[Management of nipple-areolar complex anomalies]. / Comment j'explore une atteinte de la plaque aréolo-mamelonnaire.

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.

Les anomalies de la plaque aréolo-mamelonnaire peuvent être secondaires à de nombreuses étiologies, allant de simples variantes anatomiques à des pathologies malignes telles que la maladie de Paget ou un cancer invasif, tout en passant par des pathologies bénignes localement agressives comme l'adénomatose érosive du mamelon. Le diagnostic différentiel n'est pas toujours aisé. Si l'examen clinique et le bilan radiologique standard ne permettent pas d'affirmer la bénignité de la lésion, un prélèvement biopsique sera réalisé afin de permettre une analyse anatomopathologique. Un diagnostic précis pourra alors être posé pour guider la prise en charge optimale. Cet article a pour but de détailler la mise au point d'une atteinte de la plaque aréolo-mamelonnaire par l'intermédiaire d'un cas clinique peu fréquent associant de manière indépendante un cancer invasif rétro-aréolaire et une atteinte dermatologique de l'aréole mimant une maladie de Paget.

[Breast cancer : individualized risk assessment for tailor-made screening]. / Cancer du sein : évaluation individualisée du risque en vue d'un dépistage sur mesure.

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.

Le cancer du sein est la première cause de mortalité par néoplasie chez la femme de par le monde. À l'ère d'une médecine personnalisée, légitimement attendue par nos patientes, l'avenir du dépistage du cancer du sein passera par une évaluation du risque sur base individuelle, permettant d'adapter, au mieux, l'âge de début ainsi que la fréquence et le type des examens utiles pour ce dépistage. Cet article passe en revue les trois grandes catégories de facteurs de plus haut risque disponibles pour établir un score de risque adapté à chaque patiente.

[A new approach to breast cancer screening]. / Nouvelle approche du dépistage du cancer du sein.

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.

Nous avons testé, en Province de Liège, une approche qui tend à individualiser le dépistage de masse du cancer du sein en tenant compte de la densité mammaire et de la notion de plus haut risque. Nous avons comparé les anciennes recommandations (janvier à juin 2012) dans les tranches d'âge de 40-49 ans (n = 1.730) et 70-74 ans (n = 286) et les nouvelles recommandations (juin 2012 - décembre 2014) dans les tranches d'âge de 40-49 ans (n = 11.123) et 70-74 ans (n = 2.008). Selon les nouvelles recommandations, 38 % des femmes de 40 à 49 ans vont bénéficier d'une convocation biennale au dépistage en raison d'une nature principalement graisseuse de leurs seins (BI-RADS 1 et 2), tandis que 11 % sont classées en BI-RADS 3 et 1% en BI-RADS 4 et sont invitées à réaliser une échographie afin d'augmenter la sensibilité du dépistage. Un bilan sénologique complet est proposé à 6 % des femmes de 40-49 ans pour antécédents familiaux, à 0,3 % des femmes de 40-49 ans ainsi qu'à 8 % des femmes de 70-74 ans pour antécédents personnels de haut risque. Cette approche individualisée du dépistage de masse est facilement réalisable d'un point de vue pratique et le taux de détection des cancers mammaires est plus important.

Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative 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.

Oncological and surgical outcome after oncoplastic breast surgery.

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. 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. CONCLUSIONS: 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).

[Management of breast cancer in a woman with breast implants]. / Prise en charge d'un cancer du sein chez une femme porteuse de prothèses mammaires.

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.

Oncological and Surgical Outcome after Oncoplastic Breast Surgery.

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).

European inter-institutional impact study of MammaPrint.

AIM: To measure the impact of MammaPrint on adjuvant treatment decisions and to analyze the agreement in treatment decisions between hospitals from 4 European countries for the same patient cohort. METHODS: Breast cancer patients were prospectively enrolled and MammaPrint was assessed. Patients' clinical data without and then with MammaPrint results were sent to the different multidisciplinary teams and treatment advice was provided for each patient. RESULTS: Using MammaPrint, chemotherapy treatment advice for ER+/HER2- breast cancer patients was changed in 37% of patients by the Dutch, 24% by the Belgian, 28% by the Italian and 35% by the Spanish teams. MammaPrint increased the inter-institutional agreement in treatment advice (chemotherapy or no chemotherapy) from 51% to 75%. CONCLUSION: The results of this study indicate that MammaPrint impacts adjuvant chemotherapy recommendation. MammaPrint can decrease inter-institutional and inter-country variability in adjuvant treatment advice for breast cancer patients.

