Publications by authors named "Jean-Marc Classe"

72 Publications

Clinicopathological characterization of a real-world multicenter cohort of endometrioid ovarian carcinoma: Analysis of the French national ESME-Unicancer database.

Gynecol Oncol 2021 Jul 19. Epub 2021 Jul 19.

Aix-Marseille Univ., CNRS, INSERM, Institut Paoli-Calmettes, Department of Medical Oncology, CRCM, Marseille, France. Electronic address:

Background: Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes.

Methods: We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features.

Results: Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p < 0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p < 0.001).

Conclusions: Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.019DOI Listing
July 2021

Axillary Pathologic Complete Response After Neoadjuvant Systemic Therapy by Breast Cancer Subtype in Patients With Initially Clinically Node-Positive Disease: A Systematic Review and Meta-analysis.

JAMA Surg 2021 Jun 9;156(6):e210891. Epub 2021 Jun 9.

Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.

Importance: An overview of rates of axillary pathologic complete response (pCR) for all breast cancer subtypes, both for patients with and without pathologically proven clinically node-positive disease, is lacking.

Objective: To provide pooled data of all studies in the neoadjuvant setting on axillary pCR rates for different breast cancer subtypes in patients with initially clinically node-positive disease.

Data Sources: The electronic databases Embase and PubMed were used to conduct a systematic literature search on July 16, 2020. The references of the included studies were manually checked to identify other eligible studies.

Study Selection: Studies in the neoadjuvant therapy setting were identified regarding axillary pCR for different breast cancer subtypes in patients with initially clinically node-positive disease (ie, defined as node-positive before the initiation of neoadjuvant systemic therapy).

Data Extraction And Synthesis: Two reviewers independently selected eligible studies according to the inclusion criteria and extracted all data. All discrepant results were resolved during a consensus meeting. To identify the different subtypes, the subtype definitions as reported by the included articles were used. The random-effects model was used to calculate the overall pooled estimate of axillary pCR for each breast cancer subtype.

Main Outcomes And Measures: The main outcome of this study was the rate of axillary pCR and residual axillary lymph node disease after neoadjuvant systemic therapy for different breast cancer subtypes, differentiating studies with and without patients with pathologically proven clinically node-positive disease.

Results: This pooled analysis included 33 unique studies with 57 531 unique patients and showed the following axillary pCR rates for each of the 7 reported subtypes in decreasing order: 60% for hormone receptor (HR)-negative/ERBB2 (formerly HER2)-positive, 59% for ERBB2-positive (HR-negative or HR-positive), 48% for triple-negative, 45% for HR-positive/ERBB2-positive, 35% for luminal B, 18% for HR-positive/ERBB2-negative, and 13% for luminal A breast cancer. No major differences were found in the axillary pCR rates per subtype by analyzing separately the studies of patients with and without pathologically proven clinically node-positive disease before neoadjuvant systemic therapy.

Conclusions And Relevance: The HR-negative/ERBB2-positive subtype was associated with the highest axillary pCR rate. These data may help estimate axillary treatment response in the neoadjuvant setting and thus select patients for more or less invasive axillary procedures.
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http://dx.doi.org/10.1001/jamasurg.2021.0891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060891PMC
June 2021

ACOSOG Z-0011 criteria impact on axillary surgery for early breast cancer in clinical practice: Evaluation in a retrospective cohort of 1900 patients.

Eur J Obstet Gynecol Reprod Biol 2021 Jun 9;261:41-45. Epub 2021 Apr 9.

Surgery Department, Institut Cancérologie de L'ouest, Nantes, Saint Herblain, France.

Background: There is a trend towards de-escalation in early breast cancer axillary surgery. In the American College of Surgeons Oncology Group (ACOSOG) Z-0011 trial, observation was shown to be non-inferior in terms of overall survival to complementary axillary lymph node dissection (cALND) in patients with up to two sentinel lymph node (SLN) metastases. The study included patients with T1-T2 invasive breast cancer, clinically node negative, undergoing breast-conserving surgery with SLN biopsy, followed by systemic therapy and radiotherapy. The aim of our study was to evaluate the impact of applying these ACOSOG Z-0011 inclusion criteria in routine practice.

