Breast cancer is a complex disease influenced by genetic and environmental factors. Molecular profiling research has revealed significant diversity within the disease, including among tumours with similar morphological features. This diversity can lead to significant differences in tumour behaviour. Scientists have turned their attention to molecular biomarkers to predict cancer behaviour and/or response to treatment, and to ensure personalised, optimal management of breast cancer patients. This article presents four examples of molecular biomarkers and genetic tests used in the field of breast cancer, highlighting their latest advances and their clinical use as predictive and/or prognostic markers.

PDF file, 2894K, Figure S1: Cell migration and invasion analysis following siRNA mediated silencing of myoferlin (MYOF) in MDA-MB231 cells. Figure S2: Myoferlin depletion in MDA-MB468 cells results in sustained EGFR phosphorylation upon EGF stimulation and impedes the EGF-induced cell migration. Figure S3: Analysis of time dependent pEGFR and EGFR expression patterns (48h post transfection with irrelevant siRNA) following EGF stimulation and chemical inhibition of the proteasome with MG132. Figure S4: Cellular adhesion assay on selected extracellular matrix proteins. Figure S5: Modulation of vimentin expression following myoferlin silencing in MDA-MB231 cells. Figure S6: Clathrin (CLH1) colocalizes with myoferlin and pEGFR during EGF mediated receptor activation and shows no modulation at the protein level following myoferlin silencing. Supplemental Tables Table S1: List of up-regulated breast tumor proteins obtained from the analysis of 3 non-tumoral adjacent and 3 tumoral specimens. Table S2: Average values (n=3) indicating the number of unique peptides, sequence coverage and score. Table S3: Glycosylated peptides observed for the proteins displayed in the Table 1.

Nipple-areolar complex anomalies may be secondary to many etiologies from simple anatomic variations to malignant processes as Paget disease or invasive breast cancer, passing through benign locally aggressive processes as erosive adenomatosis of the nipple. Differential diagnosis is not always simple. If clinical exam and standard radiological checkup can't confirm the benignity of the lesion, a biopsy specimen will be obtained to allow an anatomopathological examination. A precise diagnosis can then be made leading to optimal management. This paper describes how to explore nipple-areolar complex anomalies through an uncommon clinical case associating independently an invasive retro-areolar cancer and a dermatological disease of the areola mimicking a Paget disease.

Breast cancer is the leading cause of neoplastic death in women around the world. In the era of personalized medicine, legitimately awaited by our patients, the future of breast cancer screening will depend on an individual-based risk assessment, making it possible to better adapt the age of onset, frequency and the type of examinations useful for this screening. This article reviews the three broad categories of highest risk factors available to establish a risk score appropriate for each patient.

Background: Despite that breast conservative therapy became the standard of care in breast cancer, modified radical mastectomy, a large mutilating surgery, is still required for an important number of patients. In order to improve the quality of life and the psychological aspects of a surgery involving the femininity of woman, we developed a new less invasive procedure called infra-radical mastectomy. It aims to save the neckline of patients by the maintenance of the peripheral skin-fatty flap that constitutes the base for implantation of the breast. This phase I study analyzed the feasibility of this procedure using outcome of anatomo-pathological analyses as primary endpoint.Methods: Between March 2015 and July 2017, all women with operable breast cancer without signs of lymph node invasion were invited to participate in the study in the 2 participating institutions. After a water-assisted dissection of the peri-glandular space, an enucleation of the breast was performed by a cold knife which represents the infra-radical mastectomy. A peri-glandular re-excision (PGR) of the skin and the fat tissue surrounding the gland was then achieved to obtain an MRM. This PGR underwent a careful pathological examination (10 samples per patient). Moreover, the tissue volume and the skin surface of the PGR were quantified.Results: A total of 53 patients (median age: 60 years) were prospectively recruited. The pathological analysis of peri-glandular biopsies revealed none residual invasive carcinoma, 1% of biopsies contained focal ductal carcinoma in situ (DCIS) and 0.4% atypical hyperplasia corresponding to 4 and 2 patients respectively. These 4 patients with residual DCIS were preoperatively diagnosed with extensive DCIS. On average after an infra-radical mastectomy, 37% of the volume and 53% of the skin surface of a complete modified radical mastectomy were sparred.Conclusions: The evaluation of biopsies from peri-glandular tissue suggests that infra-radical mastectomy should be further evaluated except for patients diagnosed with extensive DCIS which must be excluded of this infra-radical approach. Additional work is needed to evaluate cosmetic outcome and impact on quality of life, the need of radiotherapy and the oncological long-term outcome.

