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1838 Survival of breast cancer patients after radically resected brain metastasis
S278
Abstracts
22 (48%) and 19 (41%) respectively of the RCTs. Overall, 25 RCTs (54%) reported significant differences in a clinical efficacy endpoint (progression free survival, overall survival, time to progression) between the treatment arms. A significant difference in HRQOL was reported in 10 (40%) of these trials where HRQOL was a secondary endpoint (5 favoring the experimental and 5 the standard arm). A benefit in HRQOL was reported in 5 (24%) of the remaining 21 RCTs where non-significant differences in clinical endpoints were reported (3 out of 5 RCTs had a primary HRQOL endpoint). Conclusions: Our findings reveal several shortcomings in reporting criteria essential to enable an informed decision, such as the lack of pre-defined research hypotheses, information on missing data, and the overemphasis of statistical significance over clinical relevance. Our review also stresses the need for further improvement in reporting of HRQOL results in ABC RCTs. No conflict of interest. 1836 POSTER Surgery and systemic therapy improve overall survival of HER2-positive breast cancer patients with central nervous system metastases C. Grasic Kuhar1 , E. Matos1 , A. Demsar1 , M. Zabukovec1 , M. Mencinger1 , T. Ovcaricek1 , D. Ribnikar1 , U. Bokal1 , S. Borstnar1 . 1 Institute of Oncology Ljubljana, Department Medical Oncology, Ljubljana, Slovenia Background: HER2-positive breast cancer (BC) is prone to central nervous system (CNS) progression. Outcome of patients (pts) with CNS metastases could be modulated by therapy: surgical, radiation and systemic therapy. Material and Methods: We retrospectively evaluated time to progression to CNS (TTP-CNS) and overall survival after CNS progression (OS-CNS) of 259 pts with metastatic HER2+ BC pts treated at Institute of Oncology Ljubljana during 2001–2014. Results: 91/259 (35%) metastatic HER2-positive BC pts progressed to CNS. 34% of them had primary metastatic disease (none with CNS involvement). Median age at diagnosis was 50 (min 30-max 77) years. Median TTP-CNS was 3.8 (95% CI 3−4.5) years. In multivariate Cox analysis tumour stage (HR 1.35; 95% CI 1.01−1.8; p = 0.043), positive progesterone receptors (HR 0.55; 95% CI 0.4−0.9; p = 0.016) and primary metastatic diasease (HR 5.7; 95% CI 2.8–11.5; p < 0.001) were prognostic factors for TTP-CNS. Age, tumour grade, nodal stage and location of metastases were not prognostic factors. CNS metastases were solitary, oligo (2−3) and multiple in 23, 4 and 61 pts, resp. Three pts had leptomeningeal metastases only. Majority of pts were treated with radiation therapy (RT)-91% and systemic therapy-78%. Surgical procedure was performed in 21% of pts. Treatment according to extension of CNS metastases is presented in Table 1. 72 (79%) of pts were treated by whole-brain RT, 2 pts with solitary metastases by stereotactic RT and 9 pts with combination of both. Pts received up to four lines of systemic therapy (chemo-, antiHER2− and/or hormonal therapy) after progression to CNS: one line 43 pts, two lines 11 pts, three lines 12 pts and four lines 5 pts. Median OS-CNS for all pts was 0.8 (95% CI 0.6−1) years. Median OS-CNS was 1.7, 1.3, 0.7 and 1.2 years with solitary, oligo- multiple and leptomeningeal metastases, resp. (p = 0.005). In multivariate Cox analysis the independent prognostic factors for OS-CNS were surgery (HR 0.3; 95% CI 0.13–0.63; p = 0.003) and systemic therapy (HR 0.29; 95% CI 0.13– 0.63; p < 0.002). Age, extension of CNS metastases and RT were not recognized as independent prognostic factors. Extension of CNS metastases
Patients n (%)
Surgery n (% of all)
Systemic therapy n (% of all)
Radiation therapy n (% of all)
Solitary Oligometastatic Multiple Leptomeningeal All
23 (25.3) 4 (4.4) 61 (67) 3 (3.3) 91 (100)
14 (15.4) 1 (1.1) 4 (4.4) 0 (0) 19 (20.9)
19 (20.9) 3 (3.3) 47 (51.6) 2 (2.2) 71 (78)
21 (23.1) 4 (4.4) 56 (61.5) 2 (2.2) 83 (91.2)
Conclusions: As one third of metastatic HER2-positive BC pts progressed to CNS, we suggest to perform brain imaging within staging procedure at diagnosis of metastatic disease. Early surgical intervention and systemic therapy improve overall survival of pts with CNS metastases. No conflict of interest. 1838 POSTER Survival of breast cancer patients after radically resected brain metastasis
