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Healthcare agents, in particular in the oncology field, are currently collecting vast amounts of diverse patient data. In this context, some decision-support systems, mostly based on deep learning techniques, have already been approved for clinical purposes. Despite all the efforts in introducing artificial intelligence methods in the workflow of clinicians, its lack of interpretability - understand how the methods make decisions - still inhibits their dissemination in clinical practice. The aim of this article is to present an easy guide for oncologists explaining how these methods make decisions and illustrating the strategies to explain them. Theoretical concepts were illustrated based on oncological examples and a literature review of research works was performed from PubMed between January 2014 to September 2020, using deep learning techniques, interpretability and oncology as keywords. Overall, more than 60% are related to breast, skin or brain cancers and the majority focused on explaining the importance of tumor characteristics (e.g. dimension, shape) in the predictions. The most used computational methods are multilayer perceptrons and convolutional neural networks. Nevertheless, despite being successfully applied in different cancers scenarios, endowing deep learning techniques with interpretability, while maintaining their performance, continues to be one of the greatest challenges of artificial intelligence.

Introduction Avapritinib (formerly known as BLU-285) is an orally available type I tyrosine kinase inhibitor that, in 2020, obtained regulatory approval for the treatment of patients with gastrointestinal stromal tumors (GISTs) harboring a primary mutation in PDGFRA exon 18, including the PDGFRA D842V mutation. Areas covered Herein, we comprehensively review the available efficacy and safety data on avapritinib, with the final goal of providing practical knowledge to both sarcoma and community-based oncologists for the correct management of this rare GIST subpopulation with this novel therapy. Expert opinion The approval of avapritinib in GIST is a milestone in precision oncology, as this is the first agent ever demonstrating unequivocal antitumoral activity in GIST driven by the multi-resistant PDGFRA D842V mutation. The safety profile is manageable and tolerability-guided dose adjustment is recommended to manage treatment-related adverse events without compromising efficacy. Based on its unprecedented activity, avapritinib should be considered as first-line therapy for GIST patients harboring this mutation. We strongly recommend to determine KIT/PDGFRA genotype in order to identify the different GIST molecular subtypes and guide treatment decision.

Background and purpose COVID‐19‐related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population‐based perspective are lacking. Methods We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. Results Among 1261 hospitalised COVID‐19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well‐defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID‐19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7–11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well‐defined CNS involvement. Conclusions We characterised the population of hospitalised COVID‐19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in‐hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID‐19 multidisciplinary patient care.

Background: Margetuximab (M) is an investigational Fc-engineered, anti-HER2 monoclonal antibody with the same epitope specificity as trastuzumab (T). Relative to T, Fc engineering of M increases binding affinity for the activating Fc receptor (FcR) CD16A and decreases affinity for the inhibitory FcR CD32B. The SOPHIA trial (NCT02492711) randomized pretreated HER2+ MBC patients to either M or T, each with chemotherapy (C). M+C improved progression-free survival (PFS) benefit over T+C. Infusion related reactions (IRR) have been observed after infusion of therapeutic proteins, typically during the first infusion, with a first-dose incidence of up to 40% for T (Herceptin Prescribing Information®). A retrospective analysis of 197 patients showed 16% IRRs on T, mostly after the first infusion; this rate was lower with (10%) compared to without (19%) premedication (Thompson, 2014). Here, we report IRR safety and tolerability data in the SOPHIA trial patients following HER2-targeted antibody therapy. Methods: The open-label Phase 3 SOPHIA trial enrolled patients with HER2+ MBC after at least 2 prior anti-HER2 therapies, including pertuzumab; 91% in both groups also received ado-trastuzumab emtansine. Randomization of 536 patients was 1:1 to M (15 mg/kg IV q3w) or T (6 [8 loading dose] mg/kg IV q3w), each with Investigator selected C (standard dose capecitabine, eribulin, gemcitabine, or vinorelbine). M was given as 120-minute infusions. T was given as a 90-minute infusion in Cycle 1, then a 30-minute infusion from Cycle 2 onward. Recommended elective premedication included acetaminophen, ibuprofen, diphenhydramine, ranitidine, dexamethasone, or equivalents. IRR safety analyses were conducted on 530 patients (264 M+C and 266 T+C) that received any study therapy. Results: A higher proportion of patients experienced IRRs on the M arm (35 [13.3%]) than on the T arm (9 [3.4%]). Most IRRs in both groups were severity Grade 1 or 2, occurred on Cycle 1 Day 1, and resolved within 24 hours. In patients receiving M, Grade 3 IRR occurred in 4 patients (1.5%), including 3 after vinorelbine and 1 after eribulin. Adverse events associated with Grade 3 IRRs included chills, fever, nausea, diarrhea, dyspnea, and/or hypertension. Two patients receiving M (0.8%) discontinued due to IRR, versus none on T. Of patients with IRRs, the most common symptoms in both treatment groups were chills (M: 17 [48.6%]; T: 5 [55.6%]) and fever (M: 13 [37.1%]; T: 2 [22.2%]). There was no observed hypotension in either group. In both groups, more than half of IRR events were addressed by dose interruption only. All IRRs all were medically manageable. IRR rates were higher in patients without premedication for both groups. Of 264 subjects receiving M, 218 (82.6%) received premedication and 46 (17.4%) did not; IRRs were observed in 28 (12.8%) of those receiving premedication and 7 (15.2%) of those not premedicated. All 4 patients on M with Grade 3 IRRs received premedication, 3 with steroids. Of 266 subjects receiving T, 173 (65%) received premedication and 93 (35%) did not; IRRs were observed in 5 (2.9%) of those receiving premedication and 4 (4.3%) of those not premedicated. IRR risk was unaffected by chemotherapy subgroup or CD16A genotype. Conclusions: In the SOPHIA trial, IRR events occurred in a greater proportion of patients on M than on T. Most were mild to moderate in severity, limited to Cycle 1, and resolved on the same day. Symptom patterns were similar between groups, and premedication did not eliminate the hazard of IRRs in either group. Severe IRRs and discontinuations due to IRRs were rare. IRRs on first infusion of M appear to resemble those observed following first infusion of T. Citation Format: Javier Cortes, Fatima Cardoso, Giuseppe Curigliano, William J Gradishar, Seock-Ah Im, Hope S Rugo, Shakeela W Bahadur, Alfredo Falcone, Serafin Morales Murillo, David A Riseberg, Antonino Musolino, Trevor M Feinstein, Miguel H Abreu, Young-Hyuck Im, Yelena Novik, Timothy Pluard, Lupe G Salazar, Rossana Berardi, Viorela Pop, Shengyan Hong, Kenneth Jacobs, Edwin Rock, Mark D Pegram. Infusion related reactions in the phase 3 SOPHIA trial of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with pretreated HER2+ metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-24.

