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Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70–101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI – 34–72) and the median time to progression was 43 months (95% CI – 22–64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival ( p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group. [ABSTRACT FROM AUTHOR]

Abstract: Tamoxifen is a selective oestrogen receptor modulator used in pre-menopausal oestrogen receptor positive breast cancer patients as adjuvant endocrine treatment. Increased risk of venous thrombo-embolism with the use of Tamoxifen is well known from published literature. This risk further increases in patients undergoing surgical procedures of high risk involving prolonged period of immobilization, therefore withholding Tamoxifen treatment in the immediate peri-operative period should be considered as a risk reducing measure. In the absence of nationally agreed guidelines on the safe duration for stoppage of treatment in the pre and post operative period without worsening cancer prognosis, operating surgeons and individual trusts have adopted their own guidelines based on individual experience. From the available evidence in the literature on the VTE risk assessments based on age, operative procedure and pharmacokinetics of the Tamoxifen drug we would like to propose a working algorithm for selecting the right patient group and safe treatment stoppage durations. These proposed guidelines are formulated taking all the risk factors of VTE, operative risks, pharmacokinetics of the drug and chemotherapy risks into consideration. With this guidance, we aim to help surgeons across different specialities in the decision making process through a structured evidence based approach. [Copyright &y& Elsevier]