The biological and prognostic role of hormone receptor status and proliferative activity have been studied in two series of patients affected by inflammatory breast carcinoma (IBC, 28 patients) and locally advanced breast cancer (LABC, 50 patients). Estrogen receptor (ER) and progesterone receptor (PgR) were measured by dextran-coated charcoal (DCC) method whereas proliferative activity was measured by 3H-thymidine autoradiographic labeling index (LI). The percentages of E R f and P g R f cases resulted lower in IBC than in LABC (ERf, 44% versus 64%; PgR+, 30% versus 51%, respectively), pertaining to both pre-menopausal and postmenopausal women. Inflammatory breast carcinoma showed a higher median LI value than LABC (3.5% versus 1.6%; P = 0.006). Regarding clinical aspects, time to progression (TTP) in IBC patients was not affected by hormone receptor status (19 evaluable patients) or by LI (17 evaluable patients); P g R t status and low LI resulted important for individualizing women with a longer median overall survival (0s). Inflammatory breast carcinoma has been verified to be a heterogeneous biological entity for which hormone receptors and cell kinetics could be useful in identifying patients with different prognoses and therefore candidates for a personalized therapy.

Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors.

The epirubicin-vinorelbine combination with G-CSF support has been shown in this study to be highly active as first-line treatment of metastatic breast cancer patients, with significant although transient toxicity. This justifies further evaluation in the neoadjuvant setting and in early-stage breast cancer.

There are no validated predictors of benefit from anthracyclines. We compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF), and epirubicin in different sequences with CMF alone in a phase III trial on operable breast cancers. Outcomes were analyzed in relation to tumor biological profiles to identify potential predictors of the efficacy of different treatments/drug combinations. Patients with N- or 1-3N+ tumors, were randomized to receive (a) epirubicin (4 cycles) followed by CMF (4 cycles); (b) CMF (4 cycles) followed by epirubicin (4 cycles), or (c) CMF (6 cycles) alone. Immunohistochemical assessments of estrogen (ER) and progesterone (PgR) receptors, HER2 and Ki67 were available for 705 patients (arm A/B/C: 276/269/160). Prognostic and predictive relevance was analyzed by log-rank tests and Cox models. Ki67 > 20 % and absent/low expression of ER and PgR were associated with worsen disease-free (DFS) and overall survival (OS). In patients with triple negative tumors (ER-, PgR-, HER2-), epirubicin-containing regimens yielded better DFS (HR 0.33, 95 % CI 0.17-0.62, P = 0.0007) and OS (HR 0.24, 95 % CI 0.10-0.57, P = 0.001) compared with CMF alone, whereas no differences were found in patients with HER2-positive (HER2+, ER-, PgR-) subtype. Treatment by subtype interaction (HER2-positive vs. others) was significant for DFS (χ (2) = 6.72, P = 0.009). In triple unfavorable (ER-, PgR-, Ki67 > 20 %) tumors, the use of epirubicin yielded better DFS (HR 0.45,95 % CI 0.26-0.78, P = 0.005) and OS (HR 0.30, 95 % CI 0.15-0.63, P = 0.001). Epirubicin-containing regimens seem to be superior to CMF alone in patients with highly proliferating, triple negative or triple unfavorable tumors.

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has proven highly effective in rapidly proliferating breast cancer (RPBC). It has also been seen that sequential administration of doxorubicin and CMF is superior to their alternation, especially in indolent tumors. In a phase III study we evaluated whether adjuvant epirubicin (E) followed by CMF is superior to the inverse sequence in RPBC.Methods Patients with node-negative or 1-3 node-positive RPBC (Thymidine Labeling Index >3% or histological grade 3 or S-phase >10% or Ki67 >20%) were randomized to receive E (100 mg/m 2 i.v. d1, q21 days for 4 cycles) followed by CMF (600, 40, 600 mg/m 2 i.v. d1 & 8, q28 days for 4 cycles) (E→CMF) or CMF followed by E (CMF→E) or CMF for 6 cycles. Conclusions No important differences in clinical outcome were observed between the two different sequences, making both a valid option in early breast 4 cancer. Further molecular characterization of the tumors might help to identify subgroups achieving higher benefit from either sequence. Results

The 37% response rate observed in this study (28% in refractory or early-relapsed patients), suggests that the synergism between CDDP and LND observed in vitro against ovarian cancer cell lines can be clinically confirmed. However, larger series and randomized studies are needed to assess definitely the revertant activity of LND on CDDP-refractory patients.

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