Background and aim Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterised by abnormal proliferation of trophoblastic tissue. Since GTD and its malignant sequel gestational trophoblastic neoplasia (GTN) are rare diseases, little evidence is available from randomised controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centres within countries. One of the goals of the ‘European Organisation for Treatment of Trophoblastic Diseases’ (EOTTD) is to harmonise treatment in Europe. To provide a basis for European standardisation of definitions, treatment and follow-up protocols in GTD, we composed a set of guidelines for minimal requirements and optimal management of GTD. Methods Members from each EOTTD country attended multiple workshops during annual EOTTD meetings. Clinical guidelines were formulated by consensus and evidence where available. The following guidelines were discussed: diagnostics of GTD and GTN, treatment of low-risk GTN, high-risk GTN, ultra-high-risk GTN, placental site and epithelioid trophoblastic tumours and follow-up. Results Between 40 and 65 EOTTD members from 17 European countries and 7 non-European countries attended the clinical workshops held on 6 occasions. Flow diagrams for patient management were composed to display minimum and best practice for most treatment situations. New agreed definitions of recurrence and chemotherapy resistance were formulated. Conclusions Despite the many differences between and within the participating countries, an important step in uniform treatment of GTD and GTN within Europe was made by the Clinical Working Party of the EOTTD. This is an example on how guidelines and harmonisation can be achieved within international networks.

Introduction: Central nervous system (CNS) metastasis are detected in approximately 10-30% of breast cancer (BC) patients, being associated with poor prognosis despite local and systemic therapeutics available. In the current study, we aimed to evaluate the association between BC subtypes and CNS metastasis development and prognosis. Methods: Retrospective analysis of 258 BC patients’ records with pathological and/or radiological documented CNS metastasis, treated at a Cancer Center between 2003-2019, median follow-up of 61 months (range: 0-351). For analysis purpose, three BC subtypes were considered according to hormone receptor status and HER-2 expression: luminal, HER-2 positive and triple negative. Survival was evaluated by Kaplan-Meier method and groups were compared with log-rank test. Independent prognostic factors were identified using Cox regression model. A p value < 0.05 was considered statistically significant. Results: Ninety four (42%) patients had HER-2 positive, 87 (39%) luminal and 41 (19%) triple negative disease. The median time between the diagnosis of BC and the detection of CNS metastasis was significantly shorter in triple negative group (18 months) compared to the others (HER-2 positive: 31 months; luminal: 54 months; p=0.001), and CNS was more often the first site of recurrence (with or without concomitant extracranial disease progression) in this group (triple negative: 25 (61%) vs. HER-2 positive: 31 (33%) vs. luminal: 27 (31%); p=0.002). Most of the patients had parenchymal metastasis (n=245), being exclusively parenchymal in 227 (88%), and 31 (12%) had leptomeningeal (LM) disease, that was isolated in 13 (5%). More than half (n=136) had multiple (>3 lesions) CNS metastasis, without differences between BC subtypes. Among the patients with LM disease, 17 (68%) had luminal tumors, 5 (20%) HER2-positive and 3 (12%) triple negative (p=0.007). Forty five patients (17%) were treated with surgery for CNS metastasis, with similar proportions between BC groups. In the patients submitted to CNS surgery, the concordance between primary tumor and metastasis subtype was higher in HER-2 positive (73%) compared to 57% in triple negative and 50% in luminal groups (p=0.004). After CNS involvement, 62% (n=24) of patients with triple negative disease did not receive any systemic therapy, compared to 44% (n=37) in luminal and 33% (n=29) in HER-2 positive groups (p=0.010). Median survival after CNS metastasis documentation was longer in HER-2 positive group (27 months vs. luminal: 18 months vs. triple-negative: 14 months, p=0.004) and also in patients submitted to surgical resection of CNS metastasis (38 months vs. 6 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastasis (HR 0.62, 95% CI: 0.47-0.84, p=0.002), regardless the therapeutic strategy. Conclusions: Pattern of CNS metastasis development and prognosis varies according to BC subtype. The association between LM disease and luminal tumors should be explored in future studies. Treatment modalities also play a decisive role in the prognosis of this patients, therefore, new and effective therapeutic strategies are needed. Citation Format: IoIanda Vieira, Miguel Abreu, Tiago Alpoim, Isabel Pereira, Susana Sousa, Isabel Azevedo, Machado Carvalho, Deolinda Pereira. Patterns of development and prognostic factors in central nervous system metastasis according to breast cancer subtypes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-60.

Background: Optimal management of bone marrow metastasis (BMM) in advanced breast cancer (ABC) remains unknown. Associated severe cytopenias often urge treatment, but they are also a challenging factor for delivering chemotherapy (CT). Since BMM in ABC is infrequent, available data are scarce. Aim: Clinical and prognostic characterization of ABC patients with BMM and its management; evaluation of the effectiveness of treating BMM with more myelosuppressive CT regimen (that we hypothesized that could be more active in the BMM) Vs. less myelosuppressive regimen. Methods: Retrospective cohort study of patients with pathological confirmation of BMM (positive myelogram or osteomedullary biopsy) between Jan'2010 and Dec'2016 in the two major Portuguese cancer centers. Patients with diagnosis of a second carcinoma or active hemato-oncological condition within 5 years before BMM were excluded. We considered the more myelosuppressive regimens those with > 5% risk of febrile neutropenia according to Truong et al 2015(1). Kaplan-Meier and log-rank methodology were used to estimate survival and Cox regression to identify the covariates with independent prognostic value. Statistical level of significance was 5%. Results: We included 74 patients: 74% with disease stage I-III at presentation, 74% ductal and 12% lobular invasive carcinomas, 58% grade 2 and 27% grade 3, 80% hormone receptor + / HER2-, 4% HER2+ and 12% triple negative (TN). Median time from ABC diagnosis to BMM was 10 months (IQR 2-36), synchronous in 34%. At diagnosis of BMM, median age was 57 years-old (IQR 47-65), 57% were post-menopausal, 97% had bone metastasis, 50% had visceral metastasis, 53% performed ≥ 2 previous palliative systemic treatments and 53% were exposed to bisphosphonates. The most frequent immunohistochemistry change in BMM biopsy was the loss of progesterone receptor expression (37%). Bicytopenia (anemia/thrombocytopenia) was the trigger for BMM investigation in 69% of cases, with grade 3-4 anemia in 16% and grade 3-4 thrombocytopenia in 26%. Median survival after BMM diagnosis was 5 months (95% CI, 3-11); overall survival at 12 and 24 months were 35% (CI 26-48%) and 24% (CI 15-36%), respectively. First treatment after BMM was CT in 58% (median survival, 11 months) and endocrine therapy in 14% (median survival, 3 months). An anti-HER2 regimen was used in 4% and 22% did not receive any treatment after BMM. On multivariate analysis, TN subtype (HR 4.02, CI 1.46-11.01), thrombocytopenia (G0 reference; G1-2: HR 2.47, CI 1.11-5.56; G3-4: HR 4.89, CI 1.85-12.91) and ≥ 2 palliative systemic treatments (HR 2.77, CI 1.46-5.27) were associated with worse prognosis. Within those treated with CT, there was a trend for a deleterious survival effect of more myelosuppressive regimens (HR 2.19, CI 0.94-5.09; 5 months Vs. 14 months, n=31), after controlling for subtype, number of previous regimens and thrombocytopenia. Conclusion: BMM was not a late event in ABC disease course and had worse prognosis in multi-treated patients, in TN subtype and in the presence of thrombocytopenia. No benefit was shown with the use of more myelosuppressive CT regimens. (1)Truong J et al, Ann Oncol. 2016 Apr;27(4):608-18. Citation Format: Martins-Branco D, Ferreira SC, Pereira I, André S, Varelas A, Leal C, Esteves S, Abreu MH, Sousa S, Moreira A, Brito M. Management of bone marrow involvement in advanced breast cancer: Retrospective multicenter cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-05.

