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Background Despite endocrine therapy being the mainstay of treatment for hormone receptor positive (HR+)/HER2− metastatic breast cancer, patients at risk of visceral crisis or doubt for endocrine sensitivity are still offered first-line chemotherapy. Maintenance hormonal therapy is generally offered at the discontinuation of chemotherapy. The MAINtenance Afinitor study is a randomised, phase III trial comparing maintenance everolimus combined with aromatase inhibitors (AIs) versus AI monotherapy in patients with disease control after first-line chemotherapy. Methods Patients with stable disease, partial response or complete response after first-line chemotherapy were randomised to everolimus plus AIs (exemestane or letrozole or anastrozole) or to AIs alone. Primary aim was progression-free survival (PFS). Secondary aims included response rate, safety and overall survival (OS). Results In total, 110 patients were randomised to everolimus + AIs (n = 52) or to AIs (n = 58). Median PFS was 11.0 months (95% confidence interval [CI] 8.1–13.8) in the everolimus + AI arm and 7.2 months (95% CI 4.7–10.9) in the AI monotherapy arm (hazard ratio [HR] 0.71, 95% CI 0.47–1.06). Objective response rate was 22.4% in everolimus + AI arm and 19.2% in AI monotherapy arm. A higher proportion of disease progression as best response was reported in the AI monotherapy arm (28.8% versus 14.3%). Median OS was 35.7 months (95% CI 26.0–47.8) in the combination arm versus 33.5 (95% CI 26.4–42.7) in the AI alone arm (HR 1.0, 95% CI 0.61–1.62). Conclusions EVE + AIs did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first-line chemotherapy. Also taking into account treatment tolerability, maintenance endocrine therapy remains the standard. Trial registration EudraCT: 2013-004153-24.

Extraskeletal myxoid chondrosarcoma is a rare form of malignant mesenchymal neoplasm mainly localized into the limbs, particularly in the thigh and popliteal fossa. It has been classified as a low-grade sarcoma so far, but it shows a tendency to relapse and metastasize. In the early stage of disease, surgery represents the only chance of cure. In case of diffuse metastatic disease, systemic chemotherapy with anthracyclines is the standard of care. In this paper, we present a case of a patient affected by this rare disease and the analysis of radiological, surgical and histopathological aspects.

BackgroundInvasive vulvar Paget’s disease with over-expression of the human epidermal growth factor receptor 2 (HER2) protein is potentially suitable for targeted therapy, especially in a metastatic setting where no effective treatments are available.MethodsFour consecutive patients with HER2 positive advanced vulvar Paget’s disease, treated with weekly trastuzumab (loading dose 4 mg/kg, then 2 mg/kg) and paclitaxel (80 mg/m2) followed by 3-weekly trastuzumab maintenance (6 mg/kg), are reported.ResultsMedian age and follow-up of patients were 62.5 years (45–74) and 16 months (6-54), respectively. Complete or partial responses were observed in all patients. Median time to response was 3 months (range 2–4), while median duration of response was 10 months (range 2–34). Case 1 presented with pulmonary and lymph nodes involvement. She experienced a radiological complete response after 24 treatment administrations, and a progression-free survival of 36 months. At disease progression, treatment re-challenge achieved partial response. She is currently receiving treatment with trastuzumab–emtansine. Case 2 was a 74-year-old woman who developed pulmonary metastasis after first-line cisplatin treatment. She had a partial response and a progression-free survival of 10 months. Case 3 had inguinal and para-aortic lymphadenopathy in complete response after 18 treatment administrations. She developed brain metastasis while receiving trastuzumab maintenance. Case 4 was treated for locally advanced disease and experienced a subjective benefit with relief in perineal pain and itching. No unexpected treatment-related side effects were reported.ConclusionsAdvanced vulvar Paget’s disease is a rare disorder and no standard treatment is available. In the sub-group of HER2 positive disease, weekly paclitaxel–trastuzumab appears to be active and safe, and may be considered a therapeutic option in these patients.

Aim: Discordance between primary tumor and paired metastases biology has been widely detected in metastatic breast cancer. The aim of this study was to evaluate the prognostic impact of Ki67, estrogen receptor (ER), progesterone receptor (PR) and HER2 discordance. Methods: We retrospectively analyzed a cohort of 544 patients affected by metastatic breast cancer. Variation in ER, PR, Ki67 and HER2 expression between primary site and recurrence was tested through the McNemar test. Results: A significant variation was observed in respect to ER, PR and Ki67 status (12.65%, p = 0.0072; 49.71%, p

Background: Over the last few years, the introduction of newer systemic therapies (e.g. CDKi) significantly changed the treatment paradigm of patients (pts) with MBC. The purpose of this work is to evaluate the impact of CDKi introduction in clinical practice in terms of medical oncology workload. Methods: We examined a consecutive series of 492 pts who received therapy for MBC in Academic Hospital of Udine during two historical cohorts A (2016-2017) and B (2018-2019), respectively before and after the first CDKi approval in Italy. Data about 2020 were not collected due to confounding effect of SARS-CoV-2 pandemic. Pts with no luminal MBC or enrolled in clinical trial were excluded. We performed descriptive analyses to examine any differences in terms of number and type of outpatient visits to the oncology department (i.e. planned visits, unplanned presentations and i.v. treatment sessions) between the two cohorts. Results: We analyzed a total number of 2,645 oncology activities deriving from 42 pts (cohort A) and 57 pts (cohort B) who started first line treatment for luminal MBC. Median age was 66 and 70 years respectively. In the first group, pts receiving chemotherapy were 23.8% and those treated with CDKi were 7,14%. In the second group, chemotherapy was administered in 22.8% of pts and CDKi in 49.12%. In cohort A, number of planned visits, unplanned presentations and i.v. treatment sessions were respectively 643, 82 and 418. In cohort B, number of planned visits, unplanned presentations and treatment sessions were 892, 114 and 496. During the period of observation (two years), for each pts mean number of planned visits were 15,30 (cohort A) vs 15,64 (cohort B), mean number of unplanned presentations were 1,95 (cohort A) vs 2 (cohort B), treatment i.v. sessions were 9,9 (cohort A) vs 8,7 (cohort B). Conclusions: With the limits of a retrospective analysis, no differences were found between two cohorts of pts. Notably, there was a slight decrease of i.v. treatment sessions after CDKi introduction. Other analysis are ongoing to evaluate the workload in terms of instrumental and blood chemistry tests. This data further support the handy use of this drugs into clinical practice. Legal entity responsible for the study: Azienda Sanitaria Universitaria Friuli Centrale (ASUFC) Funding: Has not received any funding. Disclosure: M. Mansutti: Financial Interests, Institutional, Advisory Board: AstraZeneca;Financial Interests, Institutional, Advisory Board, invited speaker: Novartis;Financial Interests, Institutional, Advisory Board, invited speaker: Eli Lilly;Financial Interests, Institutional, Advisory Board, invited speaker: Pfizer;Financial Interests, Institutional, Advisory Board: MSD Italia;Financial Interests, Institutional, Advisory Board, invited speaker: EISAI;Financial Interests, Institutional, Advisory Board: Pierre Fabre;Financial Interests, Institutional, Advisory Board: Roche;Financial Interests, Institutional, Advisory Board: Celgene. All other authors have declared no conflicts of interest.

