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Background: The impact of local management of pulmonary metastases on the disease course of patients with metastatic colorectal cancer is poorly assessed., Methods: REPULCO database was a retrospective cohort on 18 years that included all patients treated for lung metastases from colorectal cancer who received local and/or systemic treatments., Aims: Primary objective was overall survival, secondary were progression-free survival and survival without chemotherapy., Results: Three hundred and fifteen patients were analyzed, 157 with only systemic treatments, 78 with only local treatments, and 80 with local and systemic treatments. Overall survival at 5 years was 26.9% (IC95%: [17.7-36.9]) for systemic treatments only, 61.0% (IC95%: [40.8-76.1]) for local treatments only, and 77.8% (IC95%: [60.1-88.3]) for local and systemic treatments. Progression-free survival at 2 years was 4.8% (IC95%: [2.1-9.2]) for systemic treatment only, 28.3% (IC95%: [17.7-39.9]) for local treatments only, and 21.8% (IC95%: [13.1-31.9]) for local and systemic treatments. Median survival without chemotherapy was 2.99 months (IC95%: [2.33-3.68]) for systemic treatments, 33.97 months (IC95%: [19.06-NA]) for local treatments, and 12.85 months (IC95%: [8.18-21.06]) for local and systemic treatments., Conclusion: Local treatments of lung metastasis led to prolonged survival and allowed long periods of time without chemotherapy in this cohort., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: Idylla epidermal growth factor receptor ( EGFR ) is a fast and fully automated mutation assay that is easy to implement. However, under the Biocartis-recommended technical conditions, tissue sections are directly introduced into the cartridge, at the risk of exhausting the tumour sample. In this study, we evaluate the performance of Idylla EGFR on extracted DNA and discuss its place within the global non-small-cell lung cancer (NSCLC) screening strategy., Methods: 577 comparative tests between Idylla EGFR on extracted DNA and next-generation sequencing (NGS) were performed across two centres., Results: Preanalytical thresholds were established (20% tumour cell content, 50 ng DNA input) and challenged prospectively in routine practice. 16.8% of samples referred for screening were considered non eligible for Idylla EGFR testing. Due to discordant by design cases, Idylla EGFR sensitivity was 86.9% for currently actionable EGFR mutations. Idylla EGFR specificity was 100% in first-line screening. NGS was always feasible on the same DNA., Conclusion: Idylla EGFR on extracted DNA is feasible and enables tumour material to be saved compared with tissue section use. It is not necessary to replace the analytical thresholds of the Biocartis algorithm. Due to both the limits of the mutational repertoire and the high increase of targetable genes in NSCLC, the use of Idylla EGFR should be restricted to clinical emergency situations accompanied by NGS., Competing Interests: Competing interests: EK has received honoraria from Biocartis. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to predict relapse., Materials and Methods: We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and we describe the immune microenvironments of the residual tumors., Results: Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into five clusters with distinct prognosis based on pathways linked to immune activation, epithelial-to-mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector antitumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort. This signature was validated in two external cohorts (KMplot and METABRIC)., Conclusions: Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patient prognosis., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BACKGROUND. A recently introduced digital breast tomosynthesis (DBT) device allows acquisition of DBT spot compression views with a small paddle during DBT acquisition. OBJECTIVE. The purpose of this study was to evaluate the impact on diagnostic performance of obtaining a DBT spot compression view for assessment of equivocal DBT findings. METHODS. This retrospective study included 102 women (mean age, 60 years) in whom a DBT spot compression view was obtained to characterize an equivocal finding on DBT at the performing radiologist's discretion. The DBT examinations were performed from December 14, 2018, to December 18, 2019. Two fellowship-trained breast radiologists and one breast imaging fellow, who were aware of the location of the equivocal lesions, independently reviewed the examinations. Readers first assigned a BI-RADS category using standard DBT views and then immediately assigned a category using the DBT spot compression view. BI-RADS categories 2 and 3 were considered negative, and categories 4A and greater were considered positive. Histology and at least 1 year of imaging follow-up served as the reference standard. Intrareader agreement for one reader and interreader agreement among all readers were evaluated with kappa coefficients. Diagnostic performance was compared between DBT with and DBT without spot compression views by use of McNemar tests. RESULTS. Intrareader agreement increased from 0.43 to 0.72, and interreader agreement increased from 0.21 to 0.45 on the basis of kappa coefficients for DBT without and with spot compression views. Eighteen cancers were present. Compared with standard DBT views, DBT spot compression views yielded significantly increased accuracy for all three readers (75% vs 90%, 74% vs 94%, 72% vs 94%); significantly increased specificity for all three readers (69% vs 90%, 75% vs 94%, 68% vs 93%); and significantly increased sensitivity for one reader (67% vs 94%) without significant change in sensitivity for the two other readers (89% vs 100%, 100% vs 89%). Radiation dose was 1.97 mGy for the DBT spot compression view versus 1.78-1.81 mGy for standard DBT craniocaudal and medio-lateral oblique views. CONCLUSION. Use of the DBT spot compression view increased intrareader agreement, interreader agreement, and diagnostic accuracy (primarily owing to improved specificity); the supplemental dose for the spot compression view was slightly higher than that for a standard DBT view. CLINICAL IMPACT. DBT spot compression may help characterize equivocal DBT findings, reducing further workup for benign findings.