Background The addition of carboplatin to an anthracycline/taxane-based chemotherapy(CT) in neoadjuvant setting has been suggested to improve pathological complete response(pCR) in TNBC. However, the impact of pCR in prognosis is unknown. We aim to study the value and feasibility of the addition of carboplatin in neoadjuvant setting. Methods Demographic and clinical data of TNBC patients treated with neoadjuvant CT in a comprehensive cancer center between 2010-2018 were retrospectively collected. Two cohorts were defined: one treated with Carboplatin/Paclitaxel followed by dose-dense Doxorrubicin/Cyclophosphamide(CP-AC) and other with AC followed by Docetaxel(AC-D). Median follow-up time was 3.1 and 6.9 years, respectively. pCR was defined as absence of residual invasive tumor in breast/axilla. Survival analysis using Kaplan-Meier method and Cox proportional-hazards model were applied. Statistical significance was set at p Results One-hundred and sixty patients were enrolled: 78 CP-AC and 38 AC-D. Groups were balanced regarding patients and tumor characteristics with exception of pre-menopausal status, more frequent in CP-AC(68% vs 47%;p=.04). Age at diagnosis was 47(28-76)years, the majority had ECOG 0(92%) ductal carcinomas(82%), clinicalT2/3 stages(76%), grade 3(81%) with lymph node involvement(N+)(57%). 14% had Inflammatory breast cancer(IBC)(CP-AC 14%;AC-D 13%; p=.9). Neutropenia was the most prevalent adverse event(G3/4: CP-AC 61%;AC-D 16%;p=.02), 12% and 16% of febrile neutropenia(p=.8). G3/4 thrombocytopenia occurred only in CP-AC(6%). Hypersensitivity reactions were more prevalent in CP-AC(19% vs 2.7%;p=.02), majority to paclitaxel, all G1/2. Hospital admission occurred in 12%(CP-AC 13%;AC-D 9%; p=.8). There were no treatment-related deaths. Treatment schedule was complete in 89%(CP-AC 87%;AC-D 92%;p=.5), with 20% dose reductions(CP-AC 25%;AC-D 11%;p=0.9). pCR was achieved in 42%(CP-AC 50%;AC-D 28%;p=.03). 1- and 3-year disease-free survival(DFS) was 94%/85% for CP-AC and 72%/58% for AC-D(p=.3). Risk of recurrence was higher in IBC(HR 25.1;CI95% 7.7-81.3;p Cancer-related deaths were 20%(CP-AC 10%;AC-D 40%;p=.001). 1- and 2-year overall survival (OS) was 99%/95% for CP-AC and 70%/61% for AC-D(p=.06). N+ disease was associated with higher risk of death in AC-D(HR 6.3;CI95% 1.1-24.6;p=.04). Risk of death was independently associated with IBC(HR 4.1;CI95% 2.1-18.7; p=.001) but not with N+ disease(HR 2.7;CI95% 0.8-9.5;p=.13) or pCR(HR 4.1;CI95% 0.9-19.7;p=.08) although pCR was statistically significant in univariate analysis (1- and 2-year OS 97% vs 92% and 94% vs 86% for pCR and non-PCR;p=.003). Conclusions Carboplatin addition clearly increased pCR with a trend to DFS and OS benefit. This regimen was associated with more, nevertheless manageable, adverse events with most of the patients able to tolerate and complete the full-dose regimen. Though we did not find a subgroup of patients that benefit with carboplatin regimen, we should consider avoiding AC-D at least in N+ disease. Citation Format: Coelho S, Abreu MH, Sales C, Lopes AR, Sousa MF, Couto R, Pousa I, Ferreira A, Ferreira M, Vieira C, Leal C, Castro F, Sousa S, Pereira D. Carboplatin-addition in neoadjuvant treatment of women with triple negative breast cancer (TNBC): Prognostic value in real-world patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-19.

Introduction/Background Cervical cancer (CC) is the second most frequent gynaecologic tumour and curative treatment often includes concomitant chemo-radiation (RT/ChT). The aim of this study was to assess the early and late impact on quality of life (QOL) of patients treated with this treatment modality. Methodology Prospective study of patients, treated in a tertiary cancer centre, with RT/ChT (weekly cisplatin) between 2014–2016 with a median follow-up of 54.7 months. QOL was assessed using validated versions of EORTC QLQ-C30 and QLQ-Cx24 questionnaires, looking for 7 principle domains: global health, role function, physical function, social function, financial issues, sexual function and symptoms. For this evaluation two distinct moments were defined: the first one at the first day of treatment and the second one after at least 3.7 years (min-max: 3.7–5.9 years). To avoid bias in long-term questionnaires’ answers (moment two) there were excluded patients that had persistent disease after RT/ChT or recurred after complete response. Patients‘ answers were converted, by linear transformation, into 0–100 score intervals. Paired Sample T-test and Wilcoxon Signed Rank Test were used to compare results. Results 50 patients were included, with average age at diagnosis of 52 years (24–74 years) and stage disease II (FIGO 2009) in 32 (64%). First and second questionnaires were answered by 50 and 34 patients, respectively. There were no differences between the two moments concerning global health (p=.41), role function (p=.72), physical function (p=.21), social function (p=.86) and financial issues (p=.21). An emotional improvement to second evaluation (p=.03) and a decrease in cognitive function (p=.007) were observed. Related to symptoms there were no differences, except for diarrhea that was worse (p=.006) and lymphedema (p=.005) that improved later in time. Although sexual dysfunction seemed similar (p=.21), there were a progressive increase of sexual worry (p=.004). Conclusion Careful assessment and handling of treatment toxicities is imperative to minimize long term sequelae of curative treatments. Particularly in these survivor’s cohort, focus on cognitive and sexual problems and diarrhea seems extremely important. Disclosures The authors declare no conflicts of interest.

