- Email: [email protected]
P207 Prognostic significance of biomarker discordance after neoadjuvant chemotherapy in breast cancer
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Poster Abstracts II / The Breast 24S1 (2015) S87–S150
P205 The relationship between dose intensity and pathological effect of nab-paclitaxel as neoadjuvant
P206 Ipsilateral breast cancer recurrence in conservative treatment for locally advanced breast cancer
H. Inoue1 *, A. Hirano1 , A. Hattori1 , N. Jibiki2 , K. Ogura1 , R. Miyamoto2 , F. Okubo1 , Y. Naritaka3 , M. Fujibayashi4 , T. Shimizu1 . 1 Breast Surgery, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan, 2 Breast Surgery, Tokyo Women’s Medical University Yachiyo Medical Center, Tokyo, Japan, 3 Surgery, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan, 4 Surgical Pathology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan
G.F.A. Carrara1 , C.S. Neto1 , L.F. Abr˜ao-Machado2 , J.S. Nunes3 , M.A.A.K. Folgueira4 , M.M. Brentani4 , R.A.C. Vieira1 *. 1 Postgraduate Course In Oncology, Barretos Cancer Hospital, Barretos, Brazil, 2 Pathology, Barretos Cancer Hospital, Barretos, Brazil, 3 Clinical Oncology, Barretos Cancer Hospital, Barretos, Brazil, 4 Oncology, USP School of Medicine, S˜ ao Paulo, Brazil
Goals: Although anthracycline followed by weekly paclitaxel (PTX) is a standard chemotherapy in the neoadjuvant setting of breast cancer, peripheral neuropathy is a problem for patients treated with weekly PTX. Since nanoparticle albumin-bound (nab)-PTX contains neither polyoxyethylene castor oil nor ethanol, reduction or rapid recovery of neuropathy is expected. Therefore we planned a phase II neoadjuvant trial with epirubicin (E)/cyclophosphamide (C) followed by weekly nab-PTX +/− trastuzumab (T). Forty patients were enrolled in this trial and their neoadjuvant chemotherapy (NAC) and operations were finished in 2013. In this trial, delay and dose-reduction of nabPTX were frequently observed. Thus, we assessed the relationship between relative dose intensity (RDI) of weekly nab-PTX and the pathological effect of NAC. Methods: Women from 20 to 70 years old with node-positive breast cancer were enrolled in this trial between 2011 and 2013. Patients received four cycles of E (90 mg/m2 ) and C (600 mg/m2 ) every 3 weeks, followed by four cycles of nab-PTX (125 mg/m2 ) on Days 1, 8 and 15 in a 28-day cycle. Fifteen cycles of T (2 mg/kg, loading 4 mg/kg) were added to the nab-PTX regimen in HER2-positive patients every week. Adverse events were assessed according to NCI-CTCAE version 4.0. Administration of nab-PTX was delayed for 1 week if grade 2 hematological or grade 1 non-hematological toxicities except for nausea, vomiting and alopecia were observed. Furthermore, dose of nab-PTX was reduced if toxicity did not improve after 2 weeks delay. The relationship between RDI and pathological complete response (pCR) in patients who received nab-PTX was analyzed. Results: Thirty-seven patients who received at least one administration of nab-PTX were analyzed, and the median age was 56 years (range 31–68 years). Fifteen patients (40.5%) were positive HER2. Fourteen patients (37.8%) achieved pCR. The median total dose of nab-PTX was 1500 (350–1500) mg/m2 . Thirty-one patients (83.8%) received 4 complete cycles of nab-PTX. The median dose intensity (DI) was 80.6 mg/m2 /week (planned DI:93.8), and the median-delivered RDI was 86%. The median total dose was 1450 mg/m2 in patients with pCR, whereas in those with non-pCR the median total dose was 1500 mg/m2 (P = 0.5375). In patients with pCR, the median RDI was 80%, whereas in those with non-pCR the median RDI was 92% (P = 0.1775). Among patients with HER2 positive, the median RDI in the pCR-group was 83% whereas in the non-pCR group the median RDI was 97% (P = 0.0673). Conclusion: In this trial, the median RDI of weekly nab-PTX was low (86%) because administration was delayed and dose reduction was carried out in many patients. However, the tendency was seen that the RDI in the pCR group was lower than that in the non-pCR group, suggesting that the same pathological effect would be obtained in HER2 positive patients even if the dose intensity of nab-PTX were reduced. Disclosure of Interest: No significant relationships.