whole brain radiation (WBRT) and systemic therapy is the therapy of choice that prolongs survival. The purpose of our study was to evaluate the survival of BC pts after surgery for BM. Materials and Methods: This was a retrospective review of 30 consecutive BC pts treated at Institute if Oncology Ljubljana who underwent radical surgery for BM from May 2006 to December 2010. Descriptive statistics was performed. Results: 19 were HR+, 11 HR−, 17 HER2+, 8 HER2−, 5 had distant metastases at the presentation, 3 of them solitary BM with no other distant metastases. BM were first distant recurrence in 15 pts, 8 of them were HER2+. All but 3 were postoperatively treated with WBRT and systemic therapy according to treating physician’s choice. After median follow up period of 7.5 years, 6 pts were still alive, median survival was 34 months (0.7–108.3 months). Median time from diagnosis of BC to BM relapse was 17.9 months (0–141.8 months). Survival longer than double median survival was recorded in 4 pts. In 11 pts BM was reported as cause of death (data unknown for 13). Median time to first relapse after surgery was 12,2 months (0.6–55.3 months) in 22 pts with known first relapse (BM in 8, other distant relapse in 14) data not available in 5 pts and 3 had no relapse to date. Conclusions: Compared to historical survival data of BC pts with BM, treatment with radical surgery, WBRT and systemic therapy prolonged survival of our pts. The multimodality treatment offered selected pts unexpectedly long survival. No conflict of interest. 1839 POSTER Association of advanced breast cancer HER-2 positive treated with trastuzumab and Killer cell immunoglobulin-like receptors (KIRs) polymorphisms according to estrogen and progesterone receptor status ´ alez ´ 1 , B. Manzanares-Mart´ın1 , C. Morales-Estevez1 , J. Lopez-Gonz 1 R. Gonzalez-Fern ´ andez ´ , M.J. Ortiz-Morales1 , I. Porras-Quintela1 , M.A. Gomez-Espa ´ na ˜ 1 , A. Moreno-Vega1 , M. Cano-Osuna1 , R. Serrano-Blanch1 , J. De la Haba-Rodr´ıguez1 , E. Aranda-Aguilar1 . 1 ´ ´ Biomedica ´ ´ Instituto Maimonides de Investigacion de Cordoba IMIBIC, Medical Oncology, Cordoba, Spain Background: Previous studies have shown associations between Killer cell immunoglobulin-like receptors (KIRs) polymorphisms, their ligands and either protection or susceptibility to breast cancer. However, either the association to these polymorphisms according to the hormonal receptor status remains unknown. Our aim was to investigate whether the prevalence of KIRs gene polymorphisms in advanced breast cancers HER-2 positive is influenced according to the estrogen and progesterone hormonal receptor status in a white European population. Material and Methods: Breast cancer HER-2 positive patients on monoclonal antibody treatment (Trastuzumab) from a cohort of advance cancer. KIR genotyping was performed using sequence-specific primers able to detect the presence of 16 different KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DL2, 3DL3, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DS1, 2DP1 and 3DP1). Results: Patients with negative progesterone receptor (PR) showed a higher rate of activating KIRs 2DS2 (29%), 2DS3 (43%) and inhibitor KIRs 2DL1 (28%), 2DL2 (29%), 2DL3 (24%) polymorphisms compared with positive PR (P < 0.05). Moreover those patients with negative estrogen receptor (ER) showed a higher rate of inhibitor KIRs 2DL2 (27%), 2DL1 (24%) polymorphisms compared with positive ER (P < 0.05). Conclusions: We have described for the first time the influence of hormonal status in advance breast cancer and the prevalence of KIRs polymorphisms. Taking into account the relationship between the response of anti-Her2 therapy and hormone receptor, one of the possible causes to explore should be the role of KIRs polymorphisms. No conflict of interest. 1840 POSTER Response to chemotherapy predicts outcome after combined modality therapy for inflammatory breast cancer
N. Snoj1 , E. Matos1 . 1 Institute of Oncology Ljubljana, medical oncology, Ljubljana, Slovenia
M. Loi1 , A. Dunant2 , A.M. Cascales-Garcia3 , A. Slocker-Escarpa3 , E. Deutsch3 , R. Arriagada3 , S. Rivera3 . 1 Universita degli Studi di Firenze, Radiation Therapy Department, Firenze, Italy; 2 Gustave Roussy, Biostatistics and Epidemiology Unit, Villejuif, France; 3 Gustave Roussy, Radiation Oncology, Villejuif, France
Background: It is generally accepted that survival of breast cancer (BC) cancer patients (pts) with brain metastasis (BM) is poor. In case of solitary or oligometastatic disease surgery or stereotactic radiosurgery followed by
Background: Inflammatory Breast Cancer (IBC) is characterized by aggressive clinical course and poor prognosis. The comprehensive treatment management combining chemotherapy (CT), surgery and radiotherapy
