Breast Cancer Res Treat https://doi.org/10.1007/s10549-017-4585-x ABSTRACTS 1st UK Interdisciplinary Breast Cancer Symposium—15th–16th January 2018 Ó Springer Science+Business Media, LLC, part of Springer Nature 2018 Contents Invited presentations Selected oral presentations: O01-O14 Poster presentations: • Clinical Biomarker: P1.1-P1.40 • Pathology: P2.1-P2.15 • Clinical Early Disease: P3.1-P3.24 • Diagnostics Imaging: P4.1-P4.6 • Epidemiology and Prevention: P5.1-P5.11 • Patient Centred Care: P6.1-P6.24 • Clinical Late Disease: P7.1-P7.7 • Trials in Progress: P8.1-P8.11 • Pre-Clinical New Treatments: P9.1-P9.9 • Pre-Clinical Biological Studies: P10.1-P10.44 123 Breast Cancer Res Treat Highlights of 2017 (II)—Early Disease mortality. Long-term morbidity from WBRT is very unusual but does occur and the small risks of cardiac toxicity and carcinogenesis need Professor Michael Gnant, MD, FACS to be considered. The publication of results derived from selected cohorts of patients Medical University of Vienna, Vienna, Austria with very low recurrence rates without WBRT has encouraged many A number of important large clinical trials in the field of early breast to focus attention on improvements in surgical techniques and margin cancer (EBC) reported results at large international meetings such as assessment as a means of avoiding a need for WBRT. Unfortunately ASCO, ESMO, and SABCS in 2017: the very low recurrence rates reported in selected series have not been In the field of extended adjuvant endocrine therapy, the IBCSG/ reflected in larger population based cohorts. BIG SOLE trial designed to evaluate the use of intermittent letrozole Efforts to improve the selection of radiotherapy by the identifi- to prolong sensitivity to endocrine treatment in postmenopausal cation of patients at higher risk of recurrence have met with mixed women with HR + BC showed that extended intermittent letrozole result. These efforts have included the development of prognostic did not improve DFS versus continuous dosing. The ABCSG-16 trial scores such as the Van Nuys Index, nomograms using other demo- of additional 2 versus additional 5 years of anastrozole after 5 years graphic and tumour-related factors and molecular classifiers such as of endocrine therapy was presented at SABCS. the Oncotype DX test for DCIS. In HER2-overexpressing breast cancer, the adjuvant APHINITY The long natural history of this disease and the associated low trial demonstrated a significantly reduced risk of recurrence for the event rates have meant that randomized prospective studies are rel- addition of pertuzumab versus placebo to trastuzumab and atively lacking and alternatives usually involving observational chemotherapy in patients with HER2+ EBC (HR: 0.81, p = 0.045), evidence have been more prominent. This is understandable and such with patients with node-positive and or HR - disease benefitting the information is very useful for the study of long-term outcomes but is most. The adjuvant ExteNET trial of ‘‘secondary’’ neratinib after the less helpful to study the impact of surgery and adjuvant therapy completion of trastuzumab in its 5-year update showed improved DFS because of the many possible confounders that exist. compared to placebo (HR 0.73, p = 0.008), but the benefit was At this point in time, definitive recommendations as to which almost exclusively driven by the HR+ cohort of patients (HR = 0.60, patients require WBRT, based on high level evidence, cannot easily p = 0.002). A comparison of 9 weeks of adjuvant trastuzumab versus be made and we continue to strive to strike a balance between under 1 year (SOLD trial) was presented at SABCS. and over treatment on an individual basis. The ongoing collection of With respect to neoadjuvant endocrine therapy, the phase II outcome information in routine practice and prospective trials linked LORELEI trial demonstrated a significant increase in overall response to efforts to derive improved molecular indicators of recurrence risk rates measured by centrally assessed MRI for the addition of the and radiotherapy benefit are a priority. PI3 K selective inhibitor taselisib to letrozole in ER-positive/HER2- negative breast cancer, with some indication that this treatment effect was more pronounced in the PIK3CA-mutated population. The The use of patient-derived tissues for advanced POETIC trial assessing the comparative clinical utility of Ki67 at preclinical models of breast cancer baseline and after 2 weeks of pre-operative AI in predicting long-term outcome was presented at SABCS. In the field of chemotherapy, the PlanB trial reported the non- Robert Clarke, PhD inferiority of the TC chemotherapy scheme compared to EC-T. In a Breast Cancer Now Research Unit, The University of Manchester, phase-III neoadjuvant trial for triple-negative breast cancer, the UK addition of carboplatin to AC led to improved pCR rates, but the addition of the PARPi veliparib did not further increase pCR rates. In Recently, there has been an interest in improving breast cancer the field of introducing immunotherapeutic approaches to BC, the models through the development of patient-derived organoid (PDO) I-SPY 2 program demonstrated that the addition of pembrolizumab 3D cultures and xenograft (PDX) tumours. Where these PDO/PDX can increase pCR rates both in triple-negative and HR+/HER2 - have been characterised, they mostly retain the principal histologic tumors. and genetic characteristics of their donor tumour, which remain stable across several passages. PDO 3D cultures and PDX tumour models are now available that represent the different molecular sub- types of breast cancer. PDX have been shown to undergo metastasis Should radiotherapy be routinely recommended to lymph nodes, liver, lung and bone, making them useful for bio- after wide local excision of DCIS? logical and preclinical modelling of patient disease. Both PDO and PDX will be vital emerging toolsets for preclinical drug evaluation, David Dodwell biomarker identification, biological studies and personalised medicine strategies. Institute of Oncology, St James’ Hospital, Leeds, UK We prospectively collected more than 300 primary breast cancer The use of whole breast radiotherapy (WBRT) after wide excision for samples and assessed 3D mammosphere colony-forming activity DCIS is commonplace but variable practice exists across the world in vitro in both primary (formation) and secondary (self-renewal) and there is substantial geographical variation within the UK. This culture, and tumour-initiating activity in vivo. variability is fuelled by the recognition that the great majority of Metastatic samples formed more mammosphere colonies than DCIS is screen-detected and patients with this condition have an EBC and had higher primary mammosphere colony formation. Tumour initiation in vivo was significantly higher in metastatic versus excellent prognosis. Other cause mortality is, in most circumstances, \ much greater than breast cancer-related mortality and there is there- EBC samples (63 vs. 38%; p 0.05). We established 20 stable PDX fore a serious risk of overtreatment. Additionally, although WBRT models at passage 2 or greater from subcutaneous implantation of reduces the risk of invasive or in situ within-breast recurrence, the five breast cancer samples. Metastases were detected in lungs of mice randomized controlled trials (RCTs) of WBRT versus no WBRT after from 14/34 PDX models and this correlated significantly with wide excision and the EBCTCG meta-analysis of four of these RCTs mammosphere colony formation in vitro. PDX models are now being have shown equivalent overall-survival and breast cancer-related utilised to study the early stages of metastasis. 123 Breast Cancer Res Treat In summary, colony formation and tumour initiation are increased way, why is a woman’s prognosis significantly better with bulky in metastatic compared to early breast cancer samples, and predict locally advanced breast cancer than with a single metastatic focus of metastasis in vivo. Thus, breast stem cell activity may predict for poor small volume? Why do patients with multiple scattered breast cancer outcome tumours, and therapy targeting this will reduce secondary cells in lymph nodes have a prognosis indistinguishable from women breast cancer. with negative nodes? And why do women with 3 versus 2 versus 1 axillary lymph node metastases all have differing prognoses? Are positive lymph nodes the source of metastases or an epiphenomenon? How can post-mastectomy radiation improve survival in some 3D in vitro modelling using material from Breast patients while not doing so when combined with lumpectomy? Why Cancer Now Tissue Bank do women with readily detected circulating breast cancer cells and positive bone marrows not develop metastatic disease even when Dr Richard Grose followed for many years? Put another way, why, unlike lung, col- orectal or many other cancers are 5 years without recurrence Barts Cancer Institute, Queen Mary University of London, UK unreliable as a predictor for cure? In fact, do we ever really cure 3D modelling fulfils a critical role in research, allowing for complex breast cancer—or at least ER-positive breast cancer? Why do changes cell behaviour and interactions to be studied in physiomimetic con- in woman’s lifestyle such as weight gain, diabetes, stress, depression ditions. With tissue banks becoming established for a number of and failure to exercise all impact recurrence of breast cancer? As cancers, researchers now have access to primary patient cells, pro- stated by Winston