Publications by authors named "Fabien Reyal"

127 Publications

Time to Pregnancy, Obstetrical and Neonatal Outcomes after Breast Cancer: A Study from the Maternity Network for Young Breast Cancer Patients.

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Centre René Hughenin, Medical Oncology Department, 92210 Saint Cloud, France.

Although an increasing number of young breast cancer (BC) patients have a pregnancy desire after BC, the time necessary to obtain a pregnancy after treatment and subsequent outcomes remain unknown. We aimed to determine the time to evolutive pregnancy in a cohort of BC survivors and subsequent obstetrical and neonatal outcomes. We analyzed BC patients treated at Institut Curie from 2005-2017, aged 18-43 years old (y.o.) at diagnosis having at least one subsequent pregnancy. 133 patients were included, representing 197 pregnancies. Mean age at BC diagnosis was 32.8 y.o. and at pregnancy beginning was 36.8 y.o. 71% pregnancies were planned, 18% unplanned and 86% spontaneous. 64% pregnancies resulted in live birth ( = 131). Median time from BC diagnosis to pregnancy beginning was 48 months and was significantly associated with endocrine therapy ( < 0.001). Median time to pregnancy was 4.3 months. Median time to evolutive pregnancy 5.6 months. In multivariate analysis, menstrual cycles before pregnancy remained significantly associated with time to pregnancy and endocrine therapy with time evolutive to pregnancy. None of the BC treatments (chemotherapy/endocrine therapy/trastuzumab) was significantly associated with obstetrical nor neonatal outcomes, that seemed comparable to global population. Our findings provide reassuring data for pregnancy counseling both in terms of delay and outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13051070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959151PMC
March 2021

Patterns of Sequelae in Women with a History of Localized Breast Cancer: Results from the French VICAN Survey.

Cancers (Basel) 2021 Mar 8;13(5). Epub 2021 Mar 8.

Department Prevention, Cancer, Environment, Léon Bérard Cancer Center, 69008 Lyon, France.

Breast cancer (BC) remains complex for women both physically and psychologically. The objectives of this study were to (1) assess the evolution of the main sequelae and treatment two and five years after diagnosis in women with early-stage breast cancer, (2) explore patterns of sequelae associated with given sociodemographic, clinical, and lifestyle factors. The current analysis was based on 654 localized BC patients enrolled in the French nationwide longitudinal survey "vie après cancer" VICAN (January-June 2010). Information about study participants was collected at enrollment, two and five years after diagnosis. Changes over time of the main sequelae were analyzed and latent class analysis was performed to identify patterns of sequelae related to BC five years after diagnosis. The mean age (±SD) of study participants at inclusion was 49.7 (±10.5) years old. Six main classes of sequelae were identified two years and five years post-diagnosis (functional, pain, esthetic, fatigue, psychological, and gynecological). A significant decrease was observed for fatigue ( = 0.03) and an increase in cognitive sequelae was reported ( = 0.03). Two latent classes were identified-functional and esthetic patterns. Substantial sequelae remain up to five years after BC diagnosis. Changes in patient care pathways are needed to identify BC patients at a high risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13051161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962808PMC
March 2021

PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy.

Cancers (Basel) 2021 Feb 11;13(4). Epub 2021 Feb 11.

Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, University Paris, 75005 Paris, France.

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors' (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden ( = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, = 0.25, and PD-L1-IC, = 0.95) or overall survival (OS) (PD-L1-TC, = 0.48, and PD-L1-IC, = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, = 0.0014, and OS, = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13040746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916886PMC
February 2021

Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore.

Br J Cancer 2021 Apr 9;124(8):1421-1427. Epub 2021 Feb 9.

Department of Surgery, Institut Curie, Paris, France.

Background: To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.

Methods: We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.

Results: RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61-0.71]) and fair for Neo-Bioscore (0.70; CI [0.65-0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.

Conclusions: Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-020-01251-3DOI Listing
April 2021

-Positive Breast Cancer Patients with Pre-Treatment Axillary Involvement or Postmenopausal Status Benefit from Neoadjuvant Rather than Adjuvant Chemotherapy Plus Trastuzumab Regimens.

Cancers (Basel) 2021 Jan 20;13(3). Epub 2021 Jan 20.

Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, Institut Curie, 75005 Paris, France.

Background: No survival benefit has yet been demonstrated for neoadjuvant chemotherapy (NAC) against -positive tumors in patients with early breast cancer (BC). The objective of this study was to compare the prognosis of -positive BC patients treated with NAC to that of patients treated with adjuvant chemotherapy (AC).

Materials And Methods: We retrospectively analyzed disease-free (DFS) and overall survival (OS) in 202 -positive patients treated with NAC and 701 patients treated with AC. All patients received trastuzumab in addition to chemotherapy. Patient data were weighted by a propensity score to overcome selection bias.

Results: After inverse probability of treatment weights (IPTW) adjustment, no difference in DFS ( = 0.3) was found between treatments for the total population. However, after multivariate analysis, an interaction was found between cN status and chemotherapy strategy (IPTW-corrected corrected Hazard ratio cHR = 0.52, 95% CI (0.3-0.9), = 0.08) and between menopausal status and chemotherapy (CT) strategy (cHR = 0.35, 95%CI (0.18-0.7)) < 0.01). NAC was more beneficial than AC strategy in cN-positive patients and in postmenopausal patients. Moreover, after IPTW adjustment, the multivariate analysis showed that the neoadjuvant strategy conferred a significant OS benefit (cHR = 0.09, 95%CI [0.02-0.35], < 0.001).

