First Female Patient with a Rare CIC-FOXO4-Translocated Sarcoma: A Case Report.

Small round cell sarcoma is a group of undifferentiated malignancies arising in the bone and soft tissue, notable for Ewing sarcoma. Recently, a new World Health Organization classification has been introduced, including an additional subset of these sarcomas, named CIC-rearranged sarcoma. Within this group, CIC-FOXO4 translocation is an exceedingly rare fusion that has been reported only 4 times in the literature. Herein, we report in-depth the pathological, clinical, and molecular features of a CIC-FOXO4 translocation-driven tumor in a 46-year-old woman.

Identifying cultural, demographic, personal health and cancer-related barriers to integrative oncology care: a retrospective case-cohort study.

PURPOSE: Integrative oncology (IO) provides complementary and integrative medicine within conventional supportive and palliative cancer care. The present study set out to identify barriers to attending an integrative physician (IP) consultation, provided without charge within an IO treatment program. STUDY METHODS: Electronic files of adult oncology patients undergoing chemotherapy were studied. Patient-related characteristics were examined to identify factors associated with attendance at the IP consultation: socio-demographic (age, gender, country of birth, place of residence, primary language spoken); health- related (BMI, smoking, independent functioning); and cancer- related (primary tumor site, localized vs. metastatic). RESULTS: Only 257 of the 1912 patients studied (13.4%) attended the IP consultation, with female patients more likely to attend (p < 0.001), as well as younger patients (p = 0.002); those residing outside the Jerusalem municipality (p = 0.008); and patients whose primary language was Hebrew (p < 0.001). Non-smokers and functionally independent patients were also more likely to attend (p = 0.007 and 0.008, respectively), as were those diagnosed with breast/gynecological (p = 0.005) or gastrointestinal tumors (p = 0.002). Multivariate analysis showed a significantly greater likelihood of attending the consultation among females (OR 1.619, 95% CI 1.065-2.460; p = 0.024); younger patients (OR 1.019, 95% CI 1.007-1.031; p = 0.001); non-Arabic speakers (OR 8.220, 95% CI 3.310-20.413; p < 0.001); and patients diagnosed with a tumor other than lung cancer (OR 2.954, 95% CI 1.259-6.933; p = 0.013). CONCLUSION: Further prospective research addressing socio-demographic, personal health- and cancer-related characteristics of oncology patients is needed to address potential barriers to the provision of IO care within a diverse, equitable and inclusive setting of care.

Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

BACKGROUND: The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype-specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first-line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) sites. METHODS: The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status ≤2, and an age ≥ 18 years. The endpoints were progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval-censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent. RESULTS: Three hundred three patients from 18 EORTC-STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score-matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2-9.7 months), 8.2 months (95% CI, 5.2-10.1 months), and 4.8 months (95% CI, 2.3-6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52-0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9-47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7-33.4 months; HR, 0.65; 95% CI, 0.40-1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0-36.3 months; HR, 0.66; 95% CI, 0.43-0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS. CONCLUSIONS: This is the largest retrospective study of first-line treatment for advanced leiomyosarcoma. In the propensity score-matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials.

Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0-10, 17.8%; RS 11-25, 62.5%; RS 26-100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0-10, 11-25, and 26-100: 2.6% (95% confidence interval [CI], 1.1-6.2%), 6.1% (95% CI, 4.4-8.6%), and 13.1% (95% CI, 9.4-18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1-5.1%), 2.2% (95% CI, 1.3-3.7%), and 9.5% (95% CI, 6.0-14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0-10/11-25), 10-year distant recurrence and BCSM rates for RS 0-10 patients were 2.7% (95% CI, 1.1-6.5%) and 0.8% (95% CI, 0.1-5.3%), respectively, and for RS 11-25 patients, 5.7% (95% CI, 3.9-8.3%) and 2.0% (95% CI, 1.1-3.7%), respectively. For RS 11-25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0-25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26-100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.

Harnessing soft tissue sarcoma with low-dose pazopanib - a matter of blood levels.