Patients And Methods: This retrospective observational study was conducted in a French comprehensive cancer center where patients treated for breast cancer with primary surgery were prospectively included between 2010 and 2016. Patients meeting ACOSOG Z-0011 inclusion criteria were analyzed.

Results: Among the 1900 included patients, 1497 (79 %) met the ACOSOG Z-0011 criteria before surgery. Of these, 390 (20 %) had one or two metastatic SLN and could have avoided cALND. Out of these patients, 319 (81 %) presented cT1 tumors. During the study period, cALND was performed in 320 (82 %) patients and was free of metastases in 80 % of cases, having an impact on eligibility for adjuvant chemotherapy in only 3 (0.8 %) patients.

Conclusions: In situations of primary breast cancer surgery, use of ACOSOG Z-0011 criteria could reduce the rate of cALND by 20 %. Further studies are needed to help select patients for whom abstention from any axillary surgery would be reasonable.
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http://dx.doi.org/10.1016/j.ejogrb.2021.04.003DOI Listing
June 2021

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.

Cancers (Basel) 2021 Mar 29;13(7). Epub 2021 Mar 29.

Department of Gynecology and Obstetrics, Klinikum Esslingen, 73730 Esslingen, Germany.

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).
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http://dx.doi.org/10.3390/cancers13071565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037995PMC
March 2021

Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients.

Cancers (Basel) 2020 Dec 11;12(12). Epub 2020 Dec 11.

Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Boulevard Professeur Jacques Monod, 44800 Saint-Herblain, France.

The selection of women with hormone receptor-positive (HR+) early breast cancer (EBC) at high risk of relapse after five years (yrs.) of adjuvant aromatase inhibitors (AIs) is crucial, as the benefit of extending AIs is counterbalanced by toxicity. We developed a clinicopathological tool to estimate the residual risk of relapse after five years of adjuvant AIs. The Institut de Cancérologie de l'Ouest (ICO) database was used to determine a prognostic score of post-five-year AI relapse. Cox regression models estimated our score's prognostic performance. In total, 1105 women were included. Median follow-up was 44 months (IQR = 21-70) post-AI treatment. From the Cox models, we designed a dichotomous prognostic score including the number of macrometastases, age (>70 yrs. vs. ≤70 yrs.), tumor size (≥T2 vs. not), and mitotic activity (≥2 vs. not). Overall, 77.5% of patients were classified as being at low risk and 22.5% at high risk of late recurrence. Low-risk patients had a five- to ten-year local or distant recurrence risk of 7.6% (95% CI, 5.4% to 10.6%) as compared with 26.9% (95% CI, 19.9% to 35.7%) for the high-risk roup. In this study, we developed a simple tool to identify women at high risk of relapse despite completing five years of AIs.
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http://dx.doi.org/10.3390/cancers12123725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763581PMC
December 2020

Quality of advanced ovarian cancer surgery: A French assessment of ESGO quality indicators.

Eur J Surg Oncol 2021 02 11;47(2):360-366. Epub 2020 Aug 11.

Department of Surgical Oncology, Institut Cancérologie de L'Ouest, Nantes, Saint Herblain, France.

Objectives: In 2016, the European Society of Gynecology Oncology (ESGO) published indicators defining the quality of surgical management of advanced ovarian cancer. The objective of the study was to assess the quality of ovarian cancer patient management in regional centers authorized for gynecological cancer, based on the ESGO list of quality indicators.

Methods: A multicenter retrospective observational cohort study was conducted from January 1 to June 30, 2016. The following quality indicators 1 "rate of complete surgical resection", 4 "center participating in clinical trials in gynecologic oncology", 5 "treatment planned and reviewed at a multidisciplinary team meeting", 6 "required preoperative workup", 8 "minimum required elements in operative reports" and 9 "minimum required elements in pathology reports" were selected.

