leptin and leptin receptor expression in patients with breast cancer and fibroadenoma of different...

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showing triple negative BC TNBC in PT, 40 patients in PT and DR with 17,7 % change to non-TNBC. Post-recurrence survival was 30,0 months for persistence in TNBC status versus 85,9 months in non-TNBC-persistence. Among these TNBC patients, phenotype in (up to now) 20 patients was analysed for the LN: in 60%, a TNBC discordance was shown- 75% for PT and LN, and only 25% for LN and recurrence. Conclusion: The results of PriMet show that the triple receptor status of PT and DR are associated with the poorest disease free survival and post- recurrence survival. We provide evidence regarding phenotype changes in PT, LN and DR and its prognostic relevance. This conrms the national and international guidelines for re-verication of immunohistochemical status of PT, LN and DR. BP32 CHANGE IN TRIPLE-RECEPTOR STATUS BETWEEN PRIMARY AND RECURRENT BREAST CANCER: PROGNOSTIC IMPACT Maria Vittoria Dieci, Elena Barbieri, Stefania Bettelli, Federico Piacentini, Guido Ficarra, PierFranco Conte, Valentina Guarneri Modena University Hospital, Modena, Italy Introduction: Breast cancer is a heterogeneous disease, and the main determinants of treatment selection are the expression of hormone receptors and HER2. The reassessment of tumor phenotype in recurrent disease might have an impact on patient management and prognosis. Aim of this analysis is to evaluate the impact of discordance in triple-receptor status between primary and recurrent tumors in patients with relapsed breast cancer. Methods: A total of 103 patients with available samples from both primary tumors and paired local recurrences or metastases were studied. HER2 status was evaluated by immunohistochemistry (IHC) and/or uorescent in situ hybridization (FISH). Samples were consid- ered as HER2-positive in case of IHC and/or FISH positivity. Estrogen receptor (ER) and Progesteron receptor (PgR) status were assessed by IHC; samples were considered as HR-positive in case of ER and/or PgR 10%. Tumor specimens were classied as triple negative (HR- and HER2-negative) or non-triple negative (HR-positive and/or HER2-posi- tive). We evaluated the impact of triple-receptor status changes between primary and recurrent tumors on post-distant progression survival (PDPS). Results: Sites of biopsied recurrent disease were: distant metastases in 79 cases (81%) and local relapses in 24 patients (19%). Sixty-four percent of primary tumors were HR-positive and HER2-negative; 16% were triple negative; 14% were HR-positive and HER2-positive and 6% were HR- negative and HER2-positive. A change in HER2 status between primary and recurrent matched samples was observed in 15.5% of cases. Of 103 patients, 78 (75.7%) maintained a non-triple negative phenotype in both primary and recurrent disease (concordant non-triple negative); 10 patients (9.7%) showed a triple-negative phenotype in both primary and recurrent sites (concordant triple negative); eight patients (7.8%) changed from non-triple negative (primary tumor) to triple negative (recurrent disease); seven patients (6.8%) had a triple negative primary tumor that became non-triple negative at recurrence. Of 103 patients with recurrent breast cancer, a distant progression was observed in 93 cases. Patients with concordant non-triple negative disease had signicantly longer PDPS than the other subgroups (p¼0.0002). In particular, the patients whose tumor phenotype changed from non-triple negative to triple negative had the worst prognosis compared to the concordant non-triple negative subgroup: median PDPS were 15 months and 36 months, respectively (HR 5.26, 95%CI 2.13-12.96; p¼0.0013). Conclusions: In this analysis, the subgroup of patients who maintained positivity of HR and/or HER2 experienced the better outcome, reect- ing the correct use of available targeted agents as well as a less aggressive tumor phenotype. The patients whose phenotype changed from non-triple negative (primary site) to triple negative (recurrent site) had a particularly poor outcome. This might be due to the lack of targeted therapies as well as to the development of a more aggressive phenotype. PO33 LEPTIN AND LEPTIN RECEPTOR EXPRESSION IN PATIENTS WITH BREAST CANCER AND FIBROADENOMA OF DIFFERENT HORMONAL STATUS Dmitry Kravchenko, Elizaveta Peredereeva, Anna Lushnikova, Anastassia Parokonnaya Russian Blokhin Cancer Research Center, Moscow, Russia Introduction: Leptin (LEP) is a multifunctional hormone which plays an important role in angiogenesis, cell proliferation induction, cell survival and anchorage-independent growth. These activities are mediated via leptin receptor (LEPR) that binds leptin molecule and stimulates Jak/STAT 3, ERK, cyclin D1 expression and other signal pathways. According to the recent data, targeting leptin signaling may reduce mammary carcino- genesis and breast cancer (BC) progression. However, the link between obesity and leptin expression in serum/breast tumor as well as its role in modulation of estrogen receptor (EsR) and HER2/neu expression is not clear. Materials and methods: We studied LEP, LEPR, EsR, HER2/neu expression in patients with sporadic, familial and pregnancy-associated BC by means of RT PCR using BC fresh tissue and primers for genes encoding LEP, LEPR, EsR-a, b. Leptin level in the patient sera was estimated also by ELISA (Leptin Sandwich DRG, Germany). The data on immunohistochemical staining of LEP, HER2/neu, EsR and PrR were also obtained. The control group consisted of the patients with benign broadenoma (BFA) and healthy women of similar age. Results: RT PCR results and immunohistochemistry/ELISA values are mainly concordant. Leptin overexpression in triple-negative tumors was observed. Leptin sera level in postmenopause patients with obesity was signicantly higher than in premenopause counterparts and in BC patients with normal body mass. Blood sera leptin level correlated positively with LEPR expression. Leptin expression in tumor tissue also correlated with HER2/neu overexpression in all BC groups involved into the study, except triple-negative ones: EsR (-), PrR(-), HER2/neu(-). Leptin serum level in BFA patients was signicantly higher than the level in healthy women and mean leptin level in the serum of BC patients (96.710.2; 17.88.3; 24.68.4, correspondingly, p<0.05) Conclusions: The obtained data indicate that LEP/LEPR expression is involved in mammary tumor progression. It indicates that LEPR suppres- sion is a possible way of targeted BC therapy, especially for triple-negative tumors, HER2/neu (-), when common hormone therapy is not effective. PO34 EXPRESSION OF MAGE-A10 CANCER/TESTIS ANTIGENS IN BREAST CANCER: A RETROSPECTIVE IMMUNOHISTOCHEMICAL STUDY Antonio Juretic 1 , Tanja Badovinac Crnjevic 1 , Giulio C. Spagnoli 3 , Martina Basic Koretic 1 , Jasminka Jakic Razumovic 2 , Paula Podolski 1 , Nera Saric 1 1 School of Medicine, Zagreb and Clinical Hospital Center Zagreb, Department of Oncology, Zagreb, Croatia 2 School of Medicine, Zagreb and Clinical Hospital Center Zagreb, Department of Pathology, Zagreb, Croatia 3 Institute for Surgical Research and Hospital Management and Department of Biomedicine, University of Basel, Basel, Switzerland Background: Cancer/testis (CT) antigens are protein antigens aber- rantly expressed in a proportion of various types of human cancer. At least a subset of this group of antigens has been found to elicit spon- taneous humoral and cell-mediated immuno responses in cancer patients, raising the possibility that this antigens could be cancer vaccine targets. Patients and Methods: Parafn tumor sections were collected retro- spectively from 165 breast cancer patients diagnosed and operated between 2002 and 2003. Immunohistochemical staining of MAGE-A10 was performed on tissue microarray cores using monoclonal antibody GA11.1 MAGE-A10 staining results were subdivided into negative (0), weak (1+), moderate (2+) and strong (3+) expression. Samples with staining Abstracts / The Breast 20 (2011) S12S55 S23

