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Advances in both access to and the technology underpinning next-generation sequencing have provided a formidable basis for the evaluation of individuals and families recognized as having a potential hereditary cancer. This article focuses on the most clinically relevant hereditary cancer predisposition syndromes such as hereditary breast and ovarian cancer syndromes and hereditary colorectal cancer. It also reviews current best practice in both surveillance for affected individuals as well as an providing an overview of the available risk-reduction strategies for affected individuals.

Therapeutic mammaplasty (TM) may be an alternative to mastectomy, but few well designed studies have evaluated the success of this approach or compared the short-term outcomes of TM with mastectomy with or without immediate breast reconstruction (IBR). Data from the national iBRA-2 and TeaM studies were combined to compare the safety and short-term outcomes of TM and mastectomy with or without IBR.The subgroup of patients in the TeaM study who underwent TM to avoid mastectomy were identified, and data on demographics, complications, oncology and adjuvant treatment were compared with those of patients undergoing mastectomy with or without IBR in the iBRA-2 study. The primary outcome was the percentage of successful breast-conserving procedures in the TM group. Secondary outcomes included postoperative complications and time to adjuvant therapy.A total of 2916 patients (TM 376; mastectomy 1532; mastectomy and IBR 1008) were included in the analysis. Patients undergoing TM were more likely to be obese and to have undergone bilateral surgery than those having IBR. However, patients undergoing mastectomy with or without IBR were more likely to experience complications than the TM group (TM: 79, 21·0 per cent; mastectomy: 570, 37·2 per cent; mastectomy and IBR: 359, 35·6 per cent; P 0·001). Breast conservation was possible in 87·0 per cent of patients who had TM, and TM did not delay adjuvant treatment.TM may allow high-risk patients who would not be candidates for IBR to avoid mastectomy safely. Further work is needed to explore the comparative patient-reported and cosmetic outcomes of the different approaches, and to establish long-term oncological safety.La mamoplastia terapéutica (therapeutic mammaplasty, TM) puede ser una alternativa a la mastectomía, pero hay pocos estudios bien diseñados que hayan evaluado el éxito de esta estrategia o hayan comparado los resultados a corto plazo de la TM con la mastectomía con o sin (+/-) reconstrucción mamaria inmediata (immediate breast reconstruction, IBR). Para comparar la seguridad y los resultados a corto plazo de la TM y la mastectomía +/- IBR se combinaron los datos de los estudios nacionales iBRA-2 y TeaM. MÉTODOS: En el estudio TeaM se identificó el subgrupo de pacientes al que se realizó una TM para evitar la mastectomía y se compararon los datos demográficos, las complicaciones, los resultados oncológicos y el tratamiento adyuvante con las pacientes sometidas a mastectomía +/- IBR del estudio iBRA-2. La variable principal fue el porcentaje de éxito de la cirugía conservadora de mama en el grupo TM. Las variables secundarias fueron las complicaciones postoperatorias y el intervalo de tiempo hasta el inicio del tratamiento adyuvante.Se incluyeron en el análisis 2.916 pacientes (TM n = 376; mastectomía n = 1.532; IBR n = 1.008). La TM era más frecuente en pacientes obesas o en las sometidas a cirugía bilateral en comparación con las pacientes con IBR. Sin embargo, las pacientes sometidas a una mastectomía +/- IBR tenían más probabilidades de desarrollar complicaciones que las del grupo TM (TM n = 79, 21,0%; mastectomía n = 570, 37,2%; mastectomía y IBR n = 359, 35,6%; P 0,001). La conservación de la mama fue posible en el 87% de las pacientes con TM y el procedimiento no retrasó el inicio del tratamiento adyuvante. CONCLUSIÓN: La TM puede permitir que pacientes de alto riesgo que no serían candidatas a IBR eviten la mastectomía de una forma segura. Se necesitan más trabajos para comparar los resultados percibidos por las pacientes y los estéticos de las diferentes estrategias terapéuticas y establecer la seguridad oncológica a largo plazo.