The similarities between sporadic basal-like breast cancer (BLBC) and BRCA1-mutated breast tumours raise the possibility that deregulation of the same pathway may underlie these tumour types. The aim of this study was to determine if PTEN aberrations are characteristic of both BRCA1 tumours and sporadic TN breast carcinomas with low BRCA1 expression, and can thus be used to identify sporadic tumours potentially sensitive to PARP inhibitors. Twelve BRCA1 tumours, 19 non-BRCA familial breast tumours and 71 unselected TN breast carcinomas were screened for PTEN mutations and assessed for PTEN expression and BRCA1 mRNA expression. Loss of PTEN expression was observed in 67% of BRCA1 tumours and more specifically in 89% of TN BRCA1 tumours highlighting the link between PTEN loss and BLBC in the context of germline BRCA1 mutations. Regarding unselected TN tumours, 56% showed PTEN expression loss and 35% displayed low BRCA1 mRNA expression. Unlike familial breast cancers with low BRCA1 mRNA expression, no significant correlation was observed between the loss of PTEN expression and low BRCA1 mRNA expression in this unselected TN tumours panel. Our data suggest that, unlike the germinal context, PTEN and BRCA1 alterations in sporadic TN breast tumours are independent events., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Guidelines do not recommend FDG-PET CT for the staging of MIBC as a standard. The objectives of the study are to assess the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification according to FDG-PET CT results in MIBC., Patients and Methods: From January 2005 to December 2017, we carried out a retrospective analysis of patients with MIBC who had a FDG-PET CT for staging in two expert centres in Bordeaux, France, and analyzed its clinical value in this setting. Nodal and metastatic staging on CT scan (CT) and FDG-PET CT were done independently., Results: Accuracy of LN staging from CT and FDG-PET CT at initial diagnosis was analyzed in 85 patients (including 70 patients treated with neoadjuvant chemotherapy (NAC)) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (80.8% versus 26.9%) but the specificity was low (54.2% vs. 83.1%). The Youden index was better for FDG-PET CT (0.35; 0.1 for CT) and FDG-PET CT appeared to be more accurate for determining LN staging of MIBC. FDG-PET CT findings enabled a treatment decision modification in 34/130 patients (26.1%): a therapeutic intensification (9.2%), including surgery not previously planned and/or modified fields of radiotherapy; or a de-escalation (16.9%), mostly avoiding surgery., Conclusion: FDG-PET CT was more sensitive for detection of LN involvement at initial diagnosis of MIBC than CT alone. In our study, treatment decisions were modified, according to FDG-PET CT results, in almost a quarter of patients., (Copyright © 2022. Published by Elsevier Inc.)

Aims: Breast hamartomas are an under-recognised lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude 'no significant lesion' or 'normal breast tissue', leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas with the aim of identifying specific signs to facilitate their diagnosis and to differentiate them from normal breast and fibroepithelial lesions., Methods and Results: Forty-seven breast hamartomas were reassessed (histological diagnosis and imaging features). An immunohistochemical study [oestrogen receptor (ER), progesterone receptor (PR), CD34, high-mobility group A2 (HMGA2)] was performed. On breast imaging, hamartomas most often presented as probably benign solid masses with circumscribed margins and variable densities. Histologically, breast hamartomas resembled normal breast, although their stromal component was predominant, separating randomly scattered epithelial elements with areas of pure collagenous stroma. Pseudoangiomatous stromal hyperplasia (PASH) was present in 93.6% of cases and CD34 antibody highlighted intralobular, perilobular and interlobular distribution of CD34-positive fibroblasts. By comparison, CD34 was mainly expressed in the intralobular normal breast tissue stroma. Hamartoma stromal cells expressed HMGA2, ER and PR in 79%, 66% and 76.3% of our cases, respectively, compared to 7.7%, 23% and 19% in normal breast tissue, respectively (P < 0.0001; P = 0.0005; P < 0.0001)., Conclusions: After ascertaining that core needle biopsy is effectively intralesional, breast hamartomas can be diagnosed with confidence by taking into account the presence of stromal changes, PASH, interlobular distribution of CD34-positive fibroblasts, HMGA2 and hormonal receptor stromal expression., (© 2021 John Wiley & Sons Ltd.)

Purpose: Neurotensin receptor-1 (NTS 1 ) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS 1 expression have not been fully clarified., Methods: We studied NTS 1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS 1 expression and clinical, pathological, and biological parameters, as well as patient outcomes., Results: Out of 1419 primary breast tumors, moderate to strong positivity for NTS 1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS 1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS 1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS 1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS 1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main "correlates" of a nuclear location of NTS 1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS 1 -positive samples, cytoplasmic expression of NTS 1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS 1 nuclear staining. Ancillary analysis showed NTS 1 expression in 73% of invaded lymph nodes from NTS 1 -positive primaries., Conclusion: NTS 1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS 1 -targeting strategy, including radiopharmaceuticals for imaging and therapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers., Methods: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts., Results: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%)., Discussion: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the diagnostic accuracy of breast MRI in identifying lesions requiring excision for patients with suspicious nipple discharge but normal mammograms and ultrasounds., Methods: Between September 2013 and May 2019, 106 female participants (mean age 57.9 years) were consecutively included in this prospective multicenter study; 102 were retained for analysis. MRI was considered negative in the absence of suspicious enhancement and positive in cases of ipsilateral abnormal enhancement (BI-RADS 3 to 5). Final diagnoses were based on histological findings of surgical or percutaneous biopsies or at 1-year follow-up. We considered all lesions requiring excision found on pathology (papilloma, atypia, nipple adenomatosis, or cancer) as positive results. We considered spontaneous resolution of the discharge at 1 year as a negative result., Results: MRI showed ipsilateral abnormal enhancement in 54 patients (53%) revealing 46 lesions requiring excision (31 benign papillomas, 5 papillomas with atypia, 2 nipple adenomatosis, and 8 cancers) and 8 benign lesions not requiring excision. No suspicious enhancement was found in the remaining 48 participants (47%). Forty-two were followed up at 1 year with spontaneous resolution of the discharge and six underwent surgery (revealing 2 benign papillomas). MRI diagnostic accuracy for the detection of a lesion requiring excision was as follows: sensitivity 96%, specificity 85%, positive predictive value 85%, and negative predictive value 96%., Conclusion: In patients with suspicious nipple discharge and normal mammogram and ultrasound, MRI demonstrates excellent performance to identify lesions for which excision is required. Normal MRI indicates it is safe to propose follow-up only management, thus avoiding unnecessary duct excision., Trial Registration: ClinicalTrials.gov NCT02819362 KEY POINTS: • Breast MRI can be useful for the management of patients with suspicious nipple discharge and negative mammogram and ultrasound. • MRI detected a lesion requiring excision in 46 participants (45%) with unexplained discharge. • If breast MRI is negative, follow-up is a safe alternative for these patients., (© 2021. European Society of Radiology.)