Background: Background: Despite surgery has become less aggressive in breast cancer, some patients remain candidates for Modified Radical Mastectomy (MRM). We evaluated if infraradical mastectomy (iRM) which preserves the skin and fat tissues surrounding the breast is safe. Aesthetic results of breast cancer could be improved by iRM because of these spared tissues.

BACKGROUNDDifferent clinical trials show beneficial effects of physical training offered during and/or after breast cancer treatment. However, given the variety of side effects that may be encountered, physical training could be combined with psychological, relational and social guidance. This kind of multidisciplinary program has been little studied so far.AIMThe aim of this study was to determine the benefits of a three-month multidisciplinary rehabilitation program among women after breast cancer treatment.DESIGNControlled no-randomized trial.SETTINGUniversity for outcomes, University Hospital Center for interventions.POPULATIONTwo hundred and nine outpatients who have been treated for a primary breast carcinoma.METHODSPatients were divided into a control group (N.=106) and an experimental group (N.=103) which has benefited from a rehabilitation program of three months including physical training and psycho-educational sessions. The assessments, performed before and after the program, included functional assessments ("Sit and Reach Test", maximal incremental exercise test and "Six-Minute Walk Test"), body composition measurements (Body Mass Index [BMI] and body fat percentage) and a questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30).RESULTSAfter three months, flexibility, walking distance and all parameters measured during the maximal incremental exercise, except maximal heart rate, were significantly improved in the experimental group. The body fat percentage was significantly decreased and a significant improvement was observed for perceived health status (quality of life), functional role, emotional state, physical, cognitive and social functions and for most symptoms. In the control group, most of these improvements didn't appear and a significant increase in BMI and body fat percentage was observed.CONCLUSIONSThis trial identifies the benefits of a well detailed multidisciplinary rehabilitation program, including physical re-conditioning and psycho-educational sessions, with important improvements in functional capacity, body composition and the majority of functions and symptoms among women after breast cancer treatment.CLINICAL REHABILITATION IMPACTThrough its results, this study could contribute to the development of hospital quality standards for oncologic rehabilitation. Physiotherapists can efficiently propose this kind of multidisciplinary rehabilitation program.

We tested, in the Province of Liege, an original approach that tends to individualize mass screening for breast cancer considering breast density and the notion of higher risk. We compared the previous recommendations (January to June 2012) in the age ranges of 40-49 years (n = 1.730) and 70-74 years (n = 286) to the new recommendations (June 2012 - December 2014) in the age ranges of 40-49 years (n = 11.123) and 70-74 years (n = 2.008). With the new recommendations, 38 % of women aged 40 to 49 years will benefit from a biennial invitation to screening due to a mainly greasy nature of their breasts (BI-RADS 1 and 2), while 11 % are classified BI-RADS 3 and 1 % BI-RADS 4 and are invited to perform an ultrasound to increase the screening sensitivity. A complete breast screening is offered to 6 % of women aged 40-49 years in view of a positive family history, and to 0.3 % of women aged 40-49 years and 8 % of women 70-74 years with a higher risk personal history. This individualized approach of mass screening is easily feasible from a practical viewpoint and the detection rate of breast cancers is increased.

