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Background: Adding immunotherapy to first-line chemotherapy might improve outcomes for patients with advanced or recurrent endometrial cancer. We aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy. Methods: MITO END-3 is an open-label, randomised, controlled, phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy. Eligible patients were aged 18 years or older with histologically confirmed advanced (FIGO stage III–IV) or recurrent endometrial cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no previous systemic anticancer therapy as primary treatment for advanced or metastatic disease. Participants were randomly assigned (1:1) using a computerised minimisation procedure stratified by centre, histology, and stage at study entry, to either receive carboplatin (area under the curve [AUC] 5 mg/mL × min) and paclitaxel (175 mg/m2; standard group) intravenously every 3 weeks for six to eight cycles or avelumab (10 mg/kg intravenously) added to carboplatin and paclitaxel (experimental group) every 3 weeks and then every 2 weeks as a single maintenance treatment after the end of chemotherapy until disease progression or unacceptable toxicity. Patients, treating clinicians, and those assessing radiological examinations were not masked to study treatment. The primary endpoint was investigator-assessed progression-free survival, measured in the intention-to-treat (ITT) population. Patients who received at least one dose of study drug were included in the safety analysis. Experimental group superiority was tested with 80% power and one-tailed α 0·20. This trial is registered with ClinicalTrials.gov (NCT03503786) and EudraCT (2016–004403–31). Findings: From April 9, 2018, to May 13, 2021, 166 women were assessed for eligibility and 39 were excluded. 125 eligible patients were randomly assigned to receive carboplatin and paclitaxel (n=62) or avelumab plus carboplatin and paclitaxel (n=63) and included in the ITT population. The median follow-up was 23·3 months (IQR 13·2–29·6) and was similar between the two groups. 91 progression-free survival events were reported, with 49 events in 62 patients in the standard group and 42 events in 63 patients in the experimental group. The median progression-free survival was 9·9 months (95% CI 6·7–12·1) in the standard group and 9·6 months (7·2–17·7) in the experimental group (HR of progression or death 0·78 [60% CI 0·65–0·93]; one-tailed p=0·085). Serious adverse events were reported more frequently in the experimental group (24 vs seven events in the standard group); neutrophil count decrease was the most frequent grade 3–4 adverse event (19 [31%] of 61 patients in the experimental group vs 26 [43%] of 61 patients in the standard group). Two deaths occurred in the experimental group during treatment (one respiratory failure following severe myositis [possibly related to treatment] and one cardiac arrest [not related to treatment]). Interpretation: Adding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of mismatch repair status is warranted.

Survivin was previously associated with tumor stage and grade in ovarian cancer and interfered with the tumor's drug sensitivity. In addition, Survivin expression was found to be regulated by the Sonic hedgehog (Shh) pathway, Krüppel-like factor (KLF) family proteins, and p53 pathway. The main aim of this study was to assess the prognostic values of immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a cohort of high-grade ovarian serous cancers. Other aims were comparison between high- and low-grade ovarian serous cancer and between platinum-resistant and the other cases. The last aim was to assess the correlations among the immunohistochemical expression of the studied proteins. Retrospective cohort study to assess immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a tissue microarray of primary tumor samples among 73 women affected by high-grade ovarian serous cancer and 9 by low-grade ovarian serous cancer. Klf5 and Shh cytoplasmic staining were associated with short overall survival (HR 6.38, 95% CI 2.25-18.01, P .05 and 2.25, 95% CI 1.19-4.23, P .05, respectively). In addition, cytoplasmic Klf5 staining, high Klf11, and p53 nuclear staining were associated with platinum resistance (P .05). Cytoplasmic Shh score was significantly correlated to the immunohistochemical expression of Klf5, Klf11, Mdm2, and Survivin. Our data highlight the possible role of Klf5 and Shh as prognostic markers, meanwhile confirming the role of the KLF family proteins and p53 in ovarian cancer drug resistance. Moreover, Shh appeared to play an important role in the intracellular network of ovarian neoplasia.

Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisation’s recent 2020 classification of female genital cancers. The pathogenesis of MLA is unknown and it remains debated whether they represent mesonephric carcinomas (Wolffian) arising in the endometrium/ovary or endometrioid carcinomas (Müllerian) closely mimicking mesonephric carcinomas. Here we report the case of a 57-year-old woman with an initial misdiagnosis of endometrioid adenocarcinoma on diagnostic biopsy. The patient came to our clinical evaluation for the appearance of menometrorrhagia complicated by anemia for several months. Therefore, she underwent pelvic echo-flowmetry, with indication for diagnostic hysteroscopy with endometrial biopsy, which yielded a positive result for endometrioid endometrial adenocarcinoma. Following staging CT scan and targeted examinations on pulmonary findings, the patient underwent surgery with surprise of definitive diagnosis deponent for endometrial MLA. Our intention is to establish a brief review of the scientific evidence in the literature and the tools available for a correct histological diagnosis, in the light of the scant anatomopathological evidence. Our question gives rise to the motive for the publication: is immunohistochemistry the right way to resolve the diagnostic error at histology, which is usually the only source of diagnostic certainty? This case is intended to alert of diagnostic error that risked having the patient treated as a neoplasm with a favorable prognosis and low degree of aggressiveness instead of for a very aggressive and poor prognosis tumor such as MLA.

Hepatoid carcinoma of the ovary (HCO) is a tumor that resembles, both histologically and cytologically, hepatocarcinoma (HCC) in a patient with a non-cirrhotic liver not involved by the disease. Hepatoid carcinoma is an extremely rare histologic subtype of ovarian cancer and should be distinguished from metastatic HCC. Here, we report the rare case of a 67-year-old woman with ovarian recurrence of HCC 12 years after first diagnosis. The patient was being followed by oncologists because she had been diagnosed with HCV-related HCC (Edmonson and Stainer grade 2, pT2 N0 M0, G2, V1) in 2009. She had undergone surgery for enlarged left hepatectomy to the 4th hepatic segment with cholecystectomy and subsequent placement of a Kehr drain. The preoperative alpha-fetoprotein (AFP) level was 8600 ng/mL, while the postoperative value was only 2.7 ng/mL. At the first diagnosis, no other localizations of the disease, including the genital tract, were found. At the time of recurrence, however, the patient was completely asymptomatic: her liver function was within normal limits with negative blood indices, except for an increased blood dosage of AFP (467 ng/mL), and CA125, which became borderline (37.4 IU/mL). The oncologist placed an indication for a thoracic abdominal CT scan, which showed that the residual liver was free of disease, and the presence of a formation with a solid–cystic appearance and some calcifications at the left adnexal site. The radiological findings were confirmed on level II gynecological ultrasound. The patient then underwent a radical surgery of hysterectomy, bilateral oophorectomy, pelvic peritonectomy, and omentectomy by a laparotomic approach, with the sending of intraoperative extemporaneous histological examination on the annexus site of the tumor mass, obtaining RT = 0. Currently, the patient continues her gyneco-oncology follow-up simultaneously clinically, in laboratory, and instrumentally every 4 months. Our study currently represents the longest elapsed time interval between first diagnosis and disease recurrence, as evidenced by current data in the literature. This was a rather unique and difficult clinical case because of the rarity of the disease, the lack of scientific evidence, and the difficulty in differentiating the primary hepatoid phenotype of the ovary from an ovarian metastasis of HCC. Several multidisciplinary meetings for proper interpretation of clinical and anamnestic data, with the aid of immunohistochemistry (IHC) on histological slides were essential for case management.

Background: There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). Methods: MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010–2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. Results: A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0–99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. Conclusions: Ki67 at diagnosis did not discriminate responders to PARPi.

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.

LBA5504 Background: Trabectedin demonstrated antitumor activity when administered as single agent in relapsed platinum sensitive ovarian cancer (OC), with an overall response rate (ORR) ranging from 26 to 43% and a median PFS of 5 months. In addition, trabectedin showed 39.4% RR, 4.5 months median progression free survival (PFS) and 18 months median overall survival (OS) in a single arm phase 2 trial in recurrent BRCA mutated and/or the BRCAness phenotype OC patients. Methods: In this open-label, phase III, randomized trial, we assigned recurrent OC patients harboring BRCA 1/2 mutations or with BRCAness phenotype (defined as patients who had received and responded to at least 2 previous platinum-based treatments) to receive trabectedin 1.3 mg/mq q 21d or physician’s choice chemotherapy (among carboplatin, gemcitabine, weekly paclitaxel, pegylated liposomal doxorubicine or topotecan). The primary endpoint was OS. Secondary endpoints were PFS, ORR and Duration of Response (DoR). The sample size was calculated based on the assumption that trabectedin would increase median OS from 10 to 15 months (two-sided log-rank test at the error alfa= 0.05 and a power of 80%). Medians and lifetables were computed using the Kaplan-Meier method and analyzed using the log-rank test. Cox proportional hazards model was used to assess the effect of treatment. Results: Two hundred and forty-four patients were randomized and analyzed based on the intent-to-treat principle. At a median follow up of 40 months, the median PFS was 4.4 and 4.9 months (HR= 1.03 p=0.848) and median OS was 17.9 and 15.8 months (HR=1.15 p=0.304), in the control and experimental arm, respectively. ORR was 20.2% in the group of patients receiving standard chemotherapies and 15.4% in the group of patients treated with trabectedin. No superior effect was reported for Trabectedin in the pre-specified sub-group analysis according to BRCA mutational status, type of chemotherapy and platinum-free interval. No new signal of toxicity were reported for all the chemotherapies employed. Conclusions: Trabectedin as single agent does not improve survival outcomes when compared to standard chemotherapy in BRCA mut and BRCAness phenotype OC patients. Clinical trial information: NCT02993705.

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: 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.

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.

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.

Background:Periostin is a secreted adhesion protein, normally expressed in mesenchime-derived cells. Aberrant expression of the periostin gene in epithelial tumours seems to play a role in angiogenesis and metastases.Aims:To investigate periostin expression in a consecutive series of breast carcinomas and correlate it with established biological and prognostic factors.Methods:A consecutive series of 206 breast carcinomas was investigated by immunohistochemistry with a specific antiperiostin antibody. Immunohistochemical expression of oestrogen and progesterone receptors, Ki-67 (MIB-1), HER-2/neu, VEGF-A, VEGFR-1 and VEGFR-2 was analysed. Periostin expression was also investigated in MCF-7 and MDA-468 cell lines by immunohistochemistry, western blot and quantitative RT-PCR. Localisation of periostin was investigated in MCF-7 cells by the green fluorescent protein (GFP) approach.Results:Periostin was highly expressed in carcinoma cells, but not in normal breast tissues. The pattern of expression was mainly cytoplasmic. However, in 12% of cases a nuclear reactivity was observed. Nuclear periostin significantly correlated with tumour size, and with expression of oestrogen receptor, progesterone receptor, VEGF-A, VEGFR-1 and VEGFR-2. A nuclear localisation of periostin was also observed in MCF-7 and MDA-468 cell lines. In MCF-7 cells the nuclear localisation of periostin was also shown by transfection of a vector expressing a GFP-periostin chimeric protein.Conclusions:Results indicate that the aberrant gene expression of periostin in breast cancer cells is associated with an abnormal nuclear localisation of the protein. The nuclear localisation of periostin in breast cancer may induce significant biological effects.

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.

The urokinase plasminogen activator (uPA) system includes uPA and plasminogen activator inhibitor types 1 (PAI-1) and 2 that mainly act by regulating extracellular matrix degradation, and it is involved in tumor progression. The –675 4G/5G polymorphism of the PAI-1 gene regulates PAI-1 activity in serum. We aimed at studying the –675 4G/5G polymorphism of the PAI-1 gene and uPA, PAI-1, and cyclooxygenase-2 (COX-2) immunohistochemical expression in a series of breast cancer cases. Homozygosity for the 4G allele of the PAI-1 gene was associated with node-positive breast cancer (P = .02). We showed a direct correlation between uPA and estrogen receptor expression (P = .03); negative uPA expression was associated with negative hormonal expression, high tumor grade, and high proliferation index (P < .05). A direct correlation was seen between uPA and PAI-1, uPA and COX-2, and PAI-1 and COX-2 expression (P < .05). Interaction between uPA and COX-2 systems in breast cancer deserves further study.

We have investigated the immunohistochemical expression of thymidine phosphorylase before and after the administration of anthracycline, and/or anthracycline/ taxane-based preoperative chemotherapy in a consecutive series of 55 patients with primary operable breast cancer. Pretreatment, large core breast biopsies and the corresponding surgical samples were retrospectively evaluated for thymidine phosphorylase immunoreactivity. Immunohistochemical expression was evaluated on tumor cells (nuclear and cytoplasmic staining) and on stromal cells (cytoplasmic staining). The cytoplasmic expression of thymidine phosphorylase was enhanced in the tumor cells after treatment (P=0.04). An increase in thymidine phosphorylase cytoplasmic tumor expression was observed in 33% (95% confidence interval: 19-50%) of patients after preoperative chemotherapy (P=0.01). No statistically significant nuclear staining changes were observed in response to treatment Similarly, no significant changes of the enzyme expression were seen in stromal cells. This study provides further evidence that, at least in breast cancer, thymidine phosphorylase is upregulated after anthracycline and/or taxane-containing chemotherapy. Accordingly, it supports the hypothesis of a synergistic effect between thymidine phosphorylase-modulating and thymidine phosphorylase-targeting anticancer agents. Translational studies, specifically designed on the basis of this rationale, are eagerly waited.

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.