Conclusion: In patients with -positive BC, the NAC strategy is more beneficial than the AC strategy, particularly in cN-positive and postmenopausal patients. NAC should be used as a first-line treatment for -positive tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13030370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864202PMC
January 2021

The Presence of an In Situ Component on Pre-Treatment Biopsy Is Not Associated with Response to Neoadjuvant Chemotherapy for Breast Cancer.

Cancers (Basel) 2021 Jan 10;13(2). Epub 2021 Jan 10.

Medical Oncology Department, Centre René Hughenin, 92210 Saint Cloud, France.

A ductal in situ (DCIS) component is often associated with invasive breast carcinoma (BC), and its effect on response to treatment is unknown. We assessed the predictive value of the DCIS component for pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). We analyzed a cohort of 1148 T1-3NxM0 breast cancer (BC) patients treated by NAC at Institut Curie between 2002 and 2012. The presence of a DCIS component was retrospectively recorded from both the pre-NAC biopsy pathological report and surgical specimens. We included 1148 BC patients treated by NAC for whom pre- and post-NAC data concerning the in situ component were available. DCIS was present before NAC in 19.6% of the population. Overall, 283 patients (19.4%) achieved pCR after NAC. There was no significant association between the presence of DCIS on pre-NAC biopsy and pCR. In a multivariate analysis including subtype, tumor size, grade, mitotic index, and Ki67 index, only BC subtype (luminal/TNBC/-positive) and Ki67 were significantly associated with pCR. The presence of a DCIS component on pre-NAC biopsy is not associated with pCR and does not seem to be a critical factor for predicting response to NAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13020235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827327PMC
January 2021

The Prognostic Value of Lymph Node Involvement after Neoadjuvant Chemotherapy Is Different among Breast Cancer Subtypes.

Cancers (Basel) 2021 Jan 6;13(2). Epub 2021 Jan 6.

Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, INSERM, University Paris, 75005 Paris, France.

Introduction: The three different breast cancer subtypes (Luminal, positive, and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype.

Methods: We retrospectively evaluated the axillary involvement (0, 1 to 3 positive nodes, ≥4 positive nodes) on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between nodal involvement (ypN) binned into three classes (0; 1 to 3; 4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes.

Results: 1197 patients were included in the analysis (luminal ( = 526, 43.9%), TNBCs ( = 376, 31.4%), -positive BCs ( = 295, 24.6%)). After a median follow-up of 110.5 months, ypN was significantly associated with RFS, but this effect was different by BC subtype ( = 0.004), and this effect was nonlinear. In the luminal subgroup, RFS was impaired in patients with 4 or more nodes involved (HR 2.8; 95% CI [1.93; 4.06], < 0.001) when compared with ypN0, while it was not in patients with 1 to 3 nodes (HR = 1.24, 95% CI = [0.86; 1.79]). In patients with TNBC, both 1-3N+ and ≥4 N+ classes were associated with a decreased RFS (HR = 3.19, 95% CI = [2.05; 4.98] and HR = 4.83, 95% CI = [3.06; 7.63], respectively ypN0, < 0.001). Similar decreased prognosis were observed among patients with -positive BC (1-3N +: HR = 2.7, 95% CI = [1.64; 4.43] and ≥4 N +: HR = 2.69, 95% CI = [1.24; 5.8] respectively, = 0.003).

Conclusion: The prognostic value of residual axillary disease should be considered differently in the 3 BC subtypes to accurately stratify patients with a high risk of recurrence after NAC who should be offered second line therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13020171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825348PMC
January 2021

Impact of Mutation Status on Tumor Infiltrating Lymphocytes (TILs), Response to Treatment, and Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Cancers (Basel) 2020 Dec 8;12(12). Epub 2020 Dec 8.

Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.

Introduction: Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to status.

Material And Methods: Out of 1199 invasive BC patients treated with NAC between 2002 and 2012, we identified 267 patients tested for a germline pathogenic variant. We evaluated pre-NAC and post-NAC immune infiltration (TILs). Response to chemotherapy was assessed by pCR rates. Association of clinical and pathological factors with TILs, pCR and survival was assessed by univariate and multivariate analyses.

Results: Among 1199 BC patients: 46 were -deficient and 221 proficient or wild type (WT). At NAC completion, pCR was observed in 84/266 (31%) patients and pCR rates were significantly higher in deficient BC ( 0.001), and this association remained statistically significant only in the luminal BC subtype ( 0.006). The interaction test between BC subtype and status was nearly significant ( = 0.056). Pre and post-NAC TILs were not significantly different between deficient and proficient carriers; however, in the luminal BC group, post-NAC TILs were significantly higher in deficient BC. Survival analysis were not different between carriers and non-carriers.

Conclusions: mutation status is associated with higher pCR rates and post-NAC TILs in patients with luminal BC. -carriers with luminal BCs may represent a subset of patients deriving higher benefit from NAC. Second line therapies, including immunotherapy after NAC, could be of interest in non-responders to NAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12123681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764707PMC
December 2020

Body Mass Index and Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.

J Natl Cancer Inst 2021 Feb;113(2):146-153

Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.

