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PO97 BRAIN METASTASES IN HER2- POSITIVE BREAST CANCER PATIENTS: A SINGLE INSTITUTE EXPERIENCE
Abstracts / The Breast 24 S3 (2015) S21–S75
(14%) received no treatment. Data on ER, PgR and HER2 was available in 172 (87%), 161 (82%) and 127 (66%) patients respectively. Expressions of the receptors were: HER2 positive (22%), HER2 negative (42%) and unknown (34 %); ER positive (49%), ER negative (38%) and unknown (12%); PgR positive (31%), PgR negative (50%), unknown (18%). Forty-one patients (21%) were confirmed triple negative. Our preliminary results show a significant difference in survival according to disease extent (1-2 BCBM vs ≥3 BCBM vs MC) (p=0.0004) (n=195). Differences were found in pairwise comparisons between 1-2 vs ≥3 BCBM (p=0.0013) and between 1-2 BCBM and MC (p=0.0059) whilst none was seen between ≥3 BCBM and MC (p=0.0812). Survival was influenced by BC subgroup (p= 0.0278) (n=127); worst outcome for patients with for TNBC but no difference in a comparison between luminal and HER2 positive BC. Time to diagnosis of BCBM was equal throughout the period (p=0.84). Data divided into intrinsic BC subgroup in the whole patient cohort after review by two independent pathologists and differences in biomarker expression between primary tumour and BCBM will be presented.
PO97 BRAIN METASTASES IN HER2- POSITIVE BREAST CANCER PATIENTS: A SINGLE INSTITUTE EXPERIENCE Tahir Mehmood3, Asma Rashid3, Muhammad Irfan3, Sumera Nighat2, Bilal Aziz1, Mazhar Ali Shah3 1 Lahore General Hospital, Radiology, Lahore, Pakistan; 2Nishter Hospital Multan, Radiology, Multan, Pakistan; 3Shaukat Khanum Memorial Cancer Hospital and Research Centre, Radiation Oncology, Lahore, Pakistan Background: Human epidermal growth factor receptor 2- positive breast cancer (HER2+ BC) accounts for approximately 20% of all cases of breast cancer and have an aggressive course in metastatic setting due to distinct natural history. Brain metastasis is diagnosed in up to 40% of patients with HER2+ BC and is associated with substantial morbidity and mortality. In the present study, we aimed to investigate the incidence of brain metastases in patients with HER2+ BC treated at our institute. Materials and Methods: Between 1995 to 2009, the hospital information system identified 513 women with pathologically confirmed HER2+ breast cancer. Median age was 45 years (range 20-75 years). AJCC stage; stage I 7%, stage II 58% and stage III 35% of the patients respectively. Histological sub-types; infiltrating ductal carcinoma 96%, infiltrating lobular carcinoma 2% and others 2% respectively. Pathological grade; grade I/II in 41% and grade III 59% of the patients. 70% of the patients were treated with primary surgery. Chemotherapy regimens; adriamycin and taxanes based 75%, adriamycin based 5%, CMF 9% and other regimens in 5% of the patients either in neo-adjuvant or adjuvant setting. Only 6% of the patients received trastuzumab therapy. 5% of the patients did not receive any type of chemotherapy or targeted therapy. Post-operative radiotherapy was delivered to 86% of the patients. Incidence and median time to brain metastases were determined. Results: Median follow-up duration was 48 months. Patterns of failure; local 5%, regional 2%, and distant metastases in 26% of the patients. 14% of the patients who failed distantly were found to have brain metastases as first site of relapse. Overall brain metastases were seen in 25% of the patients. Median time to brain metastases was 13 months (range 8–50). Conclusions: Our results suggest that HER2+ BC sub-type remains more aggressive and is associated with a very high incidence of brain metastases. Future studies should be focused on new therapeutic options like small molecule tyrosine kinase inhibitors in adjuvant setting to decrease the incidence of systemic relapse.
