Abstracts / The Breast 20 (2011) S12–S55S30

which benefit could be brought by the succession of CT lines in patientstreated for MBC and to identify women who benefit from thesetreatments.Methods: This retrospective analysis included 980 women treated with CTfor MBC at our Institution over a 7-year period (May 1999-July 2006). Withoverall survival (OS) data updated at December 1, 2008, themedian follow-up was 125 months (range 48-192), OS and time to treatment failure (TTF)were calculated according to the Kaplan-Meyer method for each CT line.Cox proportional hazards model was used to identify factors that couldinfluence TTF and OS.Results: Median OS evaluated from day 1 of each CT line decreased withthe line number from 34.8 months (980 patients, 1st line, range 4-208) to22.6 months (838 patients, 2nd line), 14.6 months (684 patients, 3rd line),12.4 months (302 patients, 4th line), 9.4 months (88 patients, 5th line),8.2 months (45 patients, seven or more lines). Median TTF ranged from9.2 months to 7.8 and 6.4 months for the first, second and third line,respectively, with no significant decrease observed beyond the 3rd line(median 5.2 months, range 4.8-6.2). In univariate analysis factors posi-tively linked to a longer duration of TTF for each CT line were positivehormonal receptor status, absence of liver metastasis, adjuvant CTexposure, response to CT for the metastatic disease; in the multivariateanalysis the duration of TTF for each CT line was the only one factor withsignificant impact on survival benefit for subsequent treatments(p<0.001).Conclusions: CT beyond the 2nd line may be beneficial in a significantsubset of women treated for MBC, with improved TTF and OS. Thesefindings could help physician in planning an appropriate strategy ofsubsequent schedules for women with symptomatic MBC who respondedto their 1st line CT, while non responder patients should be considered forclinical trials.

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BOLERO-2: EVEROLIMUS IN COMBINATION WITH EXEMESTANE IN THETREATMENT OF POSTMENOPAUSAL WOMEN WITH ESTROGENRECEPTOR-POSITIVE ADVANCED BREAST CANCER REFRACTORY TOLETROZOLE OR ANASTROZOLE

Mario Campone 1, Martine Piccart 2, Kathleen I. Pritchard 3, CindyXu 4, Michael Gnant 5, Patrick Neven 6, Barbara Pistilli 7, MikhailShtivelband 8, Louise Provencher 9, Norikazu Masuda 10, Mona El-Hashimy 4, Luc Vittori 11, Tarek Sahmoud 4, Jose Baselga 12, Gabriel N.Hortobagyi 131Centre Régional René Gauducheau, Nantes Saint Herblain, France2 Jules Bordet Institute, Brussels, Belgium3 Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto,Canada4Novartis Pharmaceuticals Corporation, Florham Park NJ, USA5Medical University of Vienna, Vienna, Austria6U.Z. Leuven, Catholic University Leuven, Leuven, Belgium7Oncology Department, Macerata Hospital, Macerata, MC, Italy8 Ironwood Cancer and Research Center, Chandler, AZ, USA9Hôpital du Saint-Sacrement, Quebec, Canada10Osaka National Hospital, Osaka, Japan11Novartis Pharma AG, Basel, Switzerland12Massachusetts General Hospital, Boston, Massachusetts, USA13 The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA

Background: The PI3K/Akt/mTOR pathway, a key regulator of cellularproliferation, metabolism, and angiogenesis, is constitutively activated inaromatase inhibitor–resistant breast cancer. Everolimus (EVE), an inhibitorof the PI3K/Akt/mTOR pathway has been found in phase II studies to beeffective in combination with endocrine therapy to treat patients withestrogen receptor–positive (ER+) breast cancer who progressed whilereceiving nonsteroidal aromatase inhibitors. This multinational, double-blind, placebo-controlled phase III study (clinicaltrials.gov: NCT00863655;Trial Sponsor: Novartis Pharmaceuticals) evaluated EVE in combinationwith exemestane (EXE) in patients with ER+ advanced breast cancer (ABC)refractory to letrozole or anastrozole.

