Is the sarcomatous component (homologous vs heterologous) the prognostic "driving force" in early-stage uterine carcinosarcomas? A retrospective multicenter study.

PURPOSE: Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS). METHODS: This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs. RESULTS: Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207-4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032-3.684, p = 0.040). CONCLUSION: Carcinomatous and sarcomatous components both played a role in tumor progression and patients' survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study.

BACKGROUND: In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. METHODS: We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). RESULTS: In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. CONCLUSIONS: Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

Pattern of recurrence in patients with endometrial cancer: A retrospective study.

INTRODUCTION: Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule. METHODS: 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate. RESULTS: Higher recurrence rate (RR) was significantly detected (p < 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p < 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p < 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01). CONCLUSION: To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

The INTERNATIONAL MISSION study: minimally invasive surgery in ovarian neoplasms after neoadjuvant chemotherapy.

OBJECTIVES: The aim of this retrospective multicenter study was to investigate the extent, feasibility, and outcomes of minimally invasive surgery at the time of interval debulking surgery in different gynecological cancer centers. METHODS/MATERIALS: In December 2016, 20 gynecological cancer centers were contacted by e-mail, to participate in the INTERNATIONAL MISSION study. Seven centers confirmed and five were included, with a total of 127 patients diagnosed with advanced epithelial ovarian cancer after neoadjuvant chemotherapy and minimally invasive interval surgery. Only women with a minimum follow-up time of 6 months from interval surgery or any cancer-related event before 6 months were included in the survival analysis. Baseline characteristics, chemotherapy, and operative data were evaluated. Survival analysis was evaluated using the Kaplan-Meier method. RESULTS : All patients had optimal cytoreduction at the time of interval surgery: among them, 122 (96.1%) patients had no residual tumor. Median operative time was 225 min (range 60 - 600) and median estimated blood loss was 100 mL (range 70 - 1320). Median time to discharge was 2 days (1-33) and estimated median time to start chemotherapy was 20 days (range 15 - 60). Six (4.7%) patients experienced intraoperative complications, with one patient experiencing two serious complications (bowel and bladder injury at the same time). There were six (4.7%) patients with postoperative short-term complications: among them, three patients had severe complications. The conversion rate to laparotomy was 3.9 %. Median follow-up time was 37 months (range 7 - 86): 74 of 127 patients recurred (58.3%) and 31 (24.4%) patients died from disease. Median progression-free survival was 23 months and survival at 5 years was 52 % (95% CI: 35 to 67). CONCLUSIONS: Minimally invasive surgery may be considered for the management of patients with advanced ovarian cancer who have undergone neoadjuvant chemotherapy, when surgery is limited to low-complexity standard cytoreductive procedures.

MetaShot: an accurate workflow for taxon classification of host-associated microbiome from shotgun metagenomic data.

SUMMARY: Shotgun metagenomics by high-throughput sequencing may allow deep and accurate characterization of host-associated total microbiomes, including bacteria, viruses, protists and fungi. However, the analysis of such sequencing data is still extremely challenging in terms of both overall accuracy and computational efficiency, and current methodologies show substantial variability in misclassification rate and resolution at lower taxonomic ranks or are limited to specific life domains (e.g. only bacteria). We present here MetaShot, a workflow for assessing the total microbiome composition from host-associated shotgun sequence data, and show its overall optimal accuracy performance by analyzing both simulated and real datasets. AVAILABILITY AND IMPLEMENTATION: https://github.com/bfosso/MetaShot. CONTACT: graziano.pesole@uniba.it. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Robotic single site staging in endometrial cancer: A multi-institution study.