Aim: A monitoring strategy for metastatic breast cancer patients (M-MBC) has been little studied. Materials & methods: This retrospective study analyzed a consecutive cohort of 382 MBC patients to analyze different M-MBC strategies to identify factors influencing intensive M-MBC. Results: Elevated baseline serum tumor markers (STM) was the strongest factor associated with increased use of STM tests. Having more frequent oncology office visits was associated with more intensive chemotherapy/magnetic resonance imaging (MRI) using. Increased use of imaging tests was associated with participation to clinical trial. Single and elderly patients were less likely to have frequent testing. Having clinically measurable disease was less likely to have more intensive M-MBC. Conclusion: STM testing and scans were frequently ordered in M-MBC. In the present study, strategies are little influenced by clinico-pathological characteristics.

Introduction/Background Patients (pts) with ovarian cancer experiencing a platinum-sensitive (PS) recurrence are generally re-exposed to platinum agents (PCT). The addition of bevacizumab (BEV) or PARP inhibitors (PARPi) as concomitant and/or maintenance therapy has shown to improve progression free survival (PFS). In the absence of direct comparisons coming from randomized trials (RCTs), we have performed a network meta-analysis to evaluate differences in terms of efficacy between BEV and PARPi in pts with PS recurrent ovarian cancer (rOC), according to BRCA status. Methodology We searched PubMed, Embase and Medline for RCTs involving pts with PS rOC treated with BEV (n=3, 1563 pts) or PARPi (n=5, 1839 pts). Only trials with PFS as primary endpoint were included. Analyses have been done pooling pts who had received PARPi in three groups, according to the available data on BRCA genes status: all comers (AC), BRCA mutated pts (BRCAm) and BRCA wild-type pts (BRCAwt). A frequentist approach has been used with R statistical software. To rank the effect size of treatments, surface under the cumulative ranking value (SUCRA) has been applied. Results In AC pts, PARPi improved PFS compared to BEV (hazard ratio [HR]=0.70, 95% CI 0.54–0.91). In BRCAm pts the gain in PFS for PARPi was even higher compared to BEV (HR=0.46, 95% CI 0.36–0.59). In BRCAwt pts the benefit of PARPi over BEV was not statistically significant (HR=0.87, 95% CI 0.63–1.20) but PARPi had the highest likelihood of being ranked as the best treatment in terms of efficacy according to SUCRA (90% and 60%, respectively for PARPi and BEV). Conclusion According to indirect comparisons, PARPi performed the best for the treatment of PS rOC, especially in BRCAm pts who had not previously received PARPi. BEV could be still an option in BRCAwt pts. Disclosure Fabio Puglisi: Roche, AstraZeneca (honoraria and research founding). No conflict of interest is to be declared for the remaining authors. The authors receive no financial support for this study.

Background Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8mg/kg loading dose, then 6mg/kg every 3weeks (q3w)] and pertuzumab (840mg loading dose, then 420mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54years; 29% had received prior trastuzumab. Median treatment duration was 16months for pertuzumab and trastuzumab and 4months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9–22.7] months overall (19.6, 23.0 and 18.1months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%–82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. ClinicalTrials.gov NCT01572038.

Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of poor prognosis inunselected breast cancer patients with NLR >3.3. Moreover, pre-treatment NLR has been associated with disease-free and overal survival (OS) in patients with early triple-negative breast cancer (TNBC). We aimed to determine whether the NLR is predictive of progression-free survival (PFS) in metastatic TNBC. Methods: We reviewed the records of 48 TNBC patients who received at least one administration of first-line (1°L) chemotherapy for advanced disease from October 2004 to April 2014. The NLR (absolute neutrophil count/absolute lymphocyte count) was calculated from the full blood count routinely performed immediately before the initiation of first-line treatment. The association between categorical variables was calculated by X2 test. PFS (from start of 1°L treatment to disease progression or death) and OS (from start of 1°L treatment to death) were estimated using Kaplan Meier method. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR (co-variables stage at diagnosis, histology, and tumor grade). Results: NLR was not associated with stage at diagnosis (p=0.214), histology (p=0.597), or tumor grade (p=0.775). After a median follow-up of 10.9 months (range 1.3-54.9), 88.6% of TNBC patients with NLR≤3.3 versus 0.0% of patients with NLR>3.3 had a 1°L PFS>3 months (p3.3 had an OS>10 months (p=0.047). Metastatic TNBC patients with NLR≤3.3 had a longer median 1°L PFS (5.2 months) and median OS (13.5 months) compared with patients with NLR>3.3 (1°L PFS 2.1 months, p3.3 is associated with a shorter PFS (hazard ratio [HR] 22.4; 95% confidence interval [CI] 6.7-75.1, p Conclusion: Our study showed that pre-treatment NLR is associated with 1°L PFS and OS in patients with metastatic TNBC. However, further investigation in larger series of metastatic TNBC is warranted. Citation Format: Fontanella C, Fanotto V, Gerratana L, Bonotto M, Cinausero M, Bozza C, Iacono D, Russo S, Andreetta C, Minisini AM, Moroso S, Mansutti M, Fasola G, Puglisi F. Usefulness of the pre-treatment neutrophil-to-lymphocyte ratio in predicting first-line progression free-survival in triple-negative breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-06.