Background: High levels of stromal tumor-infiltrating lymphocytes (sTIL) are associated with increased pathological complete response (pCR) rate and longer survival after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Here, we evaluated the value of sTIL in predicting pCR and explored prognosis in TNBC patients treated with neoadjuvant chemotherapy according to body mass index (BMI).

Methods: sTIL were scored centrally on pretreatment biopsies from 2 retrospective series of nonunderweight TNBC patients (n = 445). sTIL and BMI were considered as binary (sTIL: <30.0% vs ≥30.0%; BMI: lean vs overweight and obese) and continuous variables. Associations with pCR (ypT0/isN0) were assessed using logistic regression, and associations with event-free survival and overall survival were assessed using Cox regressions.

Results: 236 (53.0%) patients were lean and 209 (47.0%) overweight and obese. pCR was achieved in 181 of 445 (41.7%) patients. Median sTIL was 11.0%, and 99 of 445 (22.2%) tumors had high sTIL. A statistically significant interaction between sTIL and BMI, considered as categorical or continuous variables, for predicting pCR was observed in the multivariable analysis (Pinteraction = .03 and .04, respectively). High sTIL were statistically significantly associated with pCR in lean (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.10 to 8.56; P < .001) but not in heavier patients (OR = 1.48, 95% CI = 0.75 to 2.91; P = .26) in the multivariable analysis. High sTIL were further associated with increased event-free survival in lean (hazard ratio [HR] = 0.22, 95% CI = 0.08 to 0.62; P = .004) but not in heavier patients (HR = 0.53, 95% CI = 0.26 to 1.08; P = .08). Similar results were obtained for overall survival.

Conclusion: BMI is modifying the effect of sTIL on pCR and prognosis in TNBC patients treated with neoadjuvant chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djaa090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850533PMC
February 2021

No Impact of Smoking Status on Breast Cancer Tumor Infiltrating Lymphocytes, Response to Neoadjuvant Chemotherapy and Prognosis.

Cancers (Basel) 2020 Oct 12;12(10). Epub 2020 Oct 12.

Department of Medical Oncology, Institut Curie, University Paris, 75005 Paris, France.

Tobacco use is associated with an increase in breast cancer (BC) mortality. Pathologic complete response (pCR) rate to neoadjuvant chemotherapy (NAC) is influenced by tumor-infiltrating lymphocyte (TIL) levels and is associated with a better long-term survival outcome. The aim of our study is to evaluate the impact of smoking status on TIL levels, response to NAC and prognosis for BC patients. We retrospectively evaluated pre- and post-NAC stromal and intra tumoral TIL levels and pCR rates on a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012 at Institut Curie. Smoking status (current, ever, never smokers) was collected in clinical records. We analyzed the association between smoking status, TIL levels, pCR rates and survival outcomes among the whole population, and according to BC subtype. Nine hundred and fifty-six BC patients with available smoking status information were included in our analysis (current smokers, = 179 (18.7%); ever smokers, = 154 (16.1%) and never smokers, = 623 (65.2%)). Median pre-NAC TIL levels, pCR rates, or median post-NAC TIL levels were not significantly different according to smoking status, neither in the whole population, nor in any BC subtype group. With a median follow-up of 101.4 months, relapse-free survival (RFS) and overall survival (OS) were not significantly different by smoking status. We did not find any significant effect of tobacco use on pre- and post-NAC TILs nor response to NAC. Though our data seem reassuring, BC treatment should still be considered as a window of opportunity to offer BC patients accurate smoking cessation interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12102943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601636PMC
October 2020

Prognostic value of the Residual Cancer Burden index according to breast cancer subtype: Validation on a cohort of BC patients treated by neoadjuvant chemotherapy.

PLoS One 2020 24;15(6):e0234191. Epub 2020 Jun 24.

Department of Medical Oncology, Institut Curie, Saint-Cloud, France.

Introduction: The Residual Cancer Burden (RCB) quantifies residual disease after neoadjuvant chemotherapy (NAC). Its predictive value has not been validated on large cohorts with long-term follow up. The objective of this work is to independently evaluate the prognostic value of the RCB index depending on BC subtypes (Luminal, HER2-positive and triple negative (TNBCs)).

Methods: We retrospectively evaluated the RCB index on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between RCB index and relapse-free survival (RFS), overall survival (OS) among the global population, after stratification by BC subtypes.

Results: 717 patients were included (luminal BC (n = 222, 31%), TNBC (n = 319, 44.5%), HER2-positive (n = 176, 24.5%)). After a median follow-up of 99.9 months, RCB index was significantly associated with RFS. The RCB-0 patients displayed similar prognosis when compared to the RCB-I group, while patients from the RCB-II and RCB-III classes were at increased risk of relapse (RCB-II versus RCB-0: HR = 3.25 CI [2.1-5.1] p<0.001; RCB-III versus RCB-0: HR = 5.6 CI [3.5-8.9] p<0.001). The prognostic impact of RCB index was significant for TNBC and HER2-positive cancers; but not for luminal cancers (Pinteraction = 0.07). The prognosis of RCB-III patients was poor (8-years RFS: 52.7%, 95% CI [44.8-62.0]) particularly in the TNBC subgroup, where the median RFS was 12.7 months.

