Impact of Hormone Receptor Status and Tumor Subtypes of Breast Cancer in Young BRCA Carriers.

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its impact on prognosis of young patients harboring BRCA pathogenic variant (PV). PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (≤40 years) diagnosed with invasive breast cancer and harboring germline PV in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest (disease-free survival [DFS], breast cancer specific survival [BCSS] and overall survival [OS]) were first investigated according to hormone receptors expression (positive vs. negative), and then according to breast cancer subtype (luminal A-like vs. luminal B-like vs. triple-negative vs. HER2-positive breast cancer). RESULTS: From 78 centers worldwide, 4,709 BRCA carriers were included, of whom 2,143 (45.5%) had hormone receptor-positive and 2,566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% vs. 9.6%, p<0.001), while the rate of second primary breast cancer was lower (9.1% vs. 14.7%, p<0.001) compared to patients with hormone receptor-negative disease. The 8-years DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive vs. negative disease changed over time for DFS, BCSS, and OS (p<0.05 for interactions of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-years DFS: 60.8% in luminal A-like vs. 63.5% in triple-negative vs. 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive vs. negative disease warrants consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

BACKGROUND: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. RESULTS: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). CONCLUSIONS: In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.

Effect of adjuvant trastuzumab treatment in conventional clinical setting: an observational retrospective multicenter Italian study.

Clinical trials have shown the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancers, but routine clinical use awaits evaluation of compliance, safety, and effectiveness. Adjuvant trastuzumab-based therapy in routine clinical use was evaluated in the retrospective study GHEA, recording 1,002 patients treated according to the HERA protocol between March 2005 and December 2009 in 42 Italian oncology departments; 874 (87.23 %) patients completed 1-year trastuzumab treatment. In 128 patients (12.77 %), trastuzumab was withdrawn due to cardiac or non-cardiac toxicity (28 and 29 patients, respectively), disease progression (5 patients) or the clinician's decision (66 patients). In addition, 156 patients experienced minor non-cardiac toxicities; 10 and 44 patients showed CHF and decreased LVEF, respectively, at the end of treatment. Compliance and safety of adjuvant trastuzumab-based therapy in Italian hospitals were high and close to those reported in the HERA trial. With a median follow-up of 32 months, 107 breast cancer relapses were recorded (overall frequency, 10.67 %), and lymph node involvement, estrogen receptor negativity, lymphoid infiltration, and vascular invasion were identified as independent prognostic factors for tumor recurrence, indicating that relapses were associated with advanced tumor stage. Analysis of site and frequency of distant metastases showed that bone metastases were significantly more frequent during or immediately after trastuzumab (<18 months from the start of treatment) compared to recurrences in bone after the end of treatment and wash-out of the drug (>18 months from the start of treatment) (35.89 vs. 14.28 %, p = 0.0240); no significant differences were observed in recurrences in the other recorded body sites, raising the possibility that the protection exerted by trastuzumab is lower in bone metastases.

Optimizing choices and sequences in the diagnostic-therapeutic landscape of advanced triple-negative breast cancer: An Italian consensus paper and critical review.

Triple-negative (TN) metastatic breast cancer (mBC) represents the most challenging scenario withing mBC framework, and it has been only slightly affected by the tremendous advancements in terms of drug availability and survival prolongation we have witnessed in the last years for advanced disease. However, although chemotherapy still represents the mainstay of TN mBC management, in the past years, several novel effective agents have been developed and made available in the clinical practice setting. Within this framework, a panel composed of a scientific board of 17 internationally recognized breast oncologists and 42 oncologists working within local spoke centers, addressed 26 high-priority statements, including grey areas, regarding the management of TN mBC. A structured methodology based on a modified Delphi approach to administer the survey and the Nominal Group Technique to capture perceptions and preferences on the management of TN mBC within the Italian Oncology community were adopted. The Panel produced a set of prioritized considerations/consensus statements reflecting the Panel position on diagnostic and staging approach, first-line and second-line treatments of PD-L1-positive/germline BRCA (gBRCA) wild-type, PD-L1-positive/gBRCA mutated, PD-L1-negative/gBRCA wild-type and PD-L1-negative/gBRCA mutated TN mBC. The Panel critically and comprehensively discussed the most relevant and/or unexpected results and put forward possible interpretations for statements not reaching the consensus threshold.