Background: The recent COVID-19 outbreak in Italy required timely adoption of efficient triage procedures (TPs) with the aim to minimize the risk of infection spreading in the hospitals We developed a written questionnaire (items explored: fever, respiratory symptoms, previous contacts or personal positivity for COVID-19) together with body temperature (BT) measurement, to intercept patients (pts) with suspect of COVID-19 infection Methods: We conducted a monocentric observational study of a consecutive series of outpatients with diagnosis of solid tumor, accessing the Day Unit of Oncology Department at Udine Academic Cancer Center (Northern Italy) from 30 March 2020 to 30 April 2020 In this abstract we present the preliminary results of the TPs performed until 10 April 2020 Results: 1054 TPs were performed out of 586 pts, with a median of 2 TPs per pt Median age was 64 9 years, males were 35 4% Overall, 82 5% of TPs were made because of access for therapy, 10 7% for programmed procedures, radiological exams or non-oncological consultations, 1 2% for unplanned presentation (e g urgencies) The stage of neoplasm was early in 30 7% and advanced in 69 3% of pts TPs were made in pts receiving chemotherapy (58 2%), immunotherapy (10 8%), targeted therapy (18 9%), other therapies (5 2%) and in pts without active oncological therapy (6 9%) The questionnaires resulted positive in 5 5% of cases;2 9% were positive for fever, 2 9% for respiratory symptoms, 0 1% for previous contact with a case of COVID-19 Concomitant presence of 2 or more items was observed in 0 5% of questionnaires Of note, 6 TPs required medical evaluation despite a negative questionnaire and were considered to be clinically suspect BT≥37°C was observed in 7 TPs Overall, the oncologic program was postponed in 0 9% of the TPs, while in 0 5% a test for SARS-CoV-2 was performed for clinical suspect: no one resulted positive At multivariate analysis, factors associated with positive triage were diagnosis of thoracic cancer (OR 2 06;95%CI 1 02-4 12;p=0 04) and prior test for SARS-CoV-2 (OR 2 81;95%CI 1 46-5 41;p=0 001) Conclusions: A well-structured triage for COVID-19 could reduce the risk for further spreading of infection in Oncology facilities with limited impact on scheduled activities Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: F Puglisi: Honoraria (self): MSD;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Eli Lilly;Honoraria (self): Takeda;Pfizer;Advisory/Consultancy: Amgen;Novartis;Pierre Fabre;Research grant/Funding (self): Astrazeneca;Eisai;Travel/Accommodation/Expenses: Celgene;Servier C Andreetta: Advisory/Consultancy: AstraZeneca;GlaxoSmithKline;MSD A M Minisini: Advisory/Consultancy: Novartis;MSD;Pierre Fabre G Fasola: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb srl;Eli Lilly SpA ;Servier Italia SpA ;Speaker Bureau/Expert testimony: Astrazeneca;Travel/Accommodation/Expenses: Merck Sharp and Dohme S p A ;Boehringer-Ingelheim S p A All other authors have declared no conflicts of interest

e14148 Background: The increasing prevalence of cancer patients due to new effective treatments is leading to a growing demand in oncology activities, thus requiring a re-modelling towards more sustainable systems. The aim of this study is to estimate the workload generated by each new cancer patient referred to the Oncology Department of the Academic Cancer Center of Udine, Italy, within the two years from first consultation. Methods: We have utilised our electronic “Data Warehouse” accountability system to retrieve anonymous aggregate data of the 2-year oncology workload generated by each new diagnosis, leading to an initial consultation, occurring between 01.01.2012 and 31.12.2017. Initial consultations with no clinical episode in the following 12 months were excluded. Mean value per patient and standard deviations were calculated for the following clinical activities: treatment sessions, unplanned presentations, hospitalisations, re-assessments, follow-up visits and inpatient oncology advices. The total number of patients treated and of episodes were recorded. Follow-up data was collected up to 31.12.2019. Results: During the observation period, 7,454 newly diagnosed patients were referred to our Oncology Unit, resulting in a total of 92,830 clinical activities occurring over an 8-year period. In 1,788 pts (24.0%) only follow-up was needed; 3,152 pts (42.3%) were referred for adjuvant treatment and 2,514 (33.7%) for advanced disease management. Overall, the mean number of clinical activities per patient within the first 2 years was: 6.04 pre-treatment evaluations (52.9%; SD 8.81; 45,003 total episodes), 2.00 follow-up visits (17.5%; SD 1.89; 14,922 total episodes), 0.42 hospitalisations (3.7%; SD 1.21; 3,141 total episodes), 0.36 inpatient oncology advices (3.2%; SD 0.83; 2,705 total episodes), 1.57 re-assessments (13.8%; SD 2.28; 11,723 total episodes) and 1.02 unplanned presentations (8.9%; SD 2.17; 7,601 total episodes). Subgroup analysis in the different tumors and settings are ongoing. Conclusions: The landscape of cancer care is changing due to the growing prevalence of cancer patients that experience longer overall survival. Trying to estimate the amount of clinical activities generated by any new diagnosis is crucial for implementing new models of oncology management and for programming an adequate workforce supply.

Background Cancer multidisciplinary team meetings (MDMs) are commonly acknowledged as a good clinical practice. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early breast cancer (EBC). In this setting, the purpose of the study was to define whether there was agreement between the planned program (i.e. MDMs-based decision) and that actually applied (i.e. actual therapeutic choice, ATC). In addition, the study explored factors associated with discordance. Methods We conducted a monocentric retrospective study of a consecutive series of 291 pts with new diagnosis of EBC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. Results Median age was 62 years (range 27-88 years). Among invasive EBC patients, the most frequent phenotype was luminal-A (38%), followed by luminal-B (33%), HER2-positive (12%) and triple negative (5%). Thirty-four pts (12%) had diagnosis of in situ carcinoma (DCIS). Median time from MDMs discussion to first oncological examination was two weeks. Rate of discordance between MDMs-based decision and final choice, during face to face consultation with the oncologist, was 15.8% (46/291). Among cases with discordance, 19 pts (41.3%) had age > 70 years; 8 pts (17%) had a diagnosis of DCIS, 13 pts (28%) luminal-B carcinoma, 12 pts (26%) luminal-A, 9 pts (20%) HER2-positive and 4 pts (9%) triple negative EBC. The most frequent reason for changing the MDMs-based program was clinical decision by the oncologist at the first evaluation (87%). Follow-up was preferred to the chemotherapy proposed within the MDMs by 15% of pts, and to the endocrine therapy in 39% cases (among these, 44.5% had diagnosis of DCIS). In our study 16/46 pts (35%) had a therapeutic change from chemotherapy to endocrine therapy: among these pts, 7/16 had a luminal-B and 6/16 had a HER2-positive disease. Further analysis aiming at evaluating variables which could predict discordance between MDMs proposal and face to face oncological consultation are ongoing. Conclusions The results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

e13079Background: Elevated ALP and LDH levels have been associated with worse prognosis in several malignancies; however, their role in MBC remains unclear. We aim to explore the prognostic impact ...

e24014Background: The role of serum tumor markers (TM), such as Ca15-3 and CEA, in early intercepting breast cancer (BC) recurrences is still debated. Due to lack of sensitivity and specificity, TM...

Background Preclinical data have indicated a synergistic interaction between docetaxel and capecitabine by means of taxane-induced up-regulation of thymidine phosphorylase (TP). On the basis of such premises, we conducted a phase II trial to determine the activity and tolerability of weekly docetaxel plus capecitabine in patients with metastatic breast cancer (MBC). Furthermore, we explored the relationship between TP tumor expression and benefit from this regimen. Patients and methods Patients received docetaxel 36 mg/m2 i.v. on days 1, 8, and 15 and capecitabine orally 625 mg/m2 b.i.d. from days 8 to 21. Cycles were repeated every 4 weeks. In the correlative study, we evaluated the TP expression by immunohistochemistry and the TP messenger RNA expression by real-time RT–PCR in the primary tumor. Results Forty-seven women were enrolled. In the intention-to-treat analysis, objective responses were achieved in 24 patients (51%). Fourteen additional patients (30%) had stable disease. The median time to progression (TTP) was 6 months (range 1–44 months). Median survival was 17 months (range 1–48 months). Overall, the treatment was well tolerated. The most common clinical adverse events (all grades) were alopecia (55%), nail changes (53%), fatigue/asthenia (51%), nausea/vomiting (51%), neutropenia (49%), and neuropathy (49%). A significantly higher TTP was observed in patients with TP-positive tumors (log-rank test, P = 0.009). Interestingly, a subgroup analysis confirmed this TTP benefit in patients with TP-positive tumors obtaining a tumor response (log-rank test, P = 0.03), whereas the statistical significance was lost in nonresponders (log-rank test, P = 0.3). Conclusions This study indicates that a regimen with low doses of capecitabine plus weekly docetaxel is active against MBC. The correlative analysis provides preliminary evidence that TP expression may be a predictive marker for therapeutic benefit.

