To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment.
ESR1 circulating D538G and Y537S/N/C ...mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas.
Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome.
ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.
Introduction
We aimed to study post-traumatic stress disorder (PTSD) symptoms in breast cancer (BC) patients during the coronavirus disease (COVID-19) pandemic.
Materials and methods
We included BC ...patients receiving medical treatment during the first COVID-19 lockdown in France. PTSD symptoms were evaluated using the Impact of Event Scale-Revised (IES-R) questionnaire. Quality of life Functional Assessment of Cancer Therapy-General (FACT-G), cognitive complaints Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog), insomnia Insomnia Severity Index (ISI), and psychosocial experiences during lockdown were also evaluated. Multivariable logistic regression was used to identify clinical factors (from medical records) and psychosocial factors (from questionnaires) associated with PTSD symptoms.
Results
Among the 253 included BC patients (mean age: 58), 46% had metastatic cancer and 52% were treated by chemotherapy alone. COVID-19-induced adjustments in medical oncology practices were experienced by 27% of patients (mainly teleconsultations). No case of COVID-19 was reported; 23% of BC patients had PTSD symptoms. Compared to other patients, patients with PTSD symptoms had more fears relative to COVID-19 infection (83 vs. 60%,
p
= 0.009), had more feeling of isolation (69 vs. 41%,
p
= 0.003), and had more prescription or increased use of psychotropic drugs (49 vs. 20%,
p
= 0.001). In the multivariable model adjusted for clinical factors, fears relative to COVID-19 and increased use of psychotropic drugs were independently associated with PTSD symptoms (OR 95% CI = 3.01 1.20–8.44 and 3.45 1.48–8.17, respectively). Besides, patients with PTSD symptoms had poor quality of life (QoL), and more cognitive complaints and insomnia.
Conclusion
Post-traumatic stress disorder symptoms were observed in 23% of BC patients during the first COVID-19 lockdown in France. Psychological supports are needed for patients treated during the COVID-19 pandemic.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in ...patients with metastatic breast cancer (MBC).
The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers.
Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI 46.2–48.5) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect.
Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.
•This is the first large multicenter cohort reporting BMI’s effect on outcomes among patients with metastatic breast cancer.•Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype.•Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:
As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date ...real-life cohort of this clinical setting and compares it to other clinical presentations.
Methods:
We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Descriptive statistics and multivariate Cox model were used.
Results:
Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50–1.91), p < 0.001). Among the 541 (2.4%) patients with isolated CNS metastases and no intrathecal therapy (excluding leptomeningeal metastases), HER2+ cases were preponderant over TN or HR+ /HER2− cases (41.6% versus 26.1% versus 28.5%, respectively, p < 0.01). The treatment strategy consisted of a combination of local treatment and systemic therapy (49.2%), local treatment only (35.5%) or systemic therapy only (11.4%), or symptomatic therapy only (3.9%). Median PFS was 6.1 months (95% CI: 5.7–6.8). Median OS was 20.7 months (95% CI: 17.3–24.3), reaching 37.9 months (95% CI: 25.9–47.6) in the HR+ /HER2+ subgroup. Older age, TN subtype, MBC-free interval of 6–12 months, lower performance status, and WBRT were associated with poorer survival. Patients who received systemic therapy within 3 months from MBC diagnosis had longer OS (24.1 versus 16.1 months, p = 0.031), but this was not significant on multivariate analysis HR = 1.0 (95% CI: 0.7–1.3), p = 0.806.
Conclusions:
Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies.
Genomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in “intermediate” ...clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients.
This multicenter, single arm prospective study (NCT02773004) enrolled patients for which adjuvant chemotherapy was uncertain, based on predefined criteria. The primary endpoint was the proportion of change between initial adjuvant decision and final administration of chemotherapy. Secondary endpoints included post-test (Day 17) and 1-year patient reported outcomes.
One third of 200 evaluable patients had a high EpClin score (≥3.32867; 10 years cumulative risk of distance failure ≥10%). The overall change rate of chemotherapy decision was 72/200 (35.8%, 95% CI 29.2–42.4). Chemotherapy was withdrawn in 57 cases (28.4% 22.2–34.8) and added in 15 (7.5% 3.8–11.2. 6 changes (8%) were based on patients’ decisions. Anxiety and distress levels increased at Day 17 when adding chemotherapy after the test result (p < 10−7 and 0.00022 respectively), while stable in other situations. At 1-year, all patients had returned to the baseline anxiety and distress levels (mean anxiety 51.5, +/− SD = 2.5 max. 80, mean distress 3±1 max. 10).
EndoPredict ® (EpClin) is clinically useful in deciding whether or not to administer adjuvant chemotherapy in patients with intermediate risk. A single-step decision is preferable since adding chemotherapy at a later stage increases anxiety and distress.
•EndoPredict ® (EpClin) allowed a chemotherapy decision modification in 35% of the patients included in the Adendom trial.•Patient-physician concertation is important: 8% of treatment changes are based on patients’ will.•A single-step decision including the test appears preferable to limit anxiety and distress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Trastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 ...blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal evaluation of these strategies.