Purpose: There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC., Methods: In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI)., Results: In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P < 0.0001, respectively). In univariate analysis of the RD group, low RCB index and high ratios of stromal tumor-infiltrating lymphocytes (TILs), CD3 + TILs, CD4 + TILs, CD8 + TILs, and IDO1-positive cells were significant favorable prognostic factors for DRFI at 3 years. In the final multivariate model, CD4 + TILs and RCB index showed a statistically independent prognostic significance for DRFI [Hazard Ratio (HR) 2.88 (95%CI 1.34-6.17), P = 0.007 and HR 12.04 (95%CI 2.78-52.23, P < 0.0001), respectively]. The CD4 + TIL levels influenced survival in the different RCB classes with a significant effect observed in RCB-II and RCB-III classes (P = 0.05 and P = 0.05, respectively)., Conclusions: These results suggest that the combination of pathological (RCB index) and tumor micro-environmental features (CD4 + TILs) help refining the prognosis of TNBC patients with RD following NAC.

Background: To determine safety and efficacy of radiofrequency ablation (RFA) for local treatment of lung metastases of renal cell carcinoma (RCC), sequenced or combined with systemic treatments., Methods: Retrospectively, we studied 53 patients treated by RFA for a maximum of six lung metastases of RCC. The endpoints were local efficacy, overall (OS), disease-free (DFS), pulmonary progression-free (PPFS) and systemic treatment-free (STFS) survivals, complications graded by the CTCAE classification and factors associated with survivals. Potential factors analysed were: clinical and pathological data, tumoral staging of TNM classification, primary tumor histology, Fuhrman's grade, age, number and size of lung metastases and extra-pulmonary metastases pre-RFA., Results: One hundred metastases were treated by RFA. Median follow-up time was 61 months (interquartile range 90-34). Five-year OS was 62% (95% confidence interval (CI): 44-75). Median DFS was 9.9 months (95% CI: 6-16). PPFS at 1 and 3 years was 58.9% (95%CI: 44.1-70.9) and 35.2% (95%CI: 21.6-49.1), respectively. We observed 3% major complications (grade 3 and 4 of CTCAE classification). Local efficacy was 91%. Median STFS was 28.3 months. Thirteen patients (25%) with lung recurrence could be treated by another RFA. T3/T4 tumors had significantly worse OS, PPFS and STFS. Having two or more lung metastases increased the risk of pulmonary progression more than threefold., Conclusion: Integrated to systemic treatment strategy, RFA is safe and effective for the treatment strategy of lung metastasis from RCC with good OS and long systemic treatment-free survival. RFA offers the possibility of repeat procedures, with low morbidity.

Purpose: To evaluate the clinical, radiological and periprocedural features associated with the occurrence or worsening of acetabular fracture (OWAF) following percutaneous cementoplasty of the acetabulum (PCA) in cancer patients., Method: All patients who underwent PCA in our comprehensive cancer center for an acetabular metastasis between January 2008 and December 2015 were included. Clinical features, characteristics of the metastasis on computed tomography (CT-scan) (location [roof, quadrilateral surface, anterior and posterior columns], number of locations, matrix, extra/intra-articular fractures, extra-osseous or subchondral extensions) and of the procedure (extra- or intra-articular cement leakage (IACL), percentage of filling of each location, complications) were reported as well as prior, concomitant or post-PCA treatments. The endpoint was OWAF on CT-scan during post-PCA follow-up. Log-rank tests and Cox models were used to identify prognostic factors., Results: 140 PCA were identified in 129 patients (11 bilateral procedures, median age: 66.6). Eighteen (18/140, 12.9%) had an initial articular fracture. IACL was seen in 12/140 (8.6%) PCA. The only feature associated with IACL was a pre-existing articular fracture (p = 0.009). Of the 111 patients with imaging follow-ups, 18 (16.2%) showed OWAF. In multivariate analysis, the presence of cement filling (even partial) of all acetabular metastatic locations was the only feature predictive of OWAF-free survival (hazard ratio = 3.8, p = 0.031)., Conclusions: Injecting cement in all areas affected by acetabular metastases could prevent OWAF. Because survival following PCA is not negligible, completing an insufficient first PCA could help preserve patients' quality of life., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: No consensus exists on how to follow patients after complete remission of a primary Soft Tissue Sarcoma (STS). Studying relapse features could help tailor guidelines for follow-up. Patients and Methods: Patients in complete remission after initial management of a localized STS at Institut Bergonié who presented a first local and/or metastatic relapse between January 1995 and July 2015 were eligible. Characteristics of relapse diagnosis were retrospectively collected. Results: 359 patients met inclusion criteria. 197 and 187 patients presented a local relapse and a metastatic relapse, respectively. In group 1 (limbs/trunk wall) and 2 (trunk/gynecological/other location), local relapse was diagnosed on clinical symptoms in 89 and 44% of cases, first detected by the patient himself in 68.5 and 34% of cases, and outside a planned visit in 67 and 36% of cases, respectively. In patients with metastatic relapse, diagnosis was made during a planned visit in 63% of cases, and by imaging in 62% of cases. Median survival after relapse was not different whether the first local relapse was diagnosed clinically or by imaging (44 [95%CI: 28-69.8] vs. 57 months [95%CI: 33.9-84.5], p = 0.35) but was longer if diagnosis of metastatic relapse was made on planned chest-CT scan rather than chest X-ray (58 [95%CI: 35.5-103.9] vs. 25 months [95%CI: 16.5-32.6], p < 0.05). Conclusion: Patient's education for regular clinical examination can be recommended for follow-up of local relapses after a primary STS of the limbs or superficial trunk. Modeling studies aiming at better understanding and predicting tumor biology to improve tailoring STS patients' follow-up are warranted.