99mTechnetium-labeled methylene diphosphonate bone scan (BS) is the most commonly used imaging test to screen for skeletal metastases in patients with breast cancer. Since its introduction into cli

The results of ~ 3700 preclinical and clinical studies were presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO) held 2 – 6 June 2006, in Atlanta, Georgia. The annual ASCO meeting is the largest forum in which oncology professionals from around the world report the latest advances in cancer research, encompassing a wide spectrum of subjects on molecular biology, prevention, diagnosis and therapy of tumours. The present report summarises some of the more important results of the studies presented at the meeting. In particular, the authors focused on findings from randomised Phase III trials that, in their opinion, are most likely to have an immediate effect on clinical practice. The top advances were grouped into four major themes (breast cancer, colorectal cancer, non-small cell lung cancer and selected presentations from the plenary session). In addition, selected Phase I and II studies on promising novel therapeutic agents were briefly described. Finally, a ‘question ...

e21632 Background: It is estimated that about half of cancer patients (pts) use at least one form of (CAM) Complementary and Alternative Medicine in their life but there is a strong reticence of pts in talking about CAM with their oncologist. Aim of this study is to inform pts about CAM. Methods:From April to December 2016, the observational pilot trial “CAMEO-PRO” prospectively enrolled 200 cancer pts that were invited to attend a tutorial about CAM at the Department of Oncology, University Hospital of Udine (Italy). Before and after the seminar, pts were asked to fill a questionnaire reporting their knowledge and opinion about CAM . Results:Median age was 61 years, 141 (72%) women and 53 (28%) men. At study entry, 139 (72%) pts declared they have never been interested in this topic before; 22 pts (12%) revealed the use of a type of alternative therapy and 53 (31%) revealed the use of complementary therapy. Overall, 111 (55.5%) pts participated to the tutorial. Table 1 shows the percentage of response and the opinion’s change about CAM before and after the tutorial. Conclusions:Informative seminars seem to have an impact on patients’ perceptions and opinions about CAM. [Table: see text]

e12010 Background: The use of adjuvant chemotherapy (CT) in small luminal-like breast cancer (BC) is still heavily debated. International guidelines identify endocrine therapy as the backbone of adjuvant treatment for these patients (pts), while the addition of CT should be limited to high risk cases. The aim of this study was to evaluate the association between patient- or disease-related factors with the prescription of adjuvant CT. Methods: This retrospective study reviewed data from 559 consecutive pts with pT1 ( < 2 cm) luminal-like BC treated between 2004 and 2015 at the Department of Oncology of Udine (Italy). No restrictions were applied regarding lymph node status. The cut-off point of 1% was used to define ER and/or PgR positivity. Factors influencing the prescription of CT were investigated through uni- and multivariate logistic regression with odds ratio (OR) calculation. Prognosis was explored through Cox regression. Results: About thirty percent (173/559) of pts received adjuvant CT. By multivariate analysis, lymph node involvement was highly associated with CT prescription (OR 16.94, 95% CI 7.86-36.50, P < 0.001 for pN1; OR 3.92, 95% CI 1.45-10.58, P = 0.007 for pNmi). Tumor size drove towards the use of CT among pts with pT1c tumors (OR 12.87, 95% CI 1.49-110.88, P = 0.020) but not in pts with pT1b BC (OR 2.38, 95% CI 0.26-21.38, P = 0.437). In addition, a higher CT use was observed in pts with luminal B-like disease (OR 3.79, 95% CI 2.16-6.65, P < 0.001) or in presence of a Ki67 > 14% (OR 1.05, 95% CI 1.03-1.07, P < 0.001). On the contrary, pts with age > 60 years had a very low chance of receiving adjuvant CT (OR 0.09, 95% CI 0.04-0.20, P < 0.001). Notably, the use of CT was not associated with Disease Free Survival or Overall Survival (HR 1.3, 95% CI 0.77-2.17, P = 0.320; HR 1.05, 95% CI 0.56-2, P = 0.866; respectively). Conclusions: Nodal status, tumor size, disease sub-type, Ki67 expression and age are determinants of adjuvant CT prescription in pts with small luminal-like BC. Prospective studies are needed to identify which pts could safely avoid CT without influencing prognosis.

No gold standard treatment exists for metastatic breast cancer (MBC). Clinical decision making is based on knowledge of prognostic and predictive factors that are extrapolated from clinical trials and, sometimes, are not reliably transferable to a real-world scenario. Moreover, misalignment between endpoints used in drug development and measures of outcome in clinical practice has been noted. The roles of overall survival (OS) and progression-free survival (PFS) as primary endpoints in the context of clinical trials are the subjects of lively debate. Information about these parameters in routine clinical practice is potentially useful to design new studies and/or to interpret the results of clinical research. This study analyzed the impact of patient and tumor characteristics on the major measures of outcome across different lines of treatment in a cohort of 472 patients treated for MBC. OS, PFS, and postprogression survival (PPS) were analyzed. The study showed how biological and clinical characteristics may have different prognostic value across different lines of therapy for MBC. After first-line treatment, the median PPS of luminal A, luminal B, and human epidermal growth factor receptor 2 (HER2)-positive groups was longer than 12 months. The choice of OS as a primary endpoint for clinical trials could not be appropriate with these subtypes. In contrast, OS could be an appropriate endpoint when PPS is expected to be low (e.g., triple-negative subtype after the first line; other subtypes after the third line). The potential implications of these findings are clinical and methodological.

The aim of the present study is to evaluate the clinical and biological factors (including markers of angiogenesis) as potential predictors of prognosis and benefit from metronomic therapy in patients with advanced breast cancer (ABC). Recent data suggest antiangiogenic activity of metronomic therapy. The study population included 62 patients with pretreated ABC who received cyclophosphamide and methotrexate orally. Tumour samples were analysed by immunohistochemistry for HER2, Ki-67, thymidine phosphorylase (TP), vascular endothelial growth factor and vascular endothelial growth factor receptor. The results from immunohistochemical analysis and clinico-pathological variables were studied to test their potential association with benefit from metronomic therapy. The median overall survival, progression-free survival and survival postprogression were 7.1 (range 0.2-38.3), 2.6 (range 0.2-28.9) and 3 (range 0-34.2) months, respectively. Among the clinical variables, age, performance status and previous therapy with taxanes were significantly associated with outcomes. Among the molecular markers, TP was found to be associated with progression-free survival. Metronomic therapy is an effective choice for ABC. Young women with a more indolent disease had the greatest benefit from this treatment. TP tumour expression might aid decision making but these findings must be confirmed in larger prospective, properly designed studies.

