mammosphere-formation-assay-from-human-breast-cancer-tissues-cell

Mammosphere Formation Assay from Human Breast Cancer Tissues and Cell Lines

Similar to healthy tissues, many blood and solid malignancies are now thought to be organised hierarchically, with a subset of stem-like cancer cells that ...

Imperial College London

Breast cancer metastasizing to the tongue.

The ethnic profile of triple-negative breast cancer.

Fulvestrant is a pure estrogen receptor (ER) antagonist with no agonist effects. We describe the experience of a single center involving 45 postmenopausal women with advanced breast cancer where fulvestrant was utilized following progression on tamoxifen and a third generation aromatase inhibitor. Patients received fulvestrant as first line one (2%), second line 18 (40%), third line 13 (29%), fourth line 10 (22%), and fifth line three (7%) treatment. Median duration of treatment with Fulvestrant was 4 months (range 1-20 months). One patient had a partial response, 14 other (31%) experienced clinical benefit (CB) (defined as response or stable disease for at least 6 months). The median time to progression (TTP) from initiation of fulvestrant was 4 months (range 1-20 months) and the median survival was 10 months (range 1-55 months). In those patients who experienced CB the median TTP was 10 months (range 6-20) and median survival was 21 months (range 7-55). Fulvestrant was well tolerated; two patients experienced side effects severe enough to stop therapy. Despite the fact that fulvestrant was used in the majority of cases, later in the treatment sequence CB was seen in a number of patients. This data suggest fulvestrant is well tolerated and is a useful treatment option in patients with advanced breast cancer who progress on prior endocrine treatment.

Fulvestrant in advanced breast cancer following tamoxifen and aromatase inhibition: a single center experience.

Members of the nuclear receptor superfamily are ligand-regulated transcription factors involved in the control of a broad range of normal physiological and disease processes. The estrogen receptor alpha (ERalpha) is a member of the steriod receptor family, which is part of the nuclear receptor superfamily. ERalpha it is important for many biological processes and plays a key role in the pathogenesis of breast cancer. Gene regulation by ERalpha requires the recruitment of a multitude of transcriptional co-regulators to the promoters of estrogen-responsive genes. There is evidence in support of the involvement of these co-regulators in breast cancer progression. We review the role of steroid receptor co-activator-3 (SRC-3), which is frequently amplified in breast cancer, and its role in breast cancer risk, outcome and response to endocrine therapy in patients with breast cancer.

The role of SRC-3 in human breast cancer.

Quantification of kinetic parameters of positron emission tomography (PET) imaging agents normally requires collecting arterial blood samples which is inconvenient for patients and difficult to implement in routine clinical practice. The aim of this study was to investigate whether a population-based input function (POP-IF) reliant on only a few individual discrete samples allows accurate estimates of tumour proliferation using [18F]fluorothymidine (FLT).

Evaluation of limited blood sampling population input approaches for kinetic quantification of [18F]fluorothymidine PET data.

This multicenter phase II trial was designed to evaluate the activity of lapatinib in metastatic breast cancer patients with HER2-negative primary tumors and HER2-positive circulating tumor cells (CTCs). In this study MBC patients with HER2-negative primary tumors and HER2-positive CTCs previously treated with at least a first-line therapy for metastatic disease received lapatinib 1500 mg/day. The CellSearch System® was used for CTCs isolation and bio-characterization. HER2 status was assessed on CTCs by immunofluorescence. A case was defined as CTCs positive if ≥2 CTC/7.5 ml of blood were isolated and HER2-positive if ≥50% of CTCs were HER2-positive. 139 HER2-negative patients were screened, 96 patients were positive for CTCs (mean number of CTCs: 85; median number of CTCs: 19; range 2-1637). Seven of the 96 patients (7%) had ≥50% HER2-positive CTCs and were eligible for treatment with lapatinib. No objective tumor responses occurred in this population. In one patient, disease stabilization lasting 254 days (8.5 months) was observed. From the findings of this study, we concluded that a subset of patients with a HER2-negative primary tumor presents HER2-positive CTCs during disease progression, although the HER2 shift rate seems to be lower than previously reported. Despite the lack of objective response, the durable disease stabilization observed in one patient cannot rule out the hypothesis that lapatinib may have some activity in this patient population. However, considering that only 1/139 screened patients may potentially have derived benefit from this approach, future trials designed according to the presented strategy cannot be recommended.

Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study.

Article	Year
Breast cancer metastasizing to the tongue. Canadian journal of surgery. Journal canadien de chirurgie\| PubMed ID: 18682793	2008
The ethnic profile of triple-negative breast cancer. Onkologie\| PubMed ID: 19145089	2008
Fulvestrant in advanced breast cancer following tamoxifen and aromatase inhibition: a single center experience. The breast journal\| PubMed ID: 19645779	2009
The role of SRC-3 in human breast cancer. Nature reviews. Clinical oncology\| PubMed ID: 20027190	2010
Evaluation of limited blood sampling population input approaches for kinetic quantification of [18F]fluorothymidine PET data. EJNMMI research\| PubMed ID: 22444834	2012
Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating... Breast cancer research and treatment\| PubMed ID: 22476856	2012

Charles R. Coombes

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