Goals: Evaluate the clinical and pathologic factors related to local and regional recurrence in locally advanced breast cancer (LABC) in women submitted to neoadjuvant chemotherapy (NC) and conservative surgery. Methods: A retrospective study was performed in patients with LABC submitted to NC and conservative treatment during 01/2006 to 06/2011. The main regimen proposed was AC-T (4 AC + 4 T). From the 421 women evaluated 97 underwent to a breast conservative surgery. We evaluated the clinical, pathologic, immunohistochemistry and surgical factors that would contribute to locoregional recurrence (LRR) and local recurrence (LR). The chi-square and logistic regression were used for association analysis. A Kaplan–Meier curve and a Cox model were used to evaluate the main factors related to free recurrence survival. Results: 88.7% were clinical stage III, 76.3% had T3 and T4 tumors, 79.4% N1 and N2 axilla, 92.8% invasive ductal carcinoma and 94.8% Nottingham grade II and III. Immunohistochemistry evaluation demonstrated that 37.6% were luminal A/B1, 18.3% triple negative, 31.2% luminal B2 and 12.9% Her2 tumors. The AC-T regime was performed in 92.7% of the women. The pathologic complete response was present in 25.8% of the tumors. 97.9% had free margins and concentric tumor decrease was present in 55.7% of the patients. Adjuvant radiotherapy was performed in 96.9% of the patients, but adjuvant trastuzumab was performed only 2.1% of the patients. The mean follow up was 53.9 months and the 5-year actuarial global survival was 83.4%. The LRR and LR was 15.5% and 7.2% respectively. The chi-square and univariate logistic regression analysis showed the clinical stage T-TNM (0.015), histologic grade (0.02) and necrosis (0.008) was related to LRR, but the presence of necrosis was the main factor in multivariate analysis (OR = 0.09; IC 0.01–0.73; p = 0.02). The only factor related to decrease of LR was necrosis (p = 0.04). The main factor related to LRR free survival and LR free survival was the molecular subtype, as Her2 tumors had decrease of free survival with the odds ratio of 3.06 and 3.27 respectively. Conclusion: Her2 tumors had a higher risk of locorregional and local disease free of recurrence. More studies are necessary to evaluate this condition in the trastuzumab era with a large number of patients. Disclosure of Interest: No significant relationships. P207 Prognostic significance of biomarker discordance after neoadjuvant chemotherapy in breast cancer A. Matsumoto1 *, H. Jinno2 , T. Ando1 , T. Fujii1 , T. Nakamura1 , J. Saito1 , M. Takahashi2 , T. Hayashida2 , Y. Kitagawa2 . 1 Department of Surgery, Inagi Municipal Hospital, Tokyo, Japan, 2 Department of Surgery, Keio University School of Medicine, Tokyo, Japan Goals: Neoadjuvant chemotherapy (NAC) was reported to change the status of biomarker including estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki-67. However, the impact of these changes on response to treatment and long-term outcomes still remains to be elucidated. The objectives of this study is to evaluate the frequency of biomarker status changes after NAC in patients with residual disease and their relationship with response to treatment and prognosis.