Breast cancer (BC) is one of the most important causes of morbidity and mortality representing the first tumor in the female sex in terms of incidence and the third in terms of mortality in the western world. An increased survival is evident in metastatic breast cancer (MBC) as a result of the introduction of novel therapeutic agents. Oncologists have several options available (chemotherapy, hormone-therapy and biologic agents such as anti-angiogenic and anti-HER2 drugs) and the challenge nowadays is the individualization of the therapy (tailored approach). Despite better diagnostic tools and new therapeutic agents, at the present the main treatment goal in MBC is still palliation. Into the attempt to better tailor treatments, the search for predictive factors deserves a huge effort. This review faces the different approaches in terms of first-line chemotherapy for MBC together with the biological therapies recently approved for the treatment of this tumor.

Chemotherapy-induced amenorrhea occurs in about 20-70% of premenopausal breast cancer patients. Chemotherapy-induced amenorrhea can affect choice of hormonal therapy, fertility, and quality of life of breast cancer survivors. We retrospectively analyzed the incidence of amenorrhea after adjuvant chemotherapy and the subsequent recovery of the menses in 145 breast cancer patients. Age, smoking, alcohol consumption, body mass index, chemotherapy regimen, previous hormonal therapies, and previous childbearing were analyzed as potential predictive factors of ovarian function recovery. Median age was 42 years at the beginning of adjuvant chemotherapy with 30.3% of patients below 40 years of age. The majority (87.6%) of patients received anthracycline-based chemotherapy, 35.2% of patients received a cyclophosphamide-methotrexate-5-fluorouracil regimen and 42.8% received a taxane. The incidence of chemotherapy-induced amenorrhea was 80, and 35.3% of these patients resumed menses after a median of 8 months. In multivariate analysis, younger age (

Breast cancer incidence is increasing among elderly patients. Age is a risk factor for toxicity after chemotherapy for breast cancer. In particular, anthracycline-induced cardiac toxicity is increased in elderly patients. Novel liposomal anthracyclines are associated with less cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is active in breast cancer patients and, has shown comparable efficacy to conventional doxorubicin in clinical trials. Most toxicities during PLD treatment are hematological and mucocutaneous (in particular stomatitis and palmo-plantar erythrodysesthesia), and cardiac toxicity is rare. Tolerability of this agent in elderly patients has been confirmed by clinical trials in the advanced disease. Due to its efficacy and safety profile, PLD is an appealing treatment option for elderly breast cancer patients.

Background and aim Capecitabine is an orally bioavailable prodrug that is converted to 5-fluorouracil through several enzymatic steps, the last of which is mediated by thymidine phosphorylase (TP). TP has been reported to be expressed at higher levels in cancer tissue compared with normal counterpart. The present study aimed at evaluating the potential relationship between TP expression and benefit from capecitabine in patients with metastatic breast cancer (BC). Methods Immunohistochemistry for TP and other biological markers was carried out on paraffin-embedded cancer tissues of 61 patients with BC treated with at least three cycles of capecitabine as single agent for metastatic disease. All patients had received capecitabine 1000 mg/m2 b.i.d. days 1–14 every 21 days. The following variables were analyzed as potential determinants of benefit from capecitabine: TP expression, estrogen receptor (ER) and progesterone receptor status, human epidermal growth factor receptor-2 (HER-2) status, MIB-1 expression, performance status at the beginning of capecitabine treatment, stage at diagnosis, grade, presence of visceral metastases at the beginning of capecitabine treatment, and previous chemotherapy. Results Overall, median time to progression (TTP) was 6.5 months (range 1.4–33). On multivariate analysis, ER status [hazard ratio (HR) for progression = 0.31; 95% confidence interval (CI) = 0.15–0.64; P = 0.002], presence of visceral metastases at the beginning of capecitabine treatment (HR = 2.30; 95% CI = 1.21–4.39; P = 0.01), and capecitabine as first- or second-line treatment (HR = 2.28; 95% CI = 1.21–4.32; P = 0.01) independently predicted TTP. TP was highly expressed in 34 of 61 cases (55.7%). In the subgroup of patients with TP-expressing tumor, TTP was significantly longer in patients who received anthracyclines and taxanes before capecitabine (median TTP 7.5 versus 3.3 months, P = 0.01, log-rank test). Similarly, patients with a TP-positive tumor showed a longer TTP if they received taxanes before capecitabine than patients with TP-positive tumor who did not receive this treatment (7.3 versus 3.4 months, P = 0.03). Conclusions These data provide further evidence that TP expression in BC could represent a biomarker of sensitivity to capecitabine treatment. Prospective studies with translational approach are desirable to confirm the predictive and prognostic role of TP.

To evaluate the in vivo effect of adding gefitinib to preoperative chemotherapy on the EGFR-dependent p42/44 MAPK in operable breast cancer (BC) patients. Secondary aims: to evaluate EGFR, (p)-EGFR, Ki67, apoptotic index (TUNEL test) and VEGFR2 expression from baseline to surgery, percentage of pathologic complete response (pCR), and toxicity. 90 patients with stage II-IIIA BC have been randomized to receive epirubicin 90 mg/sqm and paclitaxel 175 mg/sqm on day 1 plus: gefitinib 250 mg daily from day 5 to 16 (Arm A, intermittent), gefitinib 250 mg daily from day 1 to 21 (Arm B, continuous), or placebo (Arm C). Treatment plan: 4 courses every 3 weeks, followed by surgery. After preoperative therapy, 86/90 patients underwent surgery; 46 patients (51%) received breast conservative surgery. A pCR was observed in 4 patients. No significant differences in the expression of p42/44 MAPK, EGFR, (p)-EGFR, VEGFR2, proliferation index and apoptosis were observed comparing the combined Arms A + B vs C, and comparing Arm A vs B. Hematologic toxicities were not significantly different comparing Arms A + B vs Arm C, and comparing Arm A vs B. Significantly higher skin and mucosal toxicities were observed when comparing the two gefitinib Arms (A + B) vs Arm C (32% vs 9.6%, P = 0.018; 57% vs 29%, P = 0.009 respectively), while no significant differences were observed comparing Arm A vs B. Adding gefitinib to chemotherapy did not result in different effects on the EGFR-dependent pathway, proliferation, apoptosis and VEGFR2 expression as compared to placebo, while enhancing skin and mucosal toxicity. The two schedules of gefitinib (intermittent vs continuous) did not result in different biologic effects.