Conclusion: RCB index is a reliable prognostic score. RCB accurately identifies patients at a high risk of recurrence (RCB-III) with TNBC or HER2-positive BC who must be offered second-line adjuvant therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313974PMC
August 2020

Adjuvant chemotherapy for breast cancer after preoperative chemotherapy: A propensity score matched analysis.

PLoS One 2020 5;15(6):e0234173. Epub 2020 Jun 5.

Department of Surgery, Institut Curie, Paris, France.

Although identified to be at a higher risk of relapse, no consensus exists on the treatment of breast cancer (BC) patients with no pathological complete response after neoadjuvant chemotherapy (NAC). The benefit of adjuvant chemotherapy (ADJ) in this context has scarcely been studied. We evaluated the benefit of administrating adjuvant chemotherapy in a real life cohort of BC patients with invasive residual disease after NAC. 1199 female BC patients with T1-3NxM0 invasive tumors receiving NAC at Institut Curie from 2002 to 2012 were included in the analysis. 1061 had been treated by NAC only, whereas 138 had received additional adjuvant chemotherapy after NAC (FUN protocol: 5-FU-Vinorelbine). We compared disease-free survival (DFS) and overall survival (OS) rates between patients having received NAC only and patients having received NAC+ADJ. To ensure comparability of our populations, we used a propensity score (which defines the probability of treatment assignment conditional on observed baseline covariates) and matched each patient having received NAC+ADJ (n = 138) with a patient having received NAC only that had a similar propensity score value. Before propensity score matching, DFS and OS rates were significantly lower in the NAC+ADJ group compared to NAC only, after 3 years, 5 years and 10 years follow-up (p<0.01). After one-to-one PS matching, the two groups were comparable (n = 276 patients; 138 patients in each group). No significant difference was found regarding DFS (p = 0.87) or OS (p = 0.59) rates, neither in global population, nor by pathological subtype. Although our study did not show a benefit of administrating ADJ with FUN protocol (5-Florouracil- Vinorelbine) to BC patients with residual disease after NAC, further studies are warranted to determine the impact of other adjuvant regimens. Thereby, patients with little chance of responding to particular regimens could avoid the toxicity of futile therapy, and be study participants in evaluations of novel treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234173PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274443PMC
August 2020

Tumor-infiltrating lymphocytes are associated with poor prognosis in invasive lobular breast carcinoma.

Mod Pathol 2020 11 13;33(11):2198-2207. Epub 2020 May 13.

Pathology-Genetics-Immunology Department, Institut Curie, PSL Research University, Paris, France.

The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, ≤5%, >5%. Clinicopathologic features were tested by Fisher's exact tests or Chi tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan-Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with ≤5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p < 0.05). Poor OS was significantly associated with increasing TILs in the univariate Cox proportional hazards model (p < 0.001) and Kaplan-Meier estimator (p < 0.05, log-rank test). Similar results were observed for iDFS (p = 0.004 for Cox univariate and p = 0.005 for log-rank test). Notably, TILs can identify a subset of ILC patients with poor OS independently of molecular subtype and lymph node metastases (multivariate Cox, p < 0.001, OS hazard ratio (HR) = 4.38 and HR = 6.15, for ≤5% and >5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p = 0.05) and iDFS (p = 0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-0561-9DOI Listing
November 2020

BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers.

Sci Transl Med 2020 02;12(531)

Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

Topoisomerase I (TOP1) inhibitors trap TOP1 cleavage complexes resulting in DNA double-strand breaks (DSBs) during replication, which are repaired by homologous recombination (HR). Triple-negative breast cancer (TNBC) could be eligible for TOP1 inhibitors given the considerable proportion of tumors with a defect in HR-mediated repair (BRCAness). The TOP1 inhibitor irinotecan was tested in 40 patient-derived xenografts (PDXs) of TNBC. BRCAness was determined with a single-nucleotide polymorphism (SNP) assay, and expression of Schlafen family member 11 (SLFN11) and retinoblastoma transcriptional corepressor 1 (RB1) was evaluated by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry analyses. In addition, the combination of irinotecan and the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor VE-822 was tested in SLFN11-negative PDXs, and two clinical non-camptothecin TOP1 inhibitors (LMP400 and LMP776) were tested. Thirty-eight percent of the TNBC models responded to irinotecan. BRCAness combined with high SLFN11 expression and RB1 loss identified highly sensitive tumors, consistent with the notion that deficiencies in cell cycle checkpoints and DNA repair result in high sensitivity to TOP1 inhibitors. Treatment by the ATR inhibitor VE-822 increased sensitivity to irinotecan in SLFN11-negative PDXs and abolished irinotecan-induced phosphorylation of checkpoint kinase 1 (CHK1). LMP400 (indotecan) and LMP776 (indimitecan) showed high antitumor activity in BRCA1-mutated or BRCAness-positive PDXs. Last, low SLFN11 expression was associated with poor survival in 250 patients with TNBC treated with anthracycline-based chemotherapy. In conclusion, a substantial proportion of TNBC respond to irinotecan. BRCAness, high SLFN11 expression, and RB1 loss are highly predictive of response to irinotecan and the clinical indenoisoquinoline TOP1 inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aax2625DOI Listing
February 2020

[Citizens who volunteer as participants for cancer research-results of the Seintinelles Barometer 2018].

Bull Cancer 2020 Mar 7;107(3):333-343. Epub 2020 Feb 7.

