Neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios in breast cancer

n/

Clinical outcomes after palbociclib with or without endocrine therapy in postmenopausal women with hormone receptor positive and HER2-negative metastatic breast cancer enrolled in the TREnd trial

Currently, there is limited data regarding the effectiveness of standard subsequent line therapies such as endocrine therapy, chemotherapy, or targeted agents after progression on CDK4/6 inhibitor-based regimens. This paper describes time-to-treatment failure beyond progression on palbociclib or palbociclib+endocrine therapy in patients enrolled in the phase II, multicenter TREnd trial. Our results indicate that there is limited benefit from post-palbociclib treatment, regardless of the type of therapy received. A small population of long responders were identified who demonstrated ongoing benefit from a subsequent line of endocrine therapy after progression to palbociclib-based regimens. A translational research program is ongoing on this population of outliers

Pattern of metastasis and outcome in patients with breast cancer

There is growing evidence about differences in metastatic spread among breast cancer (BC) biologic subtypes (BS). Aim of this study was to analyze the pattern of metastasization according to BS and to explore the corresponding prognosis. A series of 544 consecutive patients receiving anticancer therapy for metastatic BC from 2004 to 2013, was analyzed. BS were defined by immunohistochemistry according to St Gallen 2013 criteria. Association between BS and the different distant localizations was analyzed. Prognosis was described in terms of overall survival (OS), progression free survival (PFS) and post progression survival (PPS). Results were reported taking luminal A BC as reference. Triple negative BC showed a higher tropism for lung (OR 4.30 95% CI 1.41-13.1), while non luminal HER2 subtype was associated with a higher rate of liver metastases (OR 3.61 95% CI 1.36-9.58). All subtypes were associated with a lower risk of bone-only localization. Central nervous system (CNS) involvement was more common in HER2 positive BC (OR 6.3, 95% CI 1.08-36.66). Liver, lung and CNS involvement influenced negatively OS (HR 1.64, 95% CI 1.29-2.07; HR 1.49, 95% CI 1.18-1.90; HR 2.891, 95% CI 1.85-4.51, respectively) and PFS (HR 1.39, 95% CI 1.13-1.71; HR 1.26, 95% CI 1.02-1.55; HR 1.75, 95% CI 1.12-2.71, respectively). Multivariate analysis confirmed liver involvement as independent predictor of worse OS (HR 1.64, 95% CI 1.15-2.34). Stratification by metastatic pattern showed significant differences in terms of PPS but not in terms of PFS. The study suggests that BS may be characterized by typical patterns of metastatic spread and have different impact on clinical outcome

Risk factors and survival outcomes in patients with brain metastases from breast cancer

Development of central nervous system (CNS) metastases in breast cancer (BC) is associated with poor prognosis. The incidence of CNS metastases in metastatic BC is reported to be about 10-16 %, but different subtypes of BC are associated with different risk of developing CNS metastases. We retrospectively analysed the risk of CNS metastases and the outcome in a cohort of 473 patients with metastatic BC. CNS metastases were diagnosed in 15.6 % of patients and median survival from diagnosis of CNS metastases was 7.53 (25th-75th 2.8-18.9) months. The risk of developing CNS metastases was higher in patients with grade 3, hormone receptor negative, HER2-positive, high Ki-67 BC. When compared to luminal A subtype, only HER2-positive BC was associated with increased risk of CNS metastases. Survival from diagnosis of CNS metastases was longer in patients with HER2-positive BC, while it was shorter in patients that did not receive any locoregional treatment, or with extra-CNS disease, or with more than 3 CNS lesions

Prognostic significance of Ape1/Ref-1 subcellular localization in non-small cell lung carcinomas

