cancer may favorably affect overall survival.
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