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Poster Abstracts I / The Breast 32S1 (2017) S22–S77
P078 Autophagy inhibitors facilitate cytotoxicity of Gefitinib dependent on ROS-mitochondrial apoptotic pathway in EGFR+ TNBC cells Z.-Y. Liu1,2 *, K.-W. He1,2, Q.-H. Ma2, Z.-Y. Yu2. 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, China, 2Department of Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China Epidermal growth factor receptor (EGFR) is over-expressed in about 50% of Triple negative breast cancers (TNBCs), but EGFR inhibitors have not been effective in treating TNBC patients. We found that autophagy was related with drug resistance of gefitinib in our previous study, and inhibition of autophagy induced by gefitinib (Ge) with 3-Methyladenine (3-MA) or bafilomycin A1 (Baf.A) sensitized TNBC MDA-MB-231 and MDA-MB-468 cells to Ge. However, the mechanism of autophagy in TNBC remains unclear. In the current study, we further verified the effect of autophagy inhibitors to gefitinib in TNBC cells in vivo, and investigated the specific mechanism. Our data showed that the enhanced apoptosis in TNBC cells treated with Ge and autophagy inhibitors correlated with reactive oxygen species (ROS) accumulation. The ROS-mitochondrial apoptotic pathway were activated in favor of promoting apoptosis, as evidence from G0/G1 arrest, DNA damage, and related signaling molecular such as Cytochrome C. These results highlight that targeting autophagy should be considered as an effective therapeutic strategy to enhance the sensitivity toward EGFR inhibitors in TNBC patients. Disclosure of Interest: No significant relationships. P079 Differential expression in high grade luminal breast cancer and matching histologically normal breast tissue: an ontogenetic study P. Zubor1,4 *, J. Hatok2, M. Kalman3, Z. Dankova4, A. Gondova1, A. Stefanikova2, I. Stastny1, P. Kubatka5, K. Kajo6, J. Danko1. 1 Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia, 2 Department of Biochemistry and Molecular Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia, 3 Department of Pathology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia, 4Division of Oncology, BioMed, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia, 5Department of Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia, 6Department of Pathology, St. Elisabeth Cancer Institute, Bratislava, Slovakia Aims: Gene expression profile based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending differences in origin and behavior of cancer. We hypothesized that gene expression profile of histologically normal epithelium could harbor genetic abnormalities predisposing breast tissue to develop high grade Luminal BC. The genes expression in normal (HNEpi) and BC tissue (BCTis) from patients with Luminal high grade type BC were assessed. Methods: An array study evaluating 84 pathway and disease specific genes in 34 initially enrolled BCs and tumor adjacent tissue (HNEpi, ≤2 cm) was performed on microdissected samples from frozen section. Results: We have performed gene expressions on samples from all subjects entering inclusion criteria and yealding sufficient RNA (n = 13 of 34). There were present 24 deregulated genes (28.6%) with minimal 2-fold deregulation rate. The main over-expressed genes in BCTis samples were BIRC5, CCNE1, CDKN2A, CST6, KRT8, KRT19, MKI67, MMP9, NME1, PLAU, SERPINE1, THBS1 and VEGFA. The main under-expressed genes in BCTis vs HNEpi group were ABCB1, ABCG2, CDKN1C, EGF, ESR1, IGF1, KRT5, PGR, SFRP1, SLIT2 and TFF3. The
significant differences in gene expression between both groups were observed for ABCB1 (p < 0.01) and CST6, IGF1, KRT19, MMP9, NME1 and PLAU ( p < 0.05). The borderline significance ( p < 0.06) was observed for BIRC5, JUN, KRT5 and KRT8). The gene ontology analysis has revealed that the most frequently deregulated genes influenced angiogenesis (EGF, PLAU, SERPINE1, SLIT2, THBS1, VEGFA), apoptosis (CDKN2A, IGF1, NME1, SFRP1), cell cycle regulation (CCNE1, CDKN1C, CDKN2A, MKI67), proteases (CST6, MMP9, PLAU) and xenobiotic transport (ABCB1, ABCG2). The functional signal transduction analysis showed affection of steroid-receptor mediated signalling (CCNE1, ESR1, IGF1, KRT19, PGR), glucocorticoid (NME1), AKT & PI3 kinase (IGF1), and notch signalling pathways (BIRC5). Moreover, high-grade luminal carcinomas showed specific metagene associations with tumour grade and axillary nodal status ( p < 0.001). Conclusion: The molecular profiling of HNEpi breast tissue revealed genetic abnormalities that may represent potential markers of increased risk for high grade Luminal type BC, and may participate in prognosis by suggesting ontogenetic groups for further management. Disclosure of Interest: No significant relationships.
