Paziente con carcinoma mammario metastatico, HER2-positivo, resistente a trastuzumab e pertuzumab ma responsivo a lapatinib

Lapatinib is an intracellular tyrosine kinase inhibitor of EGFR (ErbB1) and HER2 (ErbB2) receptors, approved for the treatment of metastatic breast carcinoma pre-treated with anti-HER2 antibodies. We report the case of a 60-year-old woman diagnosed with metastatic breast neoplasm, HER2-positive, progressing after treatment with trastuzumab, pertuzumab and T-DM1, who obtained a regression of hepatic metastases after treatment with lapatinib-capecitabine (Oncology)

Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively.In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatini

MORFEO enters final design phase

MORFEO (Multi-conjugate adaptive Optics Relay For ELT Observations, formerly MAORY), the MCAO system for the ELT, will provide diffraction-limited optical quality to the large field camera MICADO. MORFEO has officially passed the Preliminary Design Review and it is entering the final design phase. We present the current status of the project, with a focus on the adaptive optics system aspects and expected milestones during the next project phase

Eribulin as an effective monotherapy in a chemo-pretreated woman with metastatic breast cancer: a case report

Anthracycline- or taxane-based regimens are commonly used in the treatment of breast cancer, often in the (neo)adjuvant and first-line metastatic settings. However, to date, there is no single accepted standard of care after failure of these cytotoxic agents. Following the promising results obtained in the Phase III EMBRACE study, eribulin mesylate was approved for the treatment of metastatic breast cancer patients after progression with anthracyclines and taxanes unless contraindications. This case report describes a chemo-pretreated woman with important pleural effusion, nodal, locoregional involvement from breast cancer who had a disease response after treatment with eribulin in second line. This case underlines how this well-tolerated monochemotherapy may be able to obtain a prolonged disease control and a good clinical outcome

Gene Expression Assay in the Management of Early Breast Cancer

The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of patients could be exposed to unnecessary treatment-related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician decision-making process and to taylor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay)

Targeting Cell Cycle in Breast Cancer: CDK4/6 Inhibitors

Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been approved by FDA for the treatment of hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. These agents have been effective in improving the clinical outcomes, but the development of intrinsic or acquired resistance can limit the efficacy of these treatments. Clinical and translational research is now focused on investigation of the mechanism of sensitivity/resistance to CDK4/6 inhibition and novel therapeutic strategies aimed to improve clinical outcomes. This review summarizes the available knowledge regarding CDK4/6 inhibitor, the discovery of new biomarkers of response, and the biological rationale for new combination strategies of treatment

PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score\uae (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS\uae results in Italy and its impact on treatment decisions. Physicians' treatment recommendations (HT\u2009\ub1\u2009CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2- early BC population studied (N\u2009=\u20091738), physicians recommended CT\u2009+\u2009HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use

Human epidermal growth factor receptor 2 dual blockade with trastuzumab and pertuzumab in real life: Italian clinical practice versus the CLEOPATRA trial results

Objectives Given their inclusion and exclusion criteria, randomized clinical trials (RCT) might not include a population that truly mirrors real life (RL). This raises concerns about the applicability of RCT results in clinical practice. We evaluated the efficacy of anti-HER2 treatment with pertuzumab combined with trastuzumab and a taxane as first-line treatment for HER2-positive metastatic breast cancer in a RL setting, and compared the safety results obtained in our population versus the experimental cohort of the CLEOPATRA RCT, which led to the approval of this therapy. Materials and methods Patients treated with trastuzumab, pertuzumab and a taxane were enrolled in this retrospective study. We compared the tumor features and the patients' characteristics of the RL cohort to those of the CLEOPATRA cohort. We also compared the median progression-free survival (PFS) in the RL population versus specific patients' subgroups. Results RL patients were more frequently HR-positive, less likely to have visceral metastases (P <.001 for both) and had more frequently received (neo)adjuvant hormone therapy or trastuzumab than CLEOPATRA patients (P =.004 and P <.001, respectively). The median number of anti-HER2 cycles was 8 vs 24 and the median number of cycles was 7 vs 8 for docetaxel in the RL versus CLEOPATRA population, respectively. Adverse reactions of all grades were less frequent in RL. Median PFS was 27.8 months in the RL population and the treatment was equally effective in all patients' subgroups. Conclusion This study provides compelling evidence that pertuzumab, trastuzumab and a taxane are effective and safe also in a clinical scenario