Background Managing soft-tissue sarcoma (STS) relies on histologic grade, which is the strongest prognostic factor and a routine assessment at biopsy. However, underestimation of histologic grade may occur because of tumor heterogeneity. Purpose To identify MRI features that are associated with high-grade STS (grade III) and to determine the relationship between MRI features and patient survival. Materials and Methods In this retrospective single-center study, patients (age ≥16 years) were included if they presented with STS diagnosed between 2008 and 2015, had a baseline contrast material-enhanced MRI study, had a pathologic grade assessed on the whole surgical specimen, and had no history of neoadjuvant treatment. Visceral sarcomas, well-differentiated liposarcomas, and angiosarcomas were excluded. Images were evaluated for size, heterogeneity, architecture, margins, and surrounding tissue at T2-weighted, T1-weighted precontrast, and T1-weighted postcontrast MRI. χ 2 tests, Fisher tests, and multivariable binary logistic regression were performed to identify features associated with a final grade of III. The associations between combinations of these features and overall survival and metastasis-free survival were investigated with Kaplan-Meier curves and multivariable Cox models. Results A total of 130 patients were included (53 women [mean age ± standard deviation, 60.7 years ± 19.2]); 72 of the 130 (55.4%) STSs were grade III. At multivariable analysis, three MRI features were associated with grade III STS: peritumoral enhancement (odds ratio [OR], 3.4; P = .003), presence of an area compatible with necrosis (OR, 2.4; P = .03), and heterogeneous signal intensities greater than or equal to 50% at T2-weighted imaging (OR, 2.3; P = .04). The presence of at least two of these three features was an independent predictor of metastasis-free survival (hazard ratio, 4.5; P = .01) and overall survival (hazard ratio, 4.2; P = .04). Conclusion MRI features including necrosis, heterogeneity, and peritumoral enhancement of soft-tissue sarcomas were associated with grade III tumors, metastasis-free survival, and overall survival. © RSNA, 2019 Online supplemental material is available for this article.

Introduction: Ductal carcinoma in situ (DCIS) accounts for 15% of all breast cancers and generally, the prognosis is good if treated optimally. The standard treatment includes breast conservative surgery along with adjuvant radiotherapy. Skin-sparing mastectomy (SSM) preserves the breast skin envelope but its oncological safety poses a few concerns. Moreover, no DCIS-specific studies have compared the local recurrence (LR) rate following total mastectomy (TM) or SSM. We evaluated the LR rate in DCIS patients who underwent either TM or SSM., Methods: This is a retrospective study on women who underwent mastectomy with or without immediate breast reconstruction or secondary reconstruction for pure DCIS of the breast. All patients treated at Institut Bergonié by mastectomy for DCIS from January 1990 to December 2010 were included. LR and overall survival (OS) rates were estimated., Results: The study population included 399 patients who were categorized into two groups, 207 in the TM group and 192 in the SSM group. At 10 years of follow-up, the LR rate was 0.97% in the TM group and 1.04% in the SSM group (p = NS). The OS of the entire population was 94.7% [95% CI; 91.6-96.7], 92.8% [95% CI, 87.9-95.8] for the TM group and 96.8% [95% CI, 91.6-98.8] for the SSM group., Conclusions: In our study, the LR rate following mastectomy is low, regardless of the surgical technique used, with an excellent OS at 10 years., (Copyright © 2019. Published by Elsevier Ltd.)

Background and Objectives: Soft tissue sarcoma localization in distal extremities (DESTS) of the limbs (hand/fingers, and foot/toes) is unusual. The literature is scarce about their behavior and this study was designed to assess their epidemiological characteristics, outcomes, and prognosis compared to other limb localizations (OLSTS)., Methods: From 1980 to 2010, adult DESTS and OLSTS in 22 centers were included. Demographics, tumor type, treatment modalities, and latest follow-up status were collected. Primary endpoints were overall survival and local/metastatic recurrence incidences., Results: Two hundred five DESTS and 3001 OLSTS were included. The patients were younger, with more female and smaller tumors in DESTS. There were more clear cell/epithelioid sarcomas, synovial sarcomas, and myxoid liposarcomas vs more dedifferentiated liposarcomas in OLSTS. DESTS tumors were less irradiated and more often amputated (24.3% vs 3.4%). The five-year survival rate was 78.2% compared to 68.6% in OLSTS and after multivariate analysis, STS localization did not impact survival or local/metastatic recurrence., Conclusion: Though rare and smaller than other limb localizations, DESTS are to be considered as aggressive. Despite a higher amputation rate, the prognosis remains the same as in OLSTS. Limb sparing vs amputation should be carefully assessed in DESTS, especially if grade 3 or of a poor prognosis histological subtype., (© 2019 Wiley Periodicals, Inc.)

