The Role of CDK4/6 Inhibitors in Breast Cancer

Opinion statementOral inhibitors of CDK4/6 have been shown to increase response rates and prolong disease control when combined with endocrine therapy in hormone-responsive (HR+) HER2-negative advanced breast cancer. Palbociclib, ribociclib and abemaciclib are all approved in combination with non-steroidal aromatase inhibitors in first-line therapy for post-menopausal women, with a 40 –45% improvement in progression-free survival seen with the addition of any of these CDK4/6 inhibitors. Additional approved indications, including first- and second-line combination therapy for pre-menopausal women, combination with fulvestrant and use as monotherapy, vary with each agent and are reviewed fully in the subsequent texts. These agents also differ in their toxicity profiles and monitoring requirements, and prescribers should be aware of the individual requirements for each agent. Current clinical trials are investigating the expanded use of these agents in other breast cancer su btypes, such as HER2-positive and triple-negative breast cancer, as well as in the adjuvant and neoadjuvant treatments of early breast cancer. Resistance to CDK4/6 inhibition can occur through multiple mechanisms. Rational combinations with other therapies, such as PI3K inhibitors, HER2-directed the rapies and immunotherapy, are being explored.
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research

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ConclusionWe confirm previous studies showing that the PTPN2 protein is lost in half of the breast cancer cases and gene deletion occurs in 15 –18% of the cases. Furthermore, the results suggest that the role of PTPN2 is subtype-related and should be further investigated to assess how this could affect breast cancer prognosis and treatment response.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
(Stand Up To Cancer) SU2C welcomed the recent Food and Drug Administration (FDA) approval of alpelisib in combination with fulvestrant, the first and only new therapy for patients with a PIK3CA mutation in HR+/HER2- advanced metastatic breast cancer in both post-menopausal women and in men. Research by one of SU2C's inaugural Dream Teams, the SU2C PI3K Dream Team: 'Targeting The PI3K Pathway In Women's Cancers' contributed to the development of this treatment.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
A UCLA-led study has found that using a drug called ribociclib in combination with a common hormone therapy may help premenopausal women with the most common type of breast cancer live longer than if they only receive the hormone therapy.Ribociclib is considered a cyclin-dependent kinase inhibitor that works by blocking the activity of proteins called cyclin-dependent kinase 4/6 enzymes, which promote cell division and cancer growth.The study involved 672 women aged 25 to 59 when the study began who had advanced hormone-receptor positive/HER2- breast cancer. Seventy percent of the women who took the combination therapy wer...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
CONCLUSION: Neutropenia was manageable with dose modifications, without affecting palbociclib treatment duration or efficacy. TRIAL REGISTRATION: Pfizer (NCT01740427, NCT01684215, NCT01942135). PMID: 31127500 [PubMed - as supplied by publisher]
Source: Breast Cancer - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research
Authors: Ayoub NM, Yaghan RJ, Abdo NM, Matalka II, Akhu-Zaheya LM, Al-Mohtaseb AH Abstract Purpose: To investigate the association between obesity and breast cancer clinicopathologic characteristics at presentation along with prognostic impact among Jordanian breast cancer patients. Such data are lacking in Arabian countries. Methods: In this retrospective study, 348 breast cancer patients were included. Analyses were conducted for associations between body mass index (BMI) and age at diagnosis, tumor clinicopathologic characteristics, and molecular subtypes. Eight prognostic factors were considered, and total ...
Source: Journal of Obesity - Category: Eating Disorders & Weight Management Tags: J Obes Source Type: research
ConclusionsThe impact of BMI on breast cancer outcome was dependent on tumor subtype and menopausal status. In HR(+)HER2( –) patients, underweight and obesity had a negative prognostic role in pre-menopausal and post-menopausal women, respectively. These findings in Asian population should be further evaluated and compared in Western population.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
Conclusions: Our model is more reliable and stable to assist doctors predict the SLN metastasis in breast cancer patients before operation. Introduction The incidence of breast cancer is the first in female malignant tumors, in which the highest incidence of breast cancer has been reported in Europe and the United States, however, in recent years, the incidence of breast cancer in China has annually increased (1, 2). Based on surgery as an important step in the treatment of breast cancer, in recent years, different individuals have never stopped exploration of a novel and optimum approach. Besides, NSABP-04, ASCOG-...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Metastasis accounts for the majority of cancer-associated mortality and renders the targeted therapy fruitless in the patients of breast cancer. Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF-C) are thought to be involved in tumor progression and metastasis. The aim of this study was to investigate the expression of MMP-9 and VEGF-C at both mRNA and protein levels in breast cancer and to correlate with lymph node metastasis and other clinicopathological characteristics. Biopsy specimens (N = 100) of breast cancer &benign breast disease (N = ...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Tags: Mol Cell Biochem Source Type: research
CONCLUSIONS: DASH scores were inversely associated with breast cancer risk; DASH and AHEI-2010 scores excluding alcohol were particularly inversely associated with risk of ER-/PR- and ER-/PR-/HER2- breast cancers. This trial was registered at clinicaltrials.gov as NCT00047970. PMID: 30968114 [PubMed - as supplied by publisher]
Source: The American Journal of Clinical Nutrition - Category: Nutrition Authors: Tags: Am J Clin Nutr Source Type: research
Conclusion: Lean postmenopausal women had more aggressive tumours, apparently contradicting the widely held view for breast cancer in obese women.
Source: In Vivo - Category: Research Authors: Tags: Clinical Studies Source Type: research
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