OBJECTIVE: To evaluate the feasibility and the safety of robotic single site hysterectomy (RSSH) plus or less pelvic lymphadenectomy in FIGO stage I-II endometrial cancer. MATERIALS AND METHODS: We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients who underwent RSSH plus or less pelvic lymphadenectomy for clinical FIGO stage I or occult stage II endometrial carcinoma. RESULTS: From January 2012 to February 2015, 125 patients were included in our study. The median age of the patients was 59 years (range, 35-84 years) and the median body mass index was 27 kg/m(2) (range, 19-52 kg/m(2)). One patient was converted to vaginal surgery due to problems of hypercapnia. The median docking time, console time, and total operative time was 11 min (range, 4-40 min), 80 min (range, 20-240 min) and 122 min (range, 35-282 min), respectively. The median blood loss was 50 ml (range, 10-250 ml). No laparoscopic/laparotomic conversion was registered. Twenty one patients underwent pelvic lymphadenectomy (16.8%) and the median pelvic lymph nodes was 13 (range, 3-32). The median time to discharge was 2 days (range, 1-3 days). No intra-operative complications occurred, while we observed 10 (8%) early post-operative complications. CONCLUSION: RSSH plus or less pelvic lymphadenectomy is technically feasible, safe and reproducible and could be the treatment of choice for patients affected by FIGO stage I-II endometrial cancer. However, randomized controlled trials are needed to confirm these results.

Radical hysterectomy after chemoradiation in FIGO stage III cervical cancer patients versus chemoradiation and brachytherapy: Complications and 3-years survival.

BACKGROUND: To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients underwent to radical hysterectomy after chemo-radiation (CT-RT) vs. chemo-radiation alone. METHODS: Between May 1996 and April 2013 150 FIGO stage III cervical cancer patients were treated. We divide patients according to type of treatment: 77 were submitted to standard treatment (Group A), and 73 to completion hysterectomy after chemo-radiation (Group B). RESULTS: The baseline characteristics of the 2 groups were superimposable. We observed lower intra-operative and treatment-related early urinary and gastro-intestinal complications in Group B with respect to Group A (p < 0.001). Vascular complications were registered only in Group B (p < 0.001). We found a significantly higher rate of local recurrences in the Group A than in the Group B (p < 0.002). We registered 29 deaths in the Group A and 22 in the Group B (p = 0.021). The 3-years disease-free survival rate in the Group A and in the Group B was 62.9% and 68.3%, respectively (p = 0.686), and the 3-years overall survival rate in the Group A and in the Group B was 63.2% and 67.7%, respectively (p = 0.675). CONCLUSIONS: This study confirms that radical hysterectomy after CT-RT is an effective therapeutic approach for advanced cervical cancer. Further prospective and randomized studies should be performed in order to solve the question about the standard approach, and how the different pattern of complication could impact on the quality of life.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

Surgical and oncological outcome of robotic surgery compared to laparoscopic and abdominal surgery in the management of endometrial cancer.

OBJECTIVE: To compare different techniques of minimally invasive surgery (laparoscopy and robotics) to abdominal surgery in order to identify the optimal surgical technique in the treatment of endometrial cancer. METHODS AND MATERIALS: A single-institutional, matched, retrospective, cohort study was performed. All patients with clinical stage I or occult stage II endometrial cancer who underwent robotic hysterectomy, bilateral salpingo-oophorectomy ± lymphadenectomy from August 2010 and December 2013 were identified. Surgical and oncological outcomes were compared with patients matched by age, body mass index, tumor histology, and grade, who underwent abdominal or laparoscopic surgery between January 2001 and December 2013. RESULTS: Three groups were identified: 177 laparotomies (group A), 277 laparoscopies (group B) and 72 robotics (group C). There were no statistically significant differences between the three groups in terms of age, BMI and FIGO stage. The operative time was shortest in group B (p = 0.0001). Blood loss and transfusions were equivalent in group B and C, while they were greater in group A (p = 0.0001). The intra-operative, early and late postoperative complications, rate of conversion, the re-intervention and median hospital stay were lower in group C. The rate of recurrence and death from disease was similar in all three groups. CONCLUSIONS: Minimally invasive surgery was superior to abdominal surgery in terms of surgical outcomes. Robotic surgery was superior to laparoscopy in terms of intra- and post-operative complications, conversion rates, length of hospital stay and re-interventions. In terms of oncological outcomes the three groups were equivalent.

