Hormone use is associated with lymphovascular invasion in breast cancer

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Poster Abstracts I / The Breast 32S1 (2017) S22–S77

surgical main tumor section. In case 33 patients treated with neoadjuvant chemotherapy (NAC), we also performed staining on core needle biopsy specimens surgical specimen. Positive AR expression was defined as staining of 10% or more of tumor cell nuclei. The median follow-up period was 56 months after resection. Results: AR expression was positive in 49 (33.8%) in 145 TNBCs. AR expression was more frequent (P = 0.001) in older patient. Negative expression of AR was significantly associated with high nuclear grade and high score of ki-67 index (P = 0.002, P < 0.001). Whereas the rate of pathological complete response ( pCR) after NAC was significantly lower (P < 0.001), the outcome after resection was tend to be better in the patients with AR-positive than in those with AR-negative in TNBC. Patients dead Conclusion: Our study suggests that though immunohistochemically AR-positive TNBC is difficult to achieve pCR after NAC, it indicates less aggressive tumor character. Disclosure of Interest: the author mentions a conflict of interest which is not further specified. P067 Prognostic impact of high endothelial venules with TIL and Tregs in breast cancer J.-Y. Song1 *, S. Young Jeon1, Y.-Y. Park3, S.-J. Lim2. 1Department of Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, South Korea, 2Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, South Korea, 3Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea Aims: Recent studies have provided evidence that supports the action of tumor vessels in the promotion of anticancer immune responses by allowing large influxes of immune cells. These vessels with this special immunologic function are named tumor high endothelial venules (HEVs). HEVs therefore facilitate the accumulation of tumor infiltrative lymphocytes (TILs) to result in a favorable prognosis. However, regulatory T cells (Tregs) can also traffic to tumors, which may lead to an unfavorable prognosis despite the existence of HEVs. In addition, as a high density of dendritic cells (DCs) has been reported to be associated with a high HEV density, DCs are thought to be involved in the induction and maturation of HEVs. The aim of this study was to investigate the association between HEVs, Tregs, DCs, and TILs and to evaluate their impact on the prognoses of patients with primary, non-metastatic breast cancer. Methods: MECA-79+ HEVs, Foxp3+ Tregs, and CD11c+ DCs were analyzed after identification by immunohistochemistry staining. Clinicopathologic data of 85 patients with primary breast cancer who underwent breast cancer surgery in a single center from June 2006 to January 2010 were retrospectively collected. Results: Density of stromal HEVs (sHEV) is associated with density of peritumoral HEVs, peritumoral Tregs, stromal Tregs, peritumoral DCs, stromal DCs, and stromal TILs (sTIL), but there was no statistically significant association between density of sHEV and Tregs in tumor nests (tTreg) A high expression of sHEV was associated with progesterone receptor-, human epidermal growth factor receptor 2 (HER2)+, extensive intraductal component (EIC)+, or high histologic grade in univariate analysis. In Cox regression tests for analyzing prognostic factors, history of neoadjuvant chemotherapy, ER-, and HrLl (a conjoined group of the intersected patients between the high tTreg (the highest quartile) group and the low sTIL (≤10%) group) were the independent poor prognostic factors of metastasis-free survival. High nodal status, history of neoadjuvant chemotherapy, and ER- were the independent poor prognostic factors for disease-free survival. Finally, neoadjuvant chemotherapy and HrLl, and Ki67+ were the independent poor prognostic factor for overall survival (OS).