Results: 91 patients were evaluated in 16 centers. The required preoperative workup was incomplete in 25% of cases. Treatment was not planned at a multidisciplinary team meeting for 24%. An evaluation score of peritoneal involvement was included in 40% of the operative reports and the quality of surgical resection was reported in 72%. Primary surgery was most often performed in a peripheral hospital (48%), interval surgery in a private center (37%), and closure surgery in a regional cancer center (43%). No institution respected the six quality indicators evaluated. One regional cancer center respected five items and two private centers did not respect any.

Conclusion: Whilst the ESGO quality indicators provide objective, validated and evaluable support which centers can use to improve quality of care, we observed heterogeneous practices amongst the centers evaluated.
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http://dx.doi.org/10.1016/j.ejso.2020.08.003DOI Listing
February 2021

Severe perioperative morbidity after robot-assisted versus conventional laparoscopy in gynecologic oncology: Results of the randomized ROBOGYN-1004 trial.

Gynecol Oncol 2020 08 25;158(2):382-389. Epub 2020 May 25.

Institut Paoli Calmettes Cancer Center, Marseille, France.

Objective: In gynecologic oncology, minimally invasive surgery using conventional laparoscopy (CL) decreases the incidence of severe morbidity compared to open surgery. In 2005, robot-assisted laparoscopy (RL) was approved for use in gynecology in the US. This study aimed to assess whether RL is superior to CL in terms of morbidity incidence.

Methods: ROBOGYN-1004 (ClinicalTrials.gov, NCT01247779) was a multicenter, phase III, superiority randomized trial that compared RL and CL in patients with gynecologic cancer requiring minimally invasive surgery. Patients were recruited between 2010 and 2015. The primary endpoint was incidence of severe perioperative morbidity (severe complications during or 6 months after surgery).

Results: Overall, 369 of 385 patients were included in the as-treated analysis: 176 and 193 underwent RL and CL, respectively. The median operating time for RL was 190 (range, 75-432) minutes and for CL was 145 (33-407) minutes (p < 0.001). The blood loss volumes for the corresponding procedures were 100 (0-2500) and 50 (0-1000) mL (p = 0.003), respectively. The overall rates of conversion to open surgery for the corresponding procedures were 7% (10/176) and 5% (10/193), respectively (p = 0.52). Severe perioperative morbidity occurred in 28% (49/176) and 21% (41/192) of patients who underwent RL and CL, respectively (p = 0.15). At a median follow-up of 25.1 months (range, 0.6-78.2), no significant differences in overall and disease-free survival were observed between the groups.

Conclusions: RL was not found superior to CL with regard to the incidence of severe perioperative morbidity in patients with gynecologic cancer. In addition, RL involved a longer operating time than CL.
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http://dx.doi.org/10.1016/j.ygyno.2020.05.010DOI Listing
August 2020

[French Society for Surgical Oncology (SFCO) guidelines for the management of surgical oncology in the pandemic context of COVID 19].

Bull Cancer 2020 05 6;107(5):524-527. Epub 2020 Apr 6.

Université de Montpellier, institut de cancérologie de Montpellier (ICM), département de chirurgie oncologique, Montpellier, France.

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http://dx.doi.org/10.1016/j.bulcan.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135219PMC
May 2020

30 Years of Experience in the Management of Stage III and IV Epithelial Ovarian Cancer: Impact of Surgical Strategies on Survival.

Cancers (Basel) 2020 Mar 24;12(3). Epub 2020 Mar 24.

Institut Paoli Calmettes, Department of Surgical Oncology, 13009 Marseille, France.

