The impact of Oncotype DX breast cancer assay results on clinical practice: a UK experience.

BACKGROUND: Genomic tests are increasingly being used by clinicians when considering adjuvant chemotherapy for patients with oestrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2-) breast cancer. The Oncotype DX breast recurrence score assay was the first test available in the UK National Health Service. This study looked at how UK clinicians were interpreting Recurrence Scores (RS) in everyday practice. METHODS: RS, patient and tumour characteristics and adjuvant therapy details were retrospectively collected for 713 patients from 14 UK cancer centres. Risk by RS-pathology-clinical (RSPC) was calculated and compared to the low/intermediate/risk categories, both as originally defined (RS < 18, 18-30 and > 30) and also using redefined boundaries (RS < 11, 11-25 and > 25). RESULTS: 49.8%, 36.2% and 14% of patients were at low (RS < 18), intermediate (RS 18-30) and high (RS > 30) risk of recurrence, respectively. Overall 26.7% received adjuvant chemotherapy. 49.2% of those were RS > 30; 93.3% of patients were RS > 25. Concordance between RS and RSPC improved when intermediate risk was defined as RS 11-25. CONCLUSIONS: This real-world data demonstrate the value of genomic tests in reducing the use of adjuvant chemotherapy in breast cancer. Incorporating clinical characteristics or RSPC scores gives additional prognostic information which may also aid clinicians' decision making.

Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study.

BACKGROUND: Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years. METHODS: 14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities. RESULTS: 276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia. CONCLUSION: Palbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.

Src-mediated regulation of homotypic cell adhesion: implications for cancer progression and opportunities for therapeutic intervention.

Homotypic cell adhesion is fundamental to the maintenance of cell and tissue structure and function and is predominantly mediated by cadherin-containing adherens junction complexes. The integrity of these adhesion sites can be modulated by Src, a non-receptor tyrosine kinase implicated in the development and progression of a number of tumour types. Changes in homotypic cell adhesion have been shown to be central to cell migration and invasion, characteristics central to tumour metastasis and irrevocably leading to patient death. Targeting of Src may thus be an effective means to suppress migration and invasion of cancer cells and suggests the use of Src inhibitors clinically as a mechanism to delay or limit tumour spread. In this article, we review the role of Src in cell-cell adhesion and discuss data that suggests its usefulness as a therapeutic target in anti-invasive therapy.

Intermittent therapy in the palliative treatment of metastatic colorectal cancer.

After nearly 40 years of treatment of metastatic colorectal cancer with 5-fluorouracil (5-FU) or best supportive care, the treatment of this disease has evolved rapidly in the last decade. Treatment options now include several new cytotoxic and biologic agents. Combination regimens, such as folinic acid, 5-FU plus oxaliplatin (FOLFOX), and folinic acid, 5-FU plus irinotecan (FOLFIRI), have significantly improved clinical efficacy as related to response rates and overall survival. The optimum integration of chemotherapy regimens with biological agents targeting critical signaling pathways, such as, bevacizumab (monoclonal antibody targeting VEGF-A), cetuximab and panitumumab (monoclonal antibodies targeting the EGF receptor) are still under evaluation. With the availability of several treatment options, however, comes the issue of optimal duration of chemotherapy in order to achieve the dual goals of clinical efficacy and quality of life, and the issue of cost-effectiveness of treatment, particularly with the newer targeted therapies. One method of achieving this may be to accommodate planned treatment holidays so patients can recover from the physical and psychological side effects of their chemotherapy as long as clinical efficacy is not compromised. In this review, we discuss the evidence for the use of intermittent chemotherapy in metastatic colorectal cancer.