Anticancer drugs may cause neurological toxicity involving the central nervous system. Patients receiving anticancer treatment may develop encephalopathy, extrapyramidal reactions, seizures, cerebellar dysfunction, retinopathy, cerebral venous thrombosis, myelopathy, cognitive impairment, and psychiatric symptoms. Physician should carefully evaluate neurological signs and symptoms in order to recognize these drug-related adverse reactions. In this review we aimed at presenting different neurological complications of anticancer drugs and their management. PUBMED search was performed in order to retrieve all articles and case reports dealing with central nervous system toxicity related to anticancer treatments.

Breast cancer is the most common cancer among women and about 80% of breast cancers express hormone receptors. Tamoxifen has been the most important form of adjuvant endocrine therapy over the last 25 years. The third generation aromatase inhibitors (AIs) are a new class of drugs challenging the central role of tamoxifen as adjuvant endocrine treatment in postmenopausal women with hormone receptor-positive breast cancer. Their effectiveness has been demonstrated in first line therapy as well in neoadjuvant setting with a statistically significant superiority over tamoxifen. Here we considered the role of adjuvant AIs in early stage breast cancer with an analysis reviewing the main adjuvant trials. We considered efficacy, side effects, optimal timing, duration of the therapy and whether specific subgroups may achieve particular benefit. In conclusion the upfront use of adjuvant anastrozole or letrozole is superior to tamoxifen with a good relative toxicity profile. Tamoxifen will continue to have a role where recurrence risk is low or if AI is poorly tolerated. Issues including the timing of administration (up-front or sequential), the duration of the therapy and the role of biomarkers such as PgR and HER2 in optimal selection remain unresolved.

Background Bone scanning (BS), liver ultrasonography (LUS) and chest radiography (CXR) are commonly used in patients with newly diagnosed breast cancer as part of baseline staging. However, in the absence of symptomatic disease, the usefulness of this routine diagnostic work-up is not evidence-based. Methods We selected the study sample from 516 consecutive patients with newly diagnosed invasive breast cancer. For each diagnostic test (BS, LUS, CXR), we analyzed the prevalence defined as the number of patients with diagnosis of metastatic disease after an imaging technique divided by the total number of patients tested. In addition, sensitivity and specificity were calculated. Initial suspicion was confirmed by other independent tests (bone X-ray, computerized tomography scan, magnetic resonance imaging) in order to identify ‘true’ positive diagnoses. Results At baseline, BS was carried out in 412 patients, LUS in 412 patients and CXR in 428 patients. Thirty-three patients were correctly diagnosed by the initial staging investigations as having metastatic disease (true positive cases). BS detected skeletal metastases in 6.31% of patients, LUS detected liver metastases in 0.72% of patients and CXR detected lung metastases in 0.93% of patients. Before imaging tests, all patients with either LUS or CXR evidence of metastases were previously classified as having stage III disease. On the other hand, only 26.9% of bone metastases were detected in patients with stage III. Accordingly, the detection rate in stage III patients was 14%, 5.6% and 7.2%, respectively for BS, LUS and CXR. Conclusions These findings indicate that a complete diagnostic work-up to detect metastases is unnecessary in the majority of patients with newly diagnosed breast cancer, whereas it may be indicated for specific patient categories such as those with stage III disease.

e12532 Background: Few studies have described patterns of metastatic spread according to the major breast cancer biologic subtypes (BS). The aim of this study was to determine the association of BS...

e11565 Background: Despite the availability of several therapeutic options for MBC, palliative treatments beyond 1st line lack of predictive factors that could help clinical decision making. We aimed to determine which is the impact of benefit at 1stline into the benefit from subsequent therapeutic lines. Methods: We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) at the Department of Oncology of Udine, Italy, between 2004 and 2012. We evaluated Progression Free Survival at 1st (PFS1), 2nd (PFS2), 3rd (PFS3) and 4th (PFS4) line of treatment. Three distinct analyses were conducted: the first for the lines of CT, the second for the lines of ET and the third by considering both CT and ET as a line of treatment. A PFS longer than 6 months was defined as “6-month benefit". Results: Median Overall Survival was 34.5 mo (25th – 75th percentile: 14.5 – 58.8), median overall PFS1 and PFS2 was 8.9 mo and 4.3 mo respectively. Median PFS1 and PFS2 in CT lines only was 7 mo and 3.7 mo, respectively. Median PFS1 and PFS2 in ET lines only was 9.4 mo and 4.6 mo respectively. Overall, 289 patients (63.5%) presented 6-month benefit at 1st line, 128 (40.5%) at 2nd, 76 (33.8%) at 3rd and 34 (23.3%) at 4th. Not having a 6-month benefit in overall PFS1 was associated with a lack of benefit both at 2nd line (OR=0.48; p=0.0026) and at any line beyond the 1st (OR=0.39; p< 0.0001). Taking into consideration CT lines only, not having a 6-month benefit in CT PFS1 was associated with a lack of benefit both at 2nd line (OR=0.45; p=0.0072) and at any line beyond the 1st (OR=0.43; p=0.0026). A lack of benefit at the 1st ET line was not associated with further ET outcome neither in 2nd line nor in any line beyond the 1st. Stratification according to immunophenotype highlighted a statistical significance only among HER2 positive tumors (OR=0.2; p=0.0152 in 2nd line and OR=0.14; p=0.0036 beyond 1st line). Conclusions: Our results suggest that the absence of a “6-month benefit” in PFS1 predicts a lack of benefit in subsequent therapy lines, especially in HER2 positive disease. However, a lack of benefit at first line ET appears not to be detrimental to further anti-hormonal lines.

1044 Background: Obesity represents a well-known risk factor for the development of breast cancer and an adverse prognostic factor in early disease. Overweight is associated with reduced efficacy of aromatase inhibitors in adjuvant setting. Few data have been reported about the potential relationship of overweight and outcome in advanced breast cancer (ABC). Methods: We retrospectively evaluated body mass index (BMI) in a consecutive series of 400 ABC patients treated at our institution. BMI was calculated at baseline of diagnosis of ABC. We evaluated association of BMI and other prognostic and predictive markers with Progression Free Survival (PFS) and Overall Survival (OS). We evaluated PFS at first and subsequent lines of chemotherapy (CT) and endocrine therapy (ET). Overweight patients were defined as having BMI > 25. Results: Overweight patients were 52%. Median age of the population was 58 years. Median OS was 33.7 months. Overall, 76% of patients presented with ER+ and 17.7% with HER2+ ABC.Overweight was associated with increased age at diagnosis, menopausal status and luminal B or triple negative immunophenotype. At multivariate analysis, BMI > 25 was associated with better PFS at first-line ET (HR= 0.68, 95% CI 0.46-0.99). BMI was not associated with OS. Conclusions: BMI at baseline does not seem to be an adverse prognostic factor for ABC patients. Overweight may be associated with better PFS in endocrine responsive ABC treated with ET, especially in first-line setting. The role of BMI in ABC deserves to be further investigated.