: to analyze the evolution of surgical techniques and strategies, and to determine their influence on the survival of patients with stage III or IV epithelial ovarian cancer (EOC). : a retrospective data analysis was performed in two French tertiary cancer institutes. The analysis included clinical information, cytoreductive outcome (complete, optimal and suboptimal), definitive pathology, Overall Survival (OS), and Progression-Free Survival (PFS). Three surgical strategies were compared: Primary Cytoreductive Surgery (PCS), Interval Cytoreductive Surgery (ICS) after three cycles of Neo-Adjuvant Chemotherapy (NAC), and Final Cytoreductive Surgery (FCS) after at least six cycles of NAC. We analyzed four distinct time intervals: prior to 2000, between 2000 and 2004, between 2005 and 2009, and after 2009. : data from 1474 patients managed for International Federation of Gynecology and Obstetrics (FIGO) stages III (80%) or IV (20%) EOC were analyzed. Throughout the four time intervals, the rate of patients who were treated only medically increased significantly (10.1% vs. 22.6% < 0.001). NAC treatment increased from 20.1% to 52.2% ( < 0.001). Complete resection rate increased from 37% to 66.2% ( < 0.001). Of our study population, 1260 patients (85.5%) underwent surgery. OS was longer in cases of complete cytoreduction (Hazard Ratio (HR) = 2.123 CI 95% [1.816-2.481] < 0.001) but the surgical strategy itself did not affect median OS. OS was 44.9 months, 50.3 months, and 42 months for PCS, ICS, and FCS, respectively ( = 0.410). After adjusting for surgical strategies (PCS, ICS, and FCS), all patients with complete cytoreduction presented similar OS with no significant difference. However, PFS was three months shorter when FCS was compared to PCS ( < 0.001). Conclusion: In our 30 years' experience of EOC management, complete resection rate was the only independent factor that significantly improved OS and PFS, regardless of the surgical strategy.
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http://dx.doi.org/10.3390/cancers12030768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140106PMC
March 2020

[Current advances in immunotherapy in ovarian cancer].

Bull Cancer 2020 Apr 20;107(4):465-473. Epub 2020 Feb 20.

Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France.

Ovarian cancers express highly immunogenic tissue-specific antigens. The resulting immune infiltration is a major prognostic factor. There is therefore a strong biological rationale for the development of immunotherapy in ovarian cancer. However, based on Phase I and II clinical trials data, the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors (ICPIs) remains limited in monotherapy in heavily pre-treated patients. Currently, the identification of predictive biomarkers of response and resistance is one of the major areas of research. Identifying effective combination of anti-PD-1 or anti-PD-L1 with other anticancer agents is another clinical need. Several combinations were evaluated. The association of ICPIs with chemotherapy (anthracyclines or carboplatin+paclitaxel) is disappointing (JAVELIN studies). The association with PARP inhibitors, anti-angiogenic agents and CTLA-4 inhibitors seems promising. Other immune therapies such as cell therapies (adoptive transfer of intra-tumor lymphocytes, CAR T cells or vaccines from dendritic cells) could be the future of immunotherapy in ovarian cancer but only early phase studies clinical data is available at this time.
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http://dx.doi.org/10.1016/j.bulcan.2019.11.015DOI Listing
April 2020

[Retrospective study: Late surgery post chemotherapy versus after 3-4 cures in treatment of advanced ovarian cancer].

Bull Cancer 2020 Feb 16;107(2):157-170. Epub 2019 Dec 16.

Centre François-Baclesse, 2, avenue du Général-Harris, 14000 Caen, France.

Introduction: Treatment in locally advanced ovarian cancer is optimal surgery followed by chemotherapy. Patients with significant tumor spread, OMS>2, age>75 years old are poor candidates for aggressive primary surgery. Interval surgery, after neo-adjuvant chemotherapy, aims to achieve more complete surgery, increase survival, and reduce surgical morbidity. The primary endpoint was progression-free survival. Secondary outcomes were overall survival and postoperative morbidity and mortality.

Method: This is a retrospective study conducted in 2 French referral centers between January 2000 and December 2015. Patients who could not benefit from a complete initial surgery were operated after 3 cures of chemotherapy at the François Baclesse center and after least 5 cures at the center René Gauducheau.

Results: The population analyzed included 104 patients, 43 (41.0%) patients treated at the René Gauducheau center (group 1) and 61 (59.0%) patients treated at the François Baclesse center (group 2). Progression-free and overall survival were similar between the 2 groups, they were, respectively, 15.9 months and 34 months in group 1 vs. 15.4 months and 37.6 months in group 2 (P=0.72; P=0.65). Mean hospital stay and postoperative morbidity were similar in both groups.