14th St.Gallen International Breast Cancer Conference / The Breast 24S1 (2015) S87–S150
Methods: From a prospective database of 196 patients receiving NAC from January 2005 to June 2014, 156 patients (79.6%) with non-pCR were analyzed. Patients were treated with sequential anthracycline and taxane. ER, PgR, HER2 and Ki-67 were assessed in both core needle biopsy (CNB) performed prior to NAC and surgical samples. Pathological response criteria were classified as grade 0, 1, 2, or 3: grade 0 includes almost no change in cancer cells; grade 1 includes slight or marked changes in less than two thirds of the area; grade 2 includes marked changes in more than two thirds of the area; grade 3 includes necrosis or disappearance of all tumor cells. Results: The median age at diagnosis was 50.0 years and the median tumor size was 3.2 cm. Clinical nodal status was positive in 57.7% of patients before NAC. The rate of pathological response grade 0, 1 and 2 were 5.8%, 65.4% and 28.8%, respectively. Before receiving NAC, ER, PgR and HER2 were positive in 73.7%, 67.9% and 11.5% of patients. Changes in ER, PgR and HER2 status between CNB and surgical samples were 10.9% (3.8% gain; 7.1% loss), 17.9% (1.9% gain; 16.0% loss) and 5.3% (2.0% gain; 3.3% loss), respectively. After NAC, Ki-67 expression decreased in 77.8% of patients (CNB sample: 24.7%, surgical sample: 5.0%; p < 0.001). In the ER-discordant group, clinical complete response rate (41.2% vs. 15.1%; p = 0.016) and grade 2 rate of pathological response (61.1% vs. 30%, p = 0.033) was significantly higher than in the ER-concordant group, whereas discordance in PgR and HER2 status was not significantly correlated with clinical and pathological response. Although there was no correlation between Ki-67 of CNB samples and disease-free survival (DFS), patients with high (>14%) Ki-67 of surgical samples had significantly shorter DFS when compared with low (<14%) Ki-67 (28.5 months vs. 41.3 months, p = 0.003). After a median follow-up of 49.4 months, patients with a loss in hormone receptor (HR) status had a trend toward a worse DFS compared with the concordant HR-positive group (32.5 months vs. 39.0 months; p = 0.08). Conclusion: This study suggested that changes in biomarker status caused by NAC might have a prognostic value in breast cancer patients without pCR. Disclosure of Interest: No significant relationships. P208 Pathological complete response (PCR) rates after sequential CT in locally advanced BC I. Bozovic-Spasojevic1 *, S. Milosevic1 , S. Susnjar2 , Z. NeskovicKonstantinovic2 . 1 Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia, 2 Medical Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia Goals: Pathological complete response (pCR) has predicted long term survival in several neoadjuvant studies and in the recent meta-analysis (Cortazar, Lancet 2014). Hence, we conducted a single institutional study, aiming to analyze the percentage of pCR in breast cancer (BC) patients (pts) treated with neoadjuvant chemotherapy (CT) regiments. Methods: Consecutive breast cancer patients treated with neoadjuvant CT at the Institute for Oncology and Radiology of Serbia between January 2013 and April 2014, were selected for the analysis. Pts who were treated with sequential CT: 3–4 cycles of antracyclinebased CT (AC/FAC/FEC) and taxane-based CT (12 weekly paclitaxel or 3–4 cycles of 3 weekly docetaxel) with or without trastuzumab according to HER2 status, were eligible for the analysis. pCR was defined as no invasive tumor cells and no in situ residuals in breast and axillary lymph nodes (von Minckwitz, JCO 2012). Results: We identified 112 patients with a median age of 47 years (range 21–74). 57 patients had IIIB, 34 IIIA and 21 IIB UICC TNM clinical stages; the commonest histological type on core biopsy was ductal invasive carcinoma seen in 56 pts, 32 had lobular invasive carcinoma and 24 had other BC histology; grade 2 tumors had 84 pts
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and grade 3 28 pts. Tumors stained positive for ER (ER+/PR+/−) in 78 and for HER2 in 39 pts. Up to 1st of May 2014, 46 pts completed CT and were operated; 6 of them had breast conserving surgery, 2 pts had skin sparing mastectomy and the rest of the patients had radical mastectomy. 14 pts achieved pCR, defined as ypT0 ypN0; 10 pts were HER2+ and were treated with 4 cycles of neoadjuvant trastuzumab (TR) plus CT, 1 pt HER2+ER+ (treated with neoTR plus CT), 2 pts ER+ (CT) and 1 HER2−/ER− (CT). Of the partial responders there was no change in histological type; grade was available on excision in 30 pts and was different between core biopsy and final excision in 11 pts, 3 upgrades and 8 downgrades. Out of 32 stained paired pre and post tumor samples, one tumor change profile from ER weak positive to negative (Allred score 4 to 0); two changed profile from PR negative to weak positive (Allred 0 to 4 and 5 respectively) whereas one changed from weak positive to negative (Allred score 3 to 0); three HER2+ tumors (two IHC3+ and one CISH positive) changed profile to HER2 negative (all IHC 1+). Conclusion: In our single institutional-study rate of pCR after sequential anthacicline-taxane based neoadjuvant CT with/without trastuzumab, within all BC pts was 30%. Implications of changes in histological grade and receptor status following neoadjuvant CT should be further explored. Disclosure of Interest: No significant relationships. P209 Metabolic signature predicts progression and response after taxane–anthracycline neoadjuvant regimen I. Dale1 *, A. Roscher2 , A. Lopes Carvalho3 , E. Guimar˜aes Do Turco4 , R.A. Da Costa Vieira3 . 1 Gynecology Department, Federal University of S˜ ao Paulo, S˜ ao Paulo, Brazil, 2 Children’s Research Center, Ludwig-Maximilians Universit¨ at M¨ unchen, M¨ unchen, Germany, 3 Barretos Cancer Hospital, Barretos Cancer Hospital, Barretos, Brazil, 4 Surgery, Federal University of Sao Paulo, S˜ ao Paulo, Brazil Goals: To identify predictive blood metabolites signatures of complete pathologic response (pCR) defined as no histopathologic evidence of any residual invasive and/or noninvasive residual in breast or nodes (ypT0/ypN0), along with signatures able to predict stable disease and/or progression (SDPR) defined here as any response less than 30% reduction in the initial tumor volume in response to neoadjuvant treatment for stage III breast cancer. Methods: In this prospective, NIH registered, neoadjunvant taxane/anthracyclin-based protocol, we applied a targeted, quantitative mass spectrometry approach (Biocrates, Innsbruck, Austria) to measure the absolute micromolar concentrations of metabolites in plasma samples from 59 stage III breast cancer patients prior to chemotherapy and compared the results with the final tumor volume after chemotherapy. For the detection of discriminative metabolites, training and validation sets were assembled. Blinded-created data was then imported to ROC Curve Explorer & Tester (ROCCET, available at http://www.roccet.ca/ROCCET) for the computer-assisted generation of uni and multivariate Receiver Operating Characteristic (ROC) curves. Results: Complete pathologic response (pCR) and stable disease/progression (SDPR), were observed in 11% (7/59) and in 32% (19/59) of patients respectively. After training and validation sets, two predictive metabolites combinations for pCR have emerged with good discriminative characteristics, the first one with sensitivity=100.00%, specificity= 83.8, PPV= 44.44% and NPV= 100.00% in addition to a second one with sensitivity=100.00%, specificity= 89.66, PPV= 57.14% and NPV= 100.00%. The third metabolites combination was able to predict SDPR with sensitivity=100.00%, specificity= 93.10%, PPV= 84.62% and NPV= 100.00%. The identified metabolites are mainly related to glutaminolysis, glycolysis, ether lipids, biogenic amines and
Poster Abstracts II / The Breast 24S1 (2015) S87–S150
P205 The relationship between dose intensity and pathological effect of nab-paclitaxel as neoadjuvant
P206 Ipsilateral breast cancer recurrence in conservative treatment for locally advanced breast cancer
H. Inoue1 *, A. Hirano1 , A. Hattori1 , N. Jibiki2 , K. Ogura1 , R. Miyamoto2 , F. Okubo1 , Y. Naritaka3 , M. Fujibayashi4 , T. Shimizu1 . 1 Breast Surgery, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan, 2 Breast Surgery, Tokyo Women’s Medical University Yachiyo Medical Center, Tokyo, Japan, 3 Surgery, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan, 4 Surgical Pathology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan
G.F.A. Carrara1 , C.S. Neto1 , L.F. Abr˜ao-Machado2 , J.S. Nunes3 , M.A.A.K. Folgueira4 , M.M. Brentani4 , R.A.C. Vieira1 *. 1 Postgraduate Course In Oncology, Barretos Cancer Hospital, Barretos, Brazil, 2 Pathology, Barretos Cancer Hospital, Barretos, Brazil, 3 Clinical Oncology, Barretos Cancer Hospital, Barretos, Brazil, 4 Oncology, USP School of Medicine, S˜ ao Paulo, Brazil
Goals: Although anthracycline followed by weekly paclitaxel (PTX) is a standard chemotherapy in the neoadjuvant setting of breast cancer, peripheral neuropathy is a problem for patients treated with weekly PTX. Since nanoparticle albumin-bound (nab)-PTX contains neither polyoxyethylene castor oil nor ethanol, reduction or rapid recovery of neuropathy is expected. Therefore we planned a phase II neoadjuvant trial with epirubicin (E)/cyclophosphamide (C) followed by weekly nab-PTX +/− trastuzumab (T). Forty patients were enrolled in this trial and their neoadjuvant chemotherapy (NAC) and operations were finished in 2013. In this trial, delay and dose-reduction of nabPTX were frequently observed. Thus, we assessed the relationship between relative dose intensity (RDI) of weekly nab-PTX and the pathological effect of NAC. Methods: Women from 20 to 70 years old with node-positive breast cancer were enrolled in this trial between 2011 and 2013. Patients received four cycles of E (90 mg/m2 ) and C (600 mg/m2 ) every 3 weeks, followed by four cycles of nab-PTX (125 mg/m2 ) on Days 1, 8 and 15 in a 28-day cycle. Fifteen cycles of T (2 mg/kg, loading 4 mg/kg) were