Methods: Postmenopausal women �18 years old with ER+ ABC whosedisease was refractory to letrozole or anastrozole and who had a docu-mented recurrence or progression were included. Patients were stratifiedby sensitivity to prior hormonal therapy and the presence of visceralmetastasis and randomized (2:1) to EVE (10mg daily) or matching placeboorally once daily, with both arms receiving EXE (25 mg daily). Treatmentwas continued until disease progression or unacceptable toxicity occurred.Primary endpoint was progression-free survival (PFS), assessed by theinvestigators. Secondary endpoints included survival, response rate, andsafety. PFS was evaluated using Cox regression. A preplanned interimanalysis was performed and reviewed by the independent data monitoringcommittee (IDMC) after observing 359 PFS events.Results: 724 patients were randomized between 06/2009 and 01/2011from 24 countries (485: EVE+EXE; 239: EXE). Baseline characteristicswere well balanced; median age was 62 years, 56% had visceralinvolvement and 84% were sensitive to prior hormone therapy. Previoustherapy included letrozole or anastrozole (100%), tamoxifen (48%), ful-vestrant (16%) and chemotherapy (68%). At the interim analysis, the IDMCdisclosed that the trial met its primary endpoint, as assessed by localinvestigators (HR: 0.43 [95% CI: 0.35-0.54], median 6.9 vs 2.8 months;p¼1.4�10-15) and that results were consistent across the varioussubgroups. PFS analysis based on central assessment was also significant(HR: 0.36 [95% CI: 0.27-0.47], median 10.6 vs 4.1 months; p¼3.3�10-15).Both analyses crossed the pre-specified thresholds for significance basedon alpha-spending function using O'Brien-Fleming boundaries. Responserates were 9.5% and 0.4% on the EVE+EXE and EXE arms, respectively,p<0.0001. Most common grade 3/4 adverse events were stomatitis (8% vs1%), anemia (5% vs <1%), dyspnea (4% vs 1%), hyperglycemia (4% vs <1%),fatigue (3% vs 1%) and pneumonitis (3% vs 0%) for the EVE+EXE and EXEgroups, respectively.Conclusion: EVE, when added to an aromatase inhibitor, significantlyimproves PFS and response rate and has a manageable safety profile. EVEin combinationwith an aromatase inhibitor is a new therapeutic option forwomen with previously treated ABC.

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TREATMENT OF LOCALLY ADVANCED BREAST CANCER: A TUNISIANEXPERIENCE

Samir Hidar, Slim Ben Ahmed, Nouredine Bouaouina, Hédi KhairiFarhat Hached University Teaching Hospital, Sousse, Tunisia

Locally advanced breast cancer is defined by presence of primary tumorlarger than 5cm with or without chest-wall or and skin involvement orclinically N3 axillary lymph nodes. Standard treatment includes primarychemotherapy followed by radiotherapy with chemotherapy and orhormonal therapy. The aim of this study was to present outcomes of LABCpatients who received such sequence of treatment. A prospective collecteddata were retrospectively analyzed over a 5 years period from 2003 to2008.Statistical methods included Kaplan Meier and Cox regression. 135patients were initially involved but only 110 patients completed thedescribed treatment sequence were evaluated. 15 patients (13.6%) weregiven Tamoxifen as adjuvant therapy. 11 patients (10%) had completepathological response, 15 (13.6%) a complete clinical response. The 5-yearsurvival is 47.2 % complete pathological response and clinical responseswere identified by logistic regression to be the most important prognosticfactors.