Conclusion: For weak patients, to limit invasive surgery, doing more than 5 courses of chemotherapy may be a reasonable option.
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http://dx.doi.org/10.1016/j.bulcan.2019.10.004DOI Listing
February 2020

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

EBioMedicine 2019 May 2;43:253-260. Epub 2019 Apr 2.

Institut de cancérologie de l'Ouest - site Paul Papin (ICO) 15, Rue André Boquel, 49055 Angers, France.

Background: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome.

Methods: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome.

Findings: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters.

Interpretation: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.
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http://dx.doi.org/10.1016/j.ebiom.2019.03.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562019PMC
May 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.
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http://dx.doi.org/10.1177/0300891618811282DOI Listing
February 2019

Adjuvant chemotherapy in lobular carcinoma of the breast: a clinicopathological score identifies high-risk patient with survival benefit.

Breast Cancer Res Treat 2019 Jun 13;175(2):379-387. Epub 2019 Feb 13.

Department of Surgical Oncology, Aix-Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France.

Background: Invasive lobular carcinomas (ILCs) represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) is still unclear.

Methods: Our objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,319 patients who underwent primary surgery in 15 French centers between 1990 and 2014. Only ILC, hormone-positive, human epidermal growth factor 2 (HER2)-negative patients who received adjuvant endocrine therapy (ET) were included. End-points were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT, aiming to compensate for baseline characteristics, was used.

Results: Of a total of 2318 patients with ILC, 1485 patients (64%) received ET alone and 823 (36%) received ET + CT. We observed a beneficial effect of addition of CT to ET on DFS and OS in multivariate Cox model (HR = 0.61, 95% confidence interval, CI [0.41-0.90]; p = 0.01 and 0.52, 95% CI [0.31-0.87]; p = 0.01, respectively). This effect was even more pronounced when propensity score matching was used. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT.

Conclusion: ILC patients could derive significant DFS and OS benefits from CT, especially for high-risk patients.
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http://dx.doi.org/10.1007/s10549-019-05160-9DOI Listing
June 2019

Lymph node positivity in different early breast carcinoma phenotypes: a predictive model.

BMC Cancer 2019 Jan 10;19(1):45. Epub 2019 Jan 10.

Institut Paoli Calmettes et CRCM, 232 boulevard de Sainte Marguerite, 13009, Marseille, France.

Background: A strong correlation between breast cancer (BC) molecular subtypes and axillary status has been shown. It would be useful to predict the probability of lymph node (LN) positivity.

Objective: To develop the performance of multivariable models to predict LN metastases, including nomograms derived from logistic regression with clinical, pathologic variables provided by tumor surgical results or only by biopsy.

Methods: A retrospective cohort was randomly divided into two separate patient sets: a training set and a validation set. In the training set, we used multivariable logistic regression techniques to build different predictive nomograms for the risk of developing LN metastases. The discrimination ability and calibration accuracy of the resulting nomograms were evaluated on the training and validation set.

Results: Consecutive sample of 12,572 early BC patients with sentinel node biopsies and no neoadjuvant therapy. In our predictive macro metastases LN model, the areas under curve (AUC) values were 0.780 and 0.717 respectively for pathologic and pre-operative model, with a good calibration, and results with validation data set were similar: AUC respectively of 0.796 and 0.725. Among the list of candidate's regression variables, on the training set we identified age, tumor size, LVI, and molecular subtype as statistically significant factors for predicting the risk of LN metastases.

Conclusions: Several nomograms were reported to predict risk of SLN involvement and NSN involvement. We propose a new calculation model to assess this risk of positive LN with similar performance which could be useful to choose management strategies, to avoid axillary LN staging or to propose ALND for patients with high level probability of major axillary LN involvement but also to propose immediate breast reconstruction when post mastectomy radiotherapy is not required for patients without LN macro metastasis.
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http://dx.doi.org/10.1186/s12885-018-5227-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327612PMC
January 2019

Patient-centered simulations to assess the usefulness of the 70-gene signature for adjuvant chemotherapy administration in early-stage breast cancer.