Introduction: Breast cancers exhibit cellular heterogeneity, containing both stem-like and more differentiated cells. The activity of cancer stem cells (CSC) is likely to be dependent on the microenvironment or niche. Using 158 patient tumour samples, correlations between niche-independent breast CSC activity and clinical and tumour characteristics were tested. Methods: 104 early breast cancer surgical samples and 54 unrelated metastatic samples from pleural or ascitic fluid were harvested. To test CSC activity, isolated cells were grown in both primary (formation) and secondary (self-renewal) mammosphere (MS) culture. Tumour initiating activity was also tested by transplanting breast cancer fragments or cells into the sub-cutaneous flanks of NSG mice (n=84 early and n=10 metastatic). Results: No correlation was found between MS growth, MS formation (%), MS self-renewal (%) or in vivo tumour initiation and breast cancer sub-type, grade, node status or Nottingham prognostic index. 33% of the samples that formed MS in vitro initiated tumours in vivo while only 9% that failed to form MS initiated tumour growth. Metastatic compared to early BC samples grew MS more frequently (53/54 compared to 81/104), and had a higher primary MS formation efficiency (1% vs 0.6%; P Conclusions: In summary, niche-independent breast CSC activity measured in vitro by MS assay and in vivo by xenograft growth is not directly correlated with standard clinical parameters. However, both in vitro and in vivo CSC activity are increased in metastatic samples. These results suggest that breast CSC activity is independent of other prognostic indicators but may predict for poor outcome tumours. Relapse free survival data are maturing and will be presented with analysis of primary tumour ALDH1 expression. Citation Format: Sacha J Howell, Denis Alferez, Katherine Spence, Rachel Eyre, Fran Shaw, Bruno Simoes, Angelica Santiago-Gomez, Maria Bramley, Mohamed Absar, Zahida Saad, Sumohan Chatterjee, Cliona Kirwan, Ashu Gandhi, Anne C Armstrong, Andrew M Wardley, Gillian Farnie, Robert B Clarke. Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-02.

Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony-forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice. Metastatic samples formed primary mammosphere colonies significantly more frequently than early breast cancers and had significantly higher primary mammosphere colony formation efficiency (0.9 % vs. 0.6 %; p < 0.0001). Tumour initiation in vivo was significantly higher in metastatic than early breast cancer samples (63 % vs. 38 %, p = 0.04). Of 144 breast cancer samples implanted in vivo, we established 20 stable patient-derived xenograft (PDX) models at passage 2 or greater. Lung metastases were detected in mice from 14 PDX models. Mammosphere colony formation in vitro significantly correlated with the ability of a tumour to metastasise to the lungs in vivo (p = 0.05), but not with subcutaneous tumour initiation. In summary, the breast cancer stem cell activities of colony formation and tumour initiation are increased in metastatic compared to early samples, and predict metastasis in vivo. These results suggest that breast stem cell activity will predict for poor outcome tumours, and therapy targeting this activity will improve outcomes for patients with metastatic disease.

(55/918). Of the 55 patients, 22 patients were excluded (Eleven patients had mastectomy, six had more than two nodes involved, four had neo adjuvant chemotherapy and one declined surgery) leaving 33 patients. Therefore 2.2% (33/1499) of the cohort met the inclusion criteria for the ACOSOG Z0011 trial. Conclusions: In this observational study, only 2.2% (33/1499) of the patients were identified as per the ZOO11 criteria. This means only a very few number of patients could be spared from axillary lymph node dissection. So clearly it is not a practice changing trial in the axillary surgical management of our cohort of patients.