PO98 IS BRAIN METASTASES LOCATION ASSOCIATED WITH PROGNOSIS IN BREAST CANCER PATIENTS? Karolina Widera1, Dorota Gabryś2, Michał Jarząb3, Dawid Larysz2,4 1 Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Outpatient Clinic, Gliwice, Poland; 2Maria
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Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Departmant of Radiotherapy , Gliwice, Poland; 3Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwce Branch, III Department of Radiotherapy and Chemotherapy, Gliwice, Poland; 4Medical University of Silesia, Department of Neurosurgery, Katowice, Poland The paradigm of brain metastases (BM) treatment has recently shifted towards the limited use of whole-brain irradiation and widespread application of radiosurgery. The number of metastases and it’s localisation, presence of extracranial disease, are potentially important for surgical decision making, and less influential for the radiosurgical treatment. There is suggestion that the location of metastases (supravs infratentorial +/-supratentorial) is not associated with the relapse after radiosurgical treatment. The aim of this study was to analyze the influence of brain tumor location on the prognosis in breast cancer patients mainly treated by WBRT+/- radiosurgery. Material and Methods: The group of patients was retrospectively selected from the population of breast cancer patients treated due to brain metastases by radiation therapy in MSC Memorial Cancer Center and Institute of Oncology in Gliwice. By the analysis of patient’s records we identified 315 pts treated between 2005-2014. Patients’ median age at BM diagnosis was 56 years (range 28-83). The majority (51.7%) presented good performance status (ECOG 0-1). BM co-occuring with active disease outside the brain were diagnosed in 218 pts (69.2%). Eighty seven pts (27,6%) presented with a single metastatis, 68 pts (21,6%) with 2-3, and 160 pts (50,8%) with multiple BM. Supratentorially located disease was found in 133 pts (42.2%), 37 pts (11,7%) have had infratentorial BM, while in 145 pts (46%) they were located in both compartments. More detailed analysis of tumor location (lobes, deep brain structures) was also carried out. All BM were treated with radiotherapy, 89.8% underwent WBRT, 19.7% of patients underwent additional metastasectomy, 39.7% stereotactic irradiation: in combination with WBRT 29.5% or alone 10.2%. One hundred twenty two pts (38.7%) underwent systemic treatment after BM diagnosis. Statistical analysis was carried out by the use uni-and multivariate Cox regression, with overall survival from the diagnosis of brain metastases as the major endpoint in the study. Results: Median OS from BM diagnosis was 6 months (0-119 months ). The survival time was highly associated with the number of metastases (p<0.05), and associated with the biological subtype of the tumor (longest for luminal subtype, intermediate in HER2-positive disease, shortest in triple negative disease, p<0.05). The presence of extracranial disease and poor performance status were negatively impacting OS (p<0.05). In the comparison of limited number of metastases (1-3) located supratentorially, infratentorially and in both locations there were no differences in the overall survival time (n.s.). The similar pattern was observed in multiple metastases group (n.s.), although in both strata the number of BM was stronger factor than their location. Conclusion: Metastasis location in brain appears not to determine prognosis in patients treated by radiation therapy.
PO99 TREATMENT OUTCOMES OF BREAST CANCER BRAIN METASTASES Ivica Ratosa, Tanja Marinko, Andreja Gojkovic Horvat, Jasenka Gugic, Manja Sesek, Mateja Bozic, Marija Snezna Paulin Kosir, Elga Majdic Institute of Oncology Ljubljana, Department of Radiation Oncology, Ljubljana, Slovenia Background: Breast cancer (BC) brain metastases (BM) influence quality of life and survival in metastatic BC. The purpose of this retrospective study is to evaluate treatment outcomes in patients with BM, treated with whole brain radiotherapy (WBRT) regarding to molecular subtypes, clinical characteristics and available prognostic indexes (PI). Methods: We retrospectively reviewed medical records of 133 metastatic BC patients treated with WBRT from April 2005 to December 2012 at Institute of Oncology Ljubljana. Intrinsic subtypes of BC were defined as luminal A (ER+, HER2-, low Ki67, high PR+), luminal B HER2-
(14%) received no treatment. Data on ER, PgR and HER2 was available in 172 (87%), 161 (82%) and 127 (66%) patients respectively. Expressions of the receptors were: HER2 positive (22%), HER2 negative (42%) and unknown (34 %); ER positive (49%), ER negative (38%) and unknown (12%); PgR positive (31%), PgR negative (50%), unknown (18%). Forty-one patients (21%) were confirmed triple negative. Our preliminary results show a significant difference in survival according to disease extent (1-2 BCBM vs ≥3 BCBM vs MC) (p=0.0004) (n=195). Differences were found in pairwise comparisons between 1-2 vs ≥3 BCBM (p=0.0013) and between 1-2 BCBM and MC (p=0.0059) whilst none was seen between ≥3 BCBM and MC (p=0.0812). Survival was influenced by BC subgroup (p= 0.0278) (n=127); worst outcome for patients with for TNBC but no difference in a comparison between luminal and HER2 positive BC. Time to diagnosis of BCBM was equal throughout the period (p=0.84). Data divided into intrinsic BC subgroup in the whole patient cohort after review by two independent pathologists and differences in biomarker expression between primary tumour and BCBM will be presented.