Université Lumière Lyon 2, groupe de recherche en psychologie sociale (GRePS), 5, avenue Pierre-Mendès-France, 69500 Bron, France.

Introduction: Health researchers often face difficulties related to participants' recruitment for their research. However, a new strategy emerges: offering patients-but also citizens who are not ill-the possibility to volunteer as participants to hasten research processes. The French platform "Seintinelles" aims to fulfill this goal and bring together citizens who volunteered to participate to cancer related research. The "Seintinelles Barometer" aims to describe these volunteers' profile.

Methods: The Seintinelles Barometer data were collected through a web-based auto-questionnaire proposed to the "Seintinelles" members from June 2017 to November 2018.

Results: The sample presents a high level of overrepresentation of women. Participants are characterized by a high level of education. About a third of the participants had suffered from cancer. Two profile of volunteers emerged: the « patients » and the « supportive citizens ».

Discussion: The Seintinelles Barometer participants manifest a strong wish to be involved in cancer related research. Therefore, this platform seems to be a promising tool for the development of community-based research in the field of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2019.11.012DOI Listing
March 2020

Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer.

Oncoimmunology 2020 14;9(1):1677427. Epub 2019 Nov 14.

Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, U932, Immunity and Cancer, Institut Curie, PSL Research University, Paris, France.

Immunosurveillance plays an important role in breast cancer (BC) prognosis and progression, and can be geared by immunogenic chemotherapy. In a cohort of 1023 BC patients treated with neoadjuvant chemotherapy (NAC), 40% of the individuals took comedications mostly linked to aging and comorbidities. We systematically analyzed the off-target effects of 1178 concurrent comedications (classified according to the Anatomical Therapeutic Chemical (ATC) Classification System) on the density of tumor-infiltrating lymphocytes (TILs) and pathological complete responses (pCR). At level 1 of the ATC system, the main anatomical classes of drugs were those targeting the nervous system (class N, 39.1%), cardiovascular disorders (class C, 26.6%), alimentary and metabolism (class A, 16.9%), or hormonal preparations (class H, 6.5%). At level 2, the most frequent therapeutic classes were psycholeptics (N05), analgesics (N02), and psychoanaleptics (N06). Pre-NAC TIL density in triple-negative BC (TNBC) was influenced by medications from class H, N, and A, while TIL density in HER2 BC was associated with the use of class C. Psycholeptics (N05) and agents acting on the renin-angiotensin system (C09) were independently associated with pCR in the whole population of BC or TNBC, and in -positive BC, respectively. Importantly, level 3 hypnotics (N05C) alone were able to reduce tumor growth in BC bearing mice and increased the anti-cancer activity of cyclophosphamide in a T cell-dependent manner. These findings prompt for further exploration of drugs interactions in cancer, and for prospective drug-repositioning strategies to improve the efficacy of NAC in BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2019.1677427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959439PMC
November 2019

Surgical Margins and Adjuvant Therapies in Malignant Phyllodes Tumors of the Breast: A Multicenter Retrospective Study.

Ann Surg Oncol 2020 Jun 27;27(6):1818-1827. Epub 2020 Jan 27.

Department of Medical Oncology, Institut du Cancer Montpellier, Univ Montpellier, Montpellier, France.

Background: The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated.

Patients And Methods: We conducted a multicenter nationwide retrospective study of all MPT cases with central pathological review within the French Sarcoma Group. Endpoints were local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates.

Results: Overall, 212 patients were included in the study. All non-metastatic patients underwent primary surgical treatment, including 58.6% of conservative surgeries. An R0 resection was achieved in 117 patients (59.4%: 26.9% of patients with 1-2 mm margins, 12.2% of patients with 3-7 mm margins, 20.3% of patients with ≥ 8 mm margins). Ninety-four patients (45%) underwent a second surgery (SS) to obtain R0 margins, with a final mastectomy rate of 72.6%. Radiotherapy and chemotherapy were performed in 91 (43.1%) and 23 patients (10.9%), respectively, but were not associated with better outcomes. Mastectomy was significantly associated with better LRFS (p < 0.001). Margins of 0, 1, or 2 mm with SS were associated with better MFS (hazard ratio [HR] 0.3, p = 0.005) and OS (HR 0.32, p = 0.005) compared with margins of 0-1-2 mm without SS. Wider margins (> 8 mm) were not superior to margins of 3-7 mm (3-7 mm vs. > 8 mm; HR 0.81, p = 0.69). Age (HR 2.14, p = 0.038) and tumor necrosis (HR 1.96, p = 0.047) were found to be poor prognostic factors and were associated with MFS.

Conclusions: This study suggests that 3 mm margins are necessary and sufficient for surgical management of MPTs, and emphasizes the importance of SS to obtain clear margins in case of 0-1-2 mm margins. No impact of adjuvant chemotherapy or radiotherapy was detected in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-08217-yDOI Listing
June 2020

Gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent in breast implant-associated ALCL.

Blood 2020 01;135(5):360-370

Institut Mondor de Recherche Biomédicale, INSERM U955, Université Paris-Est, Créteil, France.