Triple-negative breast cancer (TNBC) patients have an increased risk of developing visceral metastases and other primary nonbreast cancers, particularly lung cancer. The differential diagnosis of TNBC metastases and primary cancers from other organs can be difficult due to lack of a TNBC standard immunoprofile. We analyzed the diagnostic value of estrogen receptor, progesterone receptor, human epidermal growth factor receptor, thyroid transcription factor-1 (TTF1), Napsin A, mammaglobin, gross cystic disease fluid protein 15 (GCDFP15), Sry-related HMg-Box gene 10 (SOX10), GATA-binding protein 3 (GATA3), and androgen receptor in a series of 207 TNBC and 152 primary lung adenocarcinomas (LA). All tested TNBCs were TTF1 and Napsin A-negative. When comparing TNBC and TTF1-positive or negative LA, SOX10 had the best sensitivity (62.3%) and specificity (100%) as a marker in favor of TNBC compared with LA, irrespective of TTF1 status (P<0.0001). GATA3 had moderate sensitivity (30.4%) and excellent specificity (98.7%) and misclassified only 2/152 LA (1.3%). GCDFP15 had a moderate sensitivity (20.8%) and excellent specificity (98%) and misclassified only 3/152 (2%) LA. Mammaglobin and androgen receptor had moderate sensitivities (38.2% and 30%), good specificities (81.6% and 86%), and misclassified 28/152 and 21/152 LAs, respectively. In multivariate analysis, the best markers, enabling the distinction between SOX10-negative TNBC and TTF1 and Napsin A-negative LA were GATA3 (odds ratio=33.5; 95% confidence interval, 7.3-153.5; P<0.0001) and GCDFP15 (odds ratio=31.7; 95% confidence interval, 6.9-145.6; P<0.0001). Only 13/207 (6.3%) TNBC cases did not express any aforementioned marker. On the basis of our results, the best sequential immunohistochemical analysis to differentiate TNBC from TTF1-negative LA is first SOX10 followed by GATA3, and finally GCDFP15. This order is important in the diagnostic workup of small biopsies from lung nodules in women with a previous history of TNBC.

Background: Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes., Patients and Methods: Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis., Results: Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex ( P  = .01), pre-operative platelets <150 g/L ( P  = .04), and aspartate aminotransferase to platelet ratio index (APRI) score >0.36 ( P  = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P  = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m 2 ( P  = .004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively)., Conclusions: There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chemotherapy (ct) is the preferred treatment option in metastatic colorectal cancer (mCRC). The objective of the study was to determine the overall survival (OS), disease-free survival (DFS) and ct-free survival (CFS) of pulmonary thermal ablation (TA) and its place in the treatment of mCRC., Patients and Methods: All consecutive patients treated (over 11 years) with percutaneous TA for lung metastasis of colorectal origin were reviewed. All sequences of treatments were considered. We determined the OS, DFS and CFS of pulmonary TA., Results: Two hundred and nine patients underwent 323 TA procedures for 630 lung metastases. Majority of the metastases (71.5%) were unilateral with a median diameter of 10 mm (2-46). A single metastasis was treated in 95 patients (45.5%), and 2-8 in 114 patients (54.5%). One hundred and thirty-two patients (63.2%) had only a single procedure, 77 patients (36.8%) had 2-5 procedures. Following the first TA (n = 209), 125 patients (59.8%) resumed ct. Sixty-four out of the 126 patients presenting lung progression were treated again with TA. The median CFS was 12.2 months (95% CI: 10.3-17.7). Patients with no extra-pulmonary metastases showed a statistically better CFS than those who had extra-pulmonary metastases with a median of 20.9 and 9.2 months, respectively (p < 0.001). Median follow-up and OS were 50 and 67.6 months, respectively., Conclusion: This study demonstrates, for the first time, that TA enables a CFS of 12.2 months that extended to 20.9 months in patients who presented with lung-only metastases. TA is a viable option for a pause in the therapy of mCRCs.

Background: The definition of parenchymal sparing surgery (PSS) for colorectal liver metastases (CRLM) diverges requiring a clarification of the concept., Method: A consecutive series of patients were treated by PSS for their CRLMs, either by resection or intra-operative ablation (IOA), whenever possible a one-stage surgery and minimal usage of portal vein embolization. Post-operative complications were the primary endpoint with a special focus on post-operative liver failure., Results: Three hundred and eighty-seven patients underwent a PSS out of which 328 patients received a median of 9 pre-operative cycles of chemotherapy. One hundred and twenty-eight patients had a major resection, combined with IOA in 137 patients and IOA alone in 50 cases. The 5yr-overall survival was 50.3%. There was no difference in post-operative complications between minor and major resections, validating our PSS definition based on the Tumor burden/Healthy liver ratio and not just the retrieved volume., Conclusions: PSS is defined as a high ratio of tumoral burden per specimen retrieved while favoring one-stage surgery approach. Our series, using combined resections and IOAs, matches this definition well. Furthermore, complications were correlated neither to chemotherapy nor to liver-induced toxicities, contrary to extended hepatectomies., (Copyright © 2017. Published by Elsevier Ltd.)