Breast Cancer Res Treat 2019 Apr 2;174(2):537-542. Epub 2019 Jan 2.

INSERM UMR 1246 -SPHERE, Nantes University, Tours University, Nantes, France.

Purpose: From the MINDACT trial, Cardoso et al. did not demonstrate a significant efficacy for adjuvant chemotherapy (CT) for women with early-stage breast cancer presenting high clinical and low genomic risks. Our objective was to assess the usefulness of the 70-gene signature in this population by using an alternative endpoint: the number of Quality-Adjusted Life-Years (QALYs), i.e., a synthetic measure of quantity and quality of life.

Methods: Based on the results of the MINDACT trial, we simulated a randomized clinical trial consisting of 1497 women with early-stage breast cancer presenting high clinical and low genomic risks. The individual preferences for the different health states and corresponding decrements were obtained from the literature.

Results: The gain in terms of 5-year disease-free survival was 2.8% (95% CI from - 0.1 to 5.7%, from 90.4% for women without CT to 93.3% for women with CT). In contrast, due to the associated side effects, CT significantly reduced the number of QALYs by 62 days (95% CI from 55 to 70 days, from 4.13 years for women without CT to 3.96 years for women with CT).

Conclusion: Our results support the conclusions published by Cardoso et al. by providing additional evidence that the 70-gene signature can be used to avoid overtreatment by CT for women with high clinical risk but low genomic risk.
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http://dx.doi.org/10.1007/s10549-018-05107-6DOI Listing
April 2019

Current Status and Future Perspectives of Axillary Management in the Neoadjuvant Setting.

Breast Care (Basel) 2018 Oct 26;13(5):337-341. Epub 2018 Sep 26.

Department of Surgery, Capio St. Göran's Hospital, Stockholm, Sweden.

Axillary surgery has undergone considerable changes in recent years, especially in relation to patients who undergo neoadjuvant chemotherapy (NACT). Due to constantly decreasing rates of recurrence and death from breast cancer, modern surgical strategies aim at de-escalating the extent of local treatment and avoiding unnecessary procedures. This relates especially to lymph node surgery which is associated with considerable morbidity. In patients who initially present with clinically node-negative disease, sentinel lymph node biopsy (SLNB) is increasingly performed after NACT. The determination of the post-NACT nodal status does not only spare patients from additional surgery but also allows the assessment of pathologic complete response which is increasingly becoming an important tool for treatment planning. Since more than 70% of these patients have a ypN0 status after NACT, future trials will aim to identify patients who might be spared any axillary surgery after NACT. In patients who initially present with positive lymph nodes, the success rates of SLNB in terms of detection and accuracy are less favorable compared to those in patients who undergo primary surgery. The clinical significance of this is unclear. To reduce unnecessary axillary dissection in patients with cN1ycN0 status, prospective outcome data after SLNB without further lymph node removal are urgently needed. Improvements in surgical technique by localizing positive nodes at the time of diagnosis and removing them in a targeted surgical procedure (targeted axillary dissection) are under evaluation. Risk assessment and patient selection (including gene expression profiles) might be other ways of safely omitting axillary dissection.
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http://dx.doi.org/10.1159/000492437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257201PMC
October 2018

Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study.

Breast Cancer Res Treat 2019 Jan 20;173(2):343-352. Epub 2018 Oct 20.

Biometrics, Institut de Cancerologie de l'ouest, Saint-Herblain, France.

Purpose: GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients.

Methods: Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone.

Results: From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3-17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed.

Conclusion: In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.
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http://dx.doi.org/10.1007/s10549-018-5004-7DOI Listing
January 2019

Isolated ipsilateral local recurrence of breast cancer: predictive factors and prognostic impact.

Breast Cancer Res Treat 2019 Jan 20;173(1):111-122. Epub 2018 Sep 20.

Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, 232 Bd de Sainte Marguerite, 13009, Marseille, France.

Background: Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points.

Methods: Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes.