ESME Data Platform (NCT03275311) included individual data from all patients aged ≥18 years, in whom first-line treatment for metastatic breast cancer (MBC) was initiated between January 1, 2008 and December 31, 2016 in one of the 18 French Comprehensive Cancer Centers. The efficacy of T-DM1 and lapatinib plus capecitabine combination, following double blockade associating trastuzumab and pertuzumab were evaluated in this national real-life database. Eligibility criteria were: female, MBC, HER2+ tumor, first-line taxane-based chemotherapy and dual HER2-blockage by trastuzumab plus pertuzumab. Cohort A received second-line T-DM1, and Cohort B second-line T-DM1 and third or fourth-line lapatinib plus capecitabine.
Cohort A comprised 233 patients, and Cohort B 47 patients. Median progression-free survival (PFS) was 7.1 months in Cohort A and 4.6 months in Cohort B. Median overall survival were 36.7 months and 12.9 months, respectively. PFS was significantly dependent on the preceding treatment line's duration. In cohort A, HER2 expression status was a significant predictive factor of PFS.
First-line trastuzumab plus pertuzumab do not markedly diminish T-DM1's efficacy in second-line. Similarly, sequential treatment with trastuzumab plus pertuzumab then T-DM1 does not noticeably modify the efficacy of lapatinib plus capecitabine.
•French real-life cohort.•Dual blockade HER2 does not markedly diminish T-DM1's activity in second-line and lapatinib's activity in third or fourth line.•The second-line (T-DM1) PFS was significantly longer when the first-line treatment with trastuzumab plus pertuzumab was ≥12 months.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
More than 10% of HER2-positive metastatic breast cancer (mBC) will develop Central Nervous System (CNS) metastases as first and isolated site of relapse on trastuzumab and pertuzumab ...first-line therapy. However, few clinical data are available to guide the best strategy in this setting.
Methods
Patients experiencing isolated CNS progression on trastuzumab and pertuzumab first-line therapy were retrospectively identified from the French Epidemiological Strategy and Medical Economics (ESME) real-life database between 2008 and 2016.
Results
Among 995 patients treated with first-line trastuzumab and pertuzumab for HER2-positive mBC, 132 patients (13%) experienced isolated CNS progression with a median time of 12 months after mBC diagnosis. Twelves patients did not receive any treatment and were excluded from the analysis. Among the 120 patients considered, 76 (63%) received CNS-directed local therapy, 73 (60%) continued trastuzumab and pertuzumab, whereas 47 (39%) started another systemic treatment.
After a median follow-up of 21 months, there was no difference in progression-free survival for patient who continued trastuzumab–pertuzumab or switched to another systemic treatment. In multivariate analysis, trastuzumab–pertuzumab continuation was associated with longer OS (HR 0,28 IC 95%: 0,14–0,54
p
< 0,001). mOS was not reached (95% 37.6-NE) and was 23.2 months (95% CI 15.5–53.6) in patients who continued trastuzumab and pertuzumab therapy and in patients who switched for another systemic therapy, respectively.
Conclusion
In this real-life cohort, trastuzumab–pertuzumab continuation after local treatment for isolated CNS progression did not negatively impact PFS and OS. Prospective trials and assessment of new strategies are warranted in this specific situation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Treatment and outcomes of patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have dramatically improved over the past 20 years. This work evaluated treatment patterns and outcomes ...according to age.
Women who initiated a treatment for HER2+ MBC between 2008 and 2016 in one of the 18 French comprehensive centers part of the ESME program were included. Objectives were the description of first-line treatment patterns, overall survival (OS), first-line progression-free survival (PFS), and prognostic factors among patients aged 70 years or more (70+), or less than 70 (<70).
Of 4045 women diagnosed with an HER2+ MBC, 814 (20%) were 70+. Standard first-line treatment (chemotherapy combined with an anti-HER2 therapy) was prescribed in 65% of 70+ versus 89% of <70 patients (p < 0.01). Median OS was 49.2 (95% CI, 47.1–52.4), 35.3 (95% CI, 31.5–37.0) and 54.2 months (95% CI, 50.8–55.7) in the whole population, in patients 70+ and <70, respectively. Corresponding median PFS1 were 12.8 (95% CI, 12.3–13.3), 11.1 (95% CI, 10.0–12.3) and 13.2 months (95% CI, 12.7–13.9), respectively. In 70+ women, initiation of non-standard first-line treatment had an independent detrimental time-varying effect on both OS and PFS (HR on OS at 1 year: chemotherapy without anti-HER2 2.79 95% CI: 2.05–3.79; endocrine therapy and/or anti-HER2 1.96 95% CI: 1.43–2.69).
In this large retrospective real-life database, older women with HER2+ MBC received standard first-line treatment less frequently than younger ones. This was independently associated with a worse outcome, but confounding factors and usual selection biases cannot be ruled out.
•Only 65% of women aged 70+ with HER2+ MBC receive a standard first-line treatment.•Median PFS1 of women 70+ with HER2+ MBC is 11.1 months (95% CI, 10.0–12.3) vs 13.2 (95% CI, 12.7–13.9) for younger ones.•Non-standard first-line treatment has a detrimental time-varying effect on both OS and PFS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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