The oncogenic events involved in breast implant-associated anaplastic large cell lymphoma (BI-ALCL) remain elusive. To clarify this point, we have characterized the genomic landscape of 34 BI-ALCLs (15 tumor and 19 in situ subtypes) collected from 54 BI-ALCL patients diagnosed through the French Lymphopath network. Whole-exome sequencing (n = 22, with paired tumor/germline DNA) and/or targeted deep sequencing (n = 24) showed recurrent mutations of epigenetic modifiers in 74% of cases, involving notably KMT2C (26%), KMT2D (9%), CHD2 (15%), and CREBBP (15%). KMT2D and KMT2C mutations correlated with a loss of H3K4 mono- and trimethylation by immunohistochemistry. Twenty cases (59%) showed mutations in ≥1 member of the JAK/STAT pathway, including STAT3 (38%), JAK1 (18%), and STAT5B (3%), and in negative regulators, including SOCS3 (6%), SOCS1 (3%), and PTPN1 (3%). These mutations were more frequent in tumor-type samples than in situ samples (P = .038). All BI-ALCLs expressed pSTAT3, regardless of the mutational status of genes in the JAK/STAT pathway. Mutations in the EOMES gene (12%) involved in lymphocyte development, PI3K-AKT/mTOR (6%), and loss-of-function mutations in TP53 (12%) were also identified. Copy-number aberration (CNA) analysis identified recurrent alterations, including gains on chromosomes 2, 9p, 12p, and 21 and losses on 4q, 8p, 15, 16, and 20. Regions of CNA encompassed genes involved in the JAK/STAT pathway and epigenetic regulators. Our results show that the BI-ALCL genomic landscape is characterized by not only JAK/STAT activating mutations but also loss-of-function alterations of epigenetic modifiers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2019001904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059458PMC
January 2020

Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study.

Ann Surg Oncol 2020 May 26;27(5):1693-1699. Epub 2019 Nov 26.

Department of Medical Oncology, Institut du cancer Montpellier, Univ Montpellier, Montpellier, France.

Background: Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs).

Patients And Methods: A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate.

Results: 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31-80 months]. Median OS was 11.5 months (95% CI 7.5-18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27-6.19; p = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14-0.78; p = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone (p = 0.049).

Conclusions: The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-019-08097-xDOI Listing
May 2020

Assessing reliability of intra-tumor heterogeneity estimates from single sample whole exome sequencing data.

PLoS One 2019 7;14(11):e0224143. Epub 2019 Nov 7.

MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Paris, France.

Tumors are made of evolving and heterogeneous populations of cells which arise from successive appearance and expansion of subclonal populations, following acquisition of mutations conferring them a selective advantage. Those subclonal populations can be sensitive or resistant to different treatments, and provide information about tumor aetiology and future evolution. Hence, it is important to be able to assess the level of heterogeneity of tumors with high reliability for clinical applications. In the past few years, a large number of methods have been proposed to estimate intra-tumor heterogeneity from whole exome sequencing (WES) data, but the accuracy and robustness of these methods on real data remains elusive. Here we systematically apply and compare 6 computational methods to estimate tumor heterogeneity on 1,697 WES samples from the cancer genome atlas (TCGA) covering 3 cancer types (breast invasive carcinoma, bladder urothelial carcinoma, and head and neck squamous cell carcinoma), and two distinct input mutation sets. We observe significant differences between the estimates produced by different methods, and identify several likely confounding factors in heterogeneity assessment for the different methods. We further show that the prognostic value of tumor heterogeneity for survival prediction is limited in those datasets, and find no evidence that it improves over prognosis based on other clinical variables. In conclusion, heterogeneity inference from WES data on a single sample, and its use in cancer prognosis, should be considered with caution. Other approaches to assess intra-tumoral heterogeneity such as those based on multiple samples may be preferable for clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224143PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837753PMC
March 2020

Text Mining in Electronic Medical Records Enables Quick and Efficient Identification of Pregnancy Cases Occurring After Breast Cancer.

JCO Clin Cancer Inform 2019 10;3:1-12

Paris 5 Research University, INSERM U932, Institut Curie, Paris, France.

Purpose: To apply text mining (TM) technology on electronic medical records (EMRs) of patients with breast cancer (BC) to retrieve the occurrence of a pregnancy after BC diagnosis and compare its performance to manual curation.

Materials And Methods: The training cohort (Cohort A) comprised 344 patients with BC age ≤ 40 years old treated at Institut Curie between 2005 and 2007. Manual curation consisted in manually reviewing each EMR to retrieve pregnancies. TM consisted of first applying a keyword filter ("accouch*" or "enceinte," French terms for "deliver*" and "pregnant," respectively) to select a subset of EMRs, and, second, checking manually EMRs to confirm the pregnancy. Then, we applied our TM algorithm on an independent cohort of patients with BC treated between 2008 and 2012 (Cohort B).

Results: In Cohort A, 36 pregnancies were identified among 344 patients (10.5%; 2,829 person-years of EMR). Thirty were identified by manual review versus 35 by TM. TM resulted in a lower percentage of manual checking (26.7% 100%, respectively) and substantial time gains (time to identify a pregnancy: 13 minutes for TM 244 minutes for manual curation, respectively). Presence of any of the two TM filters showed excellent sensitivity (97%) and negative predictive value (100%). In Cohort B, 67 pregnancies were identified among 1,226 patients (5.5%; 7,349 person-years of EMR). Similarly, for Cohort B, TM spared 904 (73.7%) EMRs from manual review and quickly generated a cohort of 67 pregnancies after BC. Incidence rate of pregnancy after BC was 0.01 pregnancy per person-year of EMR in both cohorts.