BACKGROUND: Pazopanib is a tyrosine kinase inhibitor indicated for the treatment of renal cell carcinoma and soft tissue sarcoma. Despite the high inter-patient variability in pharmacokinetic exposure, pazopanib is administered at a fixed dose of 800 mg once daily (QD). Pharmacokinetic exposure is linked to both efficacy and toxicity. In this case report, we illustrate the value of therapeutic drug monitoring by describing two patients with adequate pazopanib trough concentrations (Cmin) at an eight times lower than standard dose. CASE PRESENTATION: Patient A is a 69-year-old woman with metastatic leiomyosarcoma who had significant toxicities and a high Cmin on the standard dose. While dose reductions to 200 mg QD and later 200 mg every other day were made, pazopanib Cmin remained above the efficacy threshold. Patient B is a 50-year-old male with metastatic angiosarcoma and a history of Gilbert syndrome. Pazopanib treatment was initiated at the standard dose of 800 mg QD, but was reduced to 200 mg QD 1-week-on - 1-week-off due to total bilirubin elevation. Pazopanib Cmin was adequate in this patient as well. CONCLUSION: It could be valuable to measure pazopanib levels in case of dose reductions due to toxicity, as exposure could still be adequate at considerably lower than standard doses.

More Than 50 Subtypes of Soft Tissue Sarcoma: Paving the Path for Histology-Driven Treatments.

Sarcomas are a diverse group of cancers with mesenchymal origin. Although sarcomas comprise less than 1% of cancers, there are more than 50 different subtypes that are quite different from one another in terms of both their biology and clinical behavior. Historically, the need for adequate patient numbers in clinical trials has pushed sarcoma researchers to lump these very different malignancies together and treat the patients using a "one-size-fits-all" approach. However, with improvements in our scientific understanding, we are finally ready for a histology-tailored therapeutic approach to these complex diseases. In this review, we discuss key advances in our understanding of the biology underlying selected sarcoma subtypes and how targeting these subtypes is relevant therapeutically with respect to both molecularly targeted agents as well as immunotherapy.

Intratumoral immune-biomarkers and mismatch repair status in leiyomyosarcoma -potential predictive markers for adjuvant treatment: a pilot study.

Leiomyosarcoma is the second most frequent soft-tissue sarcoma. Tumor lymphocytic infiltration (TIL) and programed cell death ligand-1 (PD-L1) have been associated with prognosis in different malignancies while DNA mismatch-repair deficiency (MMR-D) has been associated with response to check-point inhibitors. In this pilot study, we sought to examine TIL, PD-L1 and mismatch-repair (MMR) protein expression in 11 leiomyosarcoma and its association with outcome as potential biomarkers for adjuvant treatment. Eleven primary leiomyosarcoma archived-tissues were analyzed for expression of MMR proteins (MSH2, MLH1, MSH6 and PSM2), PD-L1 expression and PD-1, CD3 or CD8. MMR-D was detected in tumor tissue from 2/11 leiomyosarcoma patients. CD3 T-cells were present in all samples, whereas CD8 staining was positive in all but one. PDL-1 was positive in 4/11 and PD-L1 in 6/11. Interestingly, the three patients with the poorest outcome had strongly positive staining for PD-L1 and CD8 while in the two patients who are alive and recurrence-free, both PD-L1 and CD8 infiltration were lacking. We found an association between tumor infiltrating CD8 cytotoxic lymphocytes, strong PD-L1 staining and survival; suggesting a role as biomarkers for treatment decisions regarding peri-operative chemotherapy. We also identified MMR-D in two patients with leiomyosarcoma comprising 18% of our sample.

Patient and physician characteristics affect adherence to screening mammography: A population-based cohort study.

BACKGROUND: Screening mammograms are widely recommended biennially for women between the ages of 50 and 74. Despite the benefits of screening mammograms, full adherence to recommendations falls below 75% in most developed countries. Many studies have identified individual (obesity, smoking, socio-economic status, and co-morbid conditions) and primary-care physician parameters (physician age, gender, clinic size and cost) that influence adherence, but little data exists from large population studies regarding the interaction of these individual factors. METHODS: We performed a historical cohort study of 44,318 Israeli women age 56-74 using data captured from electronic medical records of a large Israeli health maintenance organization. Univariate analysis was used to examine the association between each factor and adherence (none, partial or full) with screening recommendations between 2008-2014. Multivariate analysis was used to examine the significance of these factors in combination, using binary and multinomial logistic regression. RESULTS: Among 44,318 women, 42%, 43% and 15% were fully, partially and non-adherent to screening recommendations, respectively. Factors associated with inferior adherence identified in our population included: smoking, obesity, low body weight, low socio-economic status, depression, diabetes mellitus and infrequent physician visits, while, women with ischemic heart disease, female physicians, physicians between the ages of 40 and 60, and medium-sized clinics were associated with higher screening rates. Most factors remained significant in the multivariate analysis. CONCLUSIONS: Both individual and primary-care physician factors contribute to adherence to mammography screening guidelines. Strategies to improve adherence and address disparities in mammography utilization will need to address these factors.

Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma.

Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma.

Chondromyxoid fibroma of the distal fibula treated by percutaneous radiofrequency ablation.

BACKGROUND: Percutaneous radiofrequency ablation (RFA) has been shown to be an effective treatment for soft tissue lesions and also benign bone tumors, especially osteoid osteoma. There are limited data regarding this technique in other bone tumors, specifically larger and more aggressive ones. PURPOSES: To describe the use of RFA as a definitive treatment and an alternative to traditional open surgery for the treatment of chondromyxoid fibroma (CMF), a benign but locally aggressive bone tumor. CASE PRESENTATION: An 11.5-year-old girl was diagnosed with a 4-cm lytic bone lesion of the distal fibula. Evaluation, including biopsy, revealed CMF. It was managed by fluoroscopy-guided RFA only. Six-year follow-up demonstrated complete healing without damage to the adjacent distal fibular growth plate. DISCUSSION AND CONCLUSIONS: RFA induces local heat in the ablation field and causes tissue necrosis. The depth of heat penetration and the size of heated sphere are accurately controlled by modern types of ablation probes and accurate positioning. The current report demonstrates the ability to use this percutaneous technique for larger and more aggressive bone tumors than has been indicated previously.

Treatment patterns and clinical outcomes with pazopanib in patients with advanced soft tissue sarcomas in a compassionate use setting: results of the SPIRE study.

BACKGROUND: A named patient program (NPP) was designed to provide patients with advanced soft-tissue sarcoma (aSTS) access to pazopanib, a multitargeted tyrosine kinase inhibitor. The SPIRE study was a retrospective chart review of participating patients. PATIENTS AND METHODS: Eligibility criteria for the NPP and SPIRE mirrored those of the pivotal phase-III study, PALETTE, which compared pazopanib with placebo in patients ≥18 years with aSTS and whose disease had progressed during or following prior chemotherapy or were otherwise unsuitable for chemotherapy. Outcomes of interest included treatment patterns, treatment duration, relative dose intensity, progression-free survival (PFS), overall survival (OS), clinical benefit rate, adverse events (AEs) and reasons for treatment discontinuation. RESULTS: A total of 211 patients were enrolled (median age 56 years; 60% female). Most patients received pazopanib in second- and third-line therapy (28.0% and 28.4%, respectively), followed by fourth line (19.0%) and ≥ fifth line (18.5%). The median duration of pazopanib treatment was 3.1 months (95% CI: 2.8-3.8), with a mean daily dose of 715 mg equating to 92% of recommended dose. Median OS was 11.1 months and clinical benefit rate was 46%. There was evidence of some clinical benefit across most histological subtypes. At study end, 40% of patients were alive and of these, 18% remained on pazopanib. Thirteen percent (13%) of patients discontinued pazopanib due to AEs. CONCLUSIONS: The SPIRE study demonstrated activity of pazopanib in heavily pretreated aSTS patients in a compassionate use setting. No new safety concerns were noted. Reassuringly, the relative dose intensity of pazopanib was 92%.

Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients.

Molecular portraits of numerous tumors have flooded oncologists with vast amounts of data. In parallel, effective inhibitors of central pathways have shown great clinical benefit. Together, this promises potential clinical benefits to otherwise end-stage cancer patients. Here, we report a clinical service offering mutation detection of archived samples using the ion Ampliseq cancer panel coupled with clinical consultation.A multidisciplinary think tank consisting of oncologists, molecular-biologists, genetic counselors, and pathologists discussed 67 heavily pretreated, advanced cancer patient cases, taking into account mutations identified using ion Ampliseq cancer panel, medical history, and relevant literature.The team generated a treatment plan, targeting specific mutations, for 41 out of 64 cases. Three patients died before results were available. For 32 patients, the treating oncologists chose not to include the panel recommendation in the treatment plan for various reasons. Nine patients were treated as recommended by the panel, 5 with clinical benefit, and 4 with disease progression.This study suggests that routine use of massive parallel tumor sequencing is feasible and can judiciously affect treatment decisions when coupled with multidisciplinary team-based decision making. Administration of personalized based therapies at an earlier stage of disease, expansion of genetic alterations examined, and increased availability of targeted therapies may lead to further improvement in the clinical outcome of metastatic cancer patients.