A growing body of evidence suggests that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer. To understand which patients can be potential candidates for GRPR-based imaging or targeted therapy, we screened invasive breast cancers by immunohistochemistry for the presence and intensity of GRPR expression. Methods: We explored a tissue microarray of 1,432 primary breast tumors from patients who underwent surgery between 2000 and 2005 at Institut Bergonié, without prior neoadjuvant treatment. We studied associations between GRPR expression and clinical, pathologic, and biologic parameters. The association between GRPR expression and distant metastasis-free interval was also examined. Results: GRPR overexpression was found in 75.8% of the 1,432 tumors and was most strongly associated with estrogen receptor (ER) positivity (GRPR was high in 83.2% of ER-positive and 12% of ER-negative tumors; P < 0.00001). When molecular subtypes of breast cancer were considered, GRPR was overexpressed in 86.2% of luminal A-like tumors, 70.5% of luminal B-like human epidermal growth factor receptor 2 (HER2)-negative tumors, 82.8% of luminal B-like HER2-positive tumors, 21.3% of HER2-enriched tumors, and 7.8% of triple-negative tumors. Importantly, when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic lymph nodes in 94.6% of cases. Primary tumors with high GRPR expression were associated with lower risk of distant metastases at follow-up in univariate analysis (Log-rank P = 0.0084) but not in multivariate analysis. Hence, the prognostic impact of GRPR was lost when examined within specific molecular subtypes. Conclusion: Because GRPR is overexpressed in a high percentage of ER-positive tumors, GRPR targeting offers wide perspectives for imaging and treatment in patients with ER-positive breast cancer, using recently developed radiolabeled GRPR ligands., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Objectives: Conservative surgery for soft-tissue sarcoma (STS) within multimodality treatment attempts to reconcile two contradictory requirements: assuring a good oncological outcome through a wide resection and preserving the function. The aim of our study is to verify whether our conservative approach to STS met these objectives., Methods: A retrospective database analysis was performed in adults with primary limb or trunk wall STS operated in a single center from 1989 to 2012. Predictive factors for postoperative complications and functional impairment were tested in a multivariate analysis., Results: 728 patients were operated (resection R0: 68%). Neoadjuvant chemotherapy (NAC) was given to 28%, postoperative radiotherapy to 70% of patients. Median follow-up was 103 months. At five years, overall survival was 80% and local recurrences 11%. Major postoperative complications occurred in 8% and functional impairment in 13% of the patients. Independent predictive factors for postoperative complications were American Society of Anesthesiologist classes 2 and 3 (OR: 2.3, CI: 1.2-4.5 and 4.0 CI: 1.7-9.3), tumor size >80 mm (OR: 2.5, CI: 1.3-4.9), tumor site (trunk wall/lower limb, OR: 4.1, CI: 1.3-13.6) and multifocal/multicompartmental spread (OR: 2, CI: 1.1-3.6). Independent predictive factors for function impairment were postoperative complications (OR: 5.3, CI: 2.8-10.1), NAC (OR: 3.6, CI: 2.2-5.8), and bone or neurovascular involvement (OR 3.3, CI 2.0-5.3), whereas Early Rehabilitation after Surgery (ERAS) improved outcome (OR: 0.5, CI: 0.3-0.9)., Conclusion: Postoperative complications induced functional impairment. They may be reduced by acting on comorbidity factors and careful tumor evaluation prior to surgery. Furthermore, ERAS measures improved function., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Radical cystectomy (RC) and pelvic lymph-node dissection (LND) is standard treatment for non-metastatic muscle-invasive urothelial bladder cancer (MIBC). However, loco-regional recurrence (LRR) is a common early event associated with poor prognosis. We evaluate 3-year LRR-free (LRRFS), metastasis-free (MFS) and overall survivals (OS) after adjuvant radiotherapy (RT) for pathological high-risk MIBC., Material and Methods: We retrospectively reviewed data from patients in 3 institutions. Inclusion criteria were MIBC, histologically-proven urothelial carcinoma treated by RC and adjuvant RT. Patients with conservative surgery were excluded. Outcomes were evaluated by Kaplan-Meier method. Acute toxicities were recorded according to CTCAE V4.0 scale., Results: Between 2000 and 2013, 57 patients [median age 66.3 years (45-84)] were included. Post-operative pathological staging was ≤pT2, pT3 and pT4 in 16%, 44%, and 39%, respectively. PLND revealed 28% pN0, 26% pN1 and 42% pN2. Median number of lymph-nodes retrieved was 10 (2-33). Forty-eight patients (84%) received platin-based chemotherapy. For RT, clinical target volume 1 (CTV 1) encompassed pelvic lymph nodes for all patients. CTV 1 also included cystectomy bed for 37 patients (65%). CTV 1 median dose was 45 Gy (4-50). A boost of 16 Gy (5-22), corresponding to CTV 2, was administered for 30 patients, depending on pathological features. One third of patients received intensity-modulated RT. With median follow-up of 40.4 months, 8 patients (14%) had LRR. Three-year LRRFS, MFS and OS were 45% (95%CI 30-60), 37% (95%CI 24-51) and 49% (95%CI 33-63), respectively. Five (9%) patients had acute grade ≥3 toxicities (gastro-intestinal, genito-urinary and biological parameters). One patient died with intestinal fistula in a septic context., Conclusions: Because of poor prognosis, an effective post-operative standard of care is needed for pathological high-risk MIBC. Adjuvant RT is feasible and may have oncological benefits. Prospective trials evaluating this approach with current RT techniques should be undertaken.

Purpose: To evaluate the efficacy and toxicity of helical tomotherapy (HT) in the management of spine chordomas when proton therapy is unavailable or non-feasible., Methods and Materials: Between 2007 and 2013, 30 patients with biopsy-proven chordomas were treated by HT in five French institutions. Information regarding local control (LC), overall survival (OS), progression-free survival (PFS) and metastasis-free survival (MFS) was collected. Clinical efficacy, toxicity and treatment quality were evaluated., Results: Two-year actuarial LC, OS, PFS and MFS were 69.9%, 96.7%, 61.2% and 76.4%, respectively. HT treatments were well tolerated and no Grade 4-5 toxicities were observed. HT permitted the delivery of a mean dose of 68 Gy while respecting organ at risk (OAR) dose constraints, in particular in the spinal cord and cauda equina., Conclusions: This multicentric, retrospective study demonstrated the feasibility of HT in the treatment of spine chordomas, in the absence of hadron therapy.

