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Nottingham, United Kingdom

Wazir U.,University of London | Jiang W.G.,University of Cardiff | Sharma A.K.,University of London | Mokbel K.,University of London | Mokbel K.,London Breast Institute
Anticancer Research | Year: 2012

Background: This pilot study is the first to focus on the potential role for death-associated protein 3 (DAP3) in human breast cancer. Materials and Methods: A total of 153 samples were studied. The levels of transcription of DAP3 were determined using quantitative polymerase chain reaction (qPCR). Transcript levels within breast cancer specimens were compared to those of normal background tissues and correlated with clinicopathological data accumulated by over a 10-year follow-up period. Results: The expression of DAP3 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. 3, p=0.036), TNM stage (TNM1 vs. 3, p=0.07), and tumour grade (grade 1 vs. 3, p=0.08). Lower DAP3 expression levels were significantly associated with local recurrence (p=0.013), distant metastasis (p=0.0057) and mortality (p=0.019). Conclusion: This study demonstrates an inverse association between DAP3 mRNA levels and tumour stage and clinical outcome in breast cancer, consistent with the pro-apoptosis function of DAP3. Further research is required in order to confirm our findings and clarify the mechanisms that regulate DAP3 expression in human breast cancer. Source


Salhab M.,St Georges, University of London | Bismohun S.,St Georges, University of London | Mokbel K.,London Breast Institute
BMC Women's Health | Year: 2010

Background: Women who have inherited mutations in the BRCA1 or BRCA2 genes have substantially elevated risks of breast and ovarian cancer. Mutation carriers have various options, including extensive and regular surveillance, chemoprevention and risk-reducing surgery. The aim of this review is to provide an up-to-date analysis and to subsequently summarise the available literature in relation to risk-reducing strategies, with a keen focus on prophylactic surgery.Methods: The literature review is facilitated by Medline and PubMed databases. The cross-referencing of the obtained articles was used to identify other relevant studies.Results: Prophylactic surgery (bilateral mastectomy, bilateral salpingo-oophorectomy or a combination of both procedures) has proved to be the most effective risk-reducing strategy. There are no randomised controlled trials able to demonstrate the potential benefits or harms of prophylactic surgery; therefore, the evidence has been derived from retrospective and short follow-up prospective studies, in addition to hypothetical mathematical models.Based on the current knowledge, it is reasonable to recommend prophylactic oophorectomy for BRCA1 or BRCA2 mutation carriers when childbearing is completed in order to reduce the risk of developing breast and ovarian cancer. In addition, women should be offered the options of rigorous breast surveillance, chemoprevention with anti-oestrogens--especially for carriers of BRCA2--or bilateral prophylactic mastectomy.Conclusion: The selection of the most appropriate risk-reducing strategy is not a straightforward task. The impact of risk-reducing strategies on cancer risk, survival, and overall quality of life are the key criteria considered for decision-making. Notably, various other factors should be taken into consideration when evaluating individual mutation carriers' individual circumstances, namely woman's age, morbidity, type of mutation, and individual preferences and expectations.Although prospective randomised controlled trials concerned with examining the various interventions in relation to the woman's age and type of mutation are needed, randomisation is extremely difficult and rather deemed unethical given the current available evidence from retrospective studies. © 2010 Salhab et al; licensee BioMed Central Ltd. Source


Choy C.,London Breast Institute | Mokbel K.,London Breast Institute
World Journal of Clinical Oncology | Year: 2014

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer with a variable biological behavior which is difficult to accurately predict using the current clinico-pathological parameters. Randomized controlled trials have demonstrated that adjuvant radiotherapy (RT) reduces the risk of local recurrence after adequate local excision of DCIS. Tamoxifen may be considered as an adjuvant endocrine treatment in patients with high risk estrogen receptor positive disease. There is however a growing consensus that RT can be safely omitted in a subgroup of patients with favorable biological features in order to avoid overtreatment. The sentinel node biopsy is not routinely indicated but should be considered in women undergoing mastectomy for DCIS. The discovery of molecular signatures that accurately predict the biological behavior of this common malignancy will facilitate a personalized treatment approach in the future. © 2014 Baishideng Publishing Group Inc. All rights reserved. Source


Kasem A.,London Breast Institute | Mokbel K.,London Breast Institute
World Journal of Clinical Oncology | Year: 2014

Skin sparing mastectomy (SSM) can facilitate immediate breast reconstruction and is associated with an excellent aesthetic result. The procedure is safe in selected cases; including invasive tumours < 5 cm, multi-centric tumours, ductal carcinoma in situ and for risk-reduction surgery. Inflammatory breast cancers and tumours with extensive involvement of the skin represent contraindications to SSM due to an unacceptable risk of local recurrence. Prior breast irradiation or the need for post-mastectomy radiotherapy do not preclude SSM, however the aesthetic outcome may be compromised. Preservation of the nipple areola complex is safe for peripherally located node negative tumours. An intraoperative frozen section protocol for the retro-areolar tissue should be considered in these cases. The advent of acellular tissue matrix systems has enhanced the scope of implant-based immediate reconstruction following SSM. Cell-assisted fat transfer is emerging as a promising technique to optimise the aesthetic outcome. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved. Source


Wazir U.,London Breast Institute | Mokbel K.,London Breast Institute
World Journal of Clinical Oncology | Year: 2014

Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor (ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer. © 2014 Baishideng Publishing Group Inc. All rights reserved. Source

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