Conclusion: TM is highly efficient to quickly identify rare events and is a promising tool to improve rapidity, efficiency, and costs of medical research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/CCI.19.00031DOI Listing
October 2019

Domain-invariant features for mechanism of action prediction in a multi-cell-line drug screen.

Bioinformatics 2020 03;36(5):1607-1613

CBIO - Centre de Bio-Informatique, MINES ParisTech, PSL Research University, Paris 75006, France.

Motivation: High-content screening is an important tool in drug discovery and characterization. Often, high-content drug screens are performed on one single-cell line. Yet, a single-cell line cannot be thought of as a perfect disease model. Many diseases feature an important molecular heterogeneity. Consequently, a drug may be effective against one molecular subtype of a disease, but less so against another. To characterize drugs with respect to their effect not only on one cell line but on a panel of cell lines is therefore a promising strategy to streamline the drug discovery process.

Results: The contribution of this article is 2-fold. First, we investigate whether we can predict drug mechanism of action (MOA) at the molecular level without optimization of the MOA classes to the screen specificities. To this end, we benchmark a set of algorithms within a conventional pipeline, and evaluate their MOA prediction performance according to a statistically rigorous framework. Second, we extend this conventional pipeline to the simultaneous analysis of multiple cell lines, each manifesting potentially different morphological baselines. For this, we propose multi-task autoencoders, including a domain-adaptive model used to construct domain-invariant feature representations across cell lines. We apply these methods to a pilot screen of two triple negative breast cancer cell lines as models for two different molecular subtypes of the disease.

Availability And Implementation: https://github.com/jcboyd/multi-cell-line or https://zenodo.org/record/2677923.

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btz774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058179PMC
March 2020

Interaction between Molecular Subtypes and Stromal Immune Infiltration before and after Treatment in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Clin Cancer Res 2019 11 12;25(22):6731-6741. Epub 2019 Sep 12.

Residual Tumor and Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Paris, France.

Purpose: High levels of tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) are associated with higher pathologic complete response (pCR) rates and better survival in triple-negative breast cancer (TNBC) and -positive breast cancer. We investigated the value of TIL levels by evaluating lymphocyte infiltration before and after NAC.

Experimental Design: We assessed stromal TIL levels in 716 pre- and posttreatment matched paired specimens, according to the guidelines of the International TIL Working Group.

Results: Pre-NAC TIL levels were higher in tumors for which pCR was achieved than in cases with residual disease (33.9% vs. 20.3%, = 0.001). This was observed in luminal tumors and TNBCs, but not in -positive breast cancers ( = 0.001). The association between pre-NAC TIL levels and pCR was nonlinear in TNBCs ( = 0.005). Mean TIL levels decreased after chemotherapy completion (pre-NAC TILs: 24.1% vs. post-NAC TILs: 13.0%, < 0.001). This decrease was strongly associated with high pCR rates, and the variation of TIL levels was strongly inversely correlated with pre-NAC TIL levels ( = -0.80, < 0.001). Pre-NAC TILs and disease-free survival (DFS) were associated in a nonlinear manner ( < 0.001). High post-NAC TIL levels were associated with aggressive tumor characteristics and with impaired DFS in -positive breast cancers (HR, 1.04; confidence interval, 1.02-1.06; = 0.001), but not in luminal tumors or TNBCs ( = 0.04).

Conclusions: The associations of pre- and post-NAC TIL levels with response to treatment and DFS differ between breast cancer subtypes. The characterization of immune subpopulations may improve our understanding of the complex interactions between pre- or post-NAC setting, breast cancer subtype, response to treatment, and prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-3017DOI Listing
November 2019

Decentralization of Next-Generation RNA Sequencing-Based MammaPrint® and BluePrint® Kit at University Hospitals Leuven and Curie Institute Paris.

Transl Oncol 2019 Dec 9;12(12):1557-1565. Epub 2019 Sep 9.

KU Leuven - University Hospitals Leuven, Department of Pathology, B-3000 Leuven, Belgium; KU Leuven - University of Leuven, Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research.

A previously developed and centrally validated MammaPrint® (MP) and BluePrint® (BP) targeted RNA next-generation sequencing (NGS) kit was implemented and validated in two large academic European hospitals. Additionally, breast cancer molecular subtypes by MP and BP RNA sequencing were compared with immunohistochemistry (IHC). Patients with early breast cancer diagnosed at University Hospitals Leuven and Curie Institute Paris were prospectively included between September 2017 and January 2018. Formalin-fixed paraffin-embedded tissue sections were analyzed with MP and BP NGS technology at the beta sites and with both NGS and microarray technology at Agendia. Raw NGS data generated on Illumina MiSeq instruments at the beta sites were interpreted and compared with NGS and microarray data at Agendia. MP and BP NGS molecular subtypes were compared to surrogate IHC breast cancer subtypes. Equivalence of MP and BP indices was determined by Pearson's correlation coefficient. Acceptable limits were defined a priori, based on microarray data generated at Agendia between 2012 and 2016. The concordance, the Negative Percent Agreement and the Positive Percent Agreement were calculated based on the contingency tables and had to be equal to or higher than 90%. Out of 124 included samples, 48% were MP Low and 52% High Risk with microarray. Molecular subtypes were BP luminal, HER2 or basal in 82%, 8% and 10% respectively. Concordance between MP microarray at Agendia and MP NGS at the beta sites was 91.1%. Concordance of MP High and Low Risk classification between NGS at the beta sites and NGS at Agendia was 93.9%. Concordance of MP and BP molecular subtyping using NGS at the beta sites and microarray at Agendia was 89.5%. Concordance between MP and BP NGS subtyping, and IHC was 71.8% and 76.6%, for two IHC surrogate models. The MP/BP NGS kit was successfully validated in a decentralized setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2019.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742807PMC
December 2019

Innovative DIEP flap perfusion evaluation tool: Qualitative and quantitative analysis of indocyanine green-based fluorescence angiography with the SPY-Q proprietary software.

