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Abstract Aim We investigated the pathologic complete response rates (pCR) and survival outcomes of early breast cancer patients who underwent neoadjuvant chemotherapy (NAC) over 14 years at a French comprehensive cancer center and reported pCR and survival outcomes by tumor subtypes and size. Methods From January 2005 to December 2018, 1150 patients receiving NAC were identified. Correlations between cT stage, breast tumor response, axillary lymph node response, pCR, surgery, and outcomes were assessed. pCR was defined as (ypT0/ypTis) and (ypN0/pN0sn). Results A pCR was reached in 31.7% (365/1150) of patients and was strongly associated with tumor subtypes, but not with tumor size (pretreatment cT category). Luminal‐B Her2‐negative and triple‐negative (TN) subtypes, cN1 status, older age, and no‐pCR had an independent negative prognostic value. Overall survival (OS), relapse‐free survival (RFS), and metastasis‐free survival (MFS) were not significantly different for cT0‐1 compared to cT2 stages. In Cox‐model adjusted on in‐breast pCR and pN status, ypN1 had a strong negative impact (OS, RFS, and MFS: HR = 3.153, 4.677, and 6.133, respectively), higher than no in‐breast pCR (HR = 2.369, 2.252, and 2.323). A negative impact of no pCR on OS was observed for cN0 patients and TN tumors (HR = 4.972) or HER2‐positive tumors (HR = 11.706), as well as in Luminal‐B Her2‐negative tumors on MFS (HR = 2.223) and for Luminal‐A on RFS (HR = 4.465) and MFS (HR = 4.185). Conclusion Achievement of pCR, but not tumor size (pretreatment cT category), has an independent prognostic impact on survival. These results suggest potential NAC benefits in patients with small tumors (

BackgroundElderly breast cancer (BC) patients have been underrepresented in clinical trials whereas ~60% of deaths from BC occur in women aged 70 years and older. Only limited data are available on the prognostic impact of age according to treatment, especially in the triple-negative (TN) and Her2-positive because of the lower frequency of these subtypes in elderly patients. We report herein the results of a multicenter retrospective study analyzing the prognostic impact of age according to treatment delivered in TN and Her2-positive BC patients of 70 years or older, including comparison by age groups.MethodsThe medical records of 31,473 patients treated from January 1991 to December 2018 were retrieved from 13 French cancer centers for retrospective analysis. Our study population included all ≥70 patients with TN or Her2-positive BC treated by upfront surgery. Three age categories were determined: 70-74, 75-80, and > 80 years.ResultsOf 528 patients included, 243 patients were 70-74 years old (46%), 172 were 75-80 years (32.6%) and 113 were >80 years (21.4%). Half the population (51.9%, 274 patients) were TN, 30.1% (159) Her2-positive/hormone receptors (HR)-positive, and, 18% (95) Her2-positive/endocrine receptors (ER)-negative BC. Advanced tumor stage was associated with older age but no other prognostic factors (tumor subtype, tumor grade, LVI). Adjuvant chemotherapy delivery was inversely proportional to age. With 49 months median follow-up, all patient outcomes (overall survival (OS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS)) significantly decreased as age increased. In multivariate analysis, age >80, pT2-3 sizes, axillary macrometastases, lymphovascular involvement, and HR-negativity tumor negatively affected DFS and OS. Comparison between age >80 and 80 (HR=1.771, p=0.031).ConclusionTN and Her2-positive subtypes occur at similar frequency in elderly patients. Older age is associated with more advanced tumor stage presentation. Chemotherapy use decreases with older age without worse other pejorative prognostic factors. Age >80, but not ≤80, independently affected DFS and OS.

Background: There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a control group aged 36 to 50. Methods: Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36–50 years patients. Results: Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS [HR 1.56, 95% CI 1.32–1.84; p

Abstract Background Results of IBCSG‐23‐01‐trial which included breast cancer patients with involved sentinel nodes (SN) by isolated‐tumor‐cells or micro‐metastases supported the non‐inferiority of completion axillary‐lymph‐node‐dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN‐micro‐metastases. Methods To investigate the impact of cALND omission on disease‐free‐survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients

Abstract Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient’s and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p 2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient’s eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient’s and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND.