Epidemiology/Prevention/Diagnosis P085 Feasibility of a low cost life-style intervention programme for breast cancer patients by volunteer health support F. Borella1, D. De Ruvo2, G. Gregori3, P. Zola2, A. Surace2, E. Picardo1, C. Benedetto1, O. Bertetto4, E. Minniti3, M.G. Baù3 *. 1Gynecology and Obstetrics 1, Department of Surgical Sciences, University of Torino, Turin, Italy 2Gynecology and Obstetrics 2, Department of Surgical Sciences, University of Torino, Turin, Italy 3Gynaecology and Obstetrics 3, Sant’Anna Hospital, Turin, Italy 4Department Intercompany Interregional Oncological Network of Piedmont and Valle d’Aosta, City of Health and Science of Turin, Turin, Italy Aims: The primary objective of this study was to test the feasibility of a counselling lifestyle programme (exercise and nutrition) for breast cancer patients offered by volunteers, under the supervision of an Ob-Gyn resident physician. Secondary objective were to compare women who adopted the suggested programme and those who did not. Methods: We conducted a prospective study at the University of Turin, St. Anna Hospital, between September 2013 and October 2014. The study was approved by the local ethics committee. The volunteers association (AVO) is an Italian organisation that provides support to patients. Volunteers were trained to address exercise and nutrition-related issues. An Ob-Gyn resident physicians supervised the volunteer activities and ensured interprofessional collaboration. We evaluated the following parameters at baseline and 6 months visit: blood pressure, BMI, waist circumference, triglycerides, total cholesterol and fasting glucose level. All participants were given a booklet about most suitable exercise, nutrition programme and the activities available in our hospital (fitwalking course, cooking class). Results: After the counselling, 68 out of 186 (36.6%) women refused the programme, representing the control group (Group II). 118 out of 186 (63.4%) women accepted to participate constituting our sample (Group I). In the baseline condition BMI, waist circumference and triglycerides levels were significantly higher in Group II than in Group I; there were no significant differences between other parameters among the two groups. After 6 months BMI, waist circumference and triglycerides levels remained significantly higher in Group II than in Group I; furthermore, there was also a significant increase of fasting glucose levels in the control group. In Group I at 6 months visit, waist circumference decreased from 90.5±10.4 to 88.6 ±11.8 ( p = <0.001) and fasting glucose level decreased from 92.8±22.1
15th St.Gallen International Breast Cancer Conference / The Breast 32S1 (2017) S22–S77
to 88.2%±22.6% ( p = <0.001). BMI, blood systolic/dyastolic pressure, total cholesterol and triglycerides levels remained unchanged. In Group II at 6 months, fasting glucose level increased from 92.5±18.4 to 97.0±20.7 ( p = <0.001); no significant changes were seen in other parameters. Conclusion: Results from this study indicate that a low-cost counselling programme can impact on metabolic parameters in breast cancer patients. Disclosure of Interest: No significant relationships. P086 Vitamin D levels in Swiss breast cancer survivors M. Baumann1, S. Dani2 *, D. Dietrich3, A. Hochstrasser4, M.T. Mark5, W. Riesen1, T. Ruhstaller6, A.J. Templeton7, B. Thürlimann6. 1Institute for Clinical Chemistry and Haematology, St. Gallen Cantonal Hospital, St. Gallen, Switzerland, 2Department of Medical Oncology and Haematology, St. Gallen Cantonal Hospital, St. Gallen, Switzerland, 3 Statistical Office, Swiss Group for Clinical Cancer Research - SAKK, Berne, Switzerland, 4Oncology Centre, Männedorf Hospital, Zurich, Switzerland, 5Department of Oncology and Haematology, Graubuenden Cantonal Hospital, Chur, Switzerland, 6Breast Centre St. Gallen, Cantonal Hospital, St. Gallen, Switzerland, 7Department of Oncology, St. Claraspital Basel and Faculty of Medicine, University of Basel, Basel, Switzerland We conducted a cross-sectional study in 332 women in Eastern Switzerland with early, i.e. non-metastatic breast cancer. Cholecalciferol intake and serum calcidiol [25-hydroxyvitamin D, 25(OH)D] and calcitriol [1,25-dihydroxyvitamin D, 1,25(OH)2D] levels were measured at the first visit (baseline) and during a follow-up visit in median 210 days after the first visit. Patients presenting calcidiol deficiency were advised to take cholecalciferol supplementation. At baseline 60 (18%) patients had vitamin D deficiency (calcidiol ≤ 50 nmol/l) whereas 70 (21%) had insufficiency (50– 74 nmol/l). Out of 121 patients with ongoing cholecalciferol supplementation at baseline, calcidiol deficiency and insufficiency was observed in 9 (7%) and 16 (13%) patients, respectively, whereas out of 52 patients with no supplementation, 15 (29%) patients had deficiency and 19 (37%) patients had insufficiency. Only 85 (26%) patients had optimal calcidiol levels (75–100 nmol/l) at baseline. Seasonal variation was significant for calcidiol ( p = 0.042) and calcitriol ( p = 0.001) levels. Living in a rural area was associated with a higher median calcidiol concentration as compared to living in an urban area (87 nmol/l versus 72 nmol/l, p = 0.001). Regular sport activity was positively associated with calcidiol ( p = 0.045). Body mass index was inversely related to both calcidiol and calcitriol (rho = −0.24, p < 0.001; rho = −0.23, p < 0.001, respectively). The levels of calcidiol and calcitriol were correlated (rho = 0.21, p < 0.001). Age and bone mineral density had no significant correlation to the levels of calcidiol. Follow-up calcidiol was available for 230 patients, 44 (19%) of whom had calcidiol deficiency and 47 (21%) had insufficiency; 25 (41.6%) initially calcidiol-deficient patients attained sufficient calcidiol levels, whereas 33 (16.5%) patients with sufficient baseline calcidiol levels became deficient. Only 67 (30%) patients presented optimal calcidiol at the follow-up. In conclusion, a remarkable fraction of the patients had serum calcidiol below (40%) or above (30%) optimal levels and only around 30% of patients had optimal levels. Calcidiol and calcitriol levels increased on cholecalciferol supplementation, but the usual supplementation regimens were not adequate to bring calcidiol to the optimal range for a large proportion of patients. Adequate vitamin D supplementation must be tailored according to individual characteristics, needs and preferences. Disclosure of Interest: No significant relationships.