The main challenge in ovarian cancer treatment is the management of recurrences. Facing this scenario, therapy selection is based on multiple factors to define the best treatment sequence. Target therapies, such as bevacizumab and polymerase (PARP) inhibitors, improved patient survival. However, despite their achievements, ovarian cancer survival remains poor; these therapeutic options are highly costly and can be associated with potential side effects. Recently, it has been shown that the combination of repurposed, conventional, chemotherapeutic drugs could be an alternative, presenting good patient outcomes with few side effects and low costs for healthcare institutions. The main aim of this review is to strengthen the importance of repurposed drugs as therapeutic alternatives, and to propose an in vitro model to assess the therapeutic value. Herein, we compiled the current knowledge on the most promising non-oncological drugs for ovarian cancer treatment, focusing on statins, metformin, bisphosphonates, ivermectin, itraconazole, and ritonavir. We discuss the primary drug use, anticancer mechanisms, and applicability in ovarian cancer. Finally, we propose the use of these therapies to perform drug efficacy tests in ovarian cancer ex vivo cultures. This personalized testing approach could be crucial to validate the existing evidences supporting the use of repurposed drugs for ovarian cancer treatment. Funding: This manuscript was funded by HOPE: Improving ovarian cancer patients’ survival—donation from an ovarian cancer patient and by the FCT (Fundação para a Ciência e a Tecnologia) project PTDC/MEC-ONC/29503/2017.

BACKGROUND: Through the International Male Breast Cancer Program, a prospective registry for male BC was created with the goals of evaluating 1) the clinical and biological features of this disease and 2) assessing feasibility of a prospective therapeutic clinical trial. METHODS: All men, with any stage histologically proven invasive breast cancer, age 3 18 years, and newly presenting at the participating institutions (within 3 months prior) were eligible. Patients were enrolled for 30 months after activation of the first center, through February 2017. Per the study design, if RESULTS: 557 patients were enrolled: 75% in Europe, 20% in United States, 5% in other countries. 6.3% of patients had missing forms. Median age was 67 years (range 26-92). 93% were diagnosed 2010-2017. Among patients with complete data, 79% presented with a breast mass. 88% were M0 and 12% M1. Among M0 patients: 47%, 39%, 2%, and 11% had T1, T2, T3, and T4 disease respectively; 52% were N0. Overall, 98% had ER+ disease and 11% had HER2+ cancer. 14% had grade 1, 56% had grade 2, and 30% had grade 3 tumors. Among 112 men who underwent BRCA1 testing, 1 was positive. Among 118 men who had BRCA2 testing, 18 (15%) were positive. 21% of men had prior or concurrent malignancies, with the following most common sites: prostate, non-melanoma skin, colorectal, and melanoma. The prevalence of previously identified possible risk factors for male breast cancer were: overweight/obesity (72%), former/current smoker (51%), current alcohol 31 drink daily (41%), family history of breast cancer (35%), gynecomastia (16%), history radiation exposure (8%), use of anti-androgens (1%), and use of estrogens (1%). CONCLUSION: Through an international collaborative effort, we were able to prospectively accrue 557 patients to a male breast cancer registry. These results demonstrate feasibility of pursuing a therapeutic clinical trial in men with breast cancer. In addition, this study shows the relatively low uptake of BRCA testing, high rates of concurrent/prior malignancy, and the rates of potentially modifiable risk factors in this patient population. Funding from Breast Cancer Research Foundation, Susan G. Komen, Dutch Pink Ribbon Foundation, Swedish Breast Cancer Association (BRO) and EBCC Council. Citation Format: Giordano SH, Schröder CP, Poncet C, van Leeuwen-Stok E, Linderholm B, Abreu MH, Rubio I, Van Poznak C, Morganstern D, Cameron D, Vleugel MM, Smilde TJ, Bozovic-Spasojevic I, Korde L, Russell NS, den Hoed IDM, Honkoop AH, van der Velden AWG, van 't Riet M, Dijkstra N, Bogler O, Goulioti T, Hilsenbeck S, Ruddy KJ, Wolff A, van Deurzen CHM, Martens J, Bartlett JMS, Aalders K, Tryfonidis K, Cardoso F. Clinical and biological characterization of male breast cancer (BC) EORTC 10085/TBCRC 029/BOOG 2013-02/BIG 2-07: Baseline results from the prospective registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-01.