Abstract Background Robotic latissimus dorsi-flap reconstruction (RLDFR) after skin-sparing mastectomy (SSM) for breast cancer (BC) has been performed through a single nipple incision. We report results of SSM with RLDFR, mainly with analysis of feasibility, morbidity, indications, and technique standardization. Methods We determined characteristics of patients, previous treatment of BC, and type of reconstruction. Surgical technique, duration of surgery, and complication rate were reported according to three successive periods: P1–3. Results Forty RLDFR, with breast implant for 16 patients, with previous breast radiotherapy in 30% had been performed. In logistic regression, factors significantly associated with duration of surgery ≥ 300 min were P2 (OR 0.024, p = 0.004) and P3 (OR 0.012, p = 0.004) versus P1. The median mastectomy weight was 330 g and 460 g for BMI < and ≥ 23.5 (p = 0.025). Length of hospitalization was 4 days. Total complication rate was 20% (8/40): seven breast complications (four re-operations) and one RLDF complication with re-operation. Periods were significantly predictive of complications (p = 0.045). Conclusion SSM with RLDFR is feasible, safe, and reproducible. We reported a decrease of duration of surgery, length of post-operative hospitalization, and complication rate.

During the COVID-19 pandemic, it was rapidly established that cancer patients have an increased risk of developing severe forms of the 2019 coronavirus disease (COVID-19) due to a backlog of cancer diagnostics and immunosuppressive treatments. Cancer centers had to quickly adapt to continue cancer therapies despite the high infection risks and major disruptions in the French healthcare system. We described and analyzed the impact of the pandemic in our institution: management adjustments, COVID-19 infection rates in patients and staff, and impacts on clinical activities and finances during the first wave of the pandemic from March to September 2020. We also compared the results to the clinical activity data from preceding periods. A crisis unit was rapidly created that met 27 times over 66 days, generating numerous changes in hospital protocol. While our area was devastated by the pandemic, the infection rate of our staff and patients remained low (less than 1.5% of all employees). However, the lockdown period was accompanied with a reduction of most clinical activities, leading to decreases of 43%, 36%, 36%, 1%, and 10% in surgery, endoscopy, radiotherapy, and in- and out-patient chemotherapy sessions, respectively, with substantial financial loss. Our report highlights the need for the rapid creation, implementation, and adaptation of new protocols during a pandemic’s evolution to prevent disease transmission. Lessons from this situation should provide motivation to better prepare for/limit the dismantling of cancer therapies that can dramatically impact patient care and have deleterious consequences on an institution’s financial situation.

We report a case of mucinous adenocarcinoma developed on sigmoid colpoplasty, performed for a congenital agenesis vaginal. The cancer development of neovagina remains exceptional. Its management consists, in the majority of cases, in surgery for a complete excision. Adjuvant treatments are associated according to the pathological results and the neovagina reconstruction technique performed.

Abstract 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.

Abstract Background Three randomized trials have concluded at non inferiority of omission of complementary axillary lymph node dissection (cALND) for patients with involved sentinel node (SN). However, we can outline strong limitations of these trials to validate this attitude with a high scientific level. We designed the SERC randomized trial (ClinicalTrials.gov, number NCT01717131) to compare outcomes in patients with SN involvement treated with ALND or no further axillary treatment. The aim of this study was to analyze results of the first 1000 patients included. Methods SERC trial is a multicenter non-inferiority phase 3 trial. Multivariate logistic regression analysis was used to identify independent factors associated with adjuvant chemotherapy administration and non-sentinel node (NSN) involvement. Results Of the 963 patients included in the analysis set, 478 were randomized to receive cALND and 485 SLNB alone. All patient demographics and tumor characteristics were balanced between the two arms. SN ITC was present in 6.3% patients (57/903), micro metastases in 33.0% (298), macro metastases in 60.7% (548) and 289 (34.2%) were non eligible to Z0011 trial criteria. Whole breast or chest wall irradiation was delivered in 95.9% (896/934) of patients, adjuvant chemotherapy in 69.5% (644/926), endocrine therapy in 89.6% (673/751) and the proportions were similar in the two arms. The overall rate of positive NSN was 19% (84/442) for patients with cALND. Crude rates of positive NSN according to SN status were 4.5% for ITC (1/22), 9.5% for micro metastases (13/137), 23.9% for macro metastases (61/255) and were respectively 29.36% (64/218), 9.33% (7/75) and 7.94% (10/126) when chemotherapy was administered after cALND, before cALND and for patients without chemotherapy. Conclusion The main objective of SERC trial is to demonstrate non inferiority of cALND omission. A strong interaction between timing of cALND and chemotherapy with positive NSN rate was observed. Trial registration This study is registered with ClinicalTrials.gov, number NCT01717131 October 19, 2012.