S S61 P121. The importance of a chaperone e Ways to improve underuse Katy Rose, Sarah Eshelby, Paul Thiruchelvam, A. Khoo, Katy Hogben West Middlesex University Hospital NHS Trust, London, UK Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK The Royal Marsden NHS Foundation Trust, London, UK Norfolk and Norwich University Hospital, Norfolk, UK Introduction: The importance of chaperones during intimate examination is well recognised. In addition to providing reassurance and support for the patient, chaperones offer protection to the doctor as well. As a result of this, documentation of chaperones in notes is essential. Methods: This 3 stage cross sectional study was completed in a tertiary breast service unit acting as the main referral service for North West London. An initial retrospective analysis was performed and results from this found 0% documentation about chaperone use. Interventions were made: Stage 1: The findings from the initial cycle and chaperone guidelines were presented to the department along with the introduction of a “chaperone stamp” to clinical notes and a “memo pamphlet”. Stage 2: “Chaperone stamp” alone e data collected 1 year after initial data collection. Results: Stage 1: 69.9%; (p < 0.001; CI 59.04% to 80.76%) and Stage 2: 76.6% (p < 0.001; CI 66.7% to 87.13%) both demonstrated increase in documentation of chaperone use compared to initial practice. A 6.7% difference in documentation of chaperone preference was observed between the two post intervention data sets, this was not a significant difference; (p 1⁄4 0.226, CI 15.71% to 2.31%). Conclusions: In modern healthcare environments where patient choice and autonomy are paramount it is essential that clinicians who regularly perform intimate examinations fully comply with chaperone guidance. The authors would suggest that a pro forma approach, such as our chaperone stamp, is an efficacious way to comply and facilitate early identification of any issues with compliance, thus ensuring safeguarding of patients and staff involved in intimate examinations. http://dx.doi.org/10.1016/j.ejso.2015.03.159 P122. An initial experience using a titanium-coated polypropylene mesh (TiLoop Bra) for implant based breast reconstruction Anne Shrestha, Ravi Acharya, Sumohan Chatterjee Hope Hospital, Manchester, UK Introduction: Titanium-coated polypropylene mesh (TCPM) is considered as an alternative to acellular dermal matrix (ADM) in implant based breast reconstruction (IBBR). TCPM is used as a hammock to envelop the lower pole of the implant or expander, as with the ADM. The aim of this study is to examine the limitations and complications of TCPM for IBBR and associated risk factors. Methods: A retrospective analysis of 23 patients who underwent immediate or delayed IBBR using TCPM was carried out. Primary endpoint considered the incidence of removal of implant or expander with or without mesh. Results: 26 procedures IBBR with TCPM was carried out in 23 patients, 3 had bilateral procedures. Time from procedure was a median of 413 days (range 47764). 4 reconstructions failed and implants were removed. 2 patients were smokers, 1 had radiotherapy prior to reconstruction and 1 had recurrent seroma and removal was after 12 months. 3 other patients developed seroma and 2 developed skin necrosis. 16 out of 23 patients had immediate breast reconstruction after have skin sparing mastectomy, only 1 requiring contralateral reduction. 3 underwent delayed reconstruction using expander with TCPM. Conclusion: Careful selection of patients needs to be carried out to ensure possible prevention of failure of reconstruction accounting for factors affecting wound healing. Advantages include remote scar mastectomy, good inframammary fold definition and ptosis, cost reduction, acceptability in patients who prefer not to have animal products. Results seem promising, however, larger sample size and longer follow up is required. http://dx.doi.org/10.1016/j.ejso.2015.03.160 P123. What is the diagnostic value of red blood cells seen in nipple discharge cytology? Sonal Halai, Steven Goh Peterborough City Hospital, Peterborough, UK Introduction: Nipple cytology (NC) is routinely used to assess patients presenting with spontaneous nipple discharge (SND). The presence of red blood cells (RBC) in NC has routinely prompted further intervention. We evaluated the diagnostic value of RBC found in NC. Methods: A retrospective review of all patients who presented with SND between 2009 and 2014 was conducted. Clinical and radiological findings, NC and excised histology were cross-referenced for analysis. Results: A total of 482 NC were included (mean age 45 years, range 15e99). 223 samples were reported normal, 38 insufficient and 221 NC were positive for the following: RBC (164), epithelial cells (25), papillary cells (17) and atypia (15). 173 patients proceeded to have surgery. The following histology were found: 16 carcinoma, 11 DCIS, 3 atypical ductal hyperplasia, 66 papilloma, 1 tubular adenoma, 1 fibroadenoma, 59 duct ectasia and 16 benign breast changes. Defining all malignant pathologies and papilloma in the excised histology as true positive: the presence of RBC in NC has a sensitivity of 67.7%, specificity of 39.0%, positive predictive value (PPV) of 58.0%, and negative predictive value of 49.2%. RBC was present in NC for 18 of the 27 malignancies. Conclusions: 27 out of 482 (5.6%) of our patients with SND were found to have a malignant pathology. Although RBC in NC has a poor PPV in our study, it was the sole abnormality in 6 patients with malignancies. We therefore conclude that the presence of RBC in NC increases the index of suspicion, and should prompt further intervention. http://dx.doi.org/10.1016/j.ejso.2015.03.161 P124. Can increasing Body Mass Index (BMI) affect the accuracy of pre-operative axillary ultrasound scan in breast cancer patients? Habib Tafazal, Veena Vishwanath Queen Elizabeth Hospital, Birmingham, UK Introduction: Accurate pre-operative diagnosis of axillary nodal metastases may avoid further surgery. Obesity may obscure the visualisation of these nodes and can therefore reduce diagnostic accuracy of potential nodal spread. The aim of this study was to assess the relationship between patient body mass index (BMI) and subsequent accuracy of pre-operative axillary ultrasound scan in patients with breast cancer. Methods: Between January 2014 and June 2014, all patients who were diagnosed with breast cancer were retrospectively identified using an electronic patient database. Demographics, BMI, pre-operative imaging and histopathological results were analysed. Logistic regression was performed to explore if patient age, BMI and size of primary tumour may affect correct identification of axillary spread. Results: Of 159 patients identified, mean age (S.D.) was 61.0 (13.1) and median (i.q.r) BMI was 27.6 (24.6e31.6). More patients had a correct US diagnosis than those with an incorrect US diagnosis (98 vs 43 P < 0.001). BMI was similar between these two groups (Correct 27.7 (25.4e32.1) vs incorrect 27.2 (24.2e31.5) P 1⁄4 0.360). When controlling