Results: Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p < 0.0001), endocrine therapy (HR 2.05, p < 0.0001) and age < 40-years old (HR 2.28, p = 0.005) in MVA. When MVA was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR 4.96 for ILR-free interval between 2 and 5-years and HR 9.00 when < 2-years, in comparison with ≥ 5-years).

Conclusion: ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.
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http://dx.doi.org/10.1007/s10549-018-4944-2DOI Listing
January 2019

[Clinical practice for morbidly obese endometrial cancer patients: A french multicentric study].

Bull Cancer 2018 May 20;105(5):441-449. Epub 2018 Apr 20.

Institut de cancérologie de l'ouest, centre René-Gauducheau, Nantes, Saint-Herblain, boulevard Professeur Jacques-Monod, 44805 Saint-Herblain, France.

Introduction: Morbid obesity may lead to difficulties for management of endometrial cancer. The aim of this study was the assessment of management of endometrial cancer for morbidly obese women and the implementation of recommendations.

Methods: this is retrospective study including women with BMI =40kg/m treated for endometrial cancer between November 2010 and April 2017 in the university hospital in Nantes and the Cancer Center René Gauducheau in Nantes. Patients' demographics, pre-operative intra operative, post-operative data and survival were analyzed.

Results: Twenty patients met the inclusion criteria with a median age of 65.5 (28-86) and a median BMI of 47kg/m (40-60). Type I histologic was identified in 90% and of a stage I FIGO I in 75% of the cases. All the patients have benefited from a biopsy of endometrium before surgery. 70% of the patients have benefited from a MRI before surgery (14/20). The surgery was realized by laparotomy in 40%, by mini invasive surgery in 50% and by vaginal procedure in 10% of. Mini invasive surgery was converted in laparotomy in 40% (4/10). A discrepancy of the ESMO's recommandation was observed in 40% of the cases (8/20). Two patients did not benefit from the adjuvant radiotherapy recommended because of delay of healing.

Discussion: Although good prognosis, the endometrial cancer of morbidly obese women seem to be under treat. These patients do not seem benefited an optimal pre-operative assessment. The surgery is mainly realized by laparotomy with a not complete surgical stadification for one more than a third of the patients.
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http://dx.doi.org/10.1016/j.bulcan.2018.02.007DOI Listing
May 2018

Sentinel lymph node biopsy validation for large tumors.

Int J Surg 2017 Dec 24;48:275-280. Epub 2017 Nov 24.

Institut Paoli Calmettes and CRCM, 232 Bd Ste Marguerite, Marseille, France; Aix Marseille Université, Site Timone, 25 Boulevard Jean Moulin, Marseille, France. Electronic address:

Background: Sentinel lymph node biopsy (SLNB) remains under discussion for large size tumors. The aim of this work has been to study the false negative rate (FNR) of SLNB for large tumors and predictive factors of false negative (FN).

Materials And Methods: A study of a multicentric cohort, involved patients presenting N0 breast cancer with a SLNB eventually completed by complementary axillary lymph node dissection (cALND). The main criteria were the FNR and the predictive factors of FN.

Results: 12.415 patients were included: 748 with tumors ≥30 mm, 1101 with tumors >20 and < 30 mm and 10.566 with tumors ≤20 mm, with a cALND respectively for 501 patients (67%), 523 (62.1%) and 2775 (26.3%). The FNR were respectively: 3.05% (IC95%: 1.3-4.8) for tumors ≥30 mm*, 3.5% (1.8-5.2) for tumors >20 and < 30 mm*, 1.8% (1-2.4) for tumors ≤20 mm (p < 0.05) (*Not significant). At multivariate analysis, SN number harvested ≤2 (OR:2.0, p = 0.023) and tumor size >20 and < 30 mm (OR:2.07, p = 0.017) were significant predictive factors of FN, without significant value for tumor size ≥30 mm (OR:1.83, p = 0.073).

Conclusion: The FNR of SLNB was not higher amongst large size tumors compared to tumors of a smaller size. These results support the validation of SNLB for tumors up to 50 mm.
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http://dx.doi.org/10.1016/j.ijsu.2017.10.077DOI Listing
December 2017

Is post-mastectomy radiation therapy contributive in pN0-1mi breast cancer patients? Results of a French multi-centric cohort.