added to the nab-PTX regimen in HER2-positive patients every week. Adverse events were assessed according to NCI-CTCAE version 4.0. Administration of nab-PTX was delayed for 1 week if grade 2 hematological or grade 1 non-hematological toxicities except for nausea, vomiting and alopecia were observed. Furthermore, dose of nab-PTX was reduced if toxicity did not improve after 2 weeks delay. The relationship between RDI and pathological complete response (pCR) in patients who received nab-PTX was analyzed. Results: Thirty-seven patients who received at least one administration of nab-PTX were analyzed, and the median age was 56 years (range 31–68 years). Fifteen patients (40.5%) were positive HER2. Fourteen patients (37.8%) achieved pCR. The median total dose of nab-PTX was 1500 (350–1500) mg/m2 . Thirty-one patients (83.8%) received 4 complete cycles of nab-PTX. The median dose intensity (DI) was 80.6 mg/m2 /week (planned DI:93.8), and the median-delivered RDI was 86%. The median total dose was 1450 mg/m2 in patients with pCR, whereas in those with non-pCR the median total dose was 1500 mg/m2 (P = 0.5375). In patients with pCR, the median RDI was 80%, whereas in those with non-pCR the median RDI was 92% (P = 0.1775). Among patients with HER2 positive, the median RDI in the pCR-group was 83% whereas in the non-pCR group the median RDI was 97% (P = 0.0673). Conclusion: In this trial, the median RDI of weekly nab-PTX was low (86%) because administration was delayed and dose reduction was carried out in many patients. However, the tendency was seen that the RDI in the pCR group was lower than that in the non-pCR group, suggesting that the same pathological effect would be obtained in HER2 positive patients even if the dose intensity of nab-PTX were reduced. Disclosure of Interest: No significant relationships.
Goals: Evaluate the clinical and pathologic factors related to local and regional recurrence in locally advanced breast cancer (LABC) in women submitted to neoadjuvant chemotherapy (NC) and conservative surgery. Methods: A retrospective study was performed in patients with LABC submitted to NC and conservative treatment during 01/2006 to 06/2011. The main regimen proposed was AC-T (4 AC + 4 T). From the 421 women evaluated 97 underwent to a breast conservative surgery. We evaluated the clinical, pathologic, immunohistochemistry and surgical factors that would contribute to locoregional recurrence (LRR) and local recurrence (LR). The chi-square and logistic regression were used for association analysis. A Kaplan–Meier curve and a Cox model were used to evaluate the main factors related to free recurrence survival. Results: 88.7% were clinical stage III, 76.3% had T3 and T4 tumors, 79.4% N1 and N2 axilla, 92.8% invasive ductal carcinoma and 94.8% Nottingham grade II and III. Immunohistochemistry evaluation demonstrated that 37.6% were luminal A/B1, 18.3% triple negative, 31.2% luminal B2 and 12.9% Her2 tumors. The AC-T regime was performed in 92.7% of the women. The pathologic complete response was present in 25.8% of the tumors. 97.9% had free margins and concentric tumor decrease was present in 55.7% of the patients. Adjuvant radiotherapy was performed in 96.9% of the patients, but adjuvant trastuzumab was performed only 2.1% of the patients. The mean follow up was 53.9 months and the 5-year actuarial global survival was 83.4%. The LRR and LR was 15.5% and 7.2% respectively. The chi-square and univariate logistic regression analysis showed the clinical stage T-TNM (0.015), histologic grade (0.02) and necrosis (0.008) was related to LRR, but the presence of necrosis was the main factor in multivariate analysis (OR = 0.09; IC 0.01–0.73; p = 0.02). The only factor related to decrease of LR was necrosis (p = 0.04). The main factor related to LRR free survival and LR free survival was the molecular subtype, as Her2 tumors had decrease of free survival with the odds ratio of 3.06 and 3.27 respectively. Conclusion: Her2 tumors had a higher risk of locorregional and local disease free of recurrence. More studies are necessary to evaluate this condition in the trastuzumab era with a large number of patients. Disclosure of Interest: No significant relationships. P207 Prognostic significance of biomarker discordance after neoadjuvant chemotherapy in breast cancer A. Matsumoto1 *, H. Jinno2 , T. Ando1 , T. Fujii1 , T. Nakamura1 , J. Saito1 , M. Takahashi2 , T. Hayashida2 , Y. Kitagawa2 . 1 Department of Surgery, Inagi Municipal Hospital, Tokyo, Japan, 2 Department of Surgery, Keio University School of Medicine, Tokyo, Japan Goals: Neoadjuvant chemotherapy (NAC) was reported to change the status of biomarker including estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki-67. However, the impact of these changes on response to treatment and long-term outcomes still remains to be elucidated. The objectives of this study is to evaluate the frequency of biomarker status changes after NAC in patients with residual disease and their relationship with response to treatment and prognosis.