Objective: To assess the cellular DNA status of epithelial ovarian cancer cells for clinical stage identification and its effect on survival. Methods: Sixty-twopatients treated by primary surgery and six courses of platinum-based chemotherapy were enrolled. The surgical stage was analyzed in correlation with DNA ploidy, S-phase fraction and DNA index. DNA analysis was performed via image cytometry. Results: From the 62 cases,38 were International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d’Obstétrique, FIGO) stage I and II, 24 – stage III and IV. In the DNA histograms obtained, the DNA index ranged from 0.85 to 3.02. Sixteen were classified as diploid and 46 as aneuploid (18 multiploid). S-phase fraction ranged from 9.8 to 51%. The aneuploid cells with DNA content above 5C ranged from 0.0 to 77.2%. Patients diagnosed with FIGO III and IV (vs. I and II) were 3.3 times more likely to die. Only in FIGO stage I and II the survival differed significantly for the different groups of ploidy. The risk of death for the multiploid (vs. diploid) group is 6.4 times and for aneuploid (vs. diploid) 2.3 times. Overall survival was better in the group with low DNA index. The low percentage compared with a high percentage of 5C cells ploidy groups showed association with mortality. The death hazard for the S-phase >33 median group is 4.9 times the hazard in relation to the S-phase, Cel: Ocena statusu DNA komórek nabłonkowego raka jajnika w różnych stopniach zaawansowania klinicznego i jego wpływ na przeżycie. Metoda: Do badania zakwalifikowano 62 pacjentki leczone operacyjnie i za pomocą chemioterapii opartej na platynie (6 kursów). Stopień zaawansowania klinicznego nowotworu analizowano w odniesieniu do ploidalności DNA, frakcji fazy S oraz indeksu DNA. Analizę DNA przeprowadzono z zastosowaniem cytometrii obrazowej. Wyniki: Spośród 62 pacjentek 38 zakwalifikowano jako stopień zaawansowania I i II, natomiast 24 – jako stopień III i IV wg FIGO (International Federation of Gynecology and Obstetrics). W otrzymanych histogramach DNA indeks DNA wynosił 0,85–3,02. Szesnaście przypadków raka zaklasyfikowano jako diploidalne, natomiast 46 – jako aneuploidalne (18 multiploidalnych). Frakcja fazy S mieściła się w przedziale 9,8–51%. Odsetek komórek aneuploidalnych z zawartością DNA powyżej poziomu 5C wynosił 0,0–77,2%. Ryzyko śmierci było 3,3-krotnie większe w przypadku pacjentek z chorobą w stopniu zaawansowania FIGO III i IV (w porównaniu z I i II). Jedynie w przypadku stopni zaawansowania FIGO I i II odnotowano istotnie różnice w przeżywalności między poszczególnymi grupami ploidalności. Ryzyko śmierci było 6,4-krotnie większe w przypadku multiploidalności i 2,3-krotnie większe w przypadku aneuploidalności (w porównaniu z diploidalnością). Dłuższe przeżycie ogólne odnotowano w grupie o niskim indeksie DNA. Wykazano związek między niskim odsetkiem komórek 5C, w porównaniu z wysokim odsetkiem tych komórek w grupach poliploidalnych, a śmiertelnością. Ryzyko śmierci było 4,9-krotnie większe w grupie z medianą liczby komórek w fazie S >33 w porównaniu z medianą liczby komórek w fazie S

Background: During breast cancer follow-up, there is no data suggesting that, besides annual mammography, laboratory and imaging tests in asymptomatic patients lead to survival benefit. However, most available data come from a period of fewer quality of diagnostic procedures and less efficacy of treatment for advanced breast cancer. In our centre, in the absence of disease recurrence after 5 years of follow-up, and when endocrine therapy ends, we transfer the surveillance of breast cancer patients for primary care physicians. Before that, by protocol, we use to request as staging exams a bone scan, a chest x-ray and liver ultrasound, or a thoracoabdominal computed tomography, as well as the quantification of CA15.3, in order to detect asymptomatic cancer recurrence before discharge. This study aimed to evaluate the effectiveness of that strategy in detecting asymptomatic disease and its impact on patients’ outcomes, compared to those who recurred symptomatically during the following 5 years of surveillance. Methods: A retrospective cohort study of all adult patients admitted to our institution due to breast cancer in stage I-III during 2008 was performed. We included those who were asymptomatic and considered for discharge after 5 years of follow-up. Laboratory and imaging tests done at that time were reviewed. We also looked for symptomatic disease recurrence in the following 5 years of surveillance, with median follow-up of 43 months (95% CI 24.6-61.4), after discharge. Data were analyzed using descriptive statistics and survival was estimated by Kaplan-Meier method. Survival between groups was compared using log-rank test. Hazard ratios and respective 95% CI were estimated using Cox-regression models. Statistical significance was set at P< 0.05. Results: A total of 576 patients met inclusion criteria, 99.7% female (574/576), with median age of 59 years (IQR, 18). Disease was staged as IA in 48.5% of patients (279/575). At discharge, 75.2% of patients (433/576) did staging exams, and the remaining did not according to clinical criteria defined by the attending physician (mainly age, comorbidities and stage IA). Exams were positive in 2.1% of patients screened (9/433), due to bone metastasis detection in 88.9% (8/9). For these 9 patients, median PFS was 30 months (95% CI 0.0-76.7) and 5-year OS was 62.5%. During surveillance after discharge, 4.4% of patients (24/549) presented disease recurrence, 3.1% (17/549) with distant metastasis. From those, 70.6% (12/17) had visceral metastasis and 29.4% (5/17) had recurrent disease limited to bone. For these 17 patients, median PFS was 16 months (95% CI 5.3-26.7) and 2-year OS was 50.1%. For bone metastasis patients, median PFS was not different between asymptomatic and symptomatic group (p=0.378); but median OS was not reached in asymptomatic patients and was of 34 months in symptomatic patients (p=0.029). We did not find predictive factors for PFS or OS by multivariable Cox-regression analysis. Conclusion: In our cohort, asymptomatic recurrence detection rate was low, mainly presented as bone metastasis. Nevertheless, it seemed to impact positively on OS, compared to those who presented symptomatic bone disease. Disease recurrence due to visceral metastasis was detected, more frequently, in symptomatic patients. New trials are needed to reassess the question concerning staging exams in asymptomatic breast cancer patients. It would also be interesting to perform a cost-effectiveness analysis of that approach. Citation Format: Andreia Cruz, Ana Rita Lopes, Maria Leitão, Sarah Lopes, Sofia Patrão, Maria Cassiano, Cristina Oliveira, Miguel Abreu, Júlio Oliveira, Joana Bordalo Sá, Ana Rodrigues, Marta Ferreira, Rosário Couto, Inés Pousa, Cláudia Vieira, Ana Ferreira, Susana Sousa, Deolinda Pereira. The (in)effectiveness of staging exams in asymptomatic breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-03-01.

Ovarian cancer is the seventh most common cancer diagnosed in women worldwide. To date, many studies inepithelial ovarian cancer (EOC) have reported on the association HER-2/neu, p53 proteins and steroid hormones and their respective receptors with prognosis and/or the carcinogenesis process, but no definitive conclusion has been reached.Objectives: To assess the proteins c-erbB-2, p53, Ki67 and receptors of estrogen (ER) and progesterone (PR) of EOC, with regard to clinical stage findings and its effect on survival.Methods: 125 patients with a diagnosis of EOC treated by primary surgery and chemotherapy have participated. A surgical stage was noted and analyzed the correlation with c-erbB-2, p53, Ki67, ER and PR. Immunohistochemical analysis, using the anti-c-erbB-2, p53, Ki67 monoclonal antibodies, the antibody cod PR clone PgR and code ER-6-F11 Anti human estrogen. The c-erbB-2 study was complemented by genetic amplification and was reported univariate and multivariate analysis.Results: Age 55.7 ± 16; 50.2% with residual disease (< 2 cm); initial (54.6%) and advanced (45.4%) stage. Univariate analysis showed positive staining for c-erbB-2, p-53, Ki67, PR and ER. The patients with negative receptors had a significantly shortened survival time (p = 0.01) than patients with positive receptors. Multivariable analysis revealed only clinical FIGO stage as an independent prognostic of overall survival (p = 0.002). Other variables like c-erbB-2, p53, Ki67, and ER were not significantly related to survival.Conclusions: We concluded that patients with negative PR had a significantly shortened survival time than patients with positive receptors. The overexpression of markers c-erbB-2, p53, Ki67, and ER, were not significantly related to survival in EOC. Only the FIGO stage was achieved to be an independent predictor of overall survival. They should be evaluated together with the patient’s clinical status and other prognostic factors.