Increased MET and HGF gene copy numbers are associated with trastuzumab failure in HER2-positive metastatic breast cancer.

BACKGROUND: To investigate whether copy number gain of MET or hepatocyte growth factor (HGF) affect trastuzumab sensitivity in HER2-positive metastatic breast cancer (MBC). METHODS: We analysed 130 HER2-positive MBC treated with trastuzumab-based therapy. MET and HGF gene copy numbers (GCN) were assessed by fluorescence in situ hybridisation (FISH) in primary breast cancer samples. Receiver operating characteristic analysis was applied to find the best cutoff point for both MET and HGF GCN. RESULTS: MET FISH-positive cases (N=36, mean 3.72) had a significantly higher trastuzumab failure rate (44.4% vs 16.0%; P=0.001) and a significantly shorter time to progression (5.7 vs 9.9 months; HR 1.74; P=0.006) than MET FISH-negative cases (N=94, mean <3.72). Hepatocyte growth factor GCN was evaluated in 84 cases (64.6%). Receiver operating characteristic analysis identified 33 HGF FISH-positive patients (mean HGF GCN 3.01). HGF FISH-positive status was significantly associated with higher risk of failure (30.3% vs 7.8%; P=0.007) as compared with HGF FISH-negative cases (N=51, mean <3.01). MET and HGF FISH-positive status was highly correlated (P<0.001) and combination of both biomarkers did not increase predictive value of either considered separately. CONCLUSION: High GCNs of MET and HGF associate with an increased risk of trastuzumab-based therapy failure in HER2-positive MBC.

Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer.

BACKGROUND: Preclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2)-positive breast cancer cells. PATIENTS AND METHODS: Between January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression. RESULTS: Visceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease ≥6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5-10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2-5.6) and overall survival (OS) 19.4 months (95% CI 14.0-25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021). CONCLUSION: Retreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS.

Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: open-label pilot study for assessing the efficacy, tolerability and impact on quality of life.

We conducted a prospective, observational study to verify the efficacy, tolerability and impact on quality of life, mood and global neurocognitive performances of oxcarbazepine monotherapy in patients with brain tumor-related epilepsy (BTRE). Patients were followed for 12 months. We recruited 25 patients (11 females 14 males; mean age 49.7) affected with BTRE (17 de novo patients and 7 in monotherapy with other antiepileptics) and introduced oxcarbazepine monotherapy because of uncontrolled seizures and/or side effects. At first visit, patients underwent neurological examination, Qolie 31P V2, EORTC QLQC30, Zung self-depression rating scale (ZSDRS) and adverse events profile. A seizure diary was given to each patient. Follow-up duration was 1-12 months (mean 7.1 months, 5 patients died and 10 dropped out). Totals of 16 patients underwent both chemotherapy and radiotherapy, 4 chemotherapy only, 1 radiotherapy only, and 4 did not undergo any systemic therapy. Mean dosage of oxcarbazepine was 1,230 mg/day (min 600, max 2,100 mg/day). McNemar's test showed a significant difference in seizure freedom rate (P = 0.002) between baseline and final follow-up in the intent-to-treat population. Six patients (24%) had serious side effects and one patient (4%) mild. Logistic regression revealed that, in our study, chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure outcome (P = 0.658). The test evaluation at final follow-up showed a significant improvement in ZSDRS (P = 0.011) and no change over time. Oxcarbazepine seems to be efficacious in controlling seizures and in improving mood in patients with BTRE, but special caution should be taken when it is administered during radiotherapy.

Severe Outbreak of Bacterial Blight Caused by Xanthomonas arboricola pv. corylina on Hazelnut cv. Tonda di Giffoni in Central Italy.

