Background:Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in early breast cancer patients. This study aims to examine the implications of routine Oncotype DX testing in the UK.Methods:Women with oestrogen receptor positive (ER+), pNO or pN1mi breast cancer were assessed for adjuvant chemotherapy and subsequently offered Oncotype DX testing, with changes in chemotherapy decisions recorded. A subset of patients completed questionnaires about their uncertainties regarding chemotherapy decisions pre- and post-testing. All patients were asked to complete a diary of medical interactions over the next 6 months, from which economic data were extracted to model the cost-effectiveness of testing.Results:Oncotype DX testing resulted in changes in chemotherapy decisions in 38 of 142 (26.8%) women, with 26 of 57 (45.6%) spared chemotherapy and 12 of 85 (14.1%) requiring chemotherapy when not initially recommended (9.9% reduction overall). Decision conflict analysis showed that Oncotype DX testing increased patients' confidence in treatment decision making. Economic analysis showed that routine Oncotype DX testing costs £6232 per quality-adjusted life year gained.Conclusion:Oncotype DX decreased chemotherapy use and increased confidence in treatment decision making in patients with ER+ early-stage breast cancer. Based on these findings, Oncotype DX is cost-effective in the UK setting.

Recurrence Score testing led to changes in adjuvant chemotherapy use in approximately a third of patients, to an overall reduced chemotherapy use, and to more homogeneous decision making.

Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.

Aims: Treatment strategies for breast cancer continue to evolve. No uniformity exists in the UK for the management of node-positive breast cancer patients. Most centres continue to use conventional histopathology of sampled sentinel lymph nodes (SLNs), which requires delayed axillary clearance in up to 25% of patients. Some use touch imprint cytology or frozen section for intraoperative testing, although both have inherent sensitivity issues. An intraoperative molecular diagnostic approach helps to overcome some of these limitations. The aim of this study was to assess the clinical effectiveness of Metasin, a molecular method for the intraoperative evaluation of SLNs. Methods and results: RNA from 3296 lymph nodes from 1836 patients undergoing SLN assessment was analysed with Metasin. Alternate slices of tissue were examined in parallel by histology. Cases deemed to be discordant were analysed by protein gel electrophoresis. There was concordance between Metasin and histology in 94.1% of cases, with a sensitivity of 92% [95% confidence interval (CI) 88-94%] and a specificity of 97% (95% CI 2016 , 68, 875-887. DOI: 10.1111 95-97%). Positive and negative predictive values were 88% and 98%, respectively. Over half of the discordant cases (4.4%) were ascribed to tissue allocation bias (TAB).Conclusions: Clinical validation of the Metasin assay suggests that it is sufficiently sensitive and specific to make it fit for purpose in the intraoperative setting.

Background: Core biopsy is a method of choice for the triple assessment of breast disease as it can reliably distinguish between benign and malignant tumours, between in-situ and invasive cancers and can be useful to assess oestrogen receptor status. This study was carried out to assess the reliability of core biopsy in predicting the grade and type of cancer accurately as obtaining this information can influence initial therapeutic decisions.

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Breast Cancer: Current ResearchBr ea s t C a n ce r: Curre nt R e se ar ch Khawaja et al., Breast Can Curr Res 2015, 1:1 Keywords: Breast conserving surgery; Oncoplastic breast surgery;Wide local excision; Breast cancer; Cosmesis IntroductionIn women with early stage unifocal breast cancer, breast conserving surgery followed by radiotherapy is the recommended choice. However, in some women, lesions are difficult to excise without the risk of cosmetic deformity or inadequate margin clearance. These women often present with large tumors in relatively small breasts requiring an excision of approximately 15% to 20% of the breast volume or more than 30% in large breasts. Another factor affecting poor cosmesis after breast conserving surgery is tumors located in aesthetically sensitive areas such as the central, medial, and inferior quadrants [1,2].In recent years, oncoplastic breast conserving surgery (OPS) has increased in popularity. OPS combines the principles of oncologic and plastic surgery techniques to gain oncologically and aesthetically pleasing results [3]. As these techniques become more accepted there is a demand for surgeons to become familiar with the indications and skills required to make oncoplastic surgery safe and effective [4].The choice between different oncoplastic techniques are determined mainly by the site of the tumor in the breast, tumor characteristics, extent of resection, breast characteristics (size, shape and glandular density), previous surgery, and the expectations and wishes of the patient [5].OPS can be classified into two main approaches according to the reconstruction technique used. Volume displacement techniques are applied to correct quadrantectomy defects in medium to large breasts [6]. They are of particular benefit to those patients who present with ptotic dense glandular breasts. The breast glandular tissue is advanced, rotated or transpositioned to fill the defect [7]. Since this may result in a smaller sized breast, contralateral surgery may be required. Conversely, AbstractBackground: The goal of breast conserving surgery is to achieve complete excision of the tumor with adequate surgical margins, while preserving the natural shape and appearance of the breast. This is a retrospective study which compared operative outcomes in oncoplastic (OPS; n=54) versus standard wide local excision (WLE; n=265) populations. A total of 319 consecutive patients were included in the study. The primary outcomes were the size of the tumor, weight of the specimen and margin clearance. The secondary outcomes were patient satisfaction, local recurrence rates and operative time.