Laparoscopic versus robotic radical hysterectomy after neoadjuvant chemotherapy in locally advanced cervical cancer: a case control study.

OBJECTIVE: To compare the surgical outcome of robotic radical hysterectomy (RRH) versus laparoscopic radical hysterectomy (LRH) for the treatment of locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: From August 1st 2010 to July 1st 2012 a prospective data collection of women undergoing RRH for cervical cancer stage FIGO IB2 to IIB, after neoadjuvant chemotherapy, was conducted at National Cancer Institute "Regina Elena" of Rome. All patients deemed operable underwent class C1 RRH with pelvic lymphadenectomy within 4 weeks from the last chemotherapy cycle. RESULTS: A total of 25 RRH were analyzed, and compared with 25 historic LRH cases. The groups did not differ significantly in body mass index, stage, histology, number of pelvic lymph nodes removed. The median operative time was the same in the two groups with 190 min respectively. The median estimated blood loss (EBL) was statistically significant in favor of RRH group. Median length of stay was shorter, for the RRH group (4 versus 6 days, P = 0.28). There was no significant difference in terms of intraoperative and postoperative complications between groups but in the RRH group we observed a greater number of total complications compared to the control group. CONCLUSION: This study shows that RRH is safe and feasible in LACC after NACT compare to LRH. However, a comparison of oncologic outcomes and cost-benefit analysis is still needed and it has to be carefully evaluated in the future.

Mini-laparoscopic versus robotic radical hysterectomy plus systematic pelvic lymphadenectomy in early cervical cancer patients. A multi-institutional study.

OBJECTIVE: The aim of this study was to verify possible differences in terms of perioperative outcomes and complications between mini-laparoscopic radical hysterectomy with lymphadenectomy (mLRH) and robotic radical hysterectomy with lymphadenectomy (RRH) in patients with early cervical cancer (ECC). MATERIAL AND METHODS: In this retrospective study, thirty women with early stage cervical cancer who underwent mini-laparoscopic radical hysterectomy plus lymphadenectomy (mLRH) were compared with a cohort of thirty women who underwent robotic multiport radical hysterectomy (RRH). The study involved patients, between August 2010 and December 2012, from three Italian institutions: National Cancer Institute of Rome, University of Insubria, Varese, and the Catholic University of the Sacred Heart of Rome. RESULTS: No significant differences between groups were observed in terms of age, BMI, previous abdominal surgery or FIGO stage. Operative time, blood loss, need of blood transfusion, risk of intra- and post-operative complications, and lymph nodes yield were similar between mLRH and RRH in patients with ECC. The median length of hospital stay was 2 days in the mLRH group and 3 days in the RRH group (p < 0.05). CONCLUSIONS: The few differences we registered do not seem clinically relevant, thus making the two procedures comparable. The decision on how to gain best access for radical hysterectomy considers the surgeon's skill and experience with the different possible approaches. Further randomized trials are needed to determine whether mini-laparoscopic techniques truly offer any advantages.

Laparoscopic staging of apparent early stage ovarian cancer: results of a large, retrospective, multi-institutional series.

OBJECTIVE: The aim of this study is to analyze the safety, adequacy, perioperative and survival figures in a large series of laparoscopic staging of patients with apparent early stage ovarian malignancies (ESOM). PATIENTS AND METHODS: Retrospective data from seven gynecologic oncology service databases were searched for ESOM patients undergoing immediate laparoscopic staging or delayed laparoscopic staging after an incidental diagnosis of ESOM. Between May 2000 and February 2014, 300 patients were selected: 150 had been submitted to immediate laparoscopic staging (Group 1), while 150 had undergone delayed laparoscopic staging (Group 2) of ESOM. All surgical, pathologic, and oncologic outcome data were analyzed in each group and a comparison between the two was carried out. RESULTS: Longer operative time, higher blood loss, more frequently spillage/rupture of ovarian capsule and conversion to laparotomy occurred in Group 1. No significant differences of post-operative complications were observed between the two groups. Histological data revealed more frequently serous tumors (0.06), Grade 3 (p=0.0007) and final up-staging (p=0.001) in Group 1. Recurrence and death of disease were documented in 25 (8.3%), and 10 patients (3.3%%), respectively. The 3-year disease free survival (DFS) and overall survival (OS) rates were 85.1%, and 93.6%, respectively in the whole series. There was no difference between Group 1 and Group 2 in terms of DFS (p value=0.39) and OS (p value=0.27). CONCLUSION: In this very large multi-institutional study, it appears that patients with apparent ESOM can safely undergo laparoscopic surgical management.