e13070 Background: Endocrine manipulation is the cornerstone of therapy in hormone receptor (HR)-positive breast cancer. However, a significant percentage of patients who receive endocrine therapy (ET) as metastatic treatment experience de novo or acquired resistance. New clinical trials for HR-positive MBC should be tailored around immunophenotypical and clinical features. This study evaluates different potential prognostic factors in patients treated with ET for MBC. Methods: We analyzed retrospectively data from a series of 280 consecutive patients with HR-positive MBC diagnosed from January 2004 to February 2011 at University Hospital of Udine, Italy. Multivariate analysis was performed to establish the independent value of different disease and patients’ characteristics in influencing progression-free survival (PFS), overall survival (OS) and survival post-progression (SPP). Results: Median OS was 38.44 months (mo), median PFS at first-line ET was 10.05 mo. Median SPP was 22.74 mo, 15.18 mo, and 15.47 mo after first, second and third-line ET, respectively. Age >70 years and ECOG performance status >1 were independent prognostic factors for both shorter OS (HR 2.55, p = 0.019; HR 2.46, p = 0.025, respectively) and shorter SPP (HR 2.99, p = 0.003; HR 2.82, p = 0.011, respectively). Number of chemotherapy lines before first ET was an independent prognostic factor for both PFS (HR 1.45, p < 0.001) and OS (HR 1.62, p = 0.001). MIB-1 >14% was associated with shorter PFS (HR 1.98, p = 0.012); this finding underlines the poor prognosis of luminal B subtype in comparison with luminal A disease. Conclusions: Determinants of treatment decision-making in MBC include patients’ characteristics, prognostic factors, disease biology, and mechanisms of resistance. This study confirms the worse prognosis of luminal B subtype, also in presence of endocrine manipulation. Innovative therapeutic approaches are eagerly waited in order to overcome resistance to ET. This study also provides some insights for the choice of optimal endpoints in trials that enroll patients with HR-positive MBC. In particular, based on long SPP values, OS does not seem to be an appropriate endpoint in studies involving such patients’ population.

e11531 Background: Anthracyclines are currently included in several chemotherapy (CT) regimens for the treatment of breast cancer (BC). However, increasing evidence suggests that benefit from these agents is limited to some subgroups of patients (pts). Aim of this study was to identify potential predictors of tumor shrinkage (TS) in a retrospective series of pts receiving preoperative anthracycline-based CT for operable BC. Methods: The study population consisted of 94 pts with large (>2 cm), any N, operable BC treated with preoperative anthracycline-based CT. Association between clinico-biological factors and clinico-radiological TS (by caliper and MRI) was assessed. TS was calculated as the difference between the maximum tumor diameter at baseline and the maximum tumor diameter after preoperative CT/ the maximum tumor diameter at baseline x 100. Immunohistochemical analyses for biological variables (ER, PgR, HER2, MIB1, topoisomerase II alpha) were performed on pretreatment biopsies. Results: In univariate analysis, the following variables were associated with clinical TS: high MIB-1 [Odd ratio (OR) 2.6, p = 0.03], type of taxane (docetaxel vs paclitaxel: OR 0.3, p = 0.01) and number of cycles of CT (> 4 vs ≤ 4: OR 9.2, p < 0.0001). In multivariate analysis, number of cycles of CT was the only independent predictor of clinical TS (OR = 9.2, p = 0.05). In univariate analysis, the following variables were associated with MRI TS: high MIB-1 (OR 2.4, p = 0.06), tumor size (≥ 40 mm vs < 40 mm: OR 5.6, p 0 0.01), taxane CT (yes vs no: OR 4.3, p = 0.02) and number of cycles of CT (> 4 vs ≤ 4: OR 4.4, p = 0.002). In multivariate analysis, high MIB-1 was the only independent predictor of MRI TS (OR = 3.7, p = 0.03). Conclusions: High MIB-1 expression and number of cycles of chemotherapy significantly predicted tumor shrinkage in patients treated with preoperative anthracycline-based chemotherapy. Further studies are warranted to better identify patients who derive benefit from anthracyclines. No significant financial relationships to disclose.

1068 Background: Capecitabine (C) is an orally bioavailable prodrug that is converted to 5-fluorouracil in several enzymatic steps, the last of which is mediated by thymidine phosphorylase (TP). TP is expressed at high levels in over 50% of breast cancer (BC) specimens and elevated levels of TP have been hypothesized to predict therapeutic effect of C. Our study aimed at evaluating the potential relationship between immunohistochemical TP expression and benefit from C in terms of time to progression (TTP) in patients (pts) with metastatic BC. Methods: We retrospectively reviewed biopsies of 61 pts with BC treated with at least 3 cycles of C as single agent for metastatic disease, performing immunohistochemistry for TP and other biological markers. All patients received C 1,000 mg/m2 bid days 1 to 14 every 21 days. TTP was defined as the time between the beginning of therapy with C and disease progression or last follow-up. The following variables were analyzed as potential determinants of benefit from C: ...

21090 Background: Mesenchyme-specific genes are highly expressed by various types of human cancers. Recent lines of evidence suggest that periostin, a myoepithelial/basal gene, may play a role in the biology of breast cancer. Periostin is involved in metastatic process by taking part in mechanisms of adhesion and migration of epithelial cells. Furthermore, periostin seems to have a role in tumor angiogenesis through the up-regulation of vascular endothelial growth factor receptors in endothelial cells. We aimed at investigating the immunohistochemical expression of periostin in breast cancer and its correlation with established biological and prognostic factors. Methods: We performed immunohistochemical analysis of periostin in a consecutive series of 206 tumor samples from 200 patients with early breast carcinoma. To this aim, we used a specific antiperiostin antibody (Biovendor Laboratory Medicine, Inc., Palackeho 56, 612 00 Brno, Czech Republic). The intensity of immunoreactivity was scored as 0, 1, 2 or 3 denoting negative, weak, moderate and strong staining, respectively. Therefore, for statistical analysis, the periostin expression level for each case was putatively defined as positive if the predominant intensity was =1. We also analyzed immunohistochemical expression of Ki-67 (MIB-1), HER-2/neu, VEGF, VEGFR-1 and VEGFR- 2. Results: Periostin was found to be highly expressed by carcinoma cells, whereas it was absent in normal breast tissues. The pattern of expression was mainly cytoplasmic, although in some cases (11%) a nuclear reactivity was observed. A cytoplasmic expression was found in 108 out of 189 (57%) evaluable cases. Interestingly, a significant correlation was found between periostin expression and VEGF and VEGFR-1 (Spearman's rank test rho =0.37, p No significant financial relationships to disclose.