The authors asked breast cancer (BC) patients to participate in 1 of 3 mind-body interventions (cognitive-behavioral therapy (CBT), yoga, or self-hypnosis) to explore their feasibility, ease of compliance, and impact on the participants' distress, quality of life (QoL), sleep, and mental adjustment. Ninety-nine patients completed an intervention (CBT: n=10; yoga: n=21; and self-hypnosis: n=68). Results showed high feasibility and high compliance. After the interventions, there was no significant effect in the CBT group but significant positive effects on distress in the yoga and self-hypnosis groups, and, also, on QoL, sleep, and mental adjustment in the self-hypnosis group. In conclusion, mind-body interventions can decrease distress in BC patients, but RCTs are needed to confirm these findings.

Abstract Background: Surgical procedures in breast cancer have become less aggressive. However, around one in three patients must undergo modified radical mastectomy (MRM). We evaluated if infraradical mastectomy (IFM), which preserves the skin and fat tissues surrounding the breast, is safe. IFM has the potential to preserve neck opening and by the way femininity of patients. Aesthetic results obtained after breast reconstruction are also expected to be improved. Objective: The primary objective of this phase 1 trial is to evaluate the feasibility and safety of IFM. Methods: Patients were recruited in two specialized breast clinics. We performed enucleation with a cold knife to the mammary gland after a water-assisted dissection of the periglandular space using a dedicated tool. In a second step we removed the peripheral skin and fat tissue which surrounded the gland to obtain a classical MRM. Fat tissue removed in the second step underwent a careful pathological examination (10 biopsies) in order to evaluate residual invasive or in situ breast cancer and atypical hyperplasia. We also evaluated which is the percentage of tissue and skin removed in the second step with regard to the global surgical specimen because that could be left in the future if the procedure is declared safe. Results: A total of 35 patients (43 to 80 years old) were prospectively recruited from March 2015 to March 2016. The distribution of tumor type was: pTis 2.9%, pT1 45.7%, pT2 45.7% and pT3 5.7%. Pathological analysis of the periglandular tissue removed in the second step revealed: 0% invasive carcinoma, 1% focal ductal carcinoma in situ (DCIS), and 0% atypical hyperplasia. On average, the weight of an IFM was 37% lower compared to the weight of a MRM. Skin resection was reduced by 48% with IFM. No serious adverse event was observed. Conclusions: Preliminary results are promising. Our phase 1 trial suggests that the procedure is safe concerning premalignant or malignant disease left after IFM. Moreover, a high quantity of skin and fat tissue is saved by IFM. We are now recruiting a second cohort of patients in order to confirm these results. In addition, we will also quantify the amount of mammary glands left around IFM compared to MRM by performing additional biopsies and quantitative evaluation by pathologists. Presurgical selection criteria have been modified for the second cohort in order to avoid residual DCIS left after IFM. After this second cohort, we plan to begin a large prospective randomized phase 3 trial with long-term disease-free survival and aesthetic results as the primary endpoints. Citation Format: Coibion M, Lifrange E, Jossa V, Mutijima E, Crevecoeur A, Olivier F, Di Bella J, Jerusalem G. Should modified radical mastectomy be modified? A phase 1 study to evaluate infraradical mastectomy for invasive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-22.

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative screening procedure to mammography for breast cancer diagnosis.A plasma miRNA profile was determined by RT-qPCR in a cohort of 378 women. A diagnostic model was designed based on the expression of 8 miRNAs measured first in a profiling cohort composed of 41 primary breast cancers and 45 controls, and further validated in diverse cohorts composed of 108 primary breast cancers, 88 controls, 35 breast cancers in remission, 31 metastatic breast cancers and 30 gynecologic tumors.A receiver operating characteristic curve derived from the 8-miRNA random forest based diagnostic tool exhibited an area under the curve of 0.81. The accuracy of the diagnostic tool remained unchanged considering age and tumor stage. The miRNA signature correctly identified patients with metastatic breast cancer. The use of the classification model on cohorts of patients with breast cancers in remission and with gynecologic cancers yielded prediction distributions similar to that of the control group.Using a multivariate supervised learning method and a set of 8 circulating miRNAs, we designed an accurate, minimally invasive screening tool for breast cancer.

