- Email: [email protected]
P174 IMRT-SIB for locally advanced inoperable breast cancer patients
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Poster Abstracts I / The Breast 24S1 (2015) S26–S86
evaluated the efficacy and safety of eribulin as the first- to thirdline treatment in patients with MBC. Methods: This was a phase II, single-arm, open-label, multicenter study in pts with HER2-negative MBC who were previously treated with an anthracycline and taxane. The primary endpoint was the objective response rate (ORR) according to the RECIST criteria. The secondary endpoints were progression-free survival (PFS), the duration of response (DOR), overall survival (OS) and safety. Results: Fifty-three pts were enrolled between December 2011 and November 2013, and 47 pts (for a median of 7.7 cycles) met inclusion criteria for analysis. The median numbers of prior chemotherapy regimens for MBC was one. The median dose intensity and relative dose intensity for up to 6 cycles was 0.8 mg/m2 /week and 86%, respectively. Patients with higher dose intensity had more response than those with lower dose intensity. The primary endpoint of ORR by independent review was 17.0% (95% CI, 7.6% to 30.8%). The distribution of responses was zero cases of CR (0%), 8 cases of PR (17%), 23 cases of SD (49%), 12 cases of PD (26%) and four cases of NE (8%). Median PFS was 149 days (95% CI, 105 days to 213 days). and median DOR was 451 days (95% CI, 213 days to 592 days). Median OS has not been reached. The most frequent treatment-related grade 3/4 toxicities were neutropenia (55%), leukopenia (36%) and anemia (9%). Conclusion: Treatment with eribulin as the first- to third-line regimen for HER2-negative MBC is effective and safe practically. Dose intensity is important for PFS. Disclosure of Interest: No significant relationships. P172 Prognosis of hormone receptor positive recurrent breast cancer during endocrine therapy S. Akiyoshi *, M. Oikawa, Y. Koi, C. Koga, S. Nishimura, Y. Nakamura, M. Ishida, S. Ohno. Breast Oncology, National Kyushu Cancer Center, Fukuoka, Japan Goals: There are still lots of recurrence with hormone receptor positive breast cancer (HR+). More than half of recurrence of HR+ tumors occurs during post-operative endocrine therapy, and effective therapeutic strategy is necessary based on the concept of de novo and acquired resistance to endocrine therapy (ET) for patients with recurrent HR+ breast cancer. The aim of this study was to analyze the prognosis of patients with recurrent HR+ breast cancer, associated with recurrence free interval (RFI) and type of treatment. Methods: We reviewed medical records and database of patients with recurrent breast cancer who were treated at National Kyushu Cancer Center. Among 1931 patients receiving surgery for Stage I–III breast cancer, recurrence was observed in 194 patients. Recurrence was diagnosed in 65 patients within 2 years (short RFI group), in 90 between 2 and 5 years (medium RFI group), and 39 beyond 5 years after operation (long RFI group). Clinicopathological characteristics, prognosis related to treatment for recurrence were compared among those groups. Results: The median overall survival (OS) times after breast cancer recurrence were 2.5 years in short RFI group, 3.2 years in medium RFI group. The prognosis of long RFI group was good (p = 0.004). While medium RFI group had significantly larger tumors as compared to short RFI group (p = 0.013), there was no significant difference in those two groups for the other factors. As initial treatment to recurrence of short RFI group, twenty-five patients (51%) received ET and 24 (49%) were treated with chemotherapy (CT). In patients with recurrence of medium RFI group, ET and CT were given to 55 (77%) and 16 (23%), respectively. There were no difference in response rates to ET in these two groups, and clinical response was observed in 18 of 25 patients (72%) with recurrence in short RFI group, and 40 of 55 those (73%) in medium RFI group. The prognosis
