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Background: Papillomas are often found co-existing with breast carcinoma yet they are not considered to be a true precursor of the disease. Previous studies have shown that some cases may carry copy number alterations (CNA) or mutations in AKT1/PIK3CA (Troxell et al., 2010, Modern Pathology 23: 27-37) suggesting this lesion may have malignant potential. To date, a detailed study of both pure papillomas (not associated with cancer) and those seen in the same breast as a carcinoma has not been undertaken. Therefore, we set out to investigate the molecular changes associated with this lesion and whether papillomas can be clonally related to synchronous breast carcinoma. Method: Papilloma cases were identified from a hospital database and independently reviewed by consultant pathologists followed by micro-dissection of formalin-fixed paraffin-embedded tumour tissue and DNA extraction. For CNA detection either Affymetrix Molecular inversion Probe (MIP) 330K arrays were used or low-coverage whole genome sequencing using 5-10 ng of DNA (Kader et al., 2016, Genome Medicine 8: 121) where there was insufficient DNA for MIP arrays. We applied either of these 2 methods to 24 cases of pure papilloma as well as 20 papilloma with synchronous ductal carcinoma in situ (DCIS) and/or invasive ductal carcinoma (IDC). Additionally, targeted exon sequencing of breast cancer driver genes was performed for a subset of cases. Results: Among the pure papillomas 31% (5/16) showed CN change with, the most frequent change being 16q loss (2/16). Of the papillomas synchronous with DCIS/IDC analysed to date, 2/5 were shown to be clonal with the co-existing carcinoma. Final CNA analysis will be presented for 24 pure papilloma cases and 20 synchronous cases. Targeted sequencing revealed that all for pure papillomas analysed to date harboured somatic mutations in PIK3CA (3/4 cases) and PIK3R1 (1/4,) suggesting that most papillomas are driven by alterations in the PI3-kinase/AKT pathway. The final sequencing data to be presented will include an additional 5 pure papillomas and 10 synchronous cases. Conclusion: Our observation that 40% of papillomas are clonal to breast carcinoma suggests that DCIS or IDC can arise from a common ancestor as co-existing papillomas, however, most papillomas co-existing with carcinoma are likely to be independent in our cohort. Citation Format: Elder KJ, Kader T, Hill P, Opeskin K, Goode DL, Pang J-M, Fox SB, Mann GB, Campbell IG, Gorringe KL. Genomic analysis of breast papillomas [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-04-08.

Background The value of population-based mammographic screening has been questioned by those who believe that the reduction in mortality from earlier diagnosis is outweighed by harms including overdiagnosis and overtreatment. Much of these commentaries assume that all Early-Stage Breast Cancer (ESBC) is treated the same way after diagnosis; with extensive therapies including surgery, radiotherapy and chemotherapy being standard. Intensity of treatment received is rarely mentioned in the debate. We hypothesised that those diagnosed through a screening program (Active Screeners (AS)) would receive less extensive surgical treatment and less intense adjuvant therapies than those not recently screened (NRS). If demonstrated, these differences would form an important component of the debate over the role of mammographic screening. Methods Retrospective analysis of a consecutive cohort of female patients aged 50-69 and managed for ESBC (invasive or DCIS) during 2007-2013 within a large metropolitan Breast Service, diagnosed either via a population screening program (AS) or outside of the program (NRS). Data on patient characteristics, symptoms, mode of detection, tumour pathology, surgical intervention and adjuvant treatment recommendations were derived from prospectively collected Multi-Disciplinary Meeting (MDM) records. Patients with metastatic disease or prior treatment for breast cancer were excluded. Results 791 cases were identified (569 with screen-detected cancer, 53 with interval cancers and 169 cancers diagnosed in women not recently screened). Invasive cancers in the AS group were much smaller than in the NRS group – mean 17mm versus 26mm. The AS group had lower grade invasive cancer – grade 1, 2 and 3 were 27%, 42%, 31% - compared with 10%, 39% and 52% in the NRS group. The AS group were more likely to have ER+ve cancers (88% vs 80%) and less likely to have nodal involvement (26% vs 48%). For invasive breast cancer, the NRS group were more than twice as likely to undergo mastectomy than cancers in the AS group (35% vs 16%). Axillary dissections were more common in the NRS than the AS group (43% vs 19%). Adjuvant chemotherapy was recommended more frequently for the NRS group compared to the AS group (65% vs 37%), as was post mastectomy radiotherapy (58% vs 39%). Endocrine therapy was less often recommended to the NRS group (86% versus 77%). Conclusion Women diagnosed with early stage breast cancer who are participating in a population based screening program are less likely to receive mastectomy and/or axillary dissection, less likely to receive adjuvant chemotherapy and less likely to receive post-mastectomy radiotherapy. These differences in treatment intensity should be considered in the debate surrounding mammographic screening. Citation Format: Elder KJ, Nickson C, Cooke S, Machalek D, Rose A, Mou A, Collins JP, Park A, De Boer R, Phillips C, Pridmore V, Farrugia H, Mann GB. Benefits to breast screening beyond mortality reduction [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-13.