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients.

e12527 Background: Surgical procedures have become less aggressive in breast cancer. However, some patients remain candidates for modified radical mastectomy (MRM). We evaluated if infraradical mastectomy which preserves the skin and fat tissues surrounding the breast is safe. The ultimate goal is to use this new surgical technique in patients who are candidates for breast reconstruction because improved esthetic results are expected. Methods: Patients were recruited in 2 specialized breast clinics. We performed enucleation by a cold knife of the mammary gland after a water-assisted dissection of the periglandular space by a dedicated tool. In a second step we removed the peripheral fat tissue which surrounded the gland and additional skin as done in a MRM. Fat tissue removed in the second step underwent a careful pathological examination (10 biopsies) in order to evaluate residual invasive or in situ breast cancer and atypical hyperplasia. We evaluated also the % of tissue and skin removed in the second step which could be left in the future if the procedure is declared safe. Results: A total of 29 patients (43 to 80 years old) were prospectively recruited from 2-11/2015. Tumor characteristics: pTis: 3%, pT1: 48%, pT2: 41%, pT3: 7%. The pathological analysis of the periglandular tissue removed in the second step revealed (% of specimens): 0% of invasive carcinoma, 1% of focal DCIS and 0% of atypical hyperplasia. On average the weight of an infraradical mastectomy was 36% lower compared to the weight of a MRM. Skin resection was reduced by 48% with infraradial mastectomy. Conclusions: Preliminary results are promising. Our phase 1 trial suggests that the procedure is safe from an oncological point of view. The quantity of periglandular tissue left after infraradical mastectomy is high. We are now recruiting a second cohort of 30 patients in order to confirm this outcome. Presurgical selection criteria on mammography have been modified to avoid residual DCIS left after surgery. Thereafter a randomized multicenter trial (compared to MRM) is planned in order to validate definitively this new surgical technique (including also evaluation of the expected improved esthetical result after reconstructive surgery). Clinical trial information: 80M0594.

BACKGROUND:Oncoplastic surgery combines breast-conserving treatment and plastic surgery techniques. The aim of the study was to identify breast and tumor-related characteristics that contribute to the rate of complications and recurrence.MATERIAL & METHODS:This retrospective study included 72 patients with a median follow-up of 32 months. For each patient, a comprehensive set of data was collected, including epidemiology, tumor characteristics, preoperative information, detailed pathology reports, radiotherapy treatment and type of surgical technique. The rate of complications, recurrence and survival were studied.RESULTS:Complete tumor removal was performed with clear margins in all patients but in 25 of them margins were less than 2 mm. One patient had local recurrence and another developed distant metastases. The study showed that the size of the margin was not predictive of recurrence as long as not positive; the greater the resection volume, the larger the excision margin. The resection size was the only factor influencing complications and no specific tumor-related factor significantly increased the complication rate. Surgical complications did not delay the initiation of chemotherapy and radiotherapy.CONCLUSION:This is the first oncoplastic study where both tumor and breast characteristics were analyzed using the most recent criteria of the literature. Oncoplastic surgery can be considered as oncologically safe. The resection size was the sole significant risk factor for postoperative complications. Complications after oncoplastic breast surgery did not differ neoadjuvant therapy. Long-term event-free survival was excellent (96% at 7 years).

The incidence of breast cancer, currently one woman on eight, also concerns patients who underwent augmentation surgery. Breast implants have already been the subject of numerous publications concerning the risk of inducing breast cancer or of delaying its diagnosis; however, no significant causal relationship has been established. The purpose of this article is to assess the diagnostic and therapeutic consequences when breast cancer is identified in a patient with breast implants.