of patients with recurrent disease was significantly correlated to the sensitivity to the initial treatment (p < 0.0001). The median OS rates were 4.2 years for patients with response to ET, 2.4 years for those given CT, and 1.4 years for those with resistant to ET. Conclusion: Our study showed that the prognosis of patients with recurrent breast cancer during postoperative ET may depend on the sensitivity to the following ET. Disclosure of Interest: No significant relationships. P173 Breast cancer in young females: recognition of age as a prognostic factor M.M. Elsebaie1 *, H. Alzawahry2 , A. Abdalsamie2 , S. Najeeb3 . 1 Radiotherapy, National Cancer Institute, Cairo, Egypt, 2 Medical Oncology, National Cancer Institute, Cairo, Egypt, 3 Surgical Oncology, National Cancer Institute, Cairo, Egypt Goals: Explore different prognostic factors that might significantly influence treatment out come in young females with breast cancer. Methods: All cases with pathologically proven breast cancer referred to the breast cancer unit, National Cancer Institute, Cairo, Egypt, were reviewed between September 2013 till September 2014. Female patients younger than the age of forty were looked at and their different clinical, pathological and biological prognostic factors were analyzed and were correlated to their treatment outcome. Results: We elicited an incidence of 3.8% of invasive breast cancer in young females (≤40 years). The mean age at time of presentation was 33 years (27–40). Locally advanced disease (T3 & T4) was diagnosed in 38% of our cases. The majority of our cases presented with clinically positive nodes (86%). Distant metastases were evident at time of diagnosis in 10% of cases. Estrogen and progesterone receptors were strongly positive in 62% of patients and Her-2neu was positive in only 14%. Modified radical mastectomy was the most appropriate surgical approach for 55% of our cases due to poor response to neo-adjuvant chemotherapy, 20%, or being operated outside our institution, 35%. Thirty-two percent of the study cohorts were surgically managed by breast conservative surgery. Adjuvant radiation therapy was given in about 80% of cases. All the cases were reviewed to explore prognostic factors that significantly may affect the treatment-outcome in this group of patients. Conclusion: We do believe that younger age (≤40) at the time of diagnosis of breast cancer carries a poor prognosis in Egyptian females. Disclosure of Interest: No significant relationships. P174 IMRT-SIB for locally advanced inoperable breast cancer patients I. Wzie˛tek1 , S. Blamek1 , A. Namysł-Kaletka1 , R. Kulik2 , K. Trela-Janus1 *, D. Gabry´s1 . 1 Department of Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland, 2 Radiotherapy and Brachytherapy Planning Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland Goals: Radiobiological and clinical data suggest that higher dose per fraction with shortening overall treatment time in breast cancer patients may enhance locoregional control. This, ethics approved, prospective study was designed to evaluate the technical feasibility, toxicity and early results of simultaneous integrated boost (SIB) for locally advanced, breast cancer patients. Methods: Nineteen women (8 right; 11 left-sided) received radiotherapy with SIB applying various dose levels in 30 fractions. Doses were individualized according to the stage of the disease. The regional lymph nodes received 49.8–60 Gy, df 1.66–2 Gy, metastatic lymph nodes received 66–69.9 Gy, df 2.2–2.33 Gy, breast with chest wall was irradiated with a dose 49.8–60 Gy, the whole breast to
14th St.Gallen International Breast Cancer Conference / The Breast 24S1 (2015) S26–S86
60 Gy, and the highest dose was delivered to the breast tumour 69.9 Gy. Early toxicity and results were prospectively recorded using CTCAE 4.03, QLQ 30, QLQ Br23, and Lent Soma scale. All patients underwent planning CT or FDG PET-CT. The majority (13 patients) were treated with the use of Clinac IMRT-SIB, 5 patients were treated with Tomo-SIB. Results: The median age was 58 years (range 37–78). Median tumor size was 6 cm (range 1–12 cm). Almost all (13) patients presented with clinical stage IIIB of the disease, one patient with IIIA, three with IIIC. Two patients in stage IIA were not qualified to surgery, one was not suitable for resection due to medical conditions, the second did not agree for a surgery. All patients received chemotherapy, 11 patients FAC only, remaining various combinations with taxanes. Ten patients were treated with hormonal therapy, the majority of them (8 patients) were treated with tamoxifen. The mean dose to the ipsilateral lung was 16 Gy (range 12.9–20.7). The percentage of lung receiving >5 Gy was 74.9%, >10 Gy – 50%, >20 Gy – 24.5. The mean heart dose was 9.6 Gy (range 5.4–16.9) and V5 Gy was 64.4, V10 Gy – 28.6, V30 Gy – 4.9. There was significant decrease in WBC (median 6.4 vs. 5.1×103 /ul; p 0.02), PLT (238 vs. 187×103 /ul; p 0.01) before and after radiotherapy. RBC and Hb did not significantly decrease. The maximum Grade 3 early skin toxicity by the end of treatment was present only in two patients. No Grade 4 toxicities were observed. The maximum Grade 2 fatigue, Grade 1 dysphagia, Grade 1 pain with swallowing were recorded. The early skin toxicity resolved in all patients evaluated one month after finishing the treatment. There were no clinically relevant changes in patients quality of life. Conclusion: This 6-week course of definitive radiotherapy using SIB technique showed to be feasible and was associated with acceptable early skin toxicity. Long-term follow-up data are needed to assess late toxicity and clinical outcomes. Disclosure of Interest: No significant relationships. P175 Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in MBC B. Wang1 *, J. Zhang1 , J. Wang1 , Z. Shao2 , S. Fais3 , X. Hu1 . 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 2 Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China, 3 Department of Therapeutic Research and Medicines Evaluation, National Institute of Health, Roma, Italy Goals: Acidity is a hallmark of malignant tumor, representing a very efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high dosage have been shown to sensitize chemoresistant human tumor cells and tumors to cytotoxic molecules. The aim of this study was to investigate the efficacy of PPI in improving the clinical outcome of cisplatin + docetaxel therapeutic regimen in patients with metastatic breast cancer. Methods: Patients enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2 on d4, repeated every 21 days with a maximum of 6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM) 80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent administration of ESOM (3 days on 4 days off) was maintained up to maximum 66 weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at 100 mg p.o. bid. The primary endpoint was response rate. Secondary endpoints included time to progression (TTP), overall survival (OS), and safety profile. Results: From Aug. 2009 to Aug. 2011, 94 patients were randomly assigned and underwent at least one injection of chemotherapy. Response rates for arm A, arm B and arm C were 46.9%, 71.0%, and 64.5%, respectively. After a median follow up of 40 months, median TTP for arm A (n = 33), arm B (n = 30), arm C (n = 31) were 8.7, 9.4, and 9.7 months, respectively. A significant difference was
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observed between patients who had taken PPI and who not with ORR (46.9% vs. 67.7%, p = 0.049) and median TTP (9.7 months vs. 8.7 months, p = 0.045). Exploratory analysis showed that among 15 patients with triple negative breast cancer (TNBC), this difference was bigger with median TTP of 10.7 and 5.8 months, respectively (p = 0.011). PPI combination showed a marked effect on OS as well, while with a borderline significance (29.9 vs. 19.2 months, p = 0.090). No additional toxicity was observed with PPI. Conclusion: The results of this pilot clinical trial showed that intermittent high dose PPI enhance the antitumor effects of chemotherapy in MBC patients without evidence of additional toxicity, which requires urgent validation in a multicenter, randomized, phase III trial. Disclosure of Interest: No significant relationships. P176 The DETECT-study concept – circulating tumor cells (CTCs) in metastatic breast cancer A. Schramm1 *, V. Mueller2 , J. Huober1 , B. Rack3 , P.A. Fasching4 , F. Taran5 , A. Schneeweiss6 , B. Aktas7 , W. Janni1 , T. Fehm8 . 