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Abstracts / The Breast 20 (2011) S12–S55 S23

showing triple negative BC TNBC in PT, 40 patients in PT and DRwith 17,7 %change to non-TNBC. Post-recurrence survival was 30,0 months forpersistence in TNBC status versus 85,9 months in non-TNBC-persistence.Among these TNBC patients, phenotype in (up to now) 20 patients wasanalysed for the LN: in 60%, a TNBC discordancewas shown- 75% for PTandLN, and only 25% for LN and recurrence.Conclusion: The results of PriMet show that the triple receptor status of PTand DR are associated with the poorest disease free survival and post-recurrence survival. We provide evidence regarding phenotype changes inPT, LN and DR and its prognostic relevance. This confirms the national andinternational guidelines for re-verification of immunohistochemical statusof PT, LN and DR.

BP32

CHANGE IN TRIPLE-RECEPTOR STATUS BETWEEN PRIMARY ANDRECURRENT BREAST CANCER: PROGNOSTIC IMPACT

Maria Vittoria Dieci, Elena Barbieri, Stefania Bettelli, FedericoPiacentini, Guido Ficarra, PierFranco Conte, Valentina GuarneriModena University Hospital, Modena, Italy

Introduction: Breast cancer is a heterogeneous disease, and the maindeterminants of treatment selection are the expression of hormonereceptors and HER2. The reassessment of tumor phenotype in recurrentdisease might have an impact on patient management and prognosis. Aimof this analysis is to evaluate the impact of discordance in triple-receptorstatus between primary and recurrent tumors in patients with relapsedbreast cancer.Methods: A total of 103 patients with available samples from bothprimary tumors and paired local recurrences or metastases werestudied. HER2 status was evaluated by immunohistochemistry (IHC)and/or fluorescent in situ hybridization (FISH). Samples were consid-ered as HER2-positive in case of IHC and/or FISH positivity. Estrogenreceptor (ER) and Progesteron receptor (PgR) status were assessed byIHC; samples were considered as HR-positive in case of ER and/or PgR� 10%. Tumor specimens were classified as triple negative (HR- andHER2-negative) or non-triple negative (HR-positive and/or HER2-posi-tive). We evaluated the impact of triple-receptor status changesbetween primary and recurrent tumors on post-distant progressionsurvival (PDPS).Results: Sites of biopsied recurrent disease were: distant metastases in 79cases (81%) and local relapses in 24 patients (19%). Sixty-four percent ofprimary tumors were HR-positive and HER2-negative; 16% were triplenegative; 14% were HR-positive and HER2-positive and 6% were HR-negative and HER2-positive. A change in HER2 status between primary andrecurrent matched samples was observed in 15.5% of cases. Of 103patients, 78 (75.7%) maintained a non-triple negative phenotype in bothprimary and recurrent disease (concordant non-triple negative); 10patients (9.7%) showed a triple-negative phenotype in both primary andrecurrent sites (concordant triple negative); eight patients (7.8%) changedfrom non-triple negative (primary tumor) to triple negative (recurrentdisease); seven patients (6.8%) had a triple negative primary tumor thatbecame non-triple negative at recurrence. Of 103 patients with recurrentbreast cancer, a distant progressionwas observed in 93 cases. Patients withconcordant non-triple negative disease had significantly longer PDPS thanthe other subgroups (p¼0.0002). In particular, the patients whose tumorphenotype changed from non-triple negative to triple negative had theworst prognosis compared to the concordant non-triple negativesubgroup: median PDPS were 15 months and 36 months, respectively (HR5.26, 95%CI 2.13-12.96; p¼0.0013).Conclusions: In this analysis, the subgroup of patients who maintainedpositivity of HR and/or HER2 experienced the better outcome, reflect-ing the correct use of available targeted agents as well as a lessaggressive tumor phenotype. The patients whose phenotype changedfrom non-triple negative (primary site) to triple negative (recurrentsite) had a particularly poor outcome. This might be due to the lack oftargeted therapies as well as to the development of a more aggressivephenotype.