Robotic single-site hysterectomy (RSS-H) vs. laparoendoscopic single-site hysterectomy (LESS-H) in early endometrial cancer: a double-institution case-control study.

OBJECTIVE: To report our experience with single-site robotic platform for IS3000 "Da Vinci" Si Surgical System to perform robotic single site hysterectomy (RSS-H), and to compare peri-operative results with a historical series of laparoendoscopic single site hysterectomies (LESS-H). METHODS: This is a retrospective case-control study, performed at the Gynecologic Oncologic Unit, National Cancer Institute "Regina Elena", Rome, and at the Gynecologic Oncologic Unit, Catholic University of the Sacred Heart, Rome, Italy between December 2011 and January 2013. RESULTS: 19 women underwent RSS-H (cases) and 38 patients were submitted to LESS-H (controls) for early endometrial cancer. Pre-surgical procedures (port placement and docking) required a median time of 8 min in the RSS-H group and a median time of 2 min in the LESS-H group (p=0.0001). The median estimated blood loss was 75 ml in the cases and 30 ml in the controls (p=0.005). The median operative time, calculated from the beginning of intraperitoneal procedures to the skin closure, was 90 min in the cases and 107 ml in the controls (p=ns). The median time to discharge from the hospital was postoperative day two for both techniques. CONCLUSIONS: The few differences we registered do not seem clinically relevant, thus making the two procedures comparable.

A multicenter phase II randomized trial of docetaxel/gemcitabine versus docetaxel/capecitabine as first-line treatment for advanced breast cancer: a Gruppo Oncologico Italia Meridionale study.

OBJECTIVE: To evaluate two docetaxel-based regimens as first-line treatment in advanced breast cancer patients. METHODS: Patients were randomly assigned to docetaxel/gemcitabine (arm A: docetaxel 75 mg/m(2) on day 1, gemcitabine 1,000 mg/m(2) on days 1 and 8) or docetaxel/capecitabine (arm B: docetaxel 75 mg/m(2) on day 1, capecitabine 1,250 mg/m(2) twice daily on days 1-14); both chemotherapy regimens were repeated every 21 days. The primary objective of the study was to evaluate the response rate. RESULTS: Seventy-two patients were enrolled (36 each in arms A and B). Responses according to intention-to-treat analysis were as follows: arm A, 41.7% [95% confidence interval (CI) 25.6-57.8]; arm B, 38.9% (95% CI 23-54.8). Median progression-free survival was 10.9 months (95% CI 8.1-13.7) in arm A and 10 months (95% CI 8.8-11.2) in arm B. Overall survival was 26 months (95% CI 22.0-30.0) in arm A and 28 months (95% CI 23.4-32.6) in arm B. Both treatments were well tolerated; myelosuppression was the dose-limiting toxicity, with grade 3-4 neutropenia in 13.8 and 19.4% of the patients in arms A and B, respectively. No relevant differences in other toxicities were observed in the two arms, except for diarrhea (13.9%) and hand-foot syndrome (11.1%), which occurred only in arm B. CONCLUSIONS: Both regimens were active and well tolerated in advanced breast cancer.

Biological progression of breast cancer and clinical implications.