Eur J Cancer 2017 12 3;87:47-57. Epub 2017 Nov 3.

Institut Paoli Calmettes, Department of Surgery, 232 Bd Ste Marguerite, Marseille, France; Aix Marseille Université, Faculté Timone, 25 Boulevard Jean Moulin, Marseille, France.

Aim: To assess the value of post-mastectomy radiation therapy (PMRT) to breast cancer (BC) patients with no or minimal lymph node (LN) involvement.

Materials And Methods: We retrospectively analysed a French multi-centric cohort of 4283 patients treated by mastectomy and axillary dissection, with or without PMRT, between 1980 and 2013. Practices were analysed for three treatment periods (1980-1999, 2000-2005 and 2006-2013). The impact of PMRT on loco-regional recurrence (LRR), disease-free survival (DFS), BC-specific survival and overall survival was assessed in pN0-1mi patients using multivariate analyses (logistic regression and Cox model). It was subsequently assessed based on the number of clinicopathological recurrence-risk factors, generating a prognostic index (French-PMRT index), to isolate a pN0-1mi patients subgroup that might derive a benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index to discriminate between patients with significantly different outcomes and the value of PMRT in each c-PMRT prognostic group.

Results: More than half of the pN0-1mi patients of our cohort underwent PMRT, which almost significantly improved LRR-free survival and DFS. Matching pN0-1mi patients based on the number of clinicopathologic recurrence-risk factors identified a higher risk subpopulation (≥3 recurrence-risk factors), but PMRT did not improve patient outcomes. Although the c-PMRT index had the potential to predict patient outcomes, its use did not help in making the decision of whether or not to use PMRT.

Conclusion: We failed to isolate a subgroup of early BC patients without LN involvement suitable for PMRT, despite studying a large cohort.
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http://dx.doi.org/10.1016/j.ejca.2017.10.004DOI Listing
December 2017

[Impact of the preservation of the branches of intercostobrachial nerve on the quality of life of patients operated for a breast cancer].

Bull Cancer 2017 Oct 14;104(10):858-868. Epub 2017 Sep 14.

Institut de cancérologie de Lorraine, département de chirurgie, 6, avenue de Bourgogne, 54519 Vandoeuvre-les-Nancy, France; CRAN, UMR 7039, CNRS, université de Lorraine, boulevard des Aiguillettes, 54506 Vandoeuvre-les-Nancy, France. Electronic address:

Aim: The aim of this study was to assess the impact of the preservation of the intercostobrachial nerve on the quality of life of patients operated for breast cancer.

Methods: This study was ancillary to cost comparison study of axillary sentinel lymph node detection and axillary lymphadenectomy in early breast cancer. It was a prospective multicenter, observational, non-randomized study. The quality of life was assessed using two questionnaires: QLQ-C30 and specific module QLQ-BR23 Surveys have been performed before initiation of surgery, one week, and 1 month, 8 months and 12 months after discharge from hospitalization for the first surgical procedure.

Results: Five hundred and seventy-eight patients with preservation of intercostobrachial nerve without axillary lymph node dissection (C- P+), 85 without preservation of nerve and axillary lymph node dissection (C+P-) and 57 with preservation of nerve and axillary lymph node dissection (C+P+) have been included in the study. The changing arm symptoms score was significantly different during follow-up between the three groups (P<0.001). This difference between the two groups C- P+ and C+P+ was significant clinically at one week [16.9, IC95%: 11.9 to 22 (P<0.01)], and persisted for up to 12 months [9.9, IC95%: 3.2 à16.6 (P=0.022)]. There was no difference between the group C+P- and C+P+. Results for physical functioning score were similar.

Conclusion: Preservation of the intercostobral nerve is not associated with better quality of life. Only axillary lymph node dissection has an impact on quality of life.
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http://dx.doi.org/10.1016/j.bulcan.2017.08.002DOI Listing
October 2017
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