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.

Male breast cancer (MBC) patients seem to have inferior survival compared to female (FBC) ones, which is not fully explained by usual prognostic factors. Recurrence analysis could show differences in relapse patterns and/or in patients' approaches that justify these outcomes. Retrospective analysis of MBC patients treated in a cancer center between 1990 and 2014, looking for relapse. For each patient, three matched FBC patients were selected by: diagnosis' year, age (within 5 years), stage and tumors' type (only luminal-like were considered). Differences between cohorts were assessed by χ(2) test and hierarchical clustering was performed to define subgroups according to relapse local. Survival curves were calculated by Kaplan-Meier and compared using log-rank test. Statistical significance was defined as p

Male Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted.Retrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel.According to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size2 cm (HR:1.8; 95%CI:1.0-3.4 years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7-14.3 years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2-3.1 years, p0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2-16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6-7.8 years).FBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.

e13070 Background: Bone is one of the main sites of breast cancer metastasis. Staging of this kind of disease spread can be performed in locally advanced cases with PET-CT in conjunction with Bone Scintigraphy. The purpose of this work is to compare the efficiency of bone metastasis detection between PET-CT and bone scintigraphy. Methods: Prospective analysis of locally advanced breast cancer patients treated in a Comprehensive Cancer Center between 2014 and 2019 that performed PET-CT and Bone Scintigraphy in the staging. Interval between the two exams could not exceed 2 months. Clinical and pathological characteristics of the disease were collected from electronic files and independently clinical images reports were considered to evaluate the ability of each imaging modalities to identify bone disease. In discrepancy cases a re-analysis of the images by two independent nuclear physicians was performed to validate the findings. Results: We analyzed 204 cases. The majority of them had ductal carcinomas (72.5%), cT2/3 (70%), cN1/2(61.8%) and G2/3 (94.6%), luminal B- like, HER2 positive disease (49.2%). In this cohort, bone metastasis was documented in 52 (25.5%) patients. PET-CT presented 97.0% of accuracy, surpassing the 94.1% presented by Bone Scintigraphy. The latter failed to correctly detect bone metastasis in 11 (5.4%) patients and only outperformed PET-CT in 3 (1.5%) patients. The main difference between the two modalities was the non-detection of cranium lesions in PET-CT images. Conclusions: PET-CT showed higher efficiency in bone metastasis detection than Bone Scintigraphy, probably because it detects lytic lesions. The non-detection of cranium ones can be harmful and so modifications in the image acquisition are required to improve the quality of PET-CT, avoiding other exams in bone staging.

Tamoxifen remains the standard hormonotherapy for Male breast cancer patients (MBC). Previous studies, in women, tried to evaluate the impact of CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Herein we analyze the relation between CYP2D6*4 polymorphism and survival in MBC patients.Fifty-three patients, proposed to tamoxifen in adjuvant setting, were enrolled. Clinical information was collected from records and histological revision with additional immunochemistry analysis was done to better characterize the tumors. Comprehensive CYP2D6*4 genotyping from blood or tumor tissue was performed and translated into two predicted metabolic activity groups.Patients included in the two CYP2D6*4 groups did not differ concerning to age, histological characteristics, and primary treatments performed. Median age at diagnosis was 63 years-old and patients were submitted at least to mastectomy and adjuvant hormonotherapy. Recurrence was observed in 7 patients (13.2%) and 13 patients (25.5%) died with a 5-year disease-free survival of 86.2%. The poorer metabolizer group had a high risk for recurrence (p = 0.034) and this outcome effect remains in different subgroups: in tumors larger than 2 cm (p0.001), nodal status, N0 vs N+ (p = 0.04) and in advanced stage, stage III (p0.001). Poorer metabolizer patients had also a worse overall survival when tumors were larger than 2 cm (p = 0.03).In our series, there was an association between CYP2D6*4 polymorphism and a probability of recurrence, with a consistent effect in risk groups defined by classic prognostic factors. Multicentric studies with larger samples are needed to validate these results.

Breast cancer is the most frequently diagnosed cancer in women. Using historical patient information stored in clinical datasets, data mining and machine learning approaches can be applied to predict the survival of breast cancer patients. A common drawback is the absence of information, i.e., missing data, in certain clinical trials. However, most standard prediction methods are not able to handle incomplete samples and, then, missing data imputation is a widely applied approach for solving this inconvenience. Therefore, and taking into account the characteristics of each breast cancer dataset, it is required to perform a detailed analysis to determine the most appropriate imputation and prediction methods in each clinical environment. This research work analyzes a real breast cancer dataset from Institute Portuguese of Oncology of Porto with a high percentage of unknown categorical information (most clinical data of the patients are incomplete), which is a challenge in terms of complexity. Four scenarios are evaluated: (I) 5-year survival prediction without imputation and 5-year survival prediction from cleaned dataset with (II) Mode imputation, (III) Expectation-Maximization imputation and (IV) K-Nearest Neighbors imputation. Prediction models for breast cancer survivability are constructed using four different methods: K-Nearest Neighbors, Classification Trees, Logistic Regression and Support Vector Machines. Experiments are performed in a nested ten-fold cross-validation procedure and, according to the obtained results, the best results are provided by the K-Nearest Neighbors algorithm: more than 81% of accuracy and more than 0.78 of area under the Receiver Operator Characteristic curve, which constitutes very good results in this complex scenario. HighlightsA 5-year survival model is constructed in a real breast cancer context.The dataset is a challenge in terms of complexity due to its high missing data ratio.Several representative imputation and decision methods are analyzed.Obtained results are very interesting and accurate for this complex clinical dataset.

