Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME ...(Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008.
We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2−; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD).
The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference. This effect is driven by the HER2+ subcohort, where it is dramatic Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference. YOD had, however, no sustained impact on OS among patients with TNBC Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference nor among those with HR+/HER2– MBC Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2– and TNBC cohorts, respectively, whatever YOD.
OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed.
•OS of HER2+ MBC patients keeps improving over time Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference.•This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials.•OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials.•YOD had no sustained impact on OS among patients with TNBC and luminal MBC.•The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort.
Efficacy of endocrine therapy in HR+/HER2- metastatic breast cancer could differ depending on the presence of BRCA1/2 germline mutation.
The ESME metastatic breast cancer platform (NCT03275311) is a ...French real world database. Multivariable models including a time-varying approach and landmark analyses assessed the association between time-dependent gBRCA status (categorised as gBRCAm, gBRCAwt (wild type), and untested), overall survival (OS), and first-line progression-free survival (PFS1).
A total of 170 patients were gBRCAm carriers, 676 gBRCAwt, and 12,930 were untested at baseline. In the multivariable analysis, gBRCAm carriers overall had a lower OS compared to gBRCAwt (adjusted HR 95% CI 1.26 1.03-1.55). gBRCAm patients treated with front-line endocrine therapy had lower adjusted OS (adjusted HR 95% CI = 1.54 1.03-2.32) and PFS1 (adjusted HR 95% CI 1.58 1.17-2.12) compared to gBRCAwt patients. However, for patients who received frontline chemotherapy, neither OS nor PFS1 differed between gBRCAm carriers and the other groups (HR versus gBRCAwt for OS: 1.12 0.88-1.41, p = 0.350; PFS1: 1.09 0.90-1.31, p = 0.379).
In this large cohort of HR+/HER2- MBC patients treated in a pre-CDK4/6 inhibitors era, gBRCAm status was associated with a lower OS and lower PFS following first-line endocrine therapy, but not following first-line chemotherapy.
Purpose
Older cancer patients are underrepresented in clinical trials. We aimed to evaluate the enrollment of older women aged 70 years old (yo) or over with metastatic breast cancer (MBC) in ...clinical trials.
Methods
We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real-life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment in older ones.
Results
5552 women were aged ≥ 70 (median 74yo; IQR 72–77). 14,611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 95%CI 0.33–0.76 for the 80–85yo class; OR 0.17 95%CI 0.06–0.39 for the 85yo and more class), good ECOG Performance Status (PS 0–1) (OR 0.15 95%CI 0.08–0.27 for the PS 2–4 class), HER2 + disease (OR 1.78 95%CI 1.27–2.48), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 95%CI 3.13–8.18), and period (OR 1.65 95%CI 1.22–2.26 for 2012–2016, compared to 2008–2011).
Conclusion
In this large database, few older MBC patients were enrolled in a trial compared with younger ones.
The estimated rate of de novo metastatic breast cancer (dnMBC) at the time of diagnosis is between 5 to 12%. International guidelines recommend metastatic work-up (MWU) only in women with advanced ...breast cancer. The purpose of this study was to describe the characteristics and prognosis of patients with dnMBC diagnosed without an initial indication for MWU.
We conducted a retrospective, comparative study in dnMBC patients selected from the ESME-MBC cohort. Patients were treated in France between 2008 and 2016. We compared two populations: patients in whom dnMBC was diagnosed by staging although not indicated by guidelines (non-guideline staging NGS) and those in whom dnMBC was diagnosed by guideline staging (GS).
During the study period, 22,463 patients with MBC were included in the ESME cohort. Among them, 6698 were dnMBC patients. In 247 of these patients (6% of dnMBC and 1% of the overall population), dnMBC was diagnosed by non-guideline staging. Women in this group were significantly younger (57 vs. 59 years, p = 0.02) and had fewer metastatic sites at diagnosis than dnMBC-GS patients. The two groups were not significantly different in terms of the other characteristics. Overall survival (OS) and progression-free survival (PFS) were better in the dnMBC-NGS group than in the dnMBC-GS group. The impact on survival was confirmed by univariate and multivariate analysis (HR 1.83 1.31–2.57, p < 0.01).
This study provides the first description of a very specific population. These patients with dnMBC-NGS were younger and more likely to have oligometastatic disease with a better prognosis.
•T1/T2 N0 de novo metastatic breast cancer (MBC) represented 6% of all de novo MBC.•Metastatic diagnosis in this population implied an unrecommended workup.•These patients were younger with oligometastatic disease and had a better prognosis.•Locoregional therapy prior to diagnosis in this population did not change survival.
L’imagerie par résonance magnétique (IRM) est un examen clé dans le suivi des métastases cérébrales irradiées. Certaines prises de contraste suspectes posent le problème du diagnostic différentiel ...entre une récidive tumorale et une radionécrose. Les nouvelles techniques multimodales (perfusion et spectrométrie) et la tomographie par émission de positons (TEP) permettent d’affiner le diagnostic et se posent en alternative d’un prélèvement histologique par biopsie stéréotaxique, seule méthode fiable, mais invasive. Nous rapportons ici le cas d’une patiente atteinte d’une métastase frontale gauche d’un carcinome mammaire sept mois après la prise en charge chirurgicale, suivie d’une radiothérapie stéréotaxique du lit opératoire. L’IRM en zone irradiée a constaté une prise de contraste suspecte pour laquelle la distinction entre récidive tumorale et radionécrose n’a pas pu être déterminée sur les séquences de perfusion. La réalisation d’une TEP au (18F)-fluorodésoxyglucose (FDG) a permis de mettre en évidence une lésion hypermétabolique. Après exérèse chirurgicale, l’analyse histologique retrouvait principalement de la radionécrose associée à la présence de cellules carcinomateuses. Malgré l’IRM multimodale, la distinction entre une récidive tumorale et une radionécrose reste souvent difficile. La TEP-FDG est une aide diagnostique, en faveur de la récidive, en cas de lésion hypermétabolique. D’autres traceurs (fluorés ou marqués au carbone 11) sont intéressants mais ne sont pas disponibles dans tous les centres. La biopsie stéréotaxique reste à discuter si le doute persiste, avec un changement d’attitude thérapeutique à la clé.
Magnetic resonance imaging (MRI) is a method of choice for follow-up of irradiated brain metastasis. It is difficult to differentiate local tumour recurrences from radiation induced-changes in case of suspicious contrast enhancement. New advanced MRI techniques (perfusion and spectrometry) and amino acid positron-emission tomography (PET) allow to be more accurate and could avoid a stereotactic biopsy for histological assessment, the only reliable but invasive method. We report the case of a patient who underwent surgery for a single, left frontal brain metastasis of a breast carcinoma, followed by adjuvant stereotactic radiotherapy in the operative bed. Seven months after, she presented a local change in the irradiated area on the perfusion-weighted MRI, for which the differentiation between a local tumour recurrence and radionecrosis was not possible. PET with 2-deoxy-(18F)-fluoro-D-glucose (FDG) revealed a hypermetabolic lesion. After surgical resection, the histological assessment has mainly recovered radionecrosis with few carcinoma cells. The multimodal MRI has greatly contributed to refine the differential diagnosis between tumour recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve interest but are not available in all centres. Stereotactic biopsy should be discussed if any doubt remains.
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