Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.

Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony-forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice. Metastatic samples formed primary mammosphere colonies significantly more frequently than early breast cancers and had significantly higher primary mammosphere colony formation efficiency (0.9 % vs. 0.6 %; p < 0.0001). Tumour initiation in vivo was significantly higher in metastatic than early breast cancer samples (63 % vs. 38 %, p = 0.04). Of 144 breast cancer samples implanted in vivo, we established 20 stable patient-derived xenograft (PDX) models at passage 2 or greater. Lung metastases were detected in mice from 14 PDX models. Mammosphere colony formation in vitro significantly correlated with the ability of a tumour to metastasise to the lungs in vivo (p = 0.05), but not with subcutaneous tumour initiation. In summary, the breast cancer stem cell activities of colony formation and tumour initiation are increased in metastatic compared to early samples, and predict metastasis in vivo. These results suggest that breast stem cell activity will predict for poor outcome tumours, and therapy targeting this activity will improve outcomes for patients with metastatic disease.

Axillary Clearance Following Positive Sentinel Lymph Node Biopsy in Symptomatic Breast Cancer.

BACKGROUND/AIM: Symptomatic cancers display a different biological behaviour from screen-detected cancers, which may impact the management of axillary metastases. We aimed to determine the role of unselected axillary nodal clearance (ANC) in symptomatic patients with positive sentinel node biopsies (SNBs). PATIENTS AND METHODS: A case-note review was performed on 95 symptomatic breast cancer patients who underwent ANC following positive SNB. RESULTS: Thirty-eight (40%) patients were treated with a mastectomy and 57 (60%) with breast-conserving surgery. At ANC, 25 patients (26.3%) showed evidence of further lymph node metastases, with 15 (60%) having two or fewer macrometastases. The presence of more than 2 SNB macrometastases was associated with further ANC metastases (p<0.001). The presence of further metastases at ANC was not associated with either reduced overall survival or disease-free survival. CONCLUSION: A number of symptomatic breast cancer patients with positive SNBs may be overtreated. Ongoing trials examining the management of low volume SNB macrometastases need to consider the symptomatic subgroup in their conclusions.

Efficacy of botulinum toxin type A in the treatment of focal axillary hyperhidrosis.

BACKGROUND: Local intradermal injection of botulinum toxin Type A has become a recognized treatment for axillary hyperhidrosis. This study has investigated the efficacy of this method of treatment in terms of symptom-free interval between treatments and patients' satisfaction. We also investigated the reliance on patients' subjective assessment of the recurrence of symptoms in determining the timing of repeat injections. METHODS: All patients referred to our clinic between May 2001 and December 2005 with a diagnosis of focal primary axillary hyperhidrosis were included in this study. Data were collected prospectively in a standard proforma. Every patient received a questionnaire to complete over a 4-week period. The questionnaire included visual analogue scales for periprocedural pain, degree of dryness, satisfaction, regret, and complications. Final symptom-free interval was recorded when the patient requested a repeat injection. The data were recorded on a spreadsheet and analyzed using standard statistical methods. RESULTS: A total of 52 consecutive patients and 238 axillary injections were analyzed. The symptom-free interval ranged from 3 to 14 months with a median of 5.97 months. There were no significant complications from this treatment modality. A total of 97% of the patients were highly satisfied with only 1 patient regretting the treatment. CONCLUSION: Botulinum toxin Type A is an effective and well-tolerated treatment for axillary hyperhidrosis. Timing of repeat injections as determined subjectively by patients is comparable to studies using colorimetric and gravimetric techniques to quantify the severity of sweating prior to the administration of repeat injections. The authors have indicated no significant interest with commercial supporters.

Primary sigmoid adenocarcinoma metastasis to the breast in a 28-year-old female: a case study and a review of literature.

Metastasis to the breast from colorectal carcinoma is rare, only a few cases have been reported in the literature, and no cases have been reported in a young, 28-year-old patient. This report confirms the occurrence of the disease in a younger age group. The patient was referred to the Breast Clinic with a history of a gradually increasing lump in her right breast for two weeks' duration. On clinical examination, a 2-cm firm lump was noted in the upper inner quadrant of the right breast, which was clinically benign; however, histological examination of the breast core biopsy together with immunohistochemistry confirmed metastatic colorectal adenocarcinoma. The primary colorectal carcinoma was later confirmed to be a stage pT4N2M1 tumor, and the Duke stage was C1. Histology with immunohistochemistry is very important in the diagnosis of cases of this nature, but the clinical correlation should be taken into consideration at multidisciplinary team meetings to decide the final management of the patient.