1 Gynecology and Obstetrics, University of Ulm, Ulm, Germany, 2 Gynecology and Obstetrics, University Hospital Hamburg-Eppendorf, Hamburg, Germany, 3 Hospital Ludwig-Maximilians-University Munich, Munich, Germany, 4 Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany, 5 University Hospital T¨ ubingen, Tuebingen, Germany, 6 Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany, 7 University Clinics Essen, Essen, Germany, 8 Heinrich-Heine University, Duesseldorf, Germany Introduction: The prognostic relevance of circulating tumor cells (CTC) has been repeatedly shown. The importance of CTC phenotypes for therapeutic decisions and specific treatment response predicted by Her2-phenotype and other cell markers of CTCs will be investigated within the DETECT Studies. Study design and Methods: Approximately 2000 patients will be screened for CTCs. Patients with HER2-negative primary tumor and HER2 positive CTCs are recruited for the DETECT III trial. Patients are randomized to therapy of physicians’ choice (chemotherapy or endocrine therapy) with or without additional HER2-targeted lapatinib therapy. DETECT IV offers an individualized treatment for patients with HER2-negative MBC and HER2-negative CTCs. Postmenopausal patients with hormone receptor-positive primary breast cancer are treated with everolimus + endocrine therapy. For women with triple negative MBC or hormone receptor positive MBC and need for chemotherapy, the trial has been extended to a treatment arm with eribulin (DETECT IVb). Results: In DETECT V, patients with HER2-positive and hormone receptor-positive MBC are randomized to compare chemo- versus endocrine therapy in combination with dual HER2-targeted therapy (trastuzumab and pertuzumab). Perspectives: Estimation of clinical efficiency of treatment in DIII and DIV is evaluated by PFS (primary object) and CTCclearance. Primary object in DETECT V is to assess the safety of a dual HER2-targeted therapy defined by the presence of adverse events. Important translational research aim is the evaluation of an “endocrine responsiveness score”, which is based on the expression of estrogen receptor (ER) and HER2 on CTCs for assessing endocrine therapy success. Conclusion: In the DETECT trials, targeted therapy is based on molecular characterization of CTCs. Thus, efficacy of individualized therapy is investigated by the DETECT study concept and offers innovative strategies for new cancer therapy. The translational research program evaluates the association of presence and molecular characteristics of circulating tumor cells with treatment
Poster Abstracts I / The Breast 24S1 (2015) S26–S86
evaluated the efficacy and safety of eribulin as the first- to thirdline treatment in patients with MBC. Methods: This was a phase II, single-arm, open-label, multicenter study in pts with HER2-negative MBC who were previously treated with an anthracycline and taxane. The primary endpoint was the objective response rate (ORR) according to the RECIST criteria. The secondary endpoints were progression-free survival (PFS), the duration of response (DOR), overall survival (OS) and safety. Results: Fifty-three pts were enrolled between December 2011 and November 2013, and 47 pts (for a median of 7.7 cycles) met inclusion criteria for analysis. The median numbers of prior chemotherapy regimens for MBC was one. The median dose intensity and relative dose intensity for up to 6 cycles was 0.8 mg/m2 /week and 86%, respectively. Patients with higher dose intensity had more response than those with lower dose intensity. The primary endpoint of ORR by independent review was 17.0% (95% CI, 7.6% to 30.8%). The distribution of responses was zero cases of CR (0%), 8 cases of PR (17%), 23 cases of SD (49%), 12 cases of PD (26%) and four cases of NE (8%). Median PFS was 149 days (95% CI, 105 days to 213 days). and median DOR was 451 days (95% CI, 213 days to 592 days). Median OS has not been reached. The most frequent treatment-related grade 3/4 toxicities were neutropenia (55%), leukopenia (36%) and anemia (9%). Conclusion: Treatment with eribulin as the first- to third-line regimen for HER2-negative MBC is effective and safe practically. Dose intensity is important for PFS. Disclosure of Interest: No significant relationships. P172 Prognosis of hormone receptor positive recurrent breast cancer during endocrine therapy S. Akiyoshi *, M. Oikawa, Y. Koi, C. Koga, S. Nishimura, Y. Nakamura, M. Ishida, S. Ohno. Breast Oncology, National Kyushu Cancer Center, Fukuoka, Japan Goals: There are still lots of recurrence with hormone receptor positive breast cancer (HR+). More than half of recurrence