655 Background: Thymidine phosphorilase (TP) is a key enzyme involved in nucleoside metabolism. Recently, it has been hypothesized that TP modulation could enhance the therapeutic activity of TP-targeting chemotherapy such as capecitabine. In addition, some evidence exists that anticancer agents could upregulate TP. The present study analyzed TP immunohistochemical expression in response to neoadjuvant chemotherapy for primary breast cancer. Methods: Fifty-five women with operable breast cancer (T ≥ 2 cm, N0–1, M0) were treated with anthracycline-based (all cases) and anthracycline/taxane-based (n= 40 cases) neoadjuvant chemotherapy. Tumor samples from diagnostic large core biopsy (n=55) and from surgery (n=53) were available for histological evaluation and immunohistochemical analysis of TP. Immunohistochemistry was performed at a single central laboratory using a primary mouse anti-TP monoclonal antibody (Roche molecular biochemicals).TP expression was evaluated on tumor cells (nuclear and cytoplasmic staining) and on stromal cells. The intensity of cytoplasmic immunoreactivity was scored as 0, 1, 2 or 3 denoting negative, weak, moderate and strong staining, respectively. Results: An increase in TP cytoplasmic expression was observed in 35.89% (95% CI: 0.21–0.52%) of tumor samples after neoadjuvant chemotherapy. In particular, increases in cytoplasmic TP score were more common after taxane-containing regimens (40.74%, 95% CI: 0.22–0.61%) than after regimens without taxanes (25%, 95% CI: 0.05–0.57%). No significant changes of TP expression were found in nuclei of tumor cells after neoadjuvant chemotherapy. Similarly, no significant changes of TP expression were observed in stromal cells. There was no significant association between clinical or pathological response rate and TP changes in both tumor and stromal cells. Conclusions: This study provides further evidence that, at least in breast cancer, TP is upregulated after anthracycline and/or taxane-containing chemotherapy. According to these results, a strong rationale exists in combining TP-inducing and TP-targeting anticancer agents. No significant financial relationships to disclose.

8543 Background: It has been reported that anticancer treatment may alterate cognitive functions in cancer patients but very few prospective studied addressed this issue. Moreover, little is known about the cognitive impact of anticancer treatment in elderly cancer patients. We aimed at investigating the effect on cognitive functions of antiblastic chemotherapy and endocrine therapy in a consecutive series of elderly cancer outpatients. Methods: We evaluated cognitive functions by means of the Cambridge Cognitive Examination (CAMCOG) test and the Mini-Mental Scale Examination (MMSE) at baseline (before anticancer systemic treatment), after 3 months and after 6 months in cancer patients aged more than 65 years. Mood disturbances such as anxiety and depression were also evaluated (Hospital Anxiety and Depression Scale); comprehensive geriatric assessment and blood tests were performed at each evaluation. Results: Sixty patients were enrolled, 15 patients received chemotherapy (group 1), 13 patients received endocrine therapy (group 2) and 32 patients had neither chemotherapy nor endocrine therapy (group 3, control). Fifty-eight (97%) patients had no evidence of disease at the time of assessment. Median age was 71.5, 73 and 71 years in group 1, 2 and 3, respectively. At baseline, median Activities of Daily Living (ADL) score, Instrumental Activity of Daily Living (IADL) score, number of comorbidities and concomitant medications were 6, 8, 5, 1 in group 1, and 6, 8, 3, 2 in group 2, and 6, 8, 4, 2 in group 3, respectively. Median hemoglobin value was 12.9, 12.8, 13.3 g/dl in group 1, 2 and 3 respectively. At baseline, no significant unbalance was evident among groups. There was a statistically significant correlation between ADL or IADL score and CAMCOG total score (Spearman test, rho=0.4, p.05); the separate analyses for the different items in CAMCOG test did not evidence any deterioration in time in the 3 groups. No worsening was seen in MMSE. Conclusions: Our study showed that anticancer treatment is not associated with rapid cognitive deterioration in elderly cancer patients. No significant financial relationships to disclose.

10538 Background: Imaging techniques used to evaluate response during neoadjuvant chemotherapy for breast cancer include mammography (Mx), sonography (US) and MRI. This study prospectively evaluated the ability of each technique to determine pathologic response in breast cancer patients undergoing neoadjuvant chemotherapy. Methods: Forty women with operable breast cancer (T ≥ 2 cm, N0–1, M0) were treated with four cycles of anthracycline-based and taxane-based neoadjuvant chemotherapy as part of a phase II clinical trial. The longest diameter of each tumor (n = 48 neoplastic foci) was measured by Mx, US and MRI at baseline, after two cycles and after 4 cycles of chemotherapy, before surgery. Tumor size at pathology was determined and considered as gold standard of response. Differences among techniques in measuring tumor diameters were evaluated by means of t-test. Results: At baseline, US provided statistically higher measures than Mx (mean difference: 6.3 mm, p < 0.0001) or MRI (mean difference: 5.6 mm, p < 0.0001). No difference was observed between Mx and MRI (mean difference: 0.59 mm, p = 0.5). After two cycles of chemotherapy, tumor diameter measured by US was significantly longer than that measured by Mx (mean difference: 8.8 mm, p < 0.0001) and significantly shorter than that measured by MRI (mean difference: −5.1 mm, p = 0.0009). Mx provided longer measures than MRI (mean difference: 4.4 mm, p = 0.0034). After four cycles of chemotherapy, US provided significantly shorter measures than Mx (mean difference: 11.8 mm, p < 0.0001) and MRI (mean difference: −3.3 mm, p = 0.007), whereas tumor size measured by Mx was significantly longer than that measured by MRI (mean difference: 6.75 mm, p = 0.0027). In addition, the tumor diameter measured by the pathologist was longer than that measured by US (mean difference: 2.6 mm, p = 0.09) and significantly shorter than that measured by Mx (mean difference: −7.8 mm, p < 0.0001). No statistically significant difference was observed between MRI and pathological measures (mean difference: −1.0, p = 0.5). Conclusions: This study provides further evidence that, among imaging techniques, MRI is the best method to evaluate the tumor size after neoadjuvant chemotherapy for breast cancer. No significant financial relationships to disclose.

9674 Background: The molecular components of Plasminogen Activator system, Urokinase-type Plasminogen Activator (uPA) and its inhibitor PAI-1, are involved in tumor progression and have prognostic ...

6065 Background: Bone scanning (BS), liver ultrasonography (LU) and chest X-ray (CXR) are commonly used in patients (pts) with newly diagnosed breast cancer as part of baseline staging. However, in absence of symptomatic disease, the usefulness of this routine metastatic workup is not evidence based. Methods: We selected the study sample from 557 patients with newly diagnosed breast cancer who were consecutively referred to our institution between February 1999 and August 2003. For each diagnostic test we analyzed the detection rate defined as the number of pts with abnormal test results indicative of metastases divided by the total number of pts tested. In addition, sensitivity and specificity were calculated (cases categorized as suspicion by the tests were computed as positive). Initial suspicion was confirmed by other independent tests (bone X-ray, CT scan, MRI) in order to identify “true” positive diagnoses. Results: At baseline, BS was performed in 412 pts, LU in 412 pts and CXR in 428 pts. After th...