To compare the sensitivity and specificity of the traditional triple assessment of symptomatic breast lesions with contrast-enhanced dynamic magnetic resonance imaging.Although triple assessment is currently the gold standard for the assessment of symptomatic breast disease, its specificity is such that open biopsies are still required in many cases to be confident of the diagnosis. Contrast-enhanced dynamic magnetic resonance imaging of the breast represents an alternative diagnostic modality.Patients were recruited from the symptomatic breast clinics. If any of the diagnostic modalities suggested malignancy, the lesion was excised. The remaining patients were followed clinically and radiologically.Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were excised in 131 patients and benign lesions in 55 patients. The 99 patients who did not undergo surgery were followed clinically and radiologically for a median of 20 months. The sensitivity of each modality was as follows: clinical examination 84%, mammography 87.6%, fine-needle aspiration cytology 79.1%, triple assessment 99.2%, and magnetic resonance imaging 99.2%. In addition, histologically confirmed multifocal disease was detected in 40 patients on magnetic resonance imaging but in only 9 (22.5%) on mammography. The specificity for the diagnosis of benign disease was as follows: clinical examination 83.1%, ultrasound 88.9%, mammography 86.4%, fine-needle aspiration cytology 97%, triple assessment 59.1%, and magnetic resonance imaging 90.9%.Contrast-enhanced dynamic magnetic resonance imaging of the breast is as sensitive and more specific than the combined traditional triple assessment for the diagnosis of malignant breast lesions.

Inadequately treated multifocal and multicentric disease results in increased local recurrence following breast-conserving surgery. The accurate preoperative diagnosis of multifocal/ centric breast cancer would facilitate the planning of appropriate surgery and prevent reoperation for residual disease. While triple assessment remains the established diagnostic technique, its sensitivity for the diagnosis of multifocal disease remains poor. Dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) of the breast represents an alternative emerging diagnostic modality that has been shown to be highly sensitive for the delineation of primary breast cancer. The aim of this study was to prospectively compare the diagnostic accuracy of DCE-MRI of the breast with conventional triple assessment for the preoperative diagnosis of multifocal/centric breast cancer.Patients were recruited from the symptomatic breast clinics. All patients underwent standard triple assessment and DCE-MRI. The MRI scans were reported by a single radiologist blinded to the results of the triple assessment. Surgery was then planned accordingly to all available scan results and the specimens examined by a single pathologist. All patients who did not undergo surgery have been followed up for a minimum of 18 months.A total of 334 women were recruited. There were 178 (52%) cancers that were histologically confirmed and multifocal/centric breast cancer was diagnosed provisionally by the preoperative investigations in 68 (38%); multifocal n = 33, multicentric n = 35, of these patients. In this group, subsequent histology confirmed multifocal/centric disease in 50 (73.5%): multifocal n = 15, multicentric n = 35. Unifocal cancer was found in 15 (22%) and benign disease in 3 (4.4%). The resultant sensitivity, specificity, positive, and negative predictive values were 18%, 100%, 100%, and 76% for triple assessment and 100%, 86%, 73%, and 100% for DCE-MRI.DCE-MRI identified a subgroup of breast cancer patients with multifocal/centric disease not evident on standard triple assessment. MRI of the breast should be considered for the preoperative planning of surgery for primary breast cancer.