Background: Depression is the most common psychiatric disorder in geriatrics and oncology. For elderly cancer patients, it has a significant impact on quality of life, morbidity, and mortality. Nevertheless, depression is under-diagnosed and under-treated. Cancer management is key in improving the quality of care in this population. We aim to identify sociodemographic, clinical, and treatment-related factors of depression in elderly patients during chemotherapy, thus allowing early detection of patients in need of specific treatment. Further, we investigate whether chemotherapy efficacy and safety are associated with depression., Patients and Methods: A prospective multicenter cohort composed of incident cases of cancer diagnosed in patients 70 years and older, receiving first-line chemotherapy. Depressive symptoms were measured by the Geriatric Depression Scale at baseline and after four chemotherapy cycles. Associations between depressive symptoms during chemotherapy and patients' clinical and treatment characteristics were identified by logistic regression., Results: Among 344 patients measured for depression before chemotherapy, 260 had a second assessment at the fourth treatment cycle. At baseline, 45.4% were depressed, and 44.6% were depressed after the fourth cycle. Independent factors of depression were depressive symptoms at baseline (odds ratio (OR) = 6.7, p < 0.001), malnutrition (OR = 5.1, p = 0.014), and risk of malnutrition (OR = 1.6, p = 0.014). After controlling for missing data, effective chemotherapy was associated with a lower risk of depression (OR = 0.4, p = 0.018)., Conclusion: We highlight the role of depressive symptoms and nutritional status at baseline, on the occurrence of depressive symptoms during chemotherapy. These factors should be taken into account in any pre-treatment consultation and appropriate nutritional and psychiatric preventative measures established. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objectives: To retrospectively evaluate the diagnostic performance of morphological signs observed on conventional magnetic resonance (MR) imaging to differentiate benign from malignant peripheral solid tumors of soft tissue with myxoid stroma., Methods: MR images from 95 consecutive histopathologically proven tumors (26 benign and 69 malignant) of soft tissues with myxoid components were evaluated in our tertiary referral center. Two radiologists, blind to pathology results, independently reviewed conventional MR sequences including at least a) one T2-weighted sequence with or without fat suppression; b) one T1-weighted sequence without fat suppression; and c) one T1-weighted sequence with gadolinium-complex contrast enhancement and fat suppression. Multiple criteria were defined to analyze morphology, margins, architecture and tumor periphery and evaluated for each lesion. Intra- and inter-observer reproducibility and Odds ratios were calculated for each criterion., Results: The most relevant and reproducible criteria to significantly predict malignancy were: (1) ill-defined tumor margins, (2) a hemorrhagic component, (3) intra-tumoral fat, (4) fibrosis and (5) the "tail sign". A lesion is classified as malignant if any of these 5 criteria is present, and benign if none of them are observed. Therefore, this combination provides a sensitivity of 92.9% and a specificity of 93.3%., Conclusion: Conventional MR imaging provides reproducible criteria that can be combined to differentiate between benign and malignant solid tumors of soft tissue with myxoid stroma., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate the necessity of a prolonged follow-up after one year for lesions incidentally diagnosed as Breast Imaging Reporting and Data System (BI-RADS)(®) 3 on magnetic resonance imaging (MRI)., Methods: Institutional review board approved this study (CRC&#95;june 2014&#95; project 11). We retrospectively analysed 218 consecutive MRI BI-RADS(®) 3 lesions in 110 women followed-up at 6, 12, 18 and/or 24 months from 2011 through to 2015. We excluded MRI scans of BRCA mutation carriers, in staging before treatment and in patients undergoing therapy for breast cancer. Second-look ultrasound and mammography were normal. We analysed 43 masses, 46 foci and 129 non-mass enhancements. In the follow-up, the image was scored as BI-RADS(®) 2 if it was completely resolved, BI-RADS(®) 3 if it was stable, and BI-RADS(®) 4 if a suspicious change occurred., Results: Forty-four lesions (20%) completely resolved during the follow-up. Six were scored as BI-RADS(®) 4: five at 6 months (benign) and one at 12 months (8 mm invasive ductal carcinoma). One hundred and sixty eight stable lesions were assigned BI-RADS(®) 2 at 18 or 24 months. The predictive positive value of cancer for BI-RADS(®) 3 lesions is 0.5% (95% CI [0.08-2.55]) in our study., Conclusions: Our results suggest that a one year follow-up instead of two years is sufficient for BI-RADS 3 lesions, in case of using rigorous inclusion criteria. Given the very low PPV of the BI-RADS(®) 3 lesions incidentally found on MRI, further studies with very large inclusions are necessary to establish new guidelines for MRI follow-up., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

During their follow-up, patients with cancer can experience several types of recurrent events and can also die. Over the last decades, several joint models have been proposed to deal with recurrent events with dependent terminal event. Most of them require the proportional hazard assumption. In the case of long follow-up, this assumption could be violated. We propose a joint frailty model for two types of recurrent events and a dependent terminal event to account for potential dependencies between events with potentially time-varying coefficients. For that, regression splines are used to model the time-varying coefficients. Baseline hazard functions (BHF) are estimated with piecewise constant functions or with cubic M-Splines functions. The maximum likelihood estimation method provides parameter estimates. Likelihood ratio tests are performed to test the time dependency and the statistical association of the covariates. This model was driven by breast cancer data where the maximum follow-up was close to 20 years.