14th St.Gallen International Breast Cancer Conference / The Breast 24S1 (2015) S87–S150
Methods: From a prospective database of 196 patients receiving NAC from January 2005 to June 2014, 156 patients (79.6%) with non-pCR were analyzed. Patients were treated with sequential anthracycline and taxane. ER, PgR, HER2 and Ki-67 were assessed in both core needle biopsy (CNB) performed prior to NAC and surgical samples. Pathological response criteria were classified as grade 0, 1, 2, or 3: grade 0 includes almost no change in cancer cells; grade 1 includes slight or marked changes in less than two thirds of the area; grade 2 includes marked changes in more than two thirds of the area; grade 3 includes necrosis or disappearance of all tumor cells. Results: The median age at diagnosis was 50.0 years and the median tumor size was 3.2 cm. Clinical nodal status was positive in 57.7% of patients before NAC. The rate of pathological response grade 0, 1 and 2 were 5.8%, 65.4% and 28.8%, respectively. Before receiving NAC, ER, PgR and HER2 were positive in 73.7%, 67.9% and 11.5% of patients. Changes in ER, PgR and HER2 status between CNB and surgical samples were 10.9% (3.8% gain; 7.1% loss), 17.9% (1.9% gain; 16.0% loss) and 5.3% (2.0% gain; 3.3% loss), respectively. After NAC, Ki-67 expression decreased in 77.8% of patients (CNB sample: 24.7%, surgical sample: 5.0%; p < 0.001). In the ER-discordant group, clinical complete response rate (41.2% vs. 15.1%; p = 0.016) and grade 2 rate of pathological response (61.1% vs. 30%, p = 0.033) was significantly higher than in the ER-concordant group, whereas discordance in PgR and HER2 status was not significantly correlated with clinical and pathological response. Although there was no correlation between Ki-67 of CNB samples and disease-free survival (DFS), patients with high (>14%) Ki-67 of surgical samples had significantly shorter DFS when compared with low (<14%) Ki-67 (28.5 months vs. 41.3 months, p = 0.003). After a median follow-up of 49.4 months, patients with a loss in hormone receptor (HR) status had a trend toward a worse DFS compared with the concordant HR-positive group (32.5 months vs. 39.0 months; p = 0.08). Conclusion: This study suggested that changes in biomarker status caused by NAC might have a prognostic value in breast cancer patients without pCR. Disclosure of Interest: No significant relationships. P208 Pathological complete response (PCR) rates after sequential CT in locally advanced BC I. Bozovic-Spasojevic1 *, S. Milosevic1 , S. Susnjar2 , Z. NeskovicKonstantinovic2 . 1 Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia, 2 Medical Oncology Department, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia Goals: Pathological complete response (pCR) has predicted long term survival in several neoadjuvant studies and in the recent meta-analysis (Cortazar, Lancet 2014). Hence, we conducted a single institutional study, aiming to analyze the percentage of pCR in breast cancer (BC) patients (pts) treated with neoadjuvant chemotherapy (CT) regiments. Methods: Consecutive breast cancer patients treated with neoadjuvant CT at the Institute for Oncology and Radiology of Serbia between January 2013 and April 2014, were selected for the analysis. Pts who were treated with sequential CT: 3–4 cycles of antracyclinebased CT (AC/FAC/FEC) and taxane-based CT (12 weekly paclitaxel or 3–4 cycles of 3 weekly docetaxel) with or without trastuzumab according to HER2 status, were eligible for the analysis. pCR was defined as no invasive tumor cells and no in situ residuals in breast and axillary lymph nodes (von Minckwitz, JCO 2012). Results: We identified 112 patients with a median age of 47 years (range 21–74). 57 patients had IIIB, 34 IIIA and 21 IIB UICC TNM clinical stages; the commonest histological type on core biopsy was ductal invasive carcinoma seen in 56 pts, 32 had lobular invasive carcinoma and 24 had other BC histology; grade 2 tumors had 84 pts