We describe and analyze a “care as usual” strategy of a French Comprehensive Cancer Center during the COVID-19 pandemic to manage surgical patients with gynecological cancer. We conducted a retrospective analysis evaluating the surgical activity in our gynecologic oncology department between January 21 and May 12, 2020. We compared the surgical activity and surgical and oncologic outcomes during the pre-lockdown period and the pandemic period. The main objective was to evaluate the impact of the COVID-19 pandemic on surgical activity. The secondary objectives were to analyze the surgical and the oncologic outcomes. We compared the surgical activity during the 8 weeks after the national lockdown (85 procedures) to the surgical activity in the 8 weeks preceding the lockdown (127 procedures). We observed a 33% decrease in activity between the two periods. The clinical and epidemiologic characteristics were similar between the two periods. There were no differences between the surgical approaches (p = 0.592), the surgical complexity (p = 0.323), the length of stay (p = 0.85), and even for the complex procedure (p = 0.96) and the perioperative (p = 0.791) and postoperative complication rates (p = 0.102). We observed a significant decrease in the time of return to intended oncological treatment (RIOT) during the lockdown period with an average of 31.9 days compared to 46.9 days in the pre-lockdown period (p = 0.003). During the COVID-19 pandemic, “care as usual” represents an acceptable strategy without impairing the oncologic outcome in a Comprehensive Cancer Center with a patient-centered clinical pathway for gynecologic oncologic surgical patients.

BackgroundSeveral studies reported the feasibility and safety of robotic-NSM (R-NSM). The aim of our prospective study was to compare R-NSM and conventional-NSM (C-NSM).MethodsWe analyzed patients who were operated on with and without robotic assistance (R-NSM or C-NSM) and who received immediate breast reconstruction (IBR) with implant or latissimus dorsi-flap (LDF). The main objective was complication rate and secondary aims were post-operative length of hospitalization (POLH), duration of surgery, and cost.ResultsWe analyzed 87 R-NSM and 142 C-NSM with implant-IBR in 50 and 135 patients, with LDF-IBR in 37 and 7 patients, respectively. Higher durations of surgery and costs were observed for R-NSM, without a difference in POLH and interval time to adjuvant therapy between R-NSM and C-NSM. In the multivariate analysis, R-NSM was not associated with a higher breast complication rate (OR=0.608) and significant factors were breast cup-size, LDF combined with implant-IBR, tobacco and inversed-T incision. Grade 2-3 breast complications rate were 13% for R-NSM and 17.3% for C-NSM, significantly higher for LDF combined with implant-IBR, areolar/radial incisions and BMI>=30. A predictive score was calculated (AUC=0.754). In logistic regression, patient’s satisfaction between C-NSM and R-NSM were not significantly different, with unfavorable results for BMI >=25 (OR=2.139), NSM for recurrence (OR=5.371) and primary breast cancer with radiotherapy (OR=4.533). A predictive score was calculated. In conclusion, our study confirms the comparable clinical outcome between C- NSM and R-NSM, in the price of longer surgery and higher cost for R-NSM. Predictive scores of breast complications and satisfaction were significantly associated with factors known in the pre-operative period.

Purpose: Ipsilateral-breast-local-recurrence (ILBLR) is a rare event with little data on immediate-breast-reconstruction (IBR). We report post-operative results of different types of mastectomy for ILBLR with or without IBR performed during a period of 40 months in order to analyze post-operative complications as main objective.Methods: We analyzed mastectomies performed for ILBLR after initial breast conservative treatment from January 2016 to April 2019. The characteristics of patients, surgery, complication rate, postoperative hospitalization have been determined.Results: Of the 207 mastectomies, 32.8% had an IBR: 31 nipple-sparing-mastectomy (NSM) and 37 skin-sparing-mastectomy (SSM) with 37 latissimus-dorsi-flap (LDF) IBR and 31 implant-IBR. Few reconstruction was performed for patients with body-mass-index ≥30 (OR = 0.214), infiltrating ductal carcinomas (OR = 0.272) and ASA-3 patients (OR = 0.254). In multivariate analysis, LDF-IBR was more often realized for NSM and for patients with BMI ≥25. The overall complication rate was 37.4%: 45.6 and 33.1% with and without IBR, respectively (p = 0.056). In multivariate analysis, BMI ≥25 (OR 2.02, p = 0.023), IBR (OR 1.9, p = 0.046) and tobacco (OR 2.17, p = 0.055) were correlated with higher risk of complications. There was no difference for Grade 2–3 complications rates for IBR and no IBR, respectively (14.7%: 10/68 and 9.3%: 13/139). In multivariate analysis, overall survival from date of mastectomy for local recurrence was significantly associated with interval time to local recurrence (OR 6.981).Conclusion: Salvage mastectomy and IBR is a good choice for ILBLR, particularly using flap reconstruction. NSM can be considered as a good option in selected patients for ILBLR for NSM and/or LDFR.