of HR+ tumors occurs during post-operative endocrine therapy, and effective therapeutic strategy is necessary based on the concept of de novo and acquired resistance to endocrine therapy (ET) for patients with recurrent HR+ breast cancer. The aim of this study was to analyze the prognosis of patients with recurrent HR+ breast cancer, associated with recurrence free interval (RFI) and type of treatment. Methods: We reviewed medical records and database of patients with recurrent breast cancer who were treated at National Kyushu Cancer Center. Among 1931 patients receiving surgery for Stage I–III breast cancer, recurrence was observed in 194 patients. Recurrence was diagnosed in 65 patients within 2 years (short RFI group), in 90 between 2 and 5 years (medium RFI group), and 39 beyond 5 years after operation (long RFI group). Clinicopathological characteristics, prognosis related to treatment for recurrence were compared among those groups. Results: The median overall survival (OS) times after breast cancer recurrence were 2.5 years in short RFI group, 3.2 years in medium RFI group. The prognosis of long RFI group was good (p = 0.004). While medium RFI group had significantly larger tumors as compared to short RFI group (p = 0.013), there was no significant difference in those two groups for the other factors. As initial treatment to recurrence of short RFI group, twenty-five patients (51%) received ET and 24 (49%) were treated with chemotherapy (CT). In patients with recurrence of medium RFI group, ET and CT were given to 55 (77%) and 16 (23%), respectively. There were no difference in response rates to ET in these two groups, and clinical response was observed in 18 of 25 patients (72%) with recurrence in short RFI group, and 40 of 55 those (73%) in medium RFI group. The prognosis
of patients with recurrent disease was significantly correlated to the sensitivity to the initial treatment (p < 0.0001). The median OS rates were 4.2 years for patients with response to ET, 2.4 years for those given CT, and 1.4 years for those with resistant to ET. Conclusion: Our study showed that the prognosis of patients with recurrent breast cancer during postoperative ET may depend on the sensitivity to the following ET. Disclosure of Interest: No significant relationships. P173 Breast cancer in young females: recognition of age as a prognostic factor M.M. Elsebaie1 *, H. Alzawahry2 , A. Abdalsamie2 , S. Najeeb3 . 1 Radiotherapy, National Cancer Institute, Cairo, Egypt, 2 Medical Oncology, National Cancer Institute, Cairo, Egypt, 3 Surgical Oncology, National Cancer Institute, Cairo, Egypt Goals: Explore different prognostic factors that might significantly influence treatment out come in young females with breast cancer. Methods: All cases with pathologically proven breast cancer referred to the breast cancer unit, National Cancer Institute, Cairo, Egypt, were reviewed between September 2013 till September 2014. Female patients younger than the age of forty were looked at and their different clinical, pathological and biological prognostic factors were analyzed and were correlated to their treatment outcome. Results: We elicited an incidence of 3.8% of invasive breast cancer in young females (≤40 years). The mean age at time of presentation was 33 years (27–40). Locally advanced disease (T3 & T4) was diagnosed in 38% of our cases. The majority of our cases presented with clinically positive nodes (86%). Distant metastases were evident at time of diagnosis in 10% of cases. Estrogen and progesterone receptors were strongly positive in 62% of patients and Her-2neu was positive in only 14%. Modified radical mastectomy was the most appropriate surgical approach for 55% of our cases due to poor response to neo-adjuvant chemotherapy, 20%, or being operated outside our institution, 35%. Thirty-two percent of the study cohorts were surgically managed by breast conservative surgery. Adjuvant radiation therapy was given in about 80% of cases. All the cases were reviewed to explore prognostic factors that significantly may affect the treatment-outcome in this group of patients. Conclusion: We do believe that younger age (≤40) at the time of diagnosis of breast cancer carries a poor prognosis in Egyptian females. Disclosure of Interest: No significant relationships. P174 IMRT-SIB for locally advanced inoperable breast cancer patients I. Wzie˛tek1 , S. Blamek1 , A. Namysł-Kaletka1 , R. Kulik2 , K. Trela-Janus1 *, D. Gabry´s1 . 