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THE ROLE OF IN-VITRO HIGH RESOLUTION MAGIC ANGLE PROTONMAGNETIC RESONANCE SPECTROSCOPY (HRMAS) IN BREAST CANCER-A PILOT STUDY

Surender Kumar 1, Sandeep Kumar 1, Raja Roy 1,2, Ankita Rathore 1

1CSM Medical University (KGMU), Lucknow, India2Center for Biomedical Magnetic Resonance, Lucknow, India

Abstracts / The Breast 20 (2011) S12–S55 S31

Aim: To differentiate malignant, benign and normal breast tissue basedcon there metabolic profiles.Introduction: In the clinical situation of a breast lump the present diag-nostic tools like mammography, Ultrasonography, Computerized Tomog-raphy, Magnetic Resonance Imaging, FNAC and Histo-PathologicalExamination are incapable of detecting the disease before it is clinically orradiologically evident. However, the metabolic changes may occur muchbefore and these changes can be utilized for early diagnosis of the disease.High Resolution Proton Magnetic Resonance Spectroscopy (HRMAS) is oneof such techniques which can detect these metabolic changes in the formof spectra and can be used for early diagnosis.Methodology: A total of 90 tissues (20 normal, 31 benign and 31malignant) obtained after mastectomy, exicisional and incisionalbiopsy from seventy patients of benign and malignant breast disease,were snap frozen in liquid nitrogen. Thin slices of tissue (35mg - 40mg) were taken from the snap frozen specimens and were put ina 4mm HRMAS rotor and the tissues were blindly subjected to BrukerBiospin Avance 400 MHz high resolution magic angle spectroscopy.The tissue specimens used for HRMAS analysis were retrieved from therotor and was sent for histo-pathological examination. The spectro-scopic findings of the tissues were correlated with the routine histo-pathogical findings.Results: All the malignant tissue samples were diagnosed histopatholog-ically as invasive ductal carcinoma. In benign tissue group 29 wereconfirmed as fibroadenoma, 5 had benign phylloides tumor and 1 wasdiagnosed as chronic mastitis after histopathological examination. Thespectra of malignant tissues had significantly high levels of Choline,phosphocholine and glycerol phoshpocholine in the spectral region 3.21and 3.22 ppm as compared to benign tissues. Overall the HRMAS had thesensitivity and specificity of 94 and 92%.Conclusion: The study proved the efficiency of MR spectroscopy forevaluating the metabolites status in specimen of breast cancer as a reliablealternative to histopathology and immuno-histochemistry. The studyprovided a rapid evaluation of specimens. However, studies involvinga larger sample size and more frequency MRS equipment may furtherestablish the quantitative difference of metabolites in normal, benign andmalignant specimen

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BRCA-ASSOCIATED BREAST CANCER IN WOMEN YOUNG AGE

Dmitry Avtomonov, Anastassia Parokonnaya, MichailNechushkin, Ludmila Lyubchenko, Dmitry KravchenkoBlokhin Cancer Research Center, Moscow, Russia

The recent years have been marked by the constant increase of breastcancer cases. The worrying tendency is the early age of patients with thediagnosis under consideration. It is found that nowadays the majorfactor of breast cancer manifestation is a compromised family history ofpatients. Approximately 5-10% of breast cancer cases at the early age areprovoked by the germinal mutation of BRCA1 or BRCA2 . Moreover 15-20% of cases are associated with polymorphism process of genes andenvironmental influence. Our research based on investigating the casesof 74 patients at the age of 20-40 has revealed the absence of mutationsin 31(42%) patients, 13(17,5%) patients had BRCA1 mutation, 30(40,5%)patients had polymorphism of BRCA2 gene, that is not considered as theoriginal mutation of BRCA2 gene, thus we did not indentify any BRCA2gene mutations. Our monitoring of 44 women patients has resulted inthe following: the general and non-recurrent 5-year survival in thegroup of patients at the early age who do not carry BRCA1/2 mutationswas indentified as 64,1�18% and 50�17,5% correspondingly. Meanwhilewith BRCA1-carriers the general 5-year survival was indentified as87,5�11% while non-recurrent one was 86,4�12%. The differencesbetween general and non-recurrent survival are not statistically relevant(insignificant number of BRCA1-carriers). However we discovered thehigher rate of general and non-recurrent survival with young BRCA1-carriers in comparison with the patients without genetic mutationsidentified.

