All patients were assessable for safety and efficacy. Sixteen patients out of 50 (34%) were naïve from other therapies, while all the others were previously treated with local and/or systemic treatments. We achieved 5 partial responses (10%), 33 stable diseases (66%) and 12 progressions of disease (24%). Median time to progression was 7.0 months (95% CI, 3.0 to 10.9 months) and median overall survival was 12 months (95% CI, 6.3 to 17.4 months). Treatment was well tolerated. Diarrhoea (6%) and hypertension (4%) were the most frequent grade 3 toxicities. Conclusions. Our data suggest that the combination between sorafenib and long acting octreotide is active and well tolerated in patients with advanced HCC and could represent another efficacious chance for the management of this population.4

Breast cancer is the most common malignancy in women, with an incidence that varies between 40 and 90 per 100 000 (standardized rate) worldwide. Breast cancer is the most frequent female tumour in Italy, representing about 25% of all female tumours as reported in Italian registries (Zanetti et al, 1997).A positive family history is known to be a high risk factor for developing the disease: 5-10% of all breast cancers arise in individuals carrying a germline mutation and are usually considered hereditary forms (Claus et al, 1991). Two major breast cancersusceptibility genes, BRCA1 and BRCA2, have been cloned (Miki et al, 1994;Wooster et al, 1995) and both are thought to account for 30-60% of hereditary breast cancer (Serova et al, 1997;Szabo et al, 1997;Vehmanen et al, 1997aVehmanen et al, , 1997b. However, large-scale mutation analyses conducted in several populations suggest the existence of additional breast cancer-susceptibility gene(s). BRCA1 mutations are responsible for the majority of familial breast cancer associated with ovarian carcinoma, for about 50% of cases with breast cancer alone and for very few male breast cancer cases (Easton et al, 1993;Stratton et al, 1994;Narod et al, 1995). It has been estimated that women carrying a germline mutation in BRCA1 have a risk ranging from 80 to 90% for developing breast cancer and from 44 to 63% for developing ovarian cancer (Easton et al, 1993(Easton et al, , 1995Ford et al, 1994; Miki et al, 1994;Wooster et al, 1994). BRCA2 mutations account for a similar proportion of inherited breast cancer and are frequently associated with male breast cancer (Wooster et al, 1995). Breast cancer risk in females carrying BRCA2 mutations is calculated to be similar to that conferred by BRCA1 mutations (Easton et al, 1993Ford et al, 1994; Miki et al, 1994;Wooster et al, 1994). BRCA1 and particularly BRCA2 families are often affected by other tumours such as prostate, liver, pancreas, lung, stomach and colorectum (Wooster et al, 1995;Gudmundsson et al, 1996;Phelan et al, 1996;Thorlacius et al, 1996;Vehmanen et al, 1997b;Tonin et al, 1998). Except for higher incidences of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 of BRCA2 (the so-called ovarian cancer cluster region [OCCR]; Gayther et al, 1997), no other significant association between genotype and phenotype was described. BRCA1 and BRCA2 mutations are for the most part frame-shifts due to small deletions leading to premature translation termination (Wooster et al, 1995;Phelan et al, 1996;Tavtigian et al, 1996;Gayther et al, 1997).Some of these mutations are prevalent in genetically homogeneous populations as a consequence of a founder effect. A single BRCA2 mutation accounts for the majority of hereditary breast cancer in Iceland Thorlacius et al, 1996) and for 40% of male breast cancer cases , whereas three different founder mutations (185delAG and 5382insC in BRCA1, and 6174delT in BRCA2) have a high frequency in Ashkenazi Jews (Roa et al, 1996). Although at different rates, BRCA1 and BRCA2 f...

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and 424 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6 -36.8%). An additional 46 patients had long-term (424 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2 -81.4). Median time to progression (TTP) was 11 months (95% CI: 10 -12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted X6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.

BackgroundOn the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease.MethodsIn our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC.ResultsEribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3–4 toxicities were neutropaenia and neurotoxicity.ConclusionsWith the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC.

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