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and grade 3 28 pts. Tumors stained positive for ER (ER+/PR+/−) in 78 and for HER2 in 39 pts. Up to 1st of May 2014, 46 pts completed CT and were operated; 6 of them had breast conserving surgery, 2 pts had skin sparing mastectomy and the rest of the patients had radical mastectomy. 14 pts achieved pCR, defined as ypT0 ypN0; 10 pts were HER2+ and were treated with 4 cycles of neoadjuvant trastuzumab (TR) plus CT, 1 pt HER2+ER+ (treated with neoTR plus CT), 2 pts ER+ (CT) and 1 HER2−/ER− (CT). Of the partial responders there was no change in histological type; grade was available on excision in 30 pts and was different between core biopsy and final excision in 11 pts, 3 upgrades and 8 downgrades. Out of 32 stained paired pre and post tumor samples, one tumor change profile from ER weak positive to negative (Allred score 4 to 0); two changed profile from PR negative to weak positive (Allred 0 to 4 and 5 respectively) whereas one changed from weak positive to negative (Allred score 3 to 0); three HER2+ tumors (two IHC3+ and one CISH positive) changed profile to HER2 negative (all IHC 1+). Conclusion: In our single institutional-study rate of pCR after sequential anthacicline-taxane based neoadjuvant CT with/without trastuzumab, within all BC pts was 30%. Implications of changes in histological grade and receptor status following neoadjuvant CT should be further explored. Disclosure of Interest: No significant relationships. P209 Metabolic signature predicts progression and response after taxane–anthracycline neoadjuvant regimen I. Dale1 *, A. Roscher2 , A. Lopes Carvalho3 , E. Guimar˜aes Do Turco4 , R.A. Da Costa Vieira3 . 1 Gynecology Department, Federal University of S˜ ao Paulo, S˜ ao Paulo, Brazil, 2 Children’s Research Center, Ludwig-Maximilians Universit¨ at M¨ unchen, M¨ unchen, Germany, 3 Barretos Cancer Hospital, Barretos Cancer Hospital, Barretos, Brazil, 4 Surgery, Federal University of Sao Paulo, S˜ ao Paulo, Brazil Goals: To identify predictive blood metabolites signatures of complete pathologic response (pCR) defined as no histopathologic evidence of any residual invasive and/or noninvasive residual in breast or nodes (ypT0/ypN0), along with signatures able to predict stable disease and/or progression (SDPR) defined here as any response less than 30% reduction in the initial tumor volume in response to neoadjuvant treatment for stage III breast cancer. Methods: In this prospective, NIH registered, neoadjunvant taxane/anthracyclin-based protocol, we applied a targeted, quantitative mass spectrometry approach (Biocrates, Innsbruck, Austria) to measure the absolute micromolar concentrations of metabolites in plasma samples from 59 stage III breast cancer patients prior to chemotherapy and compared the results with the final tumor volume after chemotherapy. For the detection of discriminative metabolites, training and validation sets were assembled. Blinded-created data was then imported to ROC Curve Explorer & Tester (ROCCET, available at http://www.roccet.ca/ROCCET) for the computer-assisted generation of uni and multivariate Receiver Operating Characteristic (ROC) curves. Results: Complete pathologic response (pCR) and stable disease/progression (SDPR), were observed in 11% (7/59) and in 32% (19/59) of patients respectively. After training and validation sets, two predictive metabolites combinations for pCR have emerged with good discriminative characteristics, the first one with sensitivity=100.00%, specificity= 83.8, PPV= 44.44% and NPV= 100.00% in addition to a second one with sensitivity=100.00%, specificity= 89.66, PPV= 57.14% and NPV= 100.00%. The third metabolites combination was able to predict SDPR with sensitivity=100.00%, specificity= 93.10%, PPV= 84.62% and NPV= 100.00%. The identified metabolites are mainly related to glutaminolysis, glycolysis, ether lipids, biogenic amines and