e12120 Background: Breast carcinoma is a heterogeneous disease whose therapeutic approach idepends on the classification into molecular subtypes. Despite the impact the expression of hormone receptors (HR) among patients with overexpression of HER2 is already the target of some studies, there is a lack of analysis in the era of treatment with adjuvant trastuzumab. Methods: This stydy consists in a retrospective analysis of cases of tumors with overexpression of the HER2 receptor (HER2 +), and HR- treated at an oncological center, comparing their biological behavior with cases of HR +/ HER2 + tumors, thus controlling for classic prognosis. Results: We analised a total of 420 patients, of whom 210 with HR+/HER2+ tumors and 210 HR- / HER2 +, with median ages of 52 years and 53 years, respectively. They accounted for 89.5% of cases of stage I to III disease. The groups were balanced in clinical characteristics. There was a higher proportion of undifferentiated and inflammatory tumors in the RH-/ HER2 + group, and in this group higher rates of complete pathological responses to treatment were observed (50.8% vs. 30.0%, p < 0.001). During the follow-up 30 recurrences occurred, 18 in the HR- / HER2 + group, and 12 in the HR + / HER2 +. There was lower disease-free survival in the HR-/HER2 +, on average 69.1 months, compared to 74.3 months in the group HR+/HER2 + (p = 0.001). The first metastatic site involved visceral location in 13 cases (72.2%) in HR- / HER2 + tumors (CNS involved in 8 cases), and in 8 cases (66.6%) in HR + / HER2 + tumors (CNS in 1 case). There was an association between relapse and response to primary systemic treatment (p = 0.003), with no relation demonstrated with other clinicopathological characteristics. In the global sample, there were 28 deaths, corresponding to 17 in the HR-/HER2 +, and 11 in the HR+/HER2 + group. There were significant diferences in OS, showing worse prognosis of HR- disease (mean of 70.7 months vs. 106.6 months, p = 0.001). There was an association of mortality with the presentation as an inflammatory tumor and involvement of the CNS. Conclusions: This study supports the concept of two distinct entities according to the expression in HER2 + disease, justifying therapeutic approaches and eventually different follow-up strategies.

Introduction In the county of Vila Nova de Gaia (northern Portugal) in the period of 2004–2006, there were an average of 35 new cases of colorectal cancer per 100 000 population, which constitutes one of the highest rates in the world. The latest research has shown that there are many differences between colon and rectal cancers, thereby justifying an independent approach. Patients and methods The study pertained to the period 1995–2004, by using the census of 1991 and 2001 for calculating specific rates. The 399 diagnosed cases of rectal cancer were drawn from a specialized and active cancer registry, oncological registry of Gaia. Overall survival was calculated using the Kaplan–Meier method and the curves were compared using a Log Rank test. The effect of topography and histological type on survival was obtained by controlling the stage disease, using a Cox proportional hazards regression model. Results There was a slight predominance of males, with a ratio between sexes of 1 : 3. The 50% overall survival rate after 5 years increased over time. The localization of the tumour and the histological type, after adjusting by stage, were not significant factors in the prognosis. Conclusion Our study shows an increase in the number of cases over time, particularly in elderly women. The cumulative risk of having rectal cancer remains unchanged from 1981 to 2004. Unlike other studies, an increase in early lesions was not observed.

The prediction of overall survival in patients has an important role, especially in diseases with a high mortality rate. Encompassed in this reality, patients with oncological diseases, particularly the more frequent ones like woman breast cancer, can take advantage of a very good customization, which in some cases may even lead to a disease-free life. In order to achieve this customization, in this work a comparison between three algorithms (evolutionary, hierarchical and k-medoids) is proposed. After constructing a database with more than 800 breast cancer patients from a single oncology center with 15 clinical variables (heterogeneous data) and having 25% of the data missing, which illustrates a real clinical scenario, the algorithms were used to group similar patients into clusters. Using Tukey’s HSD (Honestly Significant Difference) test, from both comparison between k-medoids and the other two approaches (evolutionary and hierarchical clustering) a statistical difference were detected (p − value < 0.0000001) as well as for the other comparison (evolutionary versus hierarchical clustering) - p − value = 0.0061354 - for a significance level of 95%.

Breast Cancer is the most common type of cancer in women worldwide. In spite of this fact, there are insufficient studies that, using data mining techniques, are capable of helping medical doctors in their daily practice.

Colorectal cancer is the fourth most common cancer in men and the third most common one in women worldwide (Parkin, 2004; Parkin et al., 2005), accounting for approximately 436,000 incident cases and 212,000 deaths in 2008 (Quirke et al., 2011). This cancer has an important economic impact, estimating that in the initial, continuing and last year of life phases of care a total of more than $7 billion were spent (Yabroff et al., 2008). Randomized trials have shown that systematic screening of a target population of suitable age can reduce colorectal cancer by detecting asymptomatic lesions (Center et al., 2009). Although there are differences in the etiologies and epidemiology of colon and rectal cancer (Giovannucci & Wu, 2006), the majority of the studies chose to examine colon and rectum cancers combined. However, a better understanding of these diseases nowadays, shows that these differences have an important impact in their approaches. First of all, the location of the tumours may determines different locations of metastisation. Unlike colon cancers, distal rectal tumours may first metastasize to the lungs because the inferior rectal veins drain into the inferior vena cava rather than into the portal venous system. The histological type can also vary. The vast majority of colorectal tumours are adenocarcinomas but 11-17% are mucinous carcinomas. This type, which has a penchant for the rectum and sigmoid colon, tends to be present at a more advanced stage (Consorti et al., 2000). The carcinoid tumours have a different clinical presentation too, depending on whether they appear in the rectum or in the colon (Marshall & Badnarchuk 1993; Spread et al., 1994). The rectum carcinoids develop at a young age, most of which are less than 2 cm and tend to be indolent. In contrast, colonic carcinoid tumours can be clinically aggressive and often metastise. With a more accurate review, we can see that many habits could influence the development of rectal cancers and not colon cancers. Some studies support the view that family history, as well as the level of physical activity, is a stronger contributor to colon cancer relative to rectal cancer (Wei et al., 2004). The Women’s Health Initiative (a large cohort study) (Paskett et al., 2007) also found a significant link between active cigarette smoking (not passive exposure to cigarette smoke) and rectal but not colon cancer. These differences are important in terms of monitoring and have implications in treatment options, as well. Compared to colon cancers, the sensitivity of CT scan for detection of

e11562 Background: Male Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted as Female’s subgroups seem inadequate to identify the aggressive forms of MBC Methods: Data from 111 MBC cases treated in a single Cancer Center were retrospectively reviewed. Blinded-central pathological revision with additional immunohistochemical (IHQ) staining analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female molecular subgroups (based in ER,PR and HER2, classification A, and in ER,PR,HER2 and ki67, classification B) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel. Results: According to Female classifications, the majority of tumors were luminal A (89.2% and 60.0%) and B (7.2% and 35.8%...