Abstracts
22 (48%) and 19 (41%) respectively of the RCTs. Overall, 25 RCTs (54%) reported significant differences in a clinical efficacy endpoint (progression free survival, overall survival, time to progression) between the treatment arms. A significant difference in HRQOL was reported in 10 (40%) of these trials where HRQOL was a secondary endpoint (5 favoring the experimental and 5 the standard arm). A benefit in HRQOL was reported in 5 (24%) of the remaining 21 RCTs where non-significant differences in clinical endpoints were reported (3 out of 5 RCTs had a primary HRQOL endpoint). Conclusions: Our findings reveal several shortcomings in reporting criteria essential to enable an informed decision, such as the lack of pre-defined research hypotheses, information on missing data, and the overemphasis of statistical significance over clinical relevance. Our review also stresses the need for further improvement in reporting of HRQOL results in ABC RCTs. No conflict of interest. 1836 POSTER Surgery and systemic therapy improve overall survival of HER2-positive breast cancer patients with central nervous system metastases C. Grasic Kuhar1 , E. Matos1 , A. Demsar1 , M. Zabukovec1 , M. Mencinger1 , T. Ovcaricek1 , D. Ribnikar1 , U. Bokal1 , S. Borstnar1 . 1 Institute of Oncology Ljubljana, Department Medical Oncology, Ljubljana, Slovenia Background: HER2-positive breast cancer (BC) is prone to central nervous system (CNS) progression. Outcome of patients (pts) with CNS metastases could be modulated by therapy: surgical, radiation and systemic therapy. Material and Methods: We retrospectively evaluated time to progression to CNS (TTP-CNS) and overall survival after CNS progression (OS-CNS) of 259 pts with metastatic HER2+ BC pts treated at Institute of Oncology Ljubljana during 2001–2014. Results: 91/259 (35%) metastatic HER2-positive BC pts progressed to CNS. 34% of them had primary metastatic disease (none with CNS involvement). Median age at diagnosis was 50 (min 30-max 77) years. Median TTP-CNS was 3.8 (95% CI 3−4.5) years. In multivariate Cox analysis tumour stage (HR 1.35; 95% CI 1.01−1.8; p = 0.043), positive progesterone receptors (HR 0.55; 95% CI 0.4−0.9; p = 0.016) and primary metastatic diasease (HR 5.7; 95% CI 2.8–11.5; p < 0.001) were prognostic factors for TTP-CNS. Age, tumour grade, nodal stage and location of metastases were not prognostic factors. CNS metastases were solitary, oligo (2−3) and multiple in 23, 4 and 61 pts, resp. Three pts had leptomeningeal metastases only. Majority of pts were treated with radiation therapy (RT)-91% and systemic therapy-78%. Surgical procedure was performed in 21% of pts. Treatment according to extension of CNS metastases is presented in Table 1. 72 (79%) of pts were treated by whole-brain RT, 2 pts with solitary metastases by stereotactic RT and 9 pts with combination of both. Pts received up to four lines of systemic therapy (chemo-, antiHER2− and/or hormonal therapy) after progression to CNS: one line 43 pts, two lines 11 pts, three lines 12 pts and four lines 5 pts. Median OS-CNS for all pts was 0.8 (95% CI 0.6−1) years. Median OS-CNS was 1.7, 1.3, 0.7 and 1.2 years with solitary, oligo- multiple and leptomeningeal metastases, resp. (p = 0.005). In multivariate Cox analysis the independent prognostic factors for OS-CNS were surgery (HR 0.3; 95% CI 0.13–0.63; p = 0.003) and systemic therapy (HR 0.29; 95% CI 0.13– 0.63; p < 0.002). Age, extension of CNS metastases and RT were not recognized as independent prognostic factors. Extension of CNS metastases
Patients n (%)
Surgery n (% of all)
Systemic therapy n (% of all)
Radiation therapy n (% of all)
Solitary Oligometastatic Multiple Leptomeningeal All
23 (25.3) 4 (4.4) 61 (67) 3 (3.3) 91 (100)
14 (15.4) 1 (1.1) 4 (4.4) 0 (0) 19 (20.9)
19 (20.9) 3 (3.3) 47 (51.6) 2 (2.2) 71 (78)
21 (23.1) 4 (4.4) 56 (61.5) 2 (2.2) 83 (91.2)
Conclusions: As one third of metastatic HER2-positive BC pts progressed to CNS, we suggest to perform brain imaging within staging procedure at diagnosis of metastatic disease. Early surgical intervention and systemic therapy improve overall survival of pts with CNS metastases. No conflict of interest. 1838 POSTER Survival of breast cancer patients after radically resected brain metastasis
whole brain radiation (WBRT) and systemic therapy is the therapy of choice that prolongs survival. The purpose of our study was to evaluate the survival of BC pts after surgery for BM. Materials and Methods: This was a retrospective review of 30 consecutive BC pts treated at Institute if Oncology Ljubljana who underwent radical surgery for BM from May 2006 to December 2010. Descriptive statistics was performed. Results: 19 were HR+, 11 HR−, 17 HER2+, 8 HER2−, 5 had distant metastases at the presentation, 3 of them solitary BM with no other distant metastases. BM were first distant recurrence in 15 pts, 8 of them were HER2+. All but 3 were postoperatively treated with WBRT and systemic therapy according to treating physician’s choice. After median follow up period of 7.5 years, 6 pts were still alive, median survival was 34 months (0.7–108.3 months). Median time from diagnosis of BC to BM relapse was 17.9 months (0–141.8 months). Survival longer than double median survival was recorded in 4 pts. In 11 pts BM was reported as cause of death (data unknown for 13). Median time to first relapse after surgery was 12,2 months (0.6–55.3 months) in 22 pts with known first relapse (BM in 8, other distant relapse in 14) data not available in 5 pts and 3 had no relapse to date. Conclusions: Compared to historical survival data of BC pts with BM, treatment with radical surgery, WBRT and systemic therapy prolonged survival of our pts. The multimodality treatment offered selected pts unexpectedly long survival. No conflict of interest. 1839 POSTER Association of advanced breast cancer HER-2 positive treated with trastuzumab and Killer cell immunoglobulin-like receptors (KIRs) polymorphisms according to estrogen and progesterone receptor status ´ alez ´ 1 , B. Manzanares-Mart´ın1 , C. Morales-Estevez1 , J. Lopez-Gonz 1 R. Gonzalez-Fern ´ andez ´ , M.J. Ortiz-Morales1 , I. Porras-Quintela1 , M.A. Gomez-Espa ´ na ˜ 1 , A. Moreno-Vega1 , M. Cano-Osuna1 , R. Serrano-Blanch1 , J. De la Haba-Rodr´ıguez1 , E. Aranda-Aguilar1 . 1 ´ ´ Biomedica ´ ´ Instituto Maimonides de Investigacion de Cordoba IMIBIC, Medical Oncology, Cordoba, Spain Background: Previous studies have shown associations between Killer cell immunoglobulin-like receptors (KIRs) polymorphisms, their ligands and either protection or susceptibility to breast cancer. However, either the association to these polymorphisms according to the hormonal receptor status remains unknown. Our aim was to investigate whether the prevalence of KIRs gene polymorphisms in advanced breast cancers HER-2 positive is influenced according to the estrogen and progesterone hormonal receptor status in a white European population. Material and Methods: Breast cancer HER-2 positive patients on monoclonal antibody treatment (Trastuzumab) from a cohort of advance cancer. KIR genotyping was performed using sequence-specific primers able to detect the presence of 16 different KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DL2, 3DL3, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DS1, 2DP1 and 3DP1). Results: Patients with negative progesterone receptor (PR) showed a higher rate of activating KIRs 2DS2 (29%), 2DS3 (43%) and inhibitor KIRs 2DL1 (28%), 2DL2 (29%), 2DL3 (24%) polymorphisms compared with positive PR (P < 0.05). Moreover those patients with negative estrogen receptor (ER) showed a higher rate of inhibitor KIRs 2DL2 (27%), 2DL1 (24%) polymorphisms compared with positive ER (P < 0.05). Conclusions: We have described for the first time the influence of hormonal status in advance breast cancer and the prevalence of KIRs polymorphisms. Taking into account the relationship between the response of anti-Her2 therapy and hormone receptor, one of the possible causes to explore should be the role of KIRs polymorphisms. No conflict of interest. 1840 POSTER Response to chemotherapy predicts outcome after combined modality therapy for inflammatory breast cancer
N. Snoj1 , E. Matos1 . 1 Institute of Oncology Ljubljana, medical oncology, Ljubljana, Slovenia
M. Loi1 , A. Dunant2 , A.M. Cascales-Garcia3 , A. Slocker-Escarpa3 , E. Deutsch3 , R. Arriagada3 , S. Rivera3 . 1 Universita degli Studi di Firenze, Radiation Therapy Department, Firenze, Italy; 2 Gustave Roussy, Biostatistics and Epidemiology Unit, Villejuif, France; 3 Gustave Roussy, Radiation Oncology, Villejuif, France
Background: It is generally accepted that survival of breast cancer (BC) cancer patients (pts) with brain metastasis (BM) is poor. In case of solitary or oligometastatic disease surgery or stereotactic radiosurgery followed by
Background: Inflammatory Breast Cancer (IBC) is characterized by aggressive clinical course and poor prognosis. The comprehensive treatment management combining chemotherapy (CT), surgery and radiotherapy