Search

The landscape of therapeutic options for the treatment of hormone receptor (HR)-positive (HR + ) HER2 - breast cancer (BC) has been profoundly changed by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into the metastatic setting. Currently all CDK4/6 inhibitors are approved only in the metastatic setting by Food and Drug Administration (FDA) and European Medicine Agency (EMA), whereas their role in the neoadjuvant setting is still at an investigational stage. Exploitation of novel agents such as CDK4/6 inhibitors to improve the efficacy of neoadjuvant endocrine therapy (ET) or to overcome de novo resistance to ET is an area of research under active evaluation. We present a review of the currently available data and ongoing clinical trials that are evaluating the role of CDK4/6 inhibitors in neoadjuvant therapy of HR + HER2 - early BC, and also illustrate translational aspects, such as the potential biomarkers of response to these new therapeutic agents., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Patients with luminal early breast cancer are at risk of relapse, even after five years of adjuvant endocrine therapy. To date, no biomarkers have been clinically validated to identify those patients at risk of late recurrence, who might benefit from extended adjuvant endocrine therapy. In recent decades, multiple clinical trials have tested the role of extending adjuvant endocrine therapies in patients with luminal disease. However, the data currently at our disposal are conflicting. This article reviews all the major trials concerning extended adjuvant endocrine regimens, and formulates some general conclusions and hypotheses of future study., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pretreated patients. Preclinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multicenter study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in postmenopausal women with moderately pretreated, estrogen receptor-positive, HER2 negative advanced breast cancer., Patients and Methods: Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1 : 1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary end point was clinical benefit rate (CBR); secondary end points included progression-free survival (PFS)., Results: Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% [95% confidence interval (CI): 41.5-63.7] for combination therapy, and 60% (95% CI: 47.8-72.9) for monotherapy. Median PFS was 10.8 months (95% CI: 5.6-12.7) for combination therapy, and 6.5 months (95% CI: 5.4-8.5) for monotherapy [hazard ratio (HR) 0.69; 95% CI: 0.4-1.1, exploratory P-value = 0.12]. Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI: 0.3-0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months., Conclusion: Palbociclib has clinical activity as a single agent in women with moderately pretreated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET., Clinical Trial Information: NCT02549430.

Background: Overweight and obesity are associated with an increased risk of developing many types of cancer, including breast cancer. Moreover, increased body mass index (BMI) seems to be associated with a worse prognosis in patients with HER2-positive early breast cancer. However, little is known about the impact of BMI on the clinical outcomes of HER2-positive metastatic breast cancer (MBC)., Methods: This was a multicenter retrospective cohort study including 329 consecutive patients with HER2-positive MBC treated with first-line trastuzumab-based regimens. BMI at the time of MBC diagnosis was collected. World Health Organization BMI categories were used: underweight <18.5, normal 18.5-24.9 Kg/m 2 , overweight 25-29.9 Kg/m 2 , and obese ≥30 Kg/m 2 . The analyses were conducted using two categories: BMI < 25.0 (normal/underweight) and BMI ≥ 25 (overweight/obese). Progression-free survival (PFS) and overall survival (OS) rates were estimated using Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Cox's proportional hazards model. Disease response to therapy was analyzed using univariate and multivariate logistic regression., Results: Overall, 176 (53.5%) patients were normal/underweight and 153 (46.5%) overweight/obese. Median PFS was 14.8 months in BMI < 25 group and 15.7 months in BMI ≥ 25 group (adjusted-HR 0.88; 95% CI 0.66-1.17; p = 0.387). Median OS was 58.6 months in BMI < 25 group and 52.6 in BMI ≥ 25 group (adjusted-HR 0.88; 95% CI 0.59-1.31; p = 0.525). Overall response rate was 71.7% and 65.9% (p = 0.296) and clinical benefit rate was 82.1% and 83.3% (p = 0.781) in BMI < 25 and BMI ≥ 25 groups, respectively., Conclusions: BMI does not seem to be associated with clinical outcomes in HER2-positive MBC patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The aim of the study was to compare the patterns of care and clinical outcomes of HER2-positive metastatic breast cancer (MBC) patients with de novo or recurrent disease who underwent first-line trastuzumab-based therapy., Patients and Methods: This was a multicenter retrospective cohort study including consecutive patients with HER2-positive MBC who received first-line trastuzumab-based therapy. Analyses on treatment response and effectiveness were conducted according to type of metastatic presentation (ie, de novo vs. recurrent disease). Exploratory analyses were used to evaluate whether the use of surgery of the primary tumor in the de novo cohort influenced patients' survival., Results: From January 2000 to December 2013, 416 patients were included in the study, 113 (27.2%) presented with de novo MBC and 303 (72.8%) with recurrent disease. Compared with patients in the recurrence cohort, those in the de novo cohort had worse baseline characteristics, received more aggressive first-line treatments, and showed better survival, with an adjusted hazard ratio (HR) for progression-free survival (PFS) of 0.65 (95% confidence interval [CI], 0.43-0.97; P = .035) and for overall survival (OS) of 0.53 (95% CI, 0.30-0.95; P = .034). In the de novo cohort, the 54 patients (47.8%) who underwent surgery of the primary tumor had significantly better PFS (adjusted HR, 0.44; 95% CI, 0.26-0.72; P = .001) and OS (adjusted HR, 0.49; 95% CI, 0.26-0.93; P = .029) than those who did not undergo surgery., Conclusion: Patients with de novo HER2-positive MBC showed significantly better survival outcomes than those with recurrent disease. In this population, surgery of the primary breast tumor was associated with better outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In the era of precision medicine in oncology, pharmacogenomic assessment is a vital step in delivering personalized care. Increasing evidence points towards the importance of assessing molecular features of the advanced disease, rather than relying on the primary tumor sample, in order to appreciate the evolution of the tumor and to target relevant features. Circulating tumor cells (CTCs) represent a novel method of tumor sampling, as they offer a contemporaneous picture of the current disease state without the need for invasive needle biopsy. As they may derive from any number of metastatic sites, the potential to capture the heterogeneity of the disease is increased. Improvements in CTC capture, enrichment and isolation technology now allow sophisticated interrogation of these cells, such that pharmacogenomic assessment of CTCs is now possible, and the clinical potential is being explored. We review current and potential uses for CTCs for pharmacogenomic analysis., (Copyright © 2016. Published by Elsevier Ltd.)