Should we individualize breast cancer screening?

Publicly organized population breast cancer screening is presently hotly debated. Indeed, population screening is poorly effective, induces harms in a healthy population and is costly. However, stopping all kind of screening of low- and average-risk women would be problematic as about 70% of breast cancers are diagnosed in those subgroups, and maintaining current population screening in high-risk women would be insufficient. We propose herein a review about the advantages and the inconvenience of individualized screening. The latter could be a more efficient strategy. The principles of individualized screening are (a) to start from the age at which the breast cancer risk is equal to that for an average women aged 50 years, (b) to stop when the risk of co-mortality exceeds the risk of breast cancer mortality, (c) to adapt the exams frequency and the imaging modalities to the individual risk and to the breast density, (d) to reassess regularly and individually the screening strategy, and (e) to discuss honestly with each woman in order to help her to decide if she participates or not.

[Primary and secondary prevention for women at high risk for breast cancer]. / Prévention primaire et secondaire chez les femmes à haut risque de cancer mammaire.

Many factors determine a woman's risk of breast cancer; some genetic are related to family history, others are based on personal factors such reproductive and medical history. A high-risk woman must benefit of a specific screening regimen including breast examination, mammography, ultrasonography and contrast material-enhanced magnetic resonance. But she can also benefit of chemo prevention or/and risk-reducing surgery such bilateral prophylactic salpingo-oophorectomy and bilateral prophylactic mastectomy.

[Breast cancer in Belgium: why are we the first in Europe?]. / Le cancer du sein en Belgique: pourquoi sommes-nous les premiers en Europe?

Breast cancer incidence in Belgium is on the top of European countries, with 9.697 new cases in 2008 and 106/100.000 women/year. The explanation of this high incidence in our country is probably the accumulation of risk factors (many of them are linked to lifestyle), and the impact of screening and registration of cases. The relative impact of each of theses factors is less clear because we don't have powerful statistical studies. Belgium is slightly above the European mean for breast cancer mortality, with 19,4/100.000 women/year and an all stages 15-year survival of 75%. Breast cancers are responsible for around 3% of all-cause mortality in Belgian women. This article discusses the causes of this high Belgian incidence and of current decrease of incidence in western countries, and reviews known and less known risk factors of breast cancers, with a special focus on menopause hormonal treatments.

[Cytological sampling techniques in breast pathology]. / Techniques de prélèvements cytologiques en pathologie mammaire.

Mammary cytology is part of the breast cancer test. Its accuracy depends on both the sample quality and the cyto-pathologist's competence. Extracting cells in a liquid environment allows obtaining smears in less hemorrhagic thin layers, containing more cells and with less interference with the fixation artefact. This technique keeps materiel for further immunocytochemistry and cell biology studies if needed. It will be especially useful in automated analysis.

[Bilateral prophylactic mastectomy for women at very high risk for breast cancer: beyond the technique]. / Mastectomie bilatérale prophylactique chez les patientes à très haut risque de cancer mammaire: au-delà de la technique...

Bilateral prophylactic mastectomy is the most efficient risk management strategy for women at very high risk for breast cancer. Different methods can be used. The implementation of such a strategy must respond to the request of a well informed patient.

[Management and follow-up of a consecutive series of 411 surgically treated breast cancer patients]. / Prise en charge et suivi d'une série consécutive de 411 patientes opérées pour cancer du sein.

This study reports a consecutive serie of 427 breast neoplasms (411 patients) diagnosed and treated in our department between 1994 and 2004. Patients' records were prospectively collected including personnal medical history and the major elements of the diagnostic and the therapeutic protocol applied. 12 patients (3%) had to be excluded due to incomplete follow-up data. With a median follow-up of 8 years, a 4.5% loco-regional relapse rate is noted while 11% of patients recurred at distant sites and 9% died of their disease progression. These statistics are comparable to those published by prominant breast cancer centers. Amongst the 16% of deaths (67/411 Pts), 54% are due to breast cancer progression. The results are discussed with the aim to upgrade the diagnostic and the therapeutic protocols offered to our patients.

[Breast oncoplastic surgery]. / La chirurgie oncoplastique du sein.

Oncoplastic surgery combines large lumpectomy and defect remodeling by different plastic surgery methods. These procedures improve the cosmetic result after partial mastectomy and widens the possibilities for conservative treatment. Different techniques are used from simple glandular remodeling to more difficult techniques for breast plasties with or without simultaneous controlateral symetrisation procedure. The surgical option depends especially on the ratio between the volume of the tumor and the volume of the breast and the position of the tumor. This more effective conservative treatment facilitates also postoperative radiotherapy, reduces the sequellae and the psychological impact of breast cancer treatment.

[Sentinel lymph node biopsy and axillary reverse mapping: a tailoring axillary staging in breast cancer]. / Ganglion sentinelle et sentibras: pour un "staging" axillaire sur mesure.

The status of the axillary lymph nodes is one of the most important prognostic factors in women with early stage breast cancer. Histologic examination of removed lymph nodes is the most accurate method for assessing spread of disease to these nodes. Axillary lymph node dissection (ALND) remains the standard approach for women who have clinically palpable axillary nodes. The benefits of ALND include its impact on disease control (axillary recurrence and survival), its prognostic value, and its role in treatment selection. However, the anatomic disruption caused by ALND may result in lymphedema, nerve injury, and shoulder dysfunction, which compromise functionality and quality of life. For patients who have clinically negative axillary lymph nodes, sentinel lymph node (SLN) biopsy offers a less morbid method to determine if there are positive nodes, in which case axillary node dissection would be necessary. Patients who are SLN-positive should undergo complete ALND. Axillary reverse mapping (ARM) is a recent improvement of ALND which, like the biopsy of the GS, would reduce morbidity.

[Systemic chemotherapy and breast cancer]. / Chimiothérapie et cancer du sein.

Breast cancer mortality is decreasing, partly due to better adjuvant treatments with new drugs and new schedules. In Belgium, the overall survival is 76%. Chemotherapy is still an important treatment option. We need to better select patients who really will benefit from treatment in order to decrease toxicity and improve long term outcome.Targeting the specific population is now a priority. Prognostic and predictive factors will enable us to better define the sub-population of patients most benefiting from treatment. We will also discuss the knowledge of systemic treatment. When we have to decide wether chemotherapy is indicated, we need to well balance the treatment risks and benefits because gain in survival is important but reducing short and long term toxicity is also a challenge.

[Targeted therapies in breast cancer]. / Traitements ciblés dans le cancer du sein.

The better understanding of the biology of breast cancer has allowed the identification of new targets for anticancer therapy. Trastuzumab, a monoclonal antibody binding the HER2 receptor, is used since several years in the treatment of HER2 overexpressing breast cancer, including in the adjuvant setting. Lapatinib, a tyrosine kinase inhibitor, was introduced more recently into the clinic. New treatment options under evaluation in HER2 overexpressing breast cancer include combinations of anti-HER2 treatments, drugs targeting the downstream signaling pathway and new anti-HER2 agents such as pertuzumab and T-DM1. This article also reviews other targeted treatments of interest in the field of breast cancer including antiangiogenic agents and drugs targeting the PI3K-AKT-mTOR pathway.

[Breast cancer in young women]. / Le cancer du sein chez la femme jeune.

The outcome of very young patients with early breast cancer is worser compared to older patients with a similar clinical presentation. The triple negative, luminal B, HER2+ subtypes are more frequent in this population. Adequate local treatment (breast-conserving surgery or total mastectomy) must be discussed with the patient. The role of radiotherapy is very important in these patients with high risk of local recurrence. The progress in adjuvant treatment of very young patients requires studies of tailored treatments.

[Hormone therapy for breast cancer]. / Hormonothérapie du cancer du sein.

Following Beatson's publications in 1896, various modalities of endocrine therapy applied to breast cancer have been developed. Endocrine treatment has greatly contributed to the improvement of the disease's prognosis. Tamoxifen has established itself as a first choice adjuvant therapy for patients with tumors expressing hormone receptors. Over the last decade, third generation aromatase inhibitors have demonstrated their efficacy amongst menopausal patients, alone or in combination with tamoxifen. Efficacy of these medications is dependent on patient's compliance. This article proposes a synthesis of the main knowledges available in the field of breast cancer endocrine therapy.