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P087 Advanced stage breast cancer is less often diagnosed in women who attend breast cancer screening L. De Munck1 *, J. Fracheboud2, G. de Bock3, S. Siesling1, M. Broeders4. Netherlands Comprehensive Cancer Organisation, Utrecht, Netherlands, 2University Medical Center Rotterdam, Rotterdam, Netherlands, 3University of Groningen, University Medical Center Groningen, Groningen, Netherlands, 4Department for Health Evidence, Radboudumc and Dutch Reference Centre for Screening, Nijmegen, Netherlands 1
Aims: The contribution of screening mammography to a reduced rate of advanced breast cancer is still questioned. The aim of this study is to assess age-specific incidence rates of advanced breast cancer in women who attended the screening programme compared to nonattenders. Methods: All women, aged 49 and older, diagnosed with breast cancer between 2006 and 2011 were selected from the Netherlands Cancer Registry. Data were linked to the Netherlands breast cancer screening programme, including data of screened women between 2004 and 2011 to cover a period of at least 24 months before breast cancer diagnosis. Screen-detected cancers and interval cancers were defined as screen-related cancers diagnosed <24 months after a screening examination, all other cancers were defined as nonscreen-related cancers. Two definitions of advanced breast cancer were used: (1) advanced stage defined as stages III and IV cancers (versus stages 0, I, II), and (2) advanced T-stage defined as invasive tumour sizes ≥15 mm (versus <15 mm or DCIS), irrespective of lymph node stage. Incidence rates were age-adjusted using the European Standard Population 2013 as a reference. Multivariable logistic regression was used to estimate ratios for advanced stage between subgroups. Results: In total 72,612 breast cancers were included, of which 44,246 were screen-related cancers (61%) including 32,158 screen-detected cancers (73%). Incidence of advanced stage cancer was 38/100.000 in the screened population compared to 94/100.000 in the nonscreened population ( p < 0.001). Applying the second definition of advanced stage cancer resulted in much higher incidence rates for both populations. However, advanced T-stage was still less often diagnosed in the screened population (169/100.000 vs 194/100.000; p < 0.001). Non-screen related cancers had a three times higher risk to be advanced stage cancer compared to screen-related cancer (OR: 2.90, 95%CI: 2.78–3.02). Conclusions: Advanced breast cancer incidence rates are substantially lower in a screened population compared to a non-screened population, supporting the stage shift related to early detection of breast cancer. As the different definitions for advanced breast cancer led to significant different estimates of the incidence of advanced cancers, we recommend that in the evaluation of a breast cancer screening programme the definition of stage is clearly stated. Disclosure of Interest: No significant relationships. P088 Cancer incidence and mortality trends in urban cities of India V. Deshmane*, S. Koyande, S. Jadhav. Indian Cancer Society, Mumbai, India Introduction: The Mumbai Cancer Registry (MCR), India’s oldest population based cancer registry (PBCR) covers 603 sq. km. of Greater Mumbai as well as three other urban cities viz. Pune, Aurangabad and Nagpur. Here we report the increasing incidence in breast cancer in all the four PBCRs. Breast cancer is now the commonest cancer in women in all four cities. Mortality trend for Mumbai is also reported. Methods: Breast cancer incidence was calculated for the year 2012 in Mumbai, Pune (2014), Nagpur (2013) and Aurangabad (2015). Trends were studied for the following periods: Mumbai 1964–2012, Pune 1972–2014, Aurangabad 1990–2015 and Nagpur 1980–2013.