Background: Enhanced recovery after surgery (ERAS) programs are implemented in multiple fields of surgery, but not yet in soft-tissue sarcoma (STS) surgery. We wondered whether its introduction into STS surgery might have impacted postoperative outcome., Methods: Two hundred and fifty seven adult patients with primary limb or trunk wall STS received ERAS from 2008 to 2012 as a part of the intra-operative management. We evaluated, in retrospect, the intra-operative management, post-operative outcomes, functional and oncological results of these patients and compared them with 459 prior patients treated under a standard recovery after surgery (SRAS) program from 1989 to 2007., Results: The most visible change from SRAS to ERAS in the perioperative management was decrease of wound drainage (72% vs. 15%, p < 0.001) and increase of wound bandaging (16% vs. 66%; p < 0.001), underlining the appliance of the ERAS protocol. Post-operatively, hospital stay dropped from nine (0-74) to three (0-22) days (p < 0.001) without affecting major morbidity (8% vs. 5%, NS) or readmission to the hospital (5% vs. 4%, NS). Functional outcome improved (p = 0.009) but whether this change was due to ERAS remains to be proved because complementary treatments changed over time. Tumour control remained unaffected, with an estimated risk of local recurrence at 5 years of 12% in both groups., Conclusion: Introducing a rapid recovery program was associated with a shorter hospitalization stay without compromising surgical or oncological outcomes. The program appears to be safe and reliable to use in patients undergoing STS surgery., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: This study aims to better define prognostic factors for patients with metastatic urothelial carcinoma (mUC), and to identify patients who will benefit from first-line cisplatin-based chemotherapy. We test the hypothesis that early objective response (EOR), defined as the occurrence of an objective response following 2 or 3 courses of chemotherapy, could be a prognostic factor for overall survival (OS) and thus be used to guide treatment decisions. Data from 113 patients with evaluable mUC receiving first-line cisplatin-based treatment between January 2004 and December 2006 was collected retrospectively from prospectively-maintained databases across seven French cancer centers. Clinical factors potentially associated with survival and EOR were analyzed in univariate and multivariate analysis., Results: One hundred three patient records were complete and available for inclusion in the multivariate model. Four factors were independently associated with OS: Performance status 1 and 2 (HR 2.3 [95 % CI 1.3-3.9], p = 0.002; HR 3.4 [95 % CI 1.6-7.2], p = 0.001 respectively); presence of visceral metastases (HR 2.2 [95 % CI 1.3-3.9], p = 0.004); abnormal hemoglobin levels (HR 1.7 [95 % CI 1.01-2.8], p = 0.045); disease progression (HR 10.1 [95 % CI 4.2-24.1], p < 0.001)., Conclusions: This study confirms the prognostic factors previously reported in first-line chemotherapy for mUC. However, we failed to demonstrate that EOR was an independent predictive factor of OS. Nevertheless, an early response evaluation is recommended since early progression is an important parameter that can be used to decide whether treatment should be interrupted and changed for alternative strategies integrating the concept of personalized medicine or new immune therapies.

Significant morphological, clinical and biological prognostic factors vary according to molecular subtypes of breast tumors, yet comprehensive analysis of such factors linked to survival in each group is lacking. Clinicopathological and micro-environmental criteria, estrogen (ER), progesterone (PR) receptors, HER2, Ki67, basal markers, CD24, CD44, ALDH1, BCL2, E-Cadherin and Trio were assessed in 1070 primary operable breast cancers from a single center according to five main molecular subtypes and associations with distant metastasis-free survival (DMFS) were examined. There were 682 (64 %) luminal A (LA), 166 (16 %) Luminal B HER2 negative (LBH-), 47 (4 %) Luminal B HER2 positive (LBH+), 108 (10 %) triple negative (TN) and 67 (6 %) HER2-enriched tumors (H2+). Median follow-up was 13.7 years. At 5 years, DMFS in LA (90 %) was better than in LBH- (80.9 %), hazard ratio (HR) = 2.22 [1.44-3.43] P < 0.001; LBH+ (74.5 %), HR = 3.14 [1.69-5.84] P < 0.001, TN (71.5 %) HR = 3.63 [2.34-5.63], P < 0.001; and H2+ (65.2 %), HR = 4.69 [2.90-7.59], P < 0.001. In multivariable analysis, factors associated with shorter DMFS varied according to molecular subtype, with tumor size being associated with shorter DMFS in the LBH-, LBH+ and TN groups and the Rho GEF Trio and BCL2 phenotypes in TN tumors only. These findings help to define new clinicophenotypic models and to identify new therapeutic strategies in the specific molecular subgroups.

Background: Focusing on the current context of national and international recommendations, techniques development to evaluate and preserve fertility and patients' claims, this study aims to make a survey about the management of patients' breast cancer regarding oncofertility., Methods: Retrospective and analytic study of medical practices at Bergonié Institute of health professionals (medical oncologists, surgical oncologists, nurses) dedicated to the care of non-disseminated breast cancer patients younger than 37, needing medical treatment., Results: The number of participants was 230. The most interested practitioners in fertility theme are those of multidisciplinary consultation and surgeons (P<0.001), with an increasing interest during last years (P<0.05). The information about hypofertilizing risks of treatments are delivered most of the time by oncologists (57.7%). The motherhood project is expressed by 11 patients (4.9%) before treatment, only 4 of them receive information on the risks and 49 patients (21.7%) during follow-up. Only 24 patients (48% of the 49) are encouraged for motherhood., Conclusion: To satisfy patients' requests, several improvements have to be made regarding the patients' information, the health professionals' awareness and care coordination., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)