The need to tailor the omission of axillary lymph node dissection to patients with good prognosis and sentinel node micro-metastases.

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 <75 years old with SN-micro-metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan-Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission. RESULTS: Weighted log-rank tests comparing adjusted Kaplan-Meier survival curves showed significant differences in OS (p-value = 0.002) and borderline significant differences in DFS (p-value = 0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR = 2.77, CI95% = 1.36-5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND. CONCLUSIONS: Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time.

Contribution of endocrine therapy in oestrogen receptor-positive pT1a-b breast cancer: Results of a retrospective study.

INTRODUCTION: Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET in such patients. METHODS: Our retrospective observational study included 5545 patients with pT1a-b ER-positive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression. RESULTS: Most patients (80.3%: 4453) received ET and-when compared to those without ET-experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR = 1.275, p = 0.047, 95% CI[1.003-1.620]) but not OS or RFS in all patients, while in 2363 patients with pT1a-b ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR = 1.502, p = 0.049, 95% CI[1.001-2.252]), but not OS (HR = 1.361, p = 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC. CONCLUSION: Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC-and especially in those with grade 2-3 tumours-no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours.

Neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer: Safety and efficacy of reverse sequence compared to standard technique?

BACKGROUND: The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differed reconstruction. Our study compares overall (OS) and recurrence-free (RFS) survivals of breast cancer patients treated with reverse sequence compared to the standard technique. METHODS: In this retrospective, single center study at a Comprehensive Cancer Center in France, patients were included if: female, age <65y, had received neoadjuvant chemotherapy, mastectomy and radiotherapy, and were M0. Outcomes for patients treated by reverse sequence (RS) are compared to those for patients treated by standard sequence (ST). Data was collected from medical records. RESULTS: From January 2009 to April 2018, 222 eligible patients were treated, 46 by RS and 176 by ST. Mean follow-up was 61.7 months. Five-year OS and RFS did not differ between groups. 5-yr OS: 88.4% 95%CI [74.1-95.0] for RS and 81.5% 95%CI [74.0-87.0] for ST (P = 0.4412); 5-yr RFS: 78.3% 95%CI [61.9-88.3] for RS and 70.1% 95%CI [62.2-76.7] for ST (P = 0.3003). Overall treatment time was significantly shorter in the RS group, and the rate of severe surgical complications did not differ between groups. CONCLUSIONS: For locally advanced breast cancer patients with an indication for radiation therapy the reverse sequence offers similar safety and efficacy results as the standard treatment while allowing immediate breast reconstruction. However, careful patient selection is necessary, particularly with regard to preoperative lymph node invasion.

PTEN alterations in sporadic and BRCA1-associated triple negative breast carcinomas.

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.

Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial.

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 < 0.0001) and >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.

[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center]. / Chirurgie de réduction de risque mammaire et découverte fortuite de cancer : dix ans d'expérience dans un centre de lutte contre le cancer.

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.

A Breast-Specific MR Guided Focused Ultrasound Platform and Treatment Protocol: First-in-Human Technical Evaluation.

OBJECTIVE: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol. METHODS: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system. The described tumor targeting algorithm is evaluated both with a phantom test and in vivo during the breast MRgFUS treatments. Treatments were planned and monitored using volumetric MR-acoustic radiation force imaging (MR-ARFI) and temperature imaging (MRTI). RESULTS: Successful technical treatments were achieved in 80 % of the patients. All patients underwent the treatment with no sedation and 60 % of participants had analgesic support. The total MR treatment time ranged from 73 to 114 minutes. Mean error between desired and achieved targeting in a phantom was 2.9 ±1.8 mm while 6.2 ±1.9 mm was achieved in patient studies, assessed either with MRTI or MR-ARFI measurements. MRTI and MR-ARFI were successful in 60 % and 70 % of patients, respectively. CONCLUSION: The targeting accuracy allows the accurate placement of the focal spot using electronic steering capabilities of the transducer. The use of both volumetric MRTI and MR-ARFI provides complementary treatment planning and monitoring information during the treatment, allowing the treatment of all breast anatomies, including homogeneously fatty breasts.

External Validation of the SERC Trial Population: Comparison with the Multicenter French Cohort, the Swedish and SENOMIC Trial Populations for Breast Cancer Patients with Sentinel Node Micro-Metastasis.