Conclusions: HEV density itself seems not to affect prognosis, because HEVs are important for trafficking not only immune cells with anticancer effect but also Tregs which have immune evasive effect to stroma in tumors. Disclosure of Interest: No significant relationships. P068 Molecular analysis of JAK2 gene in patients with triple negative breast cancer in relation to disease prognosis – a pilot study L. Stanek1 *, P. Tesarova1, M. Vocka1, Z. Musil2, L. Petruzelka1. 1 Department of Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, 2Institute of Biology and Genetics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic JAK2 gene is located on chromosome 9p24.1, its product is a tyrosine kinase protein that plays a role in signal transduction between membrane receptors for growth factors and intracellular signaling molecules and is also involved in cytokine signaling. Mutation V617F JAK2 (Janus kinase 2) causes violation of autoinhibiting activity and promotes malignant transformation and proliferation. Mutations and translocations involving JAK2 gene region were observed in myeloproliferative diseases. V617F is the most frequent mutation found in this gene, in case of translocation a series of fusion partners (PCM1, BCR, ETV, SSBP2) are described. Recent studies, however, indicate a possible amplification of somatic chromosome 9p24.1 region encoding the JAK2 in triple negative breast cancer (TNBC) in connection with a poorer prognosis and shorter survival. The goal of our pilot study is to perform cytogenetic and molecularbiological analysis of JAK2 gene on a cohort of 40 patients diagnosed and confirmed with triple negative breast cancer (TNBC). FISH method will be used to analyze numerical changes and translocations, including the detection of possible fusion partners. In the next step mutational analysis using PCR and direct sequencing will be performed. Determined the results show the presence of amplification. The Following are parti- breaks JAK2 gene. Also it was detected V617F mutation. Based on the data obtained from the comprehensive molecular analysis of JAK2 gene, we will try to predict prognosis and possible use of tyrosine kinase inhibitor in TNBC patients. Disclosure of Interest: the author mentions a conflict of interest which is not further specified. Acknowledgements: This work was supported by the project Prvouk-P27/LF1/1 P069 Hormone use is associated with lymphovascular invasion in breast cancer M. Loof-Johanson1, L. Brudin2, C.E. Rudebeck3, M. Sundquist4 *. 1 Department Medical and Health Sciences, University of Linkoping, Linkoping, Sweden, 2Department of Clinical Physiology, County Hospital, Kalmar, Sweden, 3Department of Community Medicine, University of Tromso, Tromso, 4Breast Unit, County Hospital, Kalmar, Sweden, Norway Aims: The use of hormones has been associated to an increased risk of breast cancer. Our aim was to explore if the use of hormones before the diagnosis of breast cancer was associated to any specific tumour characteristics. Methods: Two hundred and fifty women diagnosed with breast cancer were interviewed regarding their previous use of hormonal therapies. Hormone use included contraceptive pills and injections, hormone coils and hormone replacement therapy. Established prognostic factors for breast cancer survival as tumour type, grade, proliferation, lymphovascular invasion (LVI), ER and PR data was retrieved from patient charts. Multivariate logistic regression with

15th St.Gallen International Breast Cancer Conference / The Breast 32S1 (2017) S22–S77

reproductive data and hormone use as independent variables and the above established prognostic factors as dependent variables adjusted for age at diagnosis was used. Results: One hundred and four women had used hormonal contraceptives and/or hormonal replacement therapy before the diagnosis of breast cancer, 146 had not. Twenty-one per cent of the patients that had used hormonal therapies had invasion of cancer cells in vascular spaces but only 10% of the never-users. The association was significant, p = 0, 04, odds ratio (95% CI) 2, 24, in the multivariate analysis. No other tumour characteristic was related to the use of hormones. Conclusion: Hormone use is significantly associated to lymphovascular invasion, LVI, in breast cancer thereby also affecting the prognosis of the disease. Disclosure of Interest: No significant relationships. P070 The role of tumor stem cells and the EMT mechanism as potential therapeutic targets in a male patient with metaplastic breast cancer A.C. Tampaki1, A. Tampakis2 *, D. Trafalis3, A. Nonni4, K. Kontzoglou1, E. Patsouris4, M. Kontos5, G. Kouraklis1. 1Second Dept. Propaedeutic Surgery, Laiko Hospital, Athens University Medical School, Athens, Greece, 2Dept. Visceral Surgery, Basel University Hospital, Basel, Switzerland, 3Dept. Pharmacology, School of Medicine, National University of Athens, Athens, Greece, 4First Dept. Pathology, School of Medicine, National University of Athens, Athens, Greece, 5First Dept. Surgery, Laiko Hospital, Athens University Medical School, Athens, Greece Aims: Metaplastic breast carcinomas represent a rare subtype appearing as highly chemoresistant, therefore showing poor outcome and high rates of recurrence. We aimed to investigate the molecular mechanisms that may be associated with the development of resistance to chemotherapy. Methods: A 37-year-old Greek man was referred with a triple negative metaplastic breast cancer classified as cT4cN3cM1. The patient received first line chemotherapy and afterwards a palliative resection of the tumor. The tissue was immunohistochemically stained with two stem cell markers (nestin and CD146 [MCAM]). Results: CT scan of the chest and abdomen revealed an 8 × 7.5 × 4.5mm enhancing lesion arising from the outer quadrants of his left breast with pathologically enlarged axillar, mediastinal and supraclavicular lymph nodes as well as a solid lesion in the lower lobe of the left lung measuring less than 1 cm. A core needle biopsy of the large mass revealed a primary triple negative breast cancer with the Ki67 cell proliferation marker reaching up to 50%. The patient received first line chemotherapy with Adriamycin 50 mg/m2 and Cyclophosphamid 750 mg/m2. Due to chemotherapy-induced thrombocytopenia along with grade IV neutropenia, the patient continued with further three cycles of small-sized liposomal Adriamycin at a dose of 40 mg/m2 every 3 weeks. A 30% partial response according to the RECIST criteria was observed and the patient received a palliative lumpectomy. The immunohistochemical staining for nestin and CD146 (MCAM) was classified as intense for both markers. Chemotherapy was further administered in 4 cycles containing liposomal Adriamycin at a dose of 40 mg/m2 and Paclitaxel at a dose of 135 mg/m2 every 3 weeks. Follow-up with CT scan demonstrated disease progression and chemotherapy plan was then changed to 4 cycles with Bevacizumab 8 mg/kg, Gemcitabine 1200 mg/m2 and Vinorelbine 30 mg/m2 on days 1 and 8 every 4 weeks. Further progression was observed with skeletal, lung and new liver metastases and the patient died 6 months after receiving initial treatment. Conclusions: Metaplastic breast cancer is consisted of cells with stem cell properties showing high resistance to conventional