The classic view of tumor progression is that genetic mutation introduced in differentiated or progenitor cells causes tumors, through the acquisition of advantages for survival, and leading to phenotypic heterogeneity. Another theory (stem cell hypothesis) considers that tumor progression derives from cells within the tumor with stem cell characteristics of self-renewal and multiple differentiation potential. It is still unknown the timing of expression of various biological characteristics of breast cancer during the progression cascade, and the existence of clonal heterogeneity within primary tumor and synchronous or asynchronous distant metastases contributes to treatments failures.

[Specificity of action of anticancer agents]. / Specificità d'azione dei farmaci antineoplastici.

Since the first cancer chemotherapy use, efforts have been made in identifying drugs with an antitumor specific action, but cancer is a very complex situation to be cured with a single agent, and to increase drugs selective cytotoxicity new agent combinations, or innovative cellular cycle related schedule, or the use of pro-drugs have been developed. Notwithstanding some relevant improvements in results, chemotherapy remains often a palliative approach. The improved knowledge of the biology of cancer, and of molecular mechanisms and specific targets, has recently modified the approach to various tumors. In particular, the identification of a single and specific genetic alteration in some tumors such as myeloid chronic leukaemia or gastrointestinal stromal tumors (GIST) led to the development of imatinib, a "target" drug with a multikinase inhibitor activity towards the specific genetic alteration; this unique opportunity is not applicable to other tumors, because usually tumors have multiple genetic alterations with very complex molecular pathways. The development of drugs with a multitarget action is probably the best approach to the majority of human cancers, but other possibility are the combination of multiple agents, each with known selective activity towards a specific molecular target, or the choice of a chemotherapic drug in combination with one or more molecularly targeted drugs. The knowledge of the multiple and extremely complex molecular pathways of the neoplastic cells will hopefully drive oncologic science towards a more "exact" science, with the use of "personalized" treatment in each cancer patient.

Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally advanced stage IB2-IIB cervical cancer patients after neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the feasibility and morbidity of total laparoscopic class C2 radical hysterectomy (TLRH) with pelvic lymphadenectomy in patients with locally advanced cervical cancer stage IB2 to IIB after neoadjuvant chemotherapy (NACT). METHODS: A prospective study was conducted from October 2004 to September 2009. Cervical cancer patients, stage IB2-IIB with complete clinical response after 3 courses of NACT with paclitaxel 175 mg/m(2), ifosfamide 5 g/m(2) and cisplatin 75 mg/m(2) (TIP) underwent TLRH. RESULTS: Forty patients were included, with a median age of 46 years (range, 25-65), BMI of 24 kg/m(2) (range, 15-49). FIGO staging was IB2 in 23, IIA > 4 cm in 6 and IIB in 11 patients. Four patients required conversion to laparotomy. Pathological evaluation showed 9 complete response (pCR), 9 partial response (pPR1) with microscopic tumour, and 15 partial response (pPR2) with macroscopic tumour. Three patients had no response. The median operative time was 305 min (range, 215-430); the median estimated blood loss was 250 ml (range, 100-400), with four postoperative blood transfusion; the median number of removed pelvic lymph nodes was 25 (range, 11-64). The median length of hospital stay was 6 days (range, 3-12). The median follow-up time was 37 months (range, 10-69), with three patients having a recurrence. One patient died of disease (DOD) after 12 months. CONCLUSIONS: TLRH can be safely performed in patients with stage IB2-IIB carcinoma of cervix after NACT, with advantages of minimal blood loss and morbidity.

Recent advances in the adjuvant treatment of early breast cancer.

The majority of breast cancers are actually diagnosed at an early stage. Selection of the best treatment in the adjuvant setting represents a paramount step to reduce the risk of recurrence and cancer-specific mortality. At the present time decision making is based on individualized risk assessment, that takes into account patient and tumor clinical-pathological characteristics. New available tools, such as gene expression profiling, offer the potential to provide accurate prognostic and predictive information, but they require further validation. The present article provides an overview of current strategies in adjuvant breast cancer setting, and addresses a number of unresolved questions related to the role of taxanes, trastuzumab and hormonal treatment.