Many trials confirmed the safety of omitting axillary dissection in the selected patients treated for early breast cancer. The external validity of these trials is questionable. Our study aimed to evaluate the accuracy of the French population representativity in the SERC trial and the differences between these two populations as well as comparing the French and the Swedish populations (the SENOMIC trial population and the Swedish National Breast Cancer Registry (NKBC) cohort) of patients with sentinel node (SN) micro-metastasis. A higher rate of smaller tumors and grade 1 tumors was observed in the French cohort when compared to the SERC population. Our findings conclude that both French populations show similar characteristics. Positive non-sentinel node (NSN) rates at completion axillary lymph node dissection (ALND) were 10.28 % and 11.3 % in the SERC trial and French cohort, respectively (p = 0.5). The rate of grade 1 tumors was lower in the SENOMIC trial (16.2%) and in the NKBC cohort (17.4%) compared to the SERC trial population (27.3%) and the French cohort (34.4%). Our findings in addition to the previously demonstrated concordance between the SENOMIC trial and the NKBC populations imply that the results of both the SERC and the SENOMIC trials can be applied to both French and Swedish real populations.

Residual cancer burden index and tumor-infiltrating lymphocyte subtypes in triple-negative breast cancer after neoadjuvant chemotherapy.

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.

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

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.

A single-center study on total mastectomy versus skin-sparing mastectomy in case of pure ductal carcinoma in situ of the breast.

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.

Sentinel lymph node biopsy validation for large tumors.

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.

[Breast reconstruction in elderly patients: Studies of the practices at institut Bergonié during 2005-2015]. / Reconstruction mammaire chez les patientes âgées : études des pratiques de l'institut Bergonié 2005­2015.

INTRODUCTION: The objective of our study is to describe the practices of breast reconstruction in patients aged 70 years and over undergoing a radical mastectomy at institut Bergonié. MATERIAL AND METHODS: We performed a detailed single-site retrospective study from January 2005 to December 2015. Through a computerized review, we have identified and analyzed all patients aged 70 years and over who underwent a breast reconstruction. RESULTS: Five hundred and ninety patients underwent a radical mastectomy during the period. Twenty-eight patients (4.7%) benefited from a breast reconstruction. Nineteen patients (67.9%) had an immediate breast reconstruction and 9 patients (32.1%) had a delayed breast reconstruction, within an average time of 2 years. Sixteen patients (57.1%) benefited from the insertion of an expander replaced by a permanent implant. Five patients (17.9%) benefited from the immediate placement of an implant. Six patients (21.4%) had a reconstruction by autologous latissimus dorsi flap and 1 patient (3.6%) by exclusive lipofilling. Four patients (14.3%) presented postoperative complications without the need for removal of an implant or flap loss. Twenty patients (71.4%) were satisfied with their final reconstruction. CONCLUSIONS: Breast reconstruction in elderly patients is possible. Further studies are needed to better describe French practices.

Therapeutic escalation - De-escalation: Data from 15.508 early breast cancer treated with upfront surgery and sentinel lymph node biopsy (SLNB).

INTRODUCTION: The aim of this study was to examine changes in therapeutic practices for early breast cancer T0-2 N0 managed by upfront surgery and SLNB. POPULATION: Between 1999 and 2012, 15.508 patients were treated. Four periods were determined: 1999-2003, 2004-2006, 2007-2009 and > 2009. Five tumor subtypes were defined according to hormonal receptors (HR) and Her2: Luminal A (HR + Her2- Grade 1-2), Her2 (Her2+ HR-), Triple-negative (HR- Her2-), Luminal B Her2- (HR + Her2- Grade 3), Luminal B Her2+ (HR + HER2+). METHODS: Rates of axillary lymph node dissection (ALND), adjuvant chemotherapy ± trastuzumab, endocrine treatment, mastectomy and post mastectomy radiotherapy (PMRT) were analyzed according to treatment periods with univariate and multivariate analysis. Overall and disease-free survivals were analyzed according to treatment periods adjusted for HR and then for tumor subtypes. RESULTS: Rates of ALND, adjuvant chemotherapy and endocrine treatment varied significantly according to treatment periods, for HR positive and negative tumors. ALND rate decreased for all tumor subtypes with a decrease of adjuvant chemotherapy rate for Luminal A tumors and an increase for Luminal B Her2+ and Her2-tumors. Endocrine treatment rate decreased for Luminal A and increased for Luminal B Her2+ tumors. In multivariate analysis, these modifications with time remained significant. Mastectomy and PMRT rates increased. In multivariate analysis, overall and disease-free survivals increased during successive periods. CONCLUSION: A global therapeutic de-escalation in ALND and adjuvant systemic treatment, combined with an actual escalation in some specific subsets was demonstrated, but without negative impact on survival.

Breast cancer in young women: Pathologic features and molecular phenotype.

PURPOSE: Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications. METHODS: We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected. RESULTS: 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01). CONCLUSION: Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.

[Ductal carcinoma in situ diagnosis: 3 French national guidelines]. / Diagnostic du carcinome canalaire in situ : 3 recommandations nationales françaises.

OBJECTIVE: Since the last guidelines published by the French National Cancer Institute (INCa) and the learning society "Société française de sénologie et de pathologie mammaire (SFSPM)" in 2009 about diagnosis and management of ductal carcinoma in situ, new data raised issues about overdiagnosis and its consequences, overtreatment. Therefore, an update was necessary, to provide healthcare professionals up-to-date guidelines and study therapeutic desescalation in particular. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary experts workgroup. The recommendations are thus based on the best available evidence and experts agreement. Prior to publication, the guidelines are also reviewed by more than 100 independent practitioners in cancer care delivery. RESULTS: This article presents French guidelines about MRI and vacuum assisted breast biopsy indications for DCIS diagnosis and the management of low-grade DCIS.

Survival impact and predictive factors of axillary recurrence after sentinel biopsy.

BACKGROUND: The rate of axillary recurrence (AR) after sentinel lymph node biopsy is usually low but few studies investigated its impact on survival. Our aim was to determine the rate and predictive factors of AR in a large cohort of breast cancer patients and its impact on survival. PATIENTS AND METHODS: From 1999 to 2013, 14,095 patients who underwent surgery for clinically N0 previously untreated breast cancer and had sentinel lymph node biopsy were analysed. A simplified score predictive of AR was established. RESULTS: Median follow-up was 55.2 months. AR was observed in 0.51% of cases, with a median time to onset of 43.4 months. In multivariate analysis, the occurrence of AR was significantly correlated with grade 2 or 3 disease, absence of radiotherapy and tumour subtype (hormonal receptor [HR]- / human estrogen receptor [HER]+). AR rates were 1% for triple-negative tumours, 2.8% for HER2-positive tumours, 0.4% for luminal A tumours, 0.9% for HER2-negative luminal B tumours, and 0.5% for HER2-positive luminal B tumours. A simplified score predictive of the occurrence of AR was established. Patients could be divided into three different score groups (p < 0.0001). In multivariate analysis, overall survival was significantly lower in cases of AR (p < 0.0001), age >50, lymphovascular invasion, grade 3 disease, sentinel node (SN) macrometastases, tumour size >20 mm, absence of chemotherapy and triple-negative phenotype. Survival in patients with AR was significantly lower in case of early-onset (2 years) AR (p = 0.017). CONCLUSIONS: Isolated AR is more common in Her2-positive/HR-negative triple-negative tumours with a more severe prognosis in triple-negative and Her2-positive/HR-negative tumours, and represents an independent adverse factor justifying an indication for systemic treatment for AR treatment. However, the benefit of any systemic treatment remains to be proven.

[Oncofertility and breast cancer: Where have we come from, where are we going?]. / Oncofertilité du cancer du sein : d'où vient-on, où allons-nous ?

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.

The Role of Sentinel Lymph Node Biopsy and Factors Associated with Invasion in Extensive DCIS of the Breast Treated by Mastectomy: The Cinnamome Prospective Multicenter Study.

BACKGROUND: When invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to determine DCIS factors associated with microinvasion or invasion. METHODS: The SLN procedure was performed during mastectomy, and for positive SLN an ALND was performed during the same intervention. A tissue microarray containing DCIS lesions from the mastectomy specimens was subsequently performed. RESULTS: From May 2008 to December 2010, 228 patients were enrolled from 14 French cancer centers, including 192 eligible patients with pure DCIS on VAB and successful SLN procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56-77 %] of all the patients who had microinvasive DCIS or DCIS associated with invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39 %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB was 14 %. High nuclear grade of DCIS was associated with greater risk of microinvasion and invasion, and HER2-amplified DCIS was associated with greater risk of invasion. CONCLUSIONS: Underestimation of invasive components is high when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds of patients with micro or invasive disease on mastectomy.