Introdution Follicular Lymphoma (FL) presents a recurrent clinical behavior. The proliferative activity of B-cells in NHL subtypes varies amongst different subtypes, being higher in high grade NHL. In FL without t(14; 18), high proliferative activity appears to be a better predictor of progression free survival (PFS). Objectives Evaluation of proliferative activity of neoplastic B cells in patients with FL and its association with underlying cytogenetic changes (such as t(14;18)). Determination of the prognostic value of proliferative activity of neoplastic B cells and t(14, 18) in patients with FL. Methods Retrospective analysis of 139 patients with FL, followed in our center from 2006 to 2011. Evaluation of the cytogenetic changes and percentage of cells in S phase at the time of diagnosis, performed on lymph nodes. The cell cycle analysis was evaluated by flow cytometry, resorting to DNA labeling kit B-NHL (Cytognos) ModFit software (Verity). The adopted cut-off of S phase cells was based on the median value. The type of response was defined in accordance with the criteria proposed by the NCCN. The patients´ characteristics were compared with a X2 test for binary variables and a Mann-Whitney test for continuous variables. The survival curves were estimated based Kaplan-Meier curves and the data for the various groups were compared with a log-rank test. The multivariate analysis was carried out using a Cox model, after the proportional hazard assumption was checked. A p value below 0.05 was considered as being statistically significant. Results The median follow-up was 34 months ([8-75]). The S phase was analysed in 45 patients with an median age of 56 years ([31-78]). 89% (n = 40) of the patients presented an Ann Arbor stage III-IV, 86.7% (n = 39) a follicular pattern, 89% (n = 40) a grade 1/2 and 57.8% (n = 26) a FLIPI ≥ 3. The t(14;18) was found in 25 patients (55.6%), in 9 patients cytogenetic analyses was not performed. In this study was given immunochemotherapy to 82.2% (n = 37) patients. Thirty patients (66.7%) achieved CR and 15.6% (n = 7) PR, with a PFS of 22 months in 53.3% of patients. In univariate Cox regression analysis, the histological pattern, the number of S-phase cells and the t(14;18) are independent predictors of PFS (p Conclusion Quantification of cells in S phase in FL, by flow cytometry, arises as a simple, fast and reproducible method with a prognosis impact on PFS. Cells in S phase ≥ 2.3% and absence of t(14;18) at diagnosis are associated with reduced risk of progression (p Disclosures: No relevant conflicts of interest to declare.

Background Male Breast Cancer (MBC) is a rare condition comparing to Female Breast Cancer (FBC). Because of that, its understanding is weak and its treatment has often been extrapolated from FBC in spite of many important differences already suggested by many studies. Objective: To evaluate risk factors, recurrence and survival in male breast cancer. Material and methods Review of clinical files of 115 male patients diagnosed with breast cancer and treated in the IPO- Porto from 1976 to 2011. Evaluation of demographic, tumor- related variables, treatment and survival were done. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p Results The median age of the treated patients was 63 years-old (33-94 years-old). Prior or active tobacco use was observed in 36,1% and alcohol use 44,8%. Over-weight or obesity was registered in 66,7% of the cases. 48,8% of the patients reported a positive family history of cancer (17,4% of breast or ovarian cancer in a first-degree member), 8,3% were BRCA2 positive and 12,5% developed secondary malignancies. Most tumors were located in left breast (55,7%), were ductal carcinomas (91,2%), G2 (54,6%), stage III (46,4%) or II (26,8%), with positive hormonal receptors (90,4%) and with limphovascular invasion (67,4%). The majority of patients underwent surgery (95,6%), followed by chemotherapy, radiotherapy and hormonotherapy (26,1%) or radiotherapy and hormonotherapy (26,1%). 32,4% relapsed, in visceral non-hepatic sites (32,4%) or hepatic (17,6%). Median recurrence-free survival was 27,3% at five years. 5-years cancer- specific survival was 71,3%. In univariate analysis were prognostic factors the advanced stage (p Conclusions This study confirmed many differences between MBC and FBC namely: older age at diagnose, high prevalence of family history, BRCA2 mutations and second malignancies. Cancer-specific survival is similar when adjusted to other factors such as stage and local of recurrence. Disclosure All authors have declared no conflicts of interest.

Introduction Malignant neoplasms of ileocecal appendix are rare, an clinical features are unspecific, often mimicking acute appendicitis. They are diagnosed in about 1% of appendicectomy specimens. The most common histologic types are mucinous adenocarcinoma, intestinal-type adenocarcinoma and carcinoid tumor. Methods The authors reviewed the primary appendix carcinomas treated in Instituto Portugues de Oncologia Francisco Gentil-Porto (IPOFG-Porto) between January 2000 and June 2011. Results Fourty two patients were treated during this period: 30 women (71%) and 12 men, aged between 20 and 90 years old (median age 58). Mucinous adenocarcinoma was the most common histologic subtype, with 27 cases (64%), followed by adenocarcinoma NOS (10 cases - 24%); carcinoids were 5 cases (12%). Fifteen percent presented as stage IV, 7% stage III, 24% stage II and 19% stage I. The primary treatment was surgery: 16 patients were submitted to appendicectomy, 6 patients to appendicectomy, ooforectomy and hysterectomy, 12 to hemicolectomy. Of patients submitted to appendicectomy, 11 (50%) had a second laparotomy in order to perform hemicolectomy. Five percent of the patients received adjuvant chemotherapy (mFOLFOX6). Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) was performed in 18 patients with stage IV disease (peritoneal carcinomatosis). The median follow-up was 35 months. Thirty three percent of the patients (n = 14) died because of disease progression and 62% (n = 26) were alive with no evidence of disease. Conclusion Appendiceal carcinomas are rare tumours and there is limited evidence on the indications for right hemicolectomy. The role of adjuvant chemotherapy for adenocarcinoma of the appendix is unknown. Optimal treatment of patients with intraperitoneal dissemination of appendiceal adenocarcinoma (mucinous peritoneal carcinomatosis) is unclear. Selected patients treated with aggressive surgical cytoreduction and HIPEC may have a favorable outcome in long term, but patient selection and the experience of the treating team are critical. The benefit of systemic chemotherapy for advanced disease is unknown. Disclosure All authors have declared no conflicts of interest.