PO33

LEPTIN AND LEPTIN RECEPTOR EXPRESSION IN PATIENTS WITHBREAST CANCER AND FIBROADENOMA OF DIFFERENT HORMONALSTATUS

Dmitry Kravchenko, Elizaveta Peredereeva, Anna Lushnikova, AnastassiaParokonnayaRussian Blokhin Cancer Research Center, Moscow, Russia

Introduction: Leptin (LEP) is a multifunctional hormone which plays animportant role in angiogenesis, cell proliferation induction, cell survivaland anchorage-independent growth. These activities are mediated vialeptin receptor (LEPR) that binds leptin molecule and stimulates Jak/STAT3, ERK, cyclin D1 expression and other signal pathways. According to therecent data, targeting leptin signaling may reduce mammary carcino-genesis and breast cancer (BC) progression. However, the link betweenobesity and leptin expression in serum/breast tumor as well as its role inmodulation of estrogen receptor (EsR) and HER2/neu expression is notclear.Materials and methods: We studied LEP, LEPR, EsR, HER2/neu expressionin patients with sporadic, familial and pregnancy-associated BC by meansof RT PCR using BC fresh tissue and primers for genes encoding LEP, LEPR,EsR-a, b. Leptin level in the patient sera was estimated also by ELISA(Leptin Sandwich DRG, Germany). The data on immunohistochemicalstaining of LEP, HER2/neu, EsR and PrR were also obtained. The controlgroup consisted of the patients with benign fibroadenoma (BFA) andhealthy women of similar age.Results: RT PCR results and immunohistochemistry/ELISA values aremainly concordant. Leptin overexpression in triple-negative tumors wasobserved. Leptin sera level in postmenopause patients with obesity wassignificantly higher than in premenopause counterparts and in BC patientswith normal body mass. Blood sera leptin level correlated positively withLEPR expression. Leptin expression in tumor tissue also correlated withHER2/neu overexpression in all BC groups involved into the study, excepttriple-negative ones: EsR (-), PrR(-), HER2/neu(-). Leptin serum level in BFApatients was significantly higher than the level in healthy women andmean leptin level in the serum of BC patients (96.7�10.2; 17.8�8.3;24.6�8.4, correspondingly, p<0.05)Conclusions: The obtained data indicate that LEP/LEPR expression isinvolved in mammary tumor progression. It indicates that LEPR suppres-sion is a possible way of targeted BC therapy, especially for triple-negativetumors, HER2/neu (-), when common hormone therapy is not effective.

PO34

EXPRESSION OF MAGE-A10 CANCER/TESTIS ANTIGENS IN BREASTCANCER: A RETROSPECTIVE IMMUNOHISTOCHEMICAL STUDY

Antonio Juretic 1, Tanja Badovinac Crnjevic 1, Giulio C. Spagnoli 3, MartinaBasic Koretic 1, Jasminka Jakic Razumovic 2, Paula Podolski 1, Nera Saric 1

1 School of Medicine, Zagreb and Clinical Hospital Center Zagreb, Departmentof Oncology, Zagreb, Croatia2 School of Medicine, Zagreb and Clinical Hospital Center Zagreb, Departmentof Pathology, Zagreb, Croatia3 Institute for Surgical Research and Hospital Management and Departmentof Biomedicine, University of Basel, Basel, Switzerland

Background: Cancer/testis (CT) antigens are protein antigens aber-rantly expressed in a proportion of various types of human cancer. Atleast a subset of this group of antigens has been found to elicit spon-taneous humoral and cell-mediated immuno responses in cancerpatients, raising the possibility that this antigens could be cancervaccine targets.Patients and Methods: Paraffin tumor sections were collected retro-spectively from 165 breast cancer patients diagnosed and operatedbetween 2002 and 2003. Immunohistochemical staining of MAGE-A10was performed on tissue microarray cores using monoclonal antibodyGA11.1 MAGE-A10 staining results were subdivided into negative (0), weak(1+), moderate (2+) and strong (3+) expression. Samples with staining