1 Department of Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland, 2 Radiotherapy and Brachytherapy Planning Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland Goals: Radiobiological and clinical data suggest that higher dose per fraction with shortening overall treatment time in breast cancer patients may enhance locoregional control. This, ethics approved, prospective study was designed to evaluate the technical feasibility, toxicity and early results of simultaneous integrated boost (SIB) for locally advanced, breast cancer patients. Methods: Nineteen women (8 right; 11 left-sided) received radiotherapy with SIB applying various dose levels in 30 fractions. Doses were individualized according to the stage of the disease. The regional lymph nodes received 49.8–60 Gy, df 1.66–2 Gy, metastatic lymph nodes received 66–69.9 Gy, df 2.2–2.33 Gy, breast with chest wall was irradiated with a dose 49.8–60 Gy, the whole breast to
14th St.Gallen International Breast Cancer Conference / The Breast 24S1 (2015) S26–S86
60 Gy, and the highest dose was delivered to the breast tumour 69.9 Gy. Early toxicity and results were prospectively recorded using CTCAE 4.03, QLQ 30, QLQ Br23, and Lent Soma scale. All patients underwent planning CT or FDG PET-CT. The majority (13 patients) were treated with the use of Clinac IMRT-SIB, 5 patients were treated with Tomo-SIB. Results: The median age was 58 years (range 37–78). Median tumor size was 6 cm (range 1–12 cm). Almost all (13) patients presented with clinical stage IIIB of the disease, one patient with IIIA, three with IIIC. Two patients in stage IIA were not qualified to surgery, one was not suitable for resection due to medical conditions, the second did not agree for a surgery. All patients received chemotherapy, 11 patients FAC only, remaining various combinations with taxanes. Ten patients were treated with hormonal therapy, the majority of them (8 patients) were treated with tamoxifen. The mean dose to the ipsilateral lung was 16 Gy (range 12.9–20.7). The percentage of lung receiving >5 Gy was 74.9%, >10 Gy – 50%, >20 Gy – 24.5. The mean heart dose was 9.6 Gy (range 5.4–16.9) and V5 Gy was 64.4, V10 Gy – 28.6, V30 Gy – 4.9. There was significant decrease in WBC (median 6.4 vs. 5.1×103 /ul; p 0.02), PLT (238 vs. 187×103 /ul; p 0.01) before and after radiotherapy. RBC and Hb did not significantly decrease. The maximum Grade 3 early skin toxicity by the end of treatment was present only in two patients. No Grade 4 toxicities were observed. The maximum Grade 2 fatigue, Grade 1 dysphagia, Grade 1 pain with swallowing were recorded. The early skin toxicity resolved in all patients evaluated one month after finishing the treatment. There were no clinically relevant changes in patients quality of life. Conclusion: This 6-week course of definitive radiotherapy using SIB technique showed to be feasible and was associated with acceptable early skin toxicity. Long-term follow-up data are needed to assess late toxicity and clinical outcomes. Disclosure of Interest: No significant relationships. P175 Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in MBC B. Wang1 *, J. Zhang1 , J. Wang1 , Z. Shao2 , S. Fais3 , X. Hu1 . 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 2 Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China, 3 Department of Therapeutic Research and Medicines Evaluation, National Institute of Health, Roma, Italy Goals: Acidity is a hallmark of malignant tumor, representing a very efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high dosage have been shown to sensitize chemoresistant human tumor cells and tumors to cytotoxic molecules. The aim of this study was to investigate the efficacy of PPI in improving the clinical outcome of cisplatin + docetaxel therapeutic regimen in patients with metastatic breast cancer. Methods: Patients enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2 on d4, repeated every 21 days with a maximum of 6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM) 80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent administration of ESOM (3 days on 4 days off) was maintained up to maximum 66 weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at 100 mg p.o. bid. The primary endpoint was response rate. Secondary endpoints included time to progression (TTP), overall survival (OS), and safety profile. Results: From Aug. 2009 to Aug. 2011, 94 patients were randomly assigned and underwent at least one injection of chemotherapy. Response rates for arm A, arm B and arm C were 46.9%, 71.0%, and 64.5%, respectively. After a median follow up of 40 months, median TTP for arm A (n = 33), arm B (n = 30), arm C (n = 31) were 8.7, 9.4, and 9.7 months, respectively. A significant difference was
S85
observed between patients who had taken PPI and who not with ORR (46.9% vs. 67.7%, p = 0.049) and median TTP (9.7 months vs. 8.7 months, p = 0.045). Exploratory analysis showed that among 15 patients with triple negative breast cancer (TNBC), this difference was bigger with median TTP of 10.7 and 5.8 months, respectively (p = 0.011). PPI combination showed a marked effect on OS as well, while with a borderline significance (29.9 vs. 19.2 months, p = 0.090). No additional toxicity was observed with PPI. Conclusion: The results of this pilot clinical trial showed that intermittent high dose PPI enhance the antitumor effects of chemotherapy in MBC patients without evidence of additional toxicity, which requires urgent validation in a multicenter, randomized, phase III trial. Disclosure of Interest: No significant relationships. P176 The DETECT-study concept – circulating tumor cells (CTCs) in metastatic breast cancer A. Schramm1 *, V. Mueller2 , J. Huober1 , B. Rack3 , P.A. Fasching4 , F. Taran5 , A. Schneeweiss6 , B. Aktas7 , W. Janni1 , T. Fehm8 . 1 Gynecology and Obstetrics, University of Ulm, Ulm, Germany, 2 Gynecology and Obstetrics, University Hospital Hamburg-Eppendorf, Hamburg, Germany, 3 Hospital Ludwig-Maximilians-University Munich, Munich, Germany, 4 Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany, 5 University Hospital T¨ ubingen, Tuebingen, Germany, 6 Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany, 7 University Clinics Essen, Essen, Germany, 8 Heinrich-Heine University, Duesseldorf, Germany Introduction: The prognostic relevance of circulating tumor cells (CTC) has been repeatedly shown. The importance of CTC phenotypes for therapeutic decisions and specific treatment response predicted by Her2-phenotype and other cell markers of CTCs will be investigated within the DETECT Studies. Study design and Methods: Approximately 2000 patients will be screened for CTCs. Patients with HER2-negative primary tumor and HER2 positive CTCs are recruited for the DETECT III trial. Patients are randomized to therapy of physicians’ choice (chemotherapy or endocrine therapy) with or without additional HER2-targeted lapatinib therapy. DETECT IV offers an individualized treatment for patients with HER2-negative MBC and HER2-negative CTCs. Postmenopausal patients with hormone receptor-positive primary breast cancer are treated with everolimus + endocrine therapy. For women with triple negative MBC or hormone receptor positive MBC and need for chemotherapy, the trial has been extended to a treatment arm with eribulin (DETECT IVb). Results: In DETECT V, patients with HER2-positive and hormone receptor-positive MBC are randomized to compare chemo- versus endocrine therapy in combination with dual HER2-targeted therapy (trastuzumab and pertuzumab). Perspectives: Estimation of clinical efficiency of treatment in DIII and DIV is evaluated by PFS (primary object) and CTCclearance. Primary object in DETECT V is to assess the safety of a dual HER2-targeted therapy defined by the presence of adverse events. Important translational research aim is the evaluation of an “endocrine responsiveness score”, which is based on the expression of estrogen receptor (ER) and HER2 on CTCs for assessing endocrine therapy success. Conclusion: In the DETECT trials, targeted therapy is based on molecular characterization of CTCs. Thus, efficacy of individualized therapy is investigated by the DETECT study concept and offers innovative strategies for new cancer therapy. The translational research program evaluates the association of presence and molecular characteristics of circulating tumor cells with treatment