PLoS One 2019 25;14(6):e0217698. Epub 2019 Jun 25.

Department of Gynecological and Breast Oncological Surgery, Curie Institute, Paris, France.

Background: Perfusion-related complications remain the most common concern in DIEP flap breast reconstruction. Indocyanine green-based fluorescence angiography can be used for the real-time intra operative assessment of flap perfusion. The SPY Elite system is the most widely used device in this setting. The main objective was to describe the use of SPY-Q proprietary software to perform qualitative and quantitative analysis of flap perfusion.

Methods: This retrospective cohort study was performed at the Curie Institute between 2013 and 2017. We included patients undergoing unilateral DIEP flap breast reconstruction for whom indocyanine green-based angiography videos were of sufficient quality for analysis. Videos were recorded with the SPY Elite System and analyzed with SPY-Q proprietary software.

Results: We included 40 patients. We used real-time dynamic color analysis to describe three different patterns of flap perfusion. SPY-Q proprietary software provides quantitative flap perfusion parameters. Our quantitative analysis confirmed that zone I is the best perfused part of the flap and zone IV the less perfused one. There was no significant association between flap perfusion pattern and perforator anatomy, patients' clinical characteristics or postoperative outcomes. After exploratory univariate analysis, quantitative perfusion parameters were significantly impaired in young patients with diabetes mellitus or under hormone therapy by tamoxifen.

Conclusions: We here describe a new approach to assess DIEP flap perfusion using the SPY Elite System proprietary software. It provides interesting qualitative and quantitative analysis that can be used in further studies to precisely assess DIEP flap perfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217698PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592538PMC
February 2020

High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer.

Nat Genet 2019 06 31;51(6):1060-1066. Epub 2019 May 31.

HiFiBiO SAS, Paris, France.

Modulation of chromatin structure via histone modification is a major epigenetic mechanism and regulator of gene expression. However, the contribution of chromatin features to tumor heterogeneity and evolution remains unknown. Here we describe a high-throughput droplet microfluidics platform to profile chromatin landscapes of thousands of cells at single-cell resolution. Using patient-derived xenograft models of acquired resistance to chemotherapy and targeted therapy in breast cancer, we found that a subset of cells within untreated drug-sensitive tumors share a common chromatin signature with resistant cells, undetectable using bulk approaches. These cells, and cells from the resistant tumors, have lost chromatin marks-H3K27me3, which is associated with stable transcriptional repression-for genes known to promote resistance to treatment. This single-cell chromatin immunoprecipitation followed by sequencing approach paves the way to study the role of chromatin heterogeneity, not just in cancer but in other diseases and healthy systems, notably during cellular differentiation and development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0424-9DOI Listing
June 2019

Tubular and mucinous breast cancer: results of a cohort of 917 patients.

Tumori 2019 Feb 20;105(1):55-62. Epub 2018 Dec 20.

1 Institut Paoli Calmettes and CRCM, Surgical Oncology Department, Marseille, France.

Objectives:: To analyze axillary lymph node involvement (ALNI) rate and survival for mucinous (MC) and tubular (TC) breast carcinomas considered being of very good prognosis and for which an axillary surgical exploration could be questioned.

Methods:: Our multicentric cohort consisted of 21,135 patients with clinically node-negative invasive breast cancer, without neoadjuvant therapy, between 1999 and 2013 in 10 French centers. ALNI rate and survival were analyzed according to patient and tumor characteristics.

Results:: Our cohort consisted of 672 TC and 245 MC. Patients were older and tumor size greater for MC and pathologic factors were more pejorative. The rate of mastectomies and adjuvant chemotherapy was higher in the MC group. Axillary lymph node status was determined by SLNB alone in 71.2% of patients. ALNI rates were 17.9% and 18% for TC and MC, respectively. ALNI rate was lesser for MC (OR 0.503, p = 0.024) and greater in case of lympho-vascular invasion (OR 5.0, p < 0.0001) and for tumors >10 mm (OR 2.17, p = 0.042). Median follow-up was 58 months. The 5- and 7-year overall survival rates were 97.1% and 95% for TC, respectively; 92.3% and 91.2% for MC ( p = 0.043); 5- and 7-year disease-free survival rates were 97.9% and 97.2% versus 95.2 and 93.6% ( p = 0.041). Lympho-vascular invasion was the only predictive factor for overall survival (hazard ratio [HR] = 2.70)' grade 2 (HR = 10) and HR-negative (HR = 4.9) were the two predictive factors for disease-free survival.

Conclusion:: This study confirms the need for an axillary exploration for these tumors even for a tumor size <10 mm and a favorable prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300891618811282DOI Listing
February 2019