Background: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. Patients and methods: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for !5 years AE abemaciclib for 2 years. Cohort 1 enrolled patients with !4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor !5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (!20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. Results: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib þ ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) ¼ 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P ¼ 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR ¼ 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR ¼ 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. Conclusion: Abemaciclib þ ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

Targeted therapies have allowed for an individualized treatment approach in non-small-cell lung cancer (NSCLC). The initial therapeutic decisions and success of targeted therapy depend on genetic identification of personal tumor profiles. Tissue biopsy is the gold standard for molecular analysis, but non-invasive or minimally invasive liquid biopsy methods are also now used in clinical practice, allowing for later monitoring and optimization of the cancer treatment. The inclusion of liquid biopsy in the management of NSCLC provides strong evidence on early treatment response, which becomes a basis for determining disease progression and the need for changes in treatment. Liquid biopsies can drive the decision making for treatment strategies to achieve better patient outcomes. Cell-free DNA and circulating tumor cells obtained from the blood are promising markers for determining patient status. They may improve cancer treatments, allow for better treatment control, enable early interventions, and change decision making from reactive actions toward more predictive early interventions. This review aimed to present current knowledge on and the usefulness of liquid biopsy studies in NSCLC from the perspective of how it has allowed individualized treatments according to gene profiling and how the method may alter the treatment decisions in the future.

Background: Human breast tissue undergoes phases of proliferation, differentiation and regression regulated by changes of the levels of circulating sex hormones during the menstrual cycle or aging. Ovarian hormones also likely play a key role in the etiology and biology of breast cancer. Reports concerning the proliferative effects of steroid hormones on the normal epithelium of human breast have been conflicting. Some studies have shown that steroid hormones may predispose breast epithelial cells to malignant changes by stimulating their proliferation, which is known to be regulated tightly by stromal cells.

T and DHT inhibited proliferation and increased apoptosis in the epithelium of cultured normal HBT and opposed E(2)-stimulated proliferation and cell survival in an AR-dependent manner. These effects were associated with changes in the proportions of ERα- and AR-positive epithelial cells.

In summary, Osp inhibited proliferation and opposed E2 stimulation in normal HBT in an efficacious, but less potent way than Ral and Tam. The ESR1 PvuII polymorphisms may influence the responsiveness of HBT to E2 and SERMs.

Introduction: Metronomic dosing is used to give continuous chemotherapy at low doses. The low doses have minimal side effects and may enable cancer treatment to be remodeled toward the management of chronic disease. Methods: We searched PubMed database to obtain relevant clinical trials studying metronomic chemotherapy (MCT). Our main focus was to find controlled phase II and phase III trials. Results: This systematic review summarizes the results of 91 clinical reports focusing on randomized phase II and phase III clinical studies between 2012 and 2018. During that time, nine randomized phase II and 10 randomized phase III studies were published. In the majority of the studies, MCT was well tolerated, and major side effects were rarely seen. Altogether, 4 phase III studies and 4 randomized phase II studies presented positive results and some clinical benefit. Discussion: Most of the studies did not show significantly improved overall survival or progressionfree survival. Typically, the metronomic dosing was explored in a maintenance setup and was added to other agents given within normal high doses, whereas no trial was performed challenging metronomic dosing and best supportive care in later treatment lines. Therefore, there is no definite evidence on the efficacy of single metronomic dosing and firm evidence of metronomic dosing is still missing. There is a need for further confirmation of the usefulness of this approach in clinical practice.

Cancer therapy decisions are often made according to the histopathological-molecular profile of tumor tissue obtained from surgery or biopsy. It has been shown that tumor profiles change with time and treatment, and that tumor tissue is heterogeneous. Thus, other approaches that are easily accessible and less invasive than surgery or biopsy to monitor responses to treatment and predict relapses are urgently needed. In the last few years, the term “liquid biopsies” has been introduced to represent multifunctional circulating biomarkers in the peripheral blood and other physiological fluids of patients with cancer. Liquid biopsies are a noninvasive alternative to tissue biopsies, but they have not been implemented in routine clinical practice for breast cancer. In addition, liquid biopsies seem to be a promising approach for personalized medicine, which enables the prediction, monitoring, and rational selection of appropriate therapy for individual patients. In this review, we outline recent progress and current challenges with liquid biopsies in clinical practice for breast cancer diagnosis, treatment choices, and responses to therapy from a clinician’s perspective.

Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of different cell types and their extracellular matrix (ECM). However, little is known about the composition of the ECM and its constituents in MBC. Decorin is a ubiquitous ECM macromolecule known of its oncosuppressive activity. As such, it provides an intriguing molecule in the development of novel therapeutics for different malignancies such as MBC. In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenotype of MBC explants by decreasing the amount of atypical cells and by inhibiting cell proliferation. The results of this study support approaches to develop new, decorin-based adjuvant therapies for MBC.Electronic supplementary materialThe online version of this article (doi:10.1007/s12307-017-0195-8) contains supplementary material, which is available to authorized users.