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Controversies exist about the definition and epidemiology of breakthrough cancer pain (BTcP), the pharmacological treatment options, drug dosing, and how to select the medications for BTcP among the new fentanyl products. Existing data were critically evaluated to provide recommendations by an expert group. An algorithm to diagnose BTcP should be used followed by a careful assessment. Fentanyl products provide efficacy and rapidity of action to counteract the temporal pattern of BTcP. The doses of opioids used for background pain should guide the choice of the doses of fentanyl products. The choice of fentanyl products should be based on individual clinical conditions.

There is growing evidence about differences in metastatic spread among breast cancer (BC) biologic subtypes (BS). Aim of this study was to analyze the pattern of metastasization according to BS and to explore the corresponding prognosis. A series of 544 consecutive patients receiving anticancer therapy for metastatic BC from 2004 to 2013, was analyzed. BS were defined by immunohistochemistry according to St Gallen 2013 criteria. Association between BS and the different distant localizations was analyzed. Prognosis was described in terms of overall survival (OS), progression free survival (PFS) and post progression survival (PPS). Results were reported taking luminal A BC as reference. Triple negative BC showed a higher tropism for lung (OR 4.30 95% CI 1.41-13.1), while non luminal HER2 subtype was associated with a higher rate of liver metastases (OR 3.61 95% CI 1.36-9.58). All subtypes were associated with a lower risk of bone-only localization. Central nervous system (CNS) involvement was more common in HER2 positive BC (OR 6.3, 95% CI 1.08-36.66). Liver, lung and CNS involvement influenced negatively OS (HR 1.64, 95% CI 1.29-2.07; HR 1.49, 95% CI 1.18-1.90; HR 2.891, 95% CI 1.85-4.51, respectively) and PFS (HR 1.39, 95% CI 1.13-1.71; HR 1.26, 95% CI 1.02-1.55; HR 1.75, 95% CI 1.12-2.71, respectively). Multivariate analysis confirmed liver involvement as independent predictor of worse OS (HR 1.64, 95% CI 1.15-2.34). Stratification by metastatic pattern showed significant differences in terms of PPS but not in terms of PFS. The study suggests that BS may be characterized by typical patterns of metastatic spread and have different impact on clinical outcome.

Background The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (+) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P + T + taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include early-relapsing patients, defined as patients experiencing tumor relapse ≤12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing ≤6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting. Patients and methods We retrospectively compared T-DM1 versus P + T + taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian ‘real-world’ setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients' characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were two-sided and a P ≤ 0.05 was considered statistically significant. Results Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P + T + taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P + T + taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P = 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P = 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (≤6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival (P = 0.095). Conclusions Our study suggests superiority for P + T + taxane over T-DM1 as up-front treatment of early-relapsing HER2+ metastatic breast cancer, which merits further assessment in larger and prospective trials., Highlights • This is the first study comparing pertuzumab + trastuzumab + taxane (P + T + taxane) with T-DM1 in early-relapsing HER2+ MBC. • The majority of early-relapsing HER2+ MBC have high-grade, node-positive, large primary tumors. • First-line T-DM1 compared with P + T + taxane is associated with worse progression-free survival. • First-line T-DM1 compared with P + T + taxane is associated with worse overall survival. • Post-progression survival does not differ between the two treatments cohorts.

Several clinical series have demonstrated a notably low overall survival for colorectal cancer patients diagnosed with a BRAF-mutant tumor. A potentially interesting predictive role has also been suggested for BRAF-mutant colorectal cancer receiving anti-EGFR monoclonal antibodies. Although a global consensus exists in indicating BRAF as a prognostic factor with a possible predictive activity, the clinical use of BRAF mutational status in colorectal tumors is still controversial. This article reviews the current knowledge on the use and implications of BRAF mutational status in colorectal tumors, in order to define its present role in the clinical practice. Also suggested are possible treatment strategies in this prognostically challenging group of patients. Finally, a comprehensive outlook on future developments for specifically directed anti-BRAF therapy is illustrated.