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NOVEL STRATEGY TO RESTORE THE ACTIVITY OF TAXANES:A MULTICENTER PHASE II STUDY OF COMBINATION THERAPY WITHTAXANES AND TOREMIFENE AT 120 MG FOR ADVANCED/RECURRENTBREAST CANCER. (KINKI MULTIDISCIPLINARY BREAST ONCOLOGYGROUP: KMBOG0612)

Takahiro Nakayama 1, Takashi Arai 2, Jun Yamamura 3, TakashiMorimoto 4, Yoshifumi Komoike 5, Katsuhide Yoshidome 6, DaisukeYasui 7, Shunji Kamigaki 2, Takashi Nomura 4, NobukiMatsunami 8, Toshihiro Kobayashi 9, Norikazu Masuda 3

1Graduate School of Medicine, Osaka University, Suita, Osaka, Japan2 Sakai Municipal Hospital, Sakai, Osaka, Japan3Osaka National Hospital, Osaka, Osaka, Japan4Yao Municipal Hospital, Yao, Osaka, Japan5Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka,Osaka, Japan6Osaka Police Hospital, Osaka, Osaka, Japan7Osaka Kaisei Hospital, Osaka, Osaka, Japan8Osaka Rousai Hospital, Sakai, Osaka, Japan9 Takatsuki Red Cross Hospital, Takatsuki, Osaka, Japan

Background: A preclinical study reported that toremifene (TOR) increasedthe level of an anticancer agent such as doxorubicin and paclitaxel　in thebreast cancer cell which has acquired resistance to them by the expressionof P-glycoprotein.Methods: The subjects were postmenopausal females with advanced/recurrent breast cancer who showed PD after PR or SD to mono therapywith taxanes (paclitaxel or docetaxel) was confirmed. In a phase IIprospective study, 120 mg of TOR was administered orally every day afterthe treatment failure of taxane mono therapy, while continuing therespective taxane regimen. As a primary end point, we assessed theresponse rate (RR) including clinical benefits. Secondary end points werethe time to progression (TTP) and adverse reactions.Results: Twenty-seven patients were registered between November 1,2006 and October 31, 2010, and 25 patients were analyzed at this time. Themedian agewas 57 years (range: 36-79) and the median ECOG PS was zero(range: 0-1). The RR, clinical benefit (CB) rate, and median TTP were 8.7%,21.7%, and 12.1 weeks (range: 3.1-69.6), respectively. Moreover, withadding TOR to taxanes, treatment duration could be extended more than100% in 5 patients (i.e., paclitaxel+TOR 323 days / paclitaxel 288 days ¼112%). Adverse reactions to this combination regimen were observed in 8patients. In 2 cases, grade 2 numbness was noted. However, the otherpatients showed grade 1 adverse reactions; this therapy was tolerable.Conclusion: Combination therapy with taxanes and TOR at 120 mg wastolerable and useful. The results suggest that TOR may restore the activityof taxanes in taxane refractory advanced/recurrent breast cancer patients.

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NEOADJUVANT CHEMOTHERAPY AND SURGICAL OPTIONS FOR LOCALLYADVANCED BREAST CANCER: A SINGLE INSTITUTION EXPERIENCE

Mohamed Abou Elmagd Salem, Hamza Abbas Hamza, Nashwa MohamedAbd El RaoufSouth Egypt Cancer Institute - Assiut University, Assiut, Egypt

Background: The therapeutic challenges of treating patients with locallyadvanced breast cancer (LABC) are well recognized, especially in terms ofincreased risk of local recurrence after locoregional treatments andbecause of a poorer overall survival. One of the main goals of surgicalmanagement of locally advanced breast cancer (LABC) is to ensure localcontrol. A commonly used approach currently involves primary chemo-therapy, followed by surgery and radiation. It has been demonstrated thatthe use of primary chemotherapy can downstage the size of breast tumor,thus allowing some patients with advanced disease with the option of BCS.Patients and Methods: Fifty six patients, presenting LABC weretreated with primary chemotherapy comprising of cyclophosphamide,