Hazelnut (Corylus avellana L.) is one of the most economically important tree crops in Italy. Xanthomonas arboricola pv. corylina (Xac) causes bacterial blight of hazelnut (4). During early summer 2010, a survey of three orchards (5 ha total) containing 4-year-old hazelnut trees (cv. Tonda di Giffoni) in Viterbo Province, Latium region, Italy, showed an 80 to 100% incidence of bacterial blight. Initially, water-soaked, necrotic spots were visible on leaves, fruit involucres, and shells, followed by lateral shoot dieback and development of cankers as longitudinal bark cracks on twigs, branches, and main trunks. Brown necrosis of the cambium was observed when bark tissue was removed. By late summer, necrosis had extended down main branches to the trunk, causing complete girdling of branches. Symptomatic tissues were collected from leaves, branches, and trunks, sections were surface-sterilized in 1% NaOCl for 1 min followed by two rinses in sterile distilled water (SDW, each for 1 min), and each section was then crushed in SDW. A loopful of the suspension was streaked onto yeast extract-dextrose-calcium carbonate agar medium (YDCA). Thirty six (12 from each type of tissue) yellow-mucoid, shiny, round bacterial colonies, each approximately 2 mm in diameter, were subcultured on YDCA. All strains were gram-negative and aerobic; negative for indole, lecithinase, urease, tyrosinase, and nitrate reduction; and positive for catalase, growth in 2% NaCl in nutrient broth, and growth at 35°C. All strains produced dark green pigment on succinate-quinate (SQ) medium. Inoculum of each of 15 isolates was prepared in nutrient broth, and washed cells from late log-phase cultures used to prepare a bacterial suspension of each isolate for inoculation of 2-year-old potted hazelnut plants cv. Tonda di Giffoni. A suspension of 106 CFU/ml for each isolate was sprayed onto leaves (10 ml/plant), and drops of inoculum were placed on wounds made on twigs with a sterile scalpel (0.10 µl/wound). For each isolate, three plants were inoculated per inoculation method. Inoculations with two reference strains of Xac (Xaco 1 from central Italy (3) and NCPPB 2896 from England) and SDW were performed on the same number of plants for positive and negative control treatments, respectively. Inoculated plants were maintained at 26 ± 1°C in a greenhouse. After 21 days, all inoculated plants had developed symptoms on leaves, while cankers developed on twigs after 40 days. Positive control plants developed the same symptoms, while negative control plants remained asymptomatic. Bacteria recovered from lesions on plants inoculated with the test strains or positive control strains had the same morphological and physiological characteristics as the original strains. No bacteria were recovered from negative control plants. Total DNA was extracted from bacterial suspensions and 16S rDNA amplified using universal primers (2). Sequences (GenBank Accession Nos. JQ861273, JQ861274, and JQ861275 for strains Xaco VT3 to VT5) had 99 to 100% identity with 16S rDNA sequences of Xac strains in GenBank. In Italy, Xac was reported by Petri in 1932 in Latium, and later in other regions on several hazelnut cultivars (1). However, to our knowledge, this is the first report of the disease causing severe damage in Italy. References: (1) M. Fiori et al. Petria 16:71, 2006. (2) J. R. Lamichhane et al. Plant Dis. 95:221, 2011. (3) J. R. Lamichhane et al. Acta Horticol.:In press. 2012. (4) OEPP/EPPO Bull. 179:179, 2004.

Adherence to endocrine therapy in women with breast cancer: development and preliminary validation of the A-BET questionnaire.

Purpose: To develop an Italian tool that measures the therapy adherence of women with breast cancer undergoing treatment with oral endocrine therapy. Methods: A two-phase study was conducted, which followed the guidelines of the European Statistical System for the development and validation of a questionnaire. In the first phase, the questionnaire was developed; in the second phase, a preliminary validation was carried out on patients with breast cancer undergoing treatment with oral hormonal therapies. Results: In its final version, the questionnaire presents 6 main items which aim to investigate the level of adherence, the degree of awareness of the nature of the drug taken and the reasons that may influence non-adherence. 82 patients were recruited in the validation study, with an average age of 56.4 years, while for the re-test 40 were selected with an average age of 57.3 years. Content validity reported excellent results. Cronbach's alpha of each item showed a strong degree of correlation. Conclusions: The creation of a tool for measuring adherence to endocrine therapy in breast cancer patients can be a valuable support for healthcare professionals involved in their care. Future studies should be aimed at using A-BET (Adherence - Breast Endocrine Therapy) on larger cohorts of patients in order to verify its validity / reliability more accurately and to be able to generalize the results.

Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine.

BACKGROUND: In the present study, we investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) treated with lapatinib and capecitabine (LC). METHODS: Of 81 HER2+ metastatic BC patients treated with LC at two Italian institutions, 30 patients with BMs eligible for the analysis were identified. All patients were pretreated with trastuzumab for metastatic disease. No patients had received prior lapatinib and/or capecitabine. RESULTS: Median age was 45 years (range 24-75) and 26 of 30 patients (86.7%) had received prior cranial radiotherapy. In the 22 patients with BMs evaluable for response, 7 partial responses (31.8%) and 6 disease stabilizations (27.3%) were observed. Overall, the median brain-specific progression-free survival was 5.6 months (95% confidence interval 4.4-6.8). Patients treated with LC had a median overall survival (from the time of development of BMs) significantly longer compared with 23 patients treated with trastuzumab-based therapies only beyond brain progression (27.9 months versus 16.7 months, respectively, P = 0.01). CONCLUSIONS: LC is active for BMs from HER2+ BC in patients not pretreated with either lapatinib or capecitabine. The introduction of LC after the development of BMs may further improve survival compared with trastuzumab-based therapies only beyond brain progression.

First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2,251 patients.

BACKGROUND: First-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer (LR/mBC). This large, open-label study further assesses first-line bevacizumab with taxane-based chemotherapy in routine oncology practice. PATIENTS AND METHODS: Patients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of zero to two and no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity or patient withdrawal. The primary end point was safety; time to progression (TtP) was a secondary end point. RESULTS: Median follow-up in 2251 treated patients was 12.7 months. Median age was 53 years and 94% of patients had ECOG PS of zero or one. Bevacizumab was most commonly administered with single-agent paclitaxel (35%), single-agent docetaxel (33%) or taxane-based combination therapy (10%). The most frequent grade ≥3 adverse event (AE) was neutropenia (5.4%). Grade ≥3 AEs previously associated with bevacizumab included hypertension (4.4%), arterial/venous thromboembolism (3.2%), proteinuria (1.7%) and bleeding (1.4%). No new bevacizumab safety signals were observed. Median TtP was 9.5 months (95% confidence interval 9.1-9.9). CONCLUSIONS: The study population in ATHENA was more representative of general oncology practice than populations enrolled into randomised trials, although there may have been some bias towards younger, fitter patients. The safety and efficacy of bevacizumab-taxane therapy in this large study were consistent with results from randomised first-line trials.

Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI).

BACKGROUND: We evaluated the efficacy and safety of the nontaxane microtubule dynamics inhibitor eribulin plus the humanized anti-VEGF monoclonal antibody bevacizumab in a novel second-line chemotherapy scheme in HER2-negative metastatic breast cancer (MBC) patients progressing after first-line paclitaxel and bevacizumab. PATIENTS AND METHODS: This is a multicenter, single-arm, Simon's two-stage, phase II study. The primary endpoint was the overall response rate, considered as the sum of partial and complete response based on the best overall response rate (BORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate. RESULTS: A total of 58 of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% CI 14.5-37.3). The clinical benefit rate was 32.8% (95% CI 21.3-46.0). The median PFS was 6.2 months (95% CI 4.0-7.8), and median OS was 14.8 months (95% CI 12.6-22.8). Overall, adverse events (AEs) were clinically manageable and the most common AEs were fatigue, paresthesia, and neutropenia. Quality of life was well preserved in most patients. CONCLUSIONS: The results of this study suggest that second-line therapy with bevacizumab in combination with eribulin has a meaningful clinical activity and may represent a potential therapeutic option for patients with HER2-negative MBC.

T-DM1 versus pertuzumab, trastuzumab and a taxane as first-line therapy of early-relapsed HER2-positive metastatic breast cancer: an Italian multicenter observational study.

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.

Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy.