ObjectiveThe aim of the study was to compare the characteristics of procedures for gynecologic cancers conducted with conventional laparoscopy (CL) or robotically assisted laparoscopy (RAL) in the context of an enhanced recovery program (ERP).MethodsThis is a secondary analysis of prospectively collected data from a cohort study conducted between 2016 (when the ERP was first implemented at the Institut Paoli-Calmettes, a comprehensive cancer center in France) and 2018. We included patients who had undergone minimally invasive surgery for gynecological cancers and followed our ERP. The endpoints were the analysis of postoperative complications, the length of postoperative hospitalization (LPO), and the proportion of combined procedures depending on the approach (RAL or CL). Combined procedures were defined by the association of at least two of the following operative items: hysterectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy.ResultsA total of 362 women underwent either CL (n = 187) or RAL (n = 175) for gynecologic cancers and followed our ERP. The proportion of combined procedures performed by RAL was significantly higher (85/175 [48.6%]) than that performed by CL (23/187 [12.3%]; p < 0.001). The proportions of postoperative complications were similar between the two groups (19.4% versus 17.1%; p = 0.59). Logistic regression analysis revealed a statistically insignificant trend in the association of RAL with a reduced likelihood of an LPO > 3 days after adjusting for predictors of prolonged hospitalization (adjusted OR = 0.573 [0.236-1.388]; p = 0.217).ConclusionExperts from our cancer center preferentially choose RAL to perform gynecologic oncological procedures that present elements of complexity. More studies are needed to determine whether this strategy is efficient in managing complex procedures in the framework of an ERP.

Abstract Background Enhanced Recovery After Surgery Programs (ERP) includes multimodal approaches of perioperative patient’s clinical pathways designed to achieve early recovery after surgery and a decreased length of hospital stay (LOS). Methods This observational study evaluated the implementation of ERP in gynaecologic oncological surgery in a minimally invasive techniques (MIT) expert center with more than 85% of procedures done with MIT. We compared a prospective cohort of 100 patients involved in ERP between December 2015 and June 2016 to a 100 patients control group, without ERP, previously managed in the same center between April 2015 and November 2015. All the included patients were referred for hysterectomy and/or pelvic or para-aortic lymphadenectomy for gynaecological cancer. The primary objective was to achieve a significant decrease of median LOS in the ERP group. Secondary objectives were decreases in proportion of patients achieving target LOS (2 days), morbidity and readmissions. Results Except a disparity in oncological indications with a higher proportion of endometrial cancer in the group with ERP vs. the group without ERP (42% vs. 22%; p = 0.003), there were no differences in patient’s characteristics and surgical procedures. ERP were associated with decreases of median LOS (2.5 [0 to 11] days vs. 3 [1 to 14] days; p = 0.002) and proportion of discharged patient at target LOS (45% vs. 24%; p = 0.002). Morbidities occurred in 25% and 26% in the groups with and without ERP and readmission rates were respectively of 6% and 8%, without any significant difference. Conclusion ERP in gynaecologic oncological surgery is associated with a decrease of LOS without increases of morbidity or readmission rates, even in a center with a high proportion of MIT. Although it is already widely accepted that MIT improves early recovery, our study shows that the addition of ERP’s clinical pathways improve surgical outcomes and patient care management.

PURPOSE: While optimal cytoreduction is the standard of care for advanced ovarian cancer, the related post-operative morbidity has not been clearly documented outside pioneering centers. Indeed most of the studies are monocentric with inclusions over several years inducing heterogeneity in techniques and goals of surgery. We assessed the morbidity of optimal cytoreduction surgery for advanced ovarian cancer within a short inclusion period in 6 referral centers dedicated to achieve complete cytoreduction. PATIENTS AND METHODS: The 30 last optimal debulking surgeries of 6 cancer centers were included. Inclusion criteria included: stage IIIc- IV ovarian cancer and optimal surgery performed at the site of inclusion. All post-operative complications within 30 days of surgery were recorded and graded using the Memorial secondary events grading system. Student-t, Chi2 and non-parametric statistical tests were performed. RESULTS: 180 patients were included. There was no demographic differences between the centers. 63 patients underwent surgery including intestinal resections (58 recto-sigmoid resection), 24 diaphragmatic resections, 17 splenectomies. 61 patients presented complications; One patient died post-operatively. Major (grade 3-5) complications requiring subsequent surgeries occurred in 21 patients (11.5%). 76% of patients with a major complication had undergone an ultraradical surgery (P = 0.004). CONCLUSION: While ultraradical surgery may result in complete resection of peritoneal disease in advanced ovarian cancer, the associated complication rate is not negligible. Patients should be carefully evaluated and the timing of their surgery optimized in order to avoid major complications.

BackgroundInflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.Methodology/findingsGenomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.ConclusionsOur results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets.