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The stock of therapeutic weapons available in metastatic colorectal cancer (mCRC) has been progressively grown over the years, with improving both survival and patients' clinical outcome: notwithstanding advances in the knowledge of mCRC biology, as well as advances in treatment, fluoropyrimidine antimetabolite drugs have been for 30 years the mainstay of chemotherapy protocols for this malignancy. 5-Fluorouracil (5FU) seems to act differently depending on administration method: elastomer-mediated continuous infusion better inhibits Thymidylate Synthase (TS), an enzyme playing a pivotal role in DNA synthetic pathway. TS overexpression is an acknowledged poor prognosis predicting factor. The simultaneous combination of 5FU and folinate salt synergistically strengthens fluorouracil cytotoxic effect. In our experience, levofolinate and 5FU together in continuous infusion prolong progression free survival of patients suffering from mCRC, moreover decreasing death risk and showing a clear clinical benefit for patients, irrespective of RAS mutational status, primitive tumor side and metastases surgery.

1554 Background: We evaluated the clinical impact of germ-line BRCA1/2 mutations and variants of unknown clinical significance (VUS) for BRCA1/2 in patients (pts) with early breast cancer (BC). Methods: Twenty-eight BRCA-positive (BRCA+) BC pts with germ-line BRCA1 /2 mutations and 16 VUS BC pts were selected from our database and matched (1:3) with 154 nonhereditary BC controls (sporadic controls, SC, defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. Clinical characteristics, recurrence (rec) pattern, disease free survival (DFS) and overall survival (OS) were analyzed. Results: Compared with VUS and SC, BRCA+ pts were less likely to express estrogen receptor (64% vs. 89% vs. 54% respectively p

In the last decades, management of epithelial ovarian cancer (EOC) has been based on the staging system of the International Federation of Gynecology and Obstetrics (FIGO), and different classifications have been proposed for EOC that take account of grade of differentiation, histological subtype, and clinical features. However, despite taxonomic efforts, EOC appears to be not a unique disease; its subtypes differ for epidemiological and genetic risk factors, precursor lesions, patterns of spread, response to chemotherapy, and prognosis. Nevertheless, carboplatin plus paclitaxel combination represents the only standard treatment in adjuvant and advanced settings. This paper summarizes theories about the classification and origin of EOC and classical and new prognostic factors. It presents data about standard treatment and novel agents. We speculate about the possibility to create tailored therapy based on specific mutations in ovarian cancer and to personalize prevention.

concurrent trastuzumab or RDI. G3/4 neutropenia was commonly seen. FN was documented in 5 pts (7.1%), although, all of them were G3 and resolved within 7 days. Other hematologic or non-hematologic toxicities were mild and tolerable. Conclusions: In Japan phase 2 (P2) study, 80 MBC pts who had received a median of 2 prior regimens obtained progression free of 112.0 days and OS of 331.0 days with 13.6% of incidence of FN by eribulin monotherapy (Aogi K, Ann Oncol, 2012). Comparing with Japan P2 study, our practice revealed lower RDI (68.05 versus 87.50%), although, sufficient disease controlling (median TTF of 119.0 days with eribulin monotherapy) with acceptable toxicities was obtained. These results suggest that eribulin has wide therapeutic window, and useful in managing MBC in practice.

e11528 Background: Hormone therapy (HT) is limited by the onset of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) with the ER antagonist Fulvestrant (F) can overcome this resistance. The aim of this study was to evaluate the efficacy and tolerability of F in postmenopausal women with hormone-responsive (HR) metastatic breast cancer (MBC) previously treated with Tamoxifen (T) or Aromatase Inhibitors (AI). Methods: From May 2006 to July 2008 83 patients with HR MBC progressing after T or AI for adjuvant or metastatic disease receiving F 250 mg/month were identified. Median time to progression (TTP), overall survival (OS), clinical benefit rate (CBR) defined as the proportion of partial or complete responses (CR, PR) or stable disease (SD) lasting ‡6 months were analyzed. Results: Six, 32, 33 and 12 patients received F as 1st, 2nd, 3rd and 4thline of HT for MBC, respectively. Fulvestrant resulted in an overall CBR of 38.6% (32/83) with 0% CR, 9% PR, 30%SD, 56% PD. Disease was not evaluable in 4.8% of cases. Median TTP to F was 4.9 months (4 - 5.8; 95% C.I.) and OS was 20.1 months (15.8 - 24.4; 95% C.I.). Patients with visceral metastases and with more advanced lines of overall therapy had worse outcome (OR 3.13, 1.17-8.37, 95% C.I.; p 0.023 and OR 0.72, 0.54-0.96, 95% C.I.; p 0.025, respectively). However, Fulvestrant showed activity up to the fourth line of endocrine therapy regardless of number of metastatic sites and previous AI or T therapy. Overall treatment was well tolerated. Arthralgia, swelling, and myalgia were the most common adverse all were grade 1 or 2. No injection-related adverse events were reported. Conclusions: Fulvestrant is an active treatment in HR MBC previously challenged with HT. Safety profile is optimal and it may be a suitable option in extensively pre-treated patients. Further exploration of its use in this patient population is warranted.

BACKGROUND: Approximately 5-10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome. METHODS: We retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months. RESULTS: BRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p