PURPOSE: To evaluate the prognostic value of the DNA repair/redox-protein Ape1/ref-1 in a retrospective series of consecutive non-small cell lung carcinomas (NSCLC). PATIENTS AND METHODS: Sections from 91 radically resected NSCLC were analyzed for immunohistochemical expression of Ape1/ref-1. For each case 1,000 tumor cells were evaluated to detect nuclear and cytoplasmic reactivity scored as a percentage of positive cells. With respect to sub-cellular localization and percentage of immunoreactive cells, each tumor was classified as "cytoplasmic" or "non cytoplasmic". The survival rate according to Ape1/ref-1 sub-cellular localization was calculated. RESULTS: The main pattern of Ape1/ref-1 expression was nuclear. No significant difference was observed in Ape1/ref-1 pattern according to histotype (squamous vs adenocarcinoma). Among adenocarcinomas, a cytoplasmic expression of Ape1/ref-1 was significantly associated with poor survival rate in univariate (p=0.01) and multivariate (p=0.07) analyses. In addition, a cytoplasmic expression of the DNA repair protein was also predictive of worse prognosis (log-rank test, p=0.02) in cases with lymph node involvement, regardless of histotype. CONCLUSION: The results suggest a potential role of Ape1/ref-1 sub-cellular localization as a prognostic indicator in patients with NSCLC. In particular, cytoplasmic localization of the protein seems to confer a poor outcome in subgroups of patients with nodal involvement or adenocarcinoma histotype

Measures of outcome inmetastatic breast cancer : insights from a real-world scenario

No gold standard treatment exists for metastatic breast cancer (MBC). Clinical decision making is based on knowledge of prognostic and predictive factors that are extrapolated from clinical trials and, sometimes, are not reliably transferable to a real-world scenario. Moreover, misalignment between endpoints used in drug development and measures of outcome in clinical practice has been noted. The roles of overall survival (OS) and progression-free survival (PFS) as primary endpoints in the context of clinical trials are the subjects of lively debate. Information about these parameters in routine clinical practice is potentially useful to design new studies and/or to interpret the results of clinical research. This study analyzed the impact of patient and tumor characteristics on the major measures of outcome across different lines of treatment in a cohort of 472 patients treated for MBC. OS, PFS, and postprogression survival (PPS) were analyzed. The study showed how biological and clinical characteristics may have different prognostic value across different lines of therapy for MBC. After first-line treatment, themedian PPS of luminal A, luminal B, and human epidermal growth factor receptor 2 (HER2)-positive groups was longer than 12 months. The choice of OS as a primary endpoint for clinical trials could not be appropriatewith these subtypes. In contrast, OS could be an appropriate endpoint when PPS is expected to be low (e.g., triple-negative subtype after the first line; other subtypes after the third line). The potential implications of these findings are clinical and methodological

Tumor shrinkage evaluation during and after preoperative doxorubicin and cyclophosphamide followed by docetaxel in patients with breast cancer

Aim: To evaluate the relative activity of the sequential administration of doxorubicin and cyclophosphamide (AC) followed by docetaxel alone, as primary systemic therapy in patients with breast cancer, using an in vivo chemosensitivity predictive assay. Patients and Methods: Patients with stage IIIII breast cancer received two cycles of AC (60/600 mg/m2 every 3 weeks) followed by two cycles of docetaxel (100 mg/m2 every 3 weeks). All patients underwent comprehensive breast imaging prior to chemotherapy, after two AC and after docetaxel. Results: Forty-two patients were accrued and evaluated by intention-totreat analysis. After two cycles of AC, the median tumor shrinkage was 18.3%, whereas treatment with docetaxel provided an additional median tumor shrinkage of 34.2%. Pathological complete remission was observed in 5 patients (11.9%), whereas 26 patients (61.9%) experienced a partial response. Conclusion: The relative contribution of docetaxel to tumor mass reduction seemed to be greater than that of AC. However, the slow rate of tumor shrinkage observed may indicate that the activity of the first 2 cycles of AC is carried over into the part of treatment with docetaxel

Everolimus Plus Exemestane in Advanced Breast Cancer: Safety Results of the BALLET Study on Patients Previously Treated Without and with Chemotherapy in the Metastatic Setting

BACKGROUND: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%). PATIENTS AND METHODS: One thousand one hundred and fifty-one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%). RESULTS: One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus-related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus-related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting. CONCLUSION: Real-life data of the Italian patients BALLET-related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The Oncologist 2017;22:1-8Implications for Practice: With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis