Neoadjuvant chemotherapy and surgical options for locally advanced breast CANCER: A Single institution experience

Neoadjuvant chemotherapy and surgical options for locally advanced breast CANCER: A Single institution experience

Abstracts / The Breast 20 (2011) S12–S55 Aim: To differentiate malignant, benign and normal breast tissue based con there metabolic profiles. Introduc...

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Abstracts / The Breast 20 (2011) S12–S55

Aim: To differentiate malignant, benign and normal breast tissue based con there metabolic profiles. Introduction: In the clinical situation of a breast lump the present diagnostic tools like mammography, Ultrasonography, Computerized Tomography, Magnetic Resonance Imaging, FNAC and Histo-Pathological Examination are incapable of detecting the disease before it is clinically or radiologically evident. However, the metabolic changes may occur much before and these changes can be utilized for early diagnosis of the disease. High Resolution Proton Magnetic Resonance Spectroscopy (HRMAS) is one of such techniques which can detect these metabolic changes in the form of spectra and can be used for early diagnosis. Methodology: A total of 90 tissues (20 normal, 31 benign and 31 malignant) obtained after mastectomy, exicisional and incisional biopsy from seventy patients of benign and malignant breast disease, were snap frozen in liquid nitrogen. Thin slices of tissue (35mg - 40 mg) were taken from the snap frozen specimens and were put in a 4mm HRMAS rotor and the tissues were blindly subjected to Bruker Biospin Avance 400 MHz high resolution magic angle spectroscopy. The tissue specimens used for HRMAS analysis were retrieved from the rotor and was sent for histo-pathological examination. The spectroscopic findings of the tissues were correlated with the routine histopathogical findings. Results: All the malignant tissue samples were diagnosed histopathologically as invasive ductal carcinoma. In benign tissue group 29 were confirmed as fibroadenoma, 5 had benign phylloides tumor and 1 was diagnosed as chronic mastitis after histopathological examination. The spectra of malignant tissues had significantly high levels of Choline, phosphocholine and glycerol phoshpocholine in the spectral region 3.21 and 3.22 ppm as compared to benign tissues. Overall the HRMAS had the sensitivity and specificity of 94 and 92%. Conclusion: The study proved the efficiency of MR spectroscopy for evaluating the metabolites status in specimen of breast cancer as a reliable alternative to histopathology and immuno-histochemistry. The study provided a rapid evaluation of specimens. However, studies involving a larger sample size and more frequency MRS equipment may further establish the quantitative difference of metabolites in normal, benign and malignant specimen

PO56 BRCA-ASSOCIATED BREAST CANCER IN WOMEN YOUNG AGE Dmitry Avtomonov, Anastassia Parokonnaya, Nechushkin, Ludmila Lyubchenko, Dmitry Kravchenko Blokhin Cancer Research Center, Moscow, Russia

Michail

The recent years have been marked by the constant increase of breast cancer cases. The worrying tendency is the early age of patients with the diagnosis under consideration. It is found that nowadays the major factor of breast cancer manifestation is a compromised family history of patients. Approximately 5-10% of breast cancer cases at the early age are provoked by the germinal mutation of BRCA1 or BRCA2 . Moreover 1520% of cases are associated with polymorphism process of genes and environmental influence. Our research based on investigating the cases of 74 patients at the age of 20-40 has revealed the absence of mutations in 31(42%) patients, 13(17,5%) patients had BRCA1 mutation, 30(40,5%) patients had polymorphism of BRCA2 gene, that is not considered as the original mutation of BRCA2 gene, thus we did not indentify any BRCA2 gene mutations. Our monitoring of 44 women patients has resulted in the following: the general and non-recurrent 5-year survival in the group of patients at the early age who do not carry BRCA1/2 mutations was indentified as 64,118% and 5017,5% correspondingly. Meanwhile with BRCA1-carriers the general 5-year survival was indentified as 87,511% while non-recurrent one was 86,412%. The differences between general and non-recurrent survival are not statistically relevant (insignificant number of BRCA1-carriers). However we discovered the higher rate of general and non-recurrent survival with young BRCA1carriers in comparison with the patients without genetic mutations identified.

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PO57 NOVEL STRATEGY TO RESTORE THE ACTIVITY OF TAXANES: A MULTICENTER PHASE II STUDY OF COMBINATION THERAPY WITH TAXANES AND TOREMIFENE AT 120 MG FOR ADVANCED/RECURRENT BREAST CANCER. (KINKI MULTIDISCIPLINARY BREAST ONCOLOGY GROUP: KMBOG0612) Takahiro Nakayama 1, Takashi Arai 2, Jun Yamamura 3, Takashi Morimoto 4, Yoshifumi Komoike 5, Katsuhide Yoshidome 6, Daisuke Shunji Kamigaki 2, Takashi Nomura 4, Nobuki Yasui 7, Matsunami 8, Toshihiro Kobayashi 9, Norikazu Masuda 3 1 Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 2 Sakai Municipal Hospital, Sakai, Osaka, Japan 3 Osaka National Hospital, Osaka, Osaka, Japan 4 Yao Municipal Hospital, Yao, Osaka, Japan 5 Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan 6 Osaka Police Hospital, Osaka, Osaka, Japan 7 Osaka Kaisei Hospital, Osaka, Osaka, Japan 8 Osaka Rousai Hospital, Sakai, Osaka, Japan 9 Takatsuki Red Cross Hospital, Takatsuki, Osaka, Japan Background: A preclinical study reported that toremifene (TOR) increased the level of an anticancer agent such as doxorubicin and paclitaxel in the breast cancer cell which has acquired resistance to them by the expression of P-glycoprotein. Methods: The subjects were postmenopausal females with advanced/ recurrent breast cancer who showed PD after PR or SD to mono therapy with taxanes (paclitaxel or docetaxel) was confirmed. In a phase II prospective study, 120 mg of TOR was administered orally every day after the treatment failure of taxane mono therapy, while continuing the respective taxane regimen. As a primary end point, we assessed the response rate (RR) including clinical benefits. Secondary end points were the 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. The median age was 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, with adding TOR to taxanes, treatment duration could be extended more than 100% in 5 patients (i.e., paclitaxel+TOR 323 days / paclitaxel 288 days ¼ 112%). Adverse reactions to this combination regimen were observed in 8 patients. In 2 cases, grade 2 numbness was noted. However, the other patients showed grade 1 adverse reactions; this therapy was tolerable. Conclusion: Combination therapy with taxanes and TOR at 120 mg was tolerable and useful. The results suggest that TOR may restore the activity of taxanes in taxane refractory advanced/recurrent breast cancer patients.

PO58 NEOADJUVANT CHEMOTHERAPY AND SURGICAL OPTIONS FOR LOCALLY ADVANCED BREAST CANCER: A SINGLE INSTITUTION EXPERIENCE Mohamed Abou Elmagd Salem, Hamza Abbas Hamza, Nashwa Mohamed Abd El Raouf South Egypt Cancer Institute - Assiut University, Assiut, Egypt Background: The therapeutic challenges of treating patients with locally advanced breast cancer (LABC) are well recognized, especially in terms of increased risk of local recurrence after locoregional treatments and because of a poorer overall survival. One of the main goals of surgical management of locally advanced breast cancer (LABC) is to ensure local control. A commonly used approach currently involves primary chemotherapy, followed by surgery and radiation. It has been demonstrated that the 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 were treated with primary chemotherapy comprising of cyclophosphamide,

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Abstracts / The Breast 20 (2011) S12–S55

doxorubicin and fluorouracil and then surgery (15 patients with BCT, 11 patients with skin sparing mastectomy and latesmus dorsi reconstruction, 30 patients underwent MRM) followed by radiotherapy were examined between the years January 2007- January 2009 retrospectively. Before neoadjuvant chemotherapy, ten patients (18%) were Stage IIB, 32 patients (57%) Stage IIIA, 9 patients (16%) Stage IIIB and 5 patients stage IIIC (9%). Result: Clinical down staging was obtained in 49 (87.5%) of patients. five (9%) patients had complete clinical response, 44 (78.5%) patients with partial response, six patients (10.7%) had stable disease and 1 (1.8%) patient with progressive disease. The primary tumor could not be palpated after chemotherapy in 7 (12.5%) of 56 patients presenting with palpable mass, therefore wire localization was performed for BCS. Median follow-up was 41.5 months (ranging 20 to 50 months). Local recurrence was detected in 9 (16%) patients. Distant metastasis developed in 11 (19.5%) patients. Eight of the patients died of distant metastases and three of them are alive at 42 months. Discussion: Negative margin is more important factor in terms of local recurrence. Histological grade, menopausal and hormonal status are important factors in term of distant metastasis. BCS can be performed safely by achieving free surgical margin in patients who have small sized tumor.

PO59 FEATURES OF RECURRENCE OF TRIPLE METASTATIC BREAST CANCER (NMBC) INSTITUTION STUDY

NEGATIVE PATIENTS:

(TN) NONA SINGLE

Ashley Alarcon-Rozas, Rosario Cueva, Jose Galarreta, Jesus Torres, Jose Ramirez, Elmer Gonzales Hospital Almenara, Lima, Peru Background: The TN is a subtype of breast cancer (BC) negative for ER, PR and Her2/neu and is the most agressive subtype. Previous studies suggested that DFS of women with TN-BC is shorter than any other subtype and they demonstrated racial differences. TN-BC is more agressive in non caucasian population. Objectives: In this retrospective study our goal is to determine the incidence of TN in non metastatic BC, the recurrence rate (RR) and the patterns of recurrence by anatomic region and the DFS. Material and Methods: We reviewed 1042 medical records of BC patients diagnosed between Jan/2000 to Dec/2005 at the Almenara Hospital in Lima Peru. 215 patients were identified as TN NMBC. We collected the clinical data including age, menopausal status, staging, hormone receptor status as well as Her2/neu status and analized by statistic software SPSS v. 17.0. Results: The incidence of TN NMBC were 20.6% (215); of them 18.6% (40) patients had recurrences. The median age in patients with recurrent disease were 52.5 years (31-93years); the median DFS were 27 months with a median follow-up of 64 months. According to initial staging the recurrences were 7.5% (3); 32.5% (13); and 60% (24) respectively for patients with stages I, II and III. Almost one third (35%) of patients with recurrences were lymphatic node negative at diagnosis after mastectomy. The most frequent involved organs were visceral (lung¼12, liver¼3) 37.5% (15); bone 25% (10); skin 20% (8); CNS 12.5% (5) and contralateral breast 5% (2). There were four nuliparus women two of them had skin recurrence and the others two had bone metastasis. Additionally we found five patients with history of first degree familiar BC four of them were stage two with lymh node negative at diagnosis. Summary: TN NMBC constitutes 20.6% of all BC in our institution; the majority of relapses were stage III (60%). The median DFS for recurrence were 27 months and the most frequent sites involved were visceral (37%) and bone (25%). It is important to know that 12.5% of recurrences were to CNS and one third of the patients were lymph node negatives. We found 20.6% of incidence of TN-BC which is close to the incidence of African American population (25%) and in contrast to Caucasian population (7%-9%) and the Asian population (7%-10%). This is to our knowledge the first study of patterns of recurrence in TN NMBC in a Latino population

PO60 FINAL RESULTS OF A PILOT STUDY OF PATHOLOGICAL COMPLETE RESPONSE (PCR) IN LABC PATIENTS TREATED WITH AC X 4 DOSE DENSE FOLLOWED BY WEEKLY PACLITAXEL X 12 WITH CAPECITABINE Ashley Alarcon-Rozas 1, Cesar De Las Casas 2, Jose Galvez 5, Romulo Cardenas 3, Diego Venegas 4, Claudia Lozada 1 1 Clinica Angloamericana, Lima, Peru 2 VA Hospital, San Antonio TX, USA 3 Hospital Militar, Lima, Peru 4 Hospital Cayetano Heredia, Lima, Peru 5 Clinica San Felipe, Lima, Peru Background: This is a multicentric study looking to achieve a pCR after preoperative chemotherapy that correlates with better OS in patients with LABC. The correlation of Hormonal Receptors and Her2 with response to this treatment is a secondary objective. Patients and Methods: Between May/2007 and January/2010 we collected 65 patients 60 of then were valuables. Patients had tumors between 2.5 and 20cm. All of them with biopsy and IHC before systemic treatment. They have received doxorrubicin 60mg/m2 and cyclophosphamide 600mg/m2 every 2 weeks times 4 with G-CSF support, then weekly paclitaxel 80mg/m2 times 12 concurrent with capecitabine 700mg/m2 2 weeks on 1 week off followed by surgery. After surgery we use Miller and Payne method to evaluate responses. pCR is defined as no evidence of malignant cells in the nodes and in the primary tumor. Results: We analized 60 patients. 5 pts. died, 4 of them due to progressive disease and 1 due to cirrosis. The median age were 56 years, 33.3% were premenopausal; 84% had tumors bigger than 5cm and 20% bigger than 10cm. The ORR were 85%, pCR were 29.7% (14/48), of them 35% (5) were triple negatives, 21.4% (3) were Her2 positive and 42% (6) were hormonal receptors positives. Patients who do not achieve more than 50% of response after anthracyclinesas and after taxanes with capecitabine were 17% and of them 85% were HR positive Her2 negative with similar profiles in 12 patients who had progressive disease. Almost 50% of all triple negative pts. achieve pCR, 33% of Her2 postive HR negatives had pCR (we do not use trastuzumab) and finally 15% of HR positives had pCR. Conclusion: To our knowledge this is the first study with anthracyclines, paclitaxel and capecitabine given concurrently in neoadjuvant setting. The pCR almost 30% is high considering that more than 80% of patients had huge tumors and in contrast with other studies this combinations works in HR positive tumors with low histological grades grades achieving 15% of pCR, probably the higest response in these subtype tumors. We need more studies to confirm this response rate in HR positives pts.

PO61 NEW TRENDS FOR SURGICAL TREATMENT OF LOCALLY ADVANCED BREAST CANCER Angelo Gustavo Zucca Matthes 1, Rene Aloisio da Costa Vieira 1, Ligia Maria Kerr 1, Raphael Luis Haikel 1, Gilberto Uemura 2 1 Hospital de Cancer de Barretos, Barretos, SP, Brazil 2 Faculdade de Medicina de Botucatu - UNESP, Botucatu, SP, Brazil Introduction: The locally advanced breast cancer is still common in developing countries. The neoadjuvant chemotherapy (NC) allows converting large tumor into operable one. Oncoplastic surgery (OS) adds new techniques to breast conservative treatment (BCT). The association between NC and OS provides the resection of large amount of breast tissue, including skin, with satisfactory aesthetic results. Objective: Evaluate the possibilities to indicate oncoplastic techniques to determine BCT after NC for large breast tumors. Material and Methods: A prospective clinical trial (www.clinicaltrials.gov, NCT00820690) study with women breast cancer patients, clinical stage III, submitted to NC, based on four cycles of doxorubicin 60mg/m2 + cyclophosphamide 600 mg/m2 and 4 cycles of paclitaxel 175mg/m2. Preoperative tattoo was realized for all patients to determine the clinical