Treatment patterns and clinical outcomes for patients with de novo versus recurrent HER2-positive metastatic breast cancer

Improvements in screening and adjuvant therapy for breast cancer are associated with decreased recurrence, which may have the effect of increasing the proportion of patients presenting with first-line de novo versus recurrent metastatic breast cancer (MBC). Here, we describe and compare patients with de novo versus recurrent human epidermal growth factor 2 (HER2)-positive MBC. registHER was a prospective observational cohort study (late 2003–early 2006) of 1,023 patients with HER2-positive MBC. Baseline characteristics, treatment patterns, and clinical outcomes were examined in patients with newly diagnosed de novo (n = 327) compared with recurrent HER2-positive MBC after prior treatment for early-stage disease (n = 674). Patients with de novo HER2-positive MBC were less likely to have lung metastases, more likely to have lymph node, bone, and/or liver metastases and >4 sites of metastases and more likely to receive combined or concurrent chemotherapy and hormonal therapy with or without trastuzumab than those with recurrent HER2-positive MBC. Median follow-up was 29 months. Median progression-free survival was 12.1 versus 9.3 months [hazard ratio = 0.716 (95 % confidence interval (CI) 0.617–0.831)], and overall survival was 41.7 versus 32.8 months [hazard ratio = 0.766 (95 % CI 0.633–0.928)] for patients with de novo versus recurrent HER2-positive MBC, respectively. Patients with recurrent HER2-positive MBC had similar outcomes regardless of whether they received prior adjuvant therapy, excluding hormonal therapy. Despite presenting with more advanced-stage disease and higher tumor burdens, patients with de novo HER2-positive MBC have more favorable clinical outcomes than those with recurrent HER2-positive MBC. These differences may be due to effects of prior drug exposure and could have implications for designing and interpreting clinical trials

A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO).

PURPOSE:To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer. PATIENTS AND METHODS:ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. RESULTS:We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31-75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10-35; cohort 1] and 37% [95% CI, 22-55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC), and 29% (hormone receptor-positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval 6 months). CONCLUSIONS:Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation

Antiangiogenic therapy for breast cancer

Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria

Erratum to: Analysis of in vitro ADCC and clinical response to trastuzumab: possible relevance of Fc\u3b3RIIIA/Fc\u3b3RIIA gene polymorphisms and HER-2 expression levels on breast cancer cell lines

BACKGROUND: Trastuzumab is a humanized monoclonal antibody (mAb) currently used for the treatment of breast cancer (BC) patients with HER-2 overexpressing tumor subtype. Previous data reported the involvement of FcγRIIIA/IIA gene polymorphisms and/or antibody-dependent cellular cytotoxicity (ADCC) in the therapeutic efficacy of trastuzumab, although results on these issues are still controversial. This study was aimed to evaluate in vitro the functional relationships among FcγRIIIA/IIA polymorphisms, ADCC intensity and HER-2 expression on tumor target cells and to correlate them with response to trastuzumab. PATIENTS AND METHODS: Twenty-five patients with HER-2 overexpressing BC, receiving trastuzumab in a neoadjuvant (NEO) or metastatic (MTS) setting, were genotyped for the FcγRIIIA 158V>F and FcγRIIA 131H>R polymorphisms by a newly developed pyrosequencing assay and by multiplex Tetra-primer-ARMS PCR, respectively. Trastuzumab-mediated ADCC of patients’ peripheral blood mononuclear cells (PBMCs) was evaluated prior to therapy and measured by (51)Chromium release using as targets three human BC cell lines showing different levels of reactivity with trastuzumab. RESULTS: We found that the FcγRIIIA 158F and/or the FcγRIIA 131R variants, commonly reported as unfavorable in BC, may actually behave as ADCC favorable genotypes, in both the NEO (P ranging from 0.009 to 0.039 and from 0.007 to 0.047, respectively) and MTS (P ranging from 0.009 to 0.032 and P = 0.034, respectively) patients. The ADCC intensity was affected by different levels of trastuzumab reactivity with BC target cells. In this context, the MCF-7 cell line, showing the lowest reactivity with trastuzumab, resulted the most suitable cell line for evaluating ADCC and response to trastuzumab. Indeed, we found a statistically significant correlation between an increased frequency of patients showing ADCC of MCF-7 and complete response to trastuzumab in the NEO setting (P = 0.006). CONCLUSIONS: Although this study was performed in a limited number of patients, it would indicate a correlation of FcγR gene polymorphisms to the ADCC extent in combination with the HER-2 expression levels on tumor target cells in BC patients. However, to confirm our findings further experimental evidences obtained from a larger cohort of BC patients are mandatory. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0680-0) contains supplementary material, which is available to authorized users

Focusing on fast food restaurants alone underestimates the relationship between neighborhood deprivation and exposure to fast food in a large rural area

<p>Abstract</p> <p>Background</p> <p>Individuals and families are relying more on food prepared outside the home as a source for at-home and away-from-home consumption. Restricting the estimation of fast-food access to fast-food restaurants alone may underestimate potential spatial access to fast food.</p> <p>Methods</p> <p>The study used data from the 2006 Brazos Valley Food Environment Project (BVFEP) and the 2000 U.S. Census Summary File 3 for six rural counties in the Texas Brazos Valley region. BVFEP ground-truthed data included identification and geocoding of all fast-food restaurants, convenience stores, supermarkets, and grocery stores in study area and on-site assessment of the availability and variety of fast-food lunch/dinner entrées and side dishes. Network distance was calculated from the population-weighted centroid of each census block group to all retail locations that marketed fast food (<it>n </it>= 205 fast-food opportunities).</p> <p>Results</p> <p>Spatial access to fast-food opportunities (FFO) was significantly better than to traditional fast-food restaurants (FFR). The median distance to the nearest FFO was 2.7 miles, compared with 4.5 miles to the nearest FFR. Residents of high deprivation neighborhoods had better spatial access to a variety of healthier fast-food entrée and side dish options than residents of low deprivation neighborhoods.</p> <p>Conclusions</p> <p>Our analyses revealed that identifying fast-food restaurants as the sole source of fast-food entrées and side dishes underestimated neighborhood exposure to fast food, in terms of both neighborhood proximity and coverage. Potential interventions must consider all retail opportunities for fast food, and not just traditional FFR.</p