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chemotherapy. Targeting nestin and CD146 might be a promising therapy as they seem to be implicated in the EMT pathway. Disclosure of Interest: No significant relationships. P071 Is there a role for intraoperative frozen section analysis in the surgical treatment of Multifocal/Multicentric breast cancers? N. Sitoh1 *, A. Thomas2, C.-M. Fong2, M. Tan3. 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 2 Parkway Laboratory Services Pte Ltd, Singapore, Singapore, 3 MammoCare, The Breast Clinic & Surgery, Singapore, Singapore Aims: Breast conservation therapy (BCT) is considered an acceptable modality of treatment for multifocal multicentric breast cancer (MFMCBC), provided clear margins can be obtained for each tumour foci in combination with reasonable cosmetic results. However, re-excision rates for MFMCBC have been reported to be as high as 73%. This study was therefore performed to assess the efficacy of intraoperative frozen section analysis (IFSA) and its impact on reexcision rates. Methods: Women treated at a single private medical facility between Jun 2004 and Dec 2012, diagnosed to have MFMCBC through a combination of preoperative imaging, clinical evaluation and biopsy were included in the study. Neoadjuvant chemotherapy was administered where downstaging was assessed to be required for successful BCT. Patients considered eligible for BCT underwent extended lobar surgery for MF disease and multisegment resection for MC lesions. The limbs were oriented according to clockface positions and sent for IFSA. Further shave margins were excised where necessary until shown to be negative on FS. All patients in this cohort underwent BCT using only volume displacement techniques. Reduction mammoplasty and volume replacement approaches with implants or flaps were not used to retain the integrity of the positions of the tumour beds in the event that re-excision was needed. Results: A total of 69 women were treated for MFMCBC during the study period. The mean age of patients was 48.7 years (range 32–72). Forty-four women (63.8%) were Chinese, 23.2% were of other Asian origin and 13.0% were Caucasian. Forty women (58%) had MF disease while 29 (42%) had MCBC. Fifty-eight patients (84.1%) in the entire cohort underwent successful BCT. Re-operations were performed in 10 women (14.5%), with 6 (8.7%) having re-excisions for margins. Four (10%) of 40 patients with MF lesions, and 2 (6.9%) with MC disease underwent re-excision for margins. One (1.4%) patient was returned to the operating room for axillary dissection following a false negative reading of a sentinel lymph node. Three had re-operations for inadvertent missed MC disease, with one having completion mastectomy after attempting BCT. Conclusions: This preliminary analysis shows that IFSA has a role in decreasing re-excision rates for MFMCBC. The low rates of re-excision for false negative margins may be attributable to a combination of surgical technique, careful orientation of tissue specimens and conscientious IFSA by the pathologist. Disclosure of Interest: No significant relationships. P072 Fat grafting does not stimulate breast cancer cell proliferation in vivo W. Tsuji1,2 *, J.E. Valentin1, V.S. Donnenberg3, A.D. Donnenberg3, K.G. Marra1,4,5, J.P. Rubin1,4,5. 1Adipose Stem Cell Center, University of Pittsburgh, Pittsburgh, USA, 2Shiga Medical Center for Adults, Moriyama, Japan, 3University of Pittsburgh Cancer Institute, Pittsburgh, USA, 4 McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, USA, 5Department of Bioengineering, University of Pittsburgh, Pittsburgh, USA Autologous fat grafting for breast reconstruction after breast cancer surgery offers several advantages over prosthetic devices,