Gemcitabine in combination with paclitaxel for advanced soft-tissue sarcomas.

A limited number of chemotherapeutic agents have been found to be active against advanced soft-tissue sarcomas (STSs), particularly sarcomas that have progressed following doxorubicin treatment. The aim of this retrospective study was to determine the response to treatment with gemcitabine plus paclitaxel in patients with STSs. Data were collected on all patients with advanced non-resectable STS who were treated with a fixed dose 700 mg/m2 gemcitabine in combination with 70 mg/m2 paclitaxel on days 1 and 8 every 3 weeks. A total of 30 patients were included, with a median age of 56.4 years (range, 40-70 years). The gemcitabine/paclitaxel combination was well tolerated, with an overall response in 27% and a clinical benefit in 57% of the patients. The median progression-free survival was 6.1 months and the overall survival was 14.3 months. In conclusion, gemcitabine plus paclitaxel was found to be tolerable and effective in patients with advanced STSs.

Tumor STAT3 tyrosine phosphorylation status, as a predictor of benefit from adjuvant chemotherapy for breast cancer.

Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signaling pathways. In breast cancer cell lines and xenograft models activated STAT3 participates in breast tumorigenesis, while studies in humans have demonstrated that phosphorylated (tyrosine705)-STAT3 is a marker of good prognosis in breast cancer. In order to resolve this paradox we hypothesized that in clinic, phospho-STAT3 has a predictive role of benefit from adjuvant chemotherapy; therefore the goal of this study was to determine the usefulness of phospho-STAT3 status as a predictor of benefit from adjuvant chemotherapy in breast cancer patients. Immunohistochemical analysis of phospho-STAT3 was performed on a tissue microarray of breast cancer specimens. The expression pattern of phospho-STAT3 was retrospectively correlated with pathological parameters and overall survival in patients who were or were not treated with adjuvant chemotherapy. Of 375 tissue specimens interpretable for phospho-STAT3, 134 (36 %) exhibited positive phospho-STAT3 nuclear expression. Among 234 patients who received adjuvant therapy, those with tumors displaying positive phospho-STAT3 nuclear expression had a better ten-year rate of overall survival than patients with tumors displaying negative phospho-STAT3 nuclear expression (P = 0.001). Among patients who did not received adjuvant chemotherapy, positive phospho-STAT3 nuclear status was not correlated with increased overall survival (P = 0.54). Positive phospho-STAT3 was correlated with improved overall survival only among patients who received adjuvant chemotherapy in a multivariate analysis adjusted for stage, grade, hormonal status, Her2 status, and age, irrespective of the chemotherapy regimen received (hazard ratio for death, 0.35 [95 % CI 0.188-0.667]; P = 0.001). These findings support the role of phospho-STAT3 as a marker of favorable outcome in breast cancer patients treated with adjuvant chemotherapy. Whether phospho-STAT3 has a predictive role of benefit from adjuvant chemotherapy has to be validated on prospective, randomized, controlled studies.

Association between patient age, volume of breast tissue excised, and local recurrence.

INTRODUCTION: Young breast cancer patients undergoing breast-conserving surgery have a significantly higher rate of local recurrence compared with older women. The aim of this study was to assess whether the volume of tissue excised may be associated with the higher local recurrence rate seen in young patients. METHODS: Medical records of patients who underwent breast-conserving surgery at a single institution between 1987 and 2001 were reviewed retrospectively. Tumor and specimen volumes were extracted from pathology reports, and specimen-to-tumor-volume ratio (STVR) was calculated. STVR and local recurrence rates were compared for women under 40 and over 50 y of age. RESULTS: Data were available for 97 patients under age 40 and 150 women over age 50. Patients under 40 had significantly more high-grade tumors (57% versus 25%, P < 0.0005). There was no significant difference in average tumor size; however, both specimen volume and STVR (log scale) were lower in younger women: 4.63 versus 5.20, P < 0.001 and 3.81 versus 4.55, P < 0.001, respectively. Younger women also had a significantly higher rate of local recurrence: 17% versus 7%, P = 0.03. On multivariate analysis, lower STVR was significantly associated with a higher recurrence rate for the entire group (P < 0.005) and, to a lesser degree, in younger women (P = 0.05). CONCLUSIONS: The volume of tissue removed in women younger than 40 undergoing breast-conserving therapy tends to be smaller than in older women. This may contribute to the higher local recurrence rates observed in young breast cancer patients.

Women's post-chemotherapy parity is affected by offspring number and marital status.

Childbearing rates post-chemotherapy for breast cancer (BC) are affected by age and chemotherapy-type but may also depend on personal characteristics. In this single institution retrospective study we evaluated post-chemotherapy fertility and its association with offspring number and marital-status at the time of BC diagnosis. We identified 65 fertile BC patients under 38y, who received adjuvant-chemotherapy. Menses resumption and pregnancies along with offspring-number and marital-status were recorded. Menses resumed in 95.4% and 33.8% gave birth. Of those who did not give birth 46.5% had at least three children at diagnosis and of those without children 83% were unmarried. Our data associates multiparity with lower childbearing post-chemotherapy, suggesting it as a possible surrogate for women's preferences in retrospective studies. Unlike multiparity, marital status association with lower childbearing may be culture-dependent and not a universal surrogate for women's intentions and would be best investigated prospectively.

Anti-tumor effects of the Notch pathway in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are driven by gain-of-function mutations of KIT or PDGFRa. The introduction of imatinib has significantly extended survival for patients. However, most patients develop resistances. Notch signaling is a conserved developmental pathway known to play a critical role in the development of several cancers, functioning as a tumor promoter or a tumor suppressor. Given that the normal progenitor cell for GIST, the interstitial cell of Cajal, has characteristics similar to those of cells of neuroendocrine origin, we hypothesized that Notch pathway impacts the biology of GIST cells. In this study, we retrovirally and pharmacologically manipulated the Notch pathway in human GIST cells. We also performed a retrospective analysis of a cohort on 15 primary tumors to determine the role of Hes1, a major target gene of Notch, as a prognostic marker for GIST. Constitutively, active intracellular domain of Notch1 (ICN1) expression potently induced growth arrest and downregulated KIT expression in vitro. Additionally, treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid caused dose-dependent upregulation of Notch1 expression and a parallel decrease in viability in these cells. Retroviral silencing of downstream targets of Notch (dominant-negative Hes1) and pharmacological inhibition of Notch activation (γ-secretase inhibition) partially rescued GIST cells from suberoylanilide hydroxamic acid treatment. GIST patients with high Hes1 mRNA levels have a significantly longer relapse-free survival. These results identify a novel anti-tumor effect of Notch1 and cross talk between the Notch and KIT pathways. Thus, activation of this pathway by treatment with histone deacetylase inhibitors is an appealing potential therapeutic strategy for GISTs. Précis: This study is the first report of the tumor suppressor effects of Notch pathway in gastrointestinal stromal tumors via a negative feedback with the oncogene KIT and may lead the development of new therapeutic strategies for GISTs patients.

[Update: adjuvant trastuzumab in HER2 positive breast cancer].

Some of the women who undergo surgery for the removal of breast cancer will need adjuvant treatment with chemotherapy, hormonal therapy, biological therapy or radiation therapy. In patients whose tumor expresses HER2, the adjuvant treatment will include Trastuzumab. In a number of prospective randomized trials performed in recent years, Trastuzumab was proven to have a significant effect in reducing by half the incidence of the recurrence of the disease and reducing the risk of death by a third. It is important to provide Trastuzumab as early as possible, together with the chemotherapy, unless treatment with doxorubicin is needed and then Trastuzumab is given later. The most significant side effect of Trastuzumab is cardiac toxicity, which is manifested in most cases by an asymptomatic decrease of the left ventricular ejection fraction in 2.3-17.3% of patients, although in most cases this has no clinical significance. Symptomatic heart failure is a rare event in Trastuzumab treated patients, occurring in 0-4% of patients and it is generally reversible with Trastuzumab discontinuation. In this review we summarize the current perspective on Trastuzumab and discuss adjuvant treatments in HER2-positive early breast cancer.