BACKGROUND: To reduce side-effects of corticosteroid-containing antiemetic regimens, tailoring antiemetic schedules to specific requirements of different patients could be of benefit. We evaluated the possibility to reduce the total dose of corticosteroids when palonosetron, a long-acting second-generation 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, is used. MATERIALS AND METHODS: Double-blind, multicentre, noninferiority study of chemotherapy-naive breast cancer patients receiving 0.25 mg palonosetron and 8 mg dexamethasone on day 1, randomly assigned to receive placebo (n = 151) or 4 mg b.i.d. dexamethasone (n = 149) on days 2 and 3. Primary end point was complete response (CR) rate (no emesis, no rescue medication) in the overall (days 1-5) period. Secondary end points were CR rates in the acute (day 1) and delayed (days 2-5) periods, rates of no emesis and no nausea and impact on daily functioning (Functional Living Index-Emesis). RESULTS: Noninferiority between the two treatments was demonstrated by similar CR rates (P = 0.487) in the overall period. Most parameters showed that palonosetron and dexamethasone on day 1 only offer chemotherapy-induced nausea and vomiting protection similar to multiple-day dexamethasone administration. CONCLUSION: In patients treated with a single injection of palonosetron on day 1, reducing dexamethasone is an option that is not associated with significant reduction in antiemetic control during the 5-day period or an impact on patient functioning.

In situ protein expression of RRM1, ERCC1, and BRCA1 in metastatic breast cancer patients treated with gemcitabine-based chemotherapy.

Ribonucleotide reductase 1 (RRM1) is a determinant of gemcitabine efficacy in non-small-cell lung cancer and pancreatic cancer. We investigated the protein levels of RRM1 and two other DNA repair enzymes, ERCC1 and BRCA1, in 55 metastatic breast cancer (MBC) patients undergoing gemcitabine-based chemotherapy. With automated in situ protein quantification (AQUA v1.6), the average scores for RRM1, ERCC1, and BRCA1 ranged from 245.6-2774.1, 74.0-410.3, and 54.4-1833.1, respectively. They were significantly associated with each other (Spearman's rho > or = .36; p < or = .007). Given their pattern of distribution, RRM1 and BRCA1 are potentially suitable markers for clinical decision making in MBC.

Metastatic or locally advanced breast cancer patients: towards an expert consensus on nab-paclitaxel treatment in HER2-negative tumours-the MACBETH project.

INTRODUCTION: Despite the large use of nab-paclitaxel as a treatment option in metastatic breast cancer (MBC) across different countries, no definitive data are available in particular clinical situations. AREAS COVERED: Efficacy, safety and schedule issues concerning available literature on nab-paclitaxel in advanced breast cancer and in specific subgroups of patients have been discussed and voted during an International Expert Meeting. Ten expert specialists in oncology, with extensive clinical experience on Nab-P and publications in the field of MBC have been identified. Six scientific areas of interest have been covered, generating 13 specific Statements for Nab-P, after literature review. For efficacy issues, a summary of research quality was performed adopting the GRADE algorithm for evidence scoring. The panel members were invited to express their opinion on the statements, in case of disagreement all the controversial opinions and the relative motivations have been made public. EXPERT OPINION: Consensus was reached in 30.8% of the Nab-P statements, mainly those regarding safety issues, whereas ones regarding efficacy and schedule still remain controversial areas, requiring further data originated by the literature.

Male breast cancer: 6-year experience.

AIM: Breast cancer in men is a very rare neoplasm accounting 1% of all breast cancer with an incidence ratio of 1:100 of men to women and about 1% of all malignancies in men. On the basis of the literature review the authors tried to determine the main characteristics of this rare neoplasm in terms of epidemiology, diagnosis, prognosis, treatment and survival. METHODS: The authors report the experience of the Breast Unit of the San Giovanni Addolorata Hospital in Rome, where 4 cases of male breast cancer were observed and treated over 784 breast cancers. RESULTS: All tumours were ductal carcinomas. The extent of disease was as follows: 3 cases with stage I and 1 case with Stage IIIB; in two cases estrogen and progesterone receptors expression was 100% and in the other two cases it was 20-80%. Median follow up was 57.5 months. At present, after 6-year follow up the three patients with stage I are in good conditions; the patient with stage III died after 27 months with metastatic disease. CONCLUSIONS: Surgical treatment remains the gold standard in male breast cancer. The prognosis for males with breast cancer is similar to female patients on equal terms of stage of disease. Adjuvant therapy is based on retrospective studies of male breast cancer conducted over the past 20 years using the guidelines for breast cancer in women.