PO97 BRAIN METASTASES IN HER2- POSITIVE BREAST CANCER PATIENTS: A SINGLE INSTITUTE EXPERIENCE Tahir Mehmood3, Asma Rashid3, Muhammad Irfan3, Sumera Nighat2, Bilal Aziz1, Mazhar Ali Shah3 1 Lahore General Hospital, Radiology, Lahore, Pakistan; 2Nishter Hospital Multan, Radiology, Multan, Pakistan; 3Shaukat Khanum Memorial Cancer Hospital and Research Centre, Radiation Oncology, Lahore, Pakistan Background: Human epidermal growth factor receptor 2- positive breast cancer (HER2+ BC) accounts for approximately 20% of all cases of breast cancer and have an aggressive course in metastatic setting due to distinct natural history. Brain metastasis is diagnosed in up to 40% of patients with HER2+ BC and is associated with substantial morbidity and mortality. In the present study, we aimed to investigate the incidence of brain metastases in patients with HER2+ BC treated at our institute. Materials and Methods: Between 1995 to 2009, the hospital information system identified 513 women with pathologically confirmed HER2+ breast cancer. Median age was 45 years (range 20-75 years). AJCC stage; stage I 7%, stage II 58% and stage III 35% of the patients respectively. Histological sub-types; infiltrating ductal carcinoma 96%, infiltrating lobular carcinoma 2% and others 2% respectively. Pathological grade; grade I/II in 41% and grade III 59% of the patients. 70% of the patients were treated with primary surgery. Chemotherapy regimens; adriamycin and taxanes based 75%, adriamycin based 5%, CMF 9% and other regimens in 5% of the patients either in neo-adjuvant or adjuvant setting. Only 6% of the patients received trastuzumab therapy. 5% of the patients did not receive any type of chemotherapy or targeted therapy. Post-operative radiotherapy was delivered to 86% of the patients. Incidence and median time to brain metastases were determined. Results: Median follow-up duration was 48 months. Patterns of failure; local 5%, regional 2%, and distant metastases in 26% of the patients. 14% of the patients who failed distantly were found to have brain metastases as first site of relapse. Overall brain metastases were seen in 25% of the patients. Median time to brain metastases was 13 months (range 8–50). Conclusions: Our results suggest that HER2+ BC sub-type remains more aggressive and is associated with a very high incidence of brain metastases. Future studies should be focused on new therapeutic options like small molecule tyrosine kinase inhibitors in adjuvant setting to decrease the incidence of systemic relapse.
PO98 IS BRAIN METASTASES LOCATION ASSOCIATED WITH PROGNOSIS IN BREAST CANCER PATIENTS? Karolina Widera1, Dorota Gabryś2, Michał Jarząb3, Dawid Larysz2,4 1 Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Outpatient Clinic, Gliwice, Poland; 2Maria
S55
Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Departmant of Radiotherapy , Gliwice, Poland; 3Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwce Branch, III Department of Radiotherapy and Chemotherapy, Gliwice, Poland; 4Medical University of Silesia, Department of Neurosurgery, Katowice, Poland The paradigm of brain metastases (BM) treatment has recently shifted towards the limited use of whole-brain irradiation and widespread application of radiosurgery. The number of metastases and it’s localisation, presence of extracranial disease, are potentially important for surgical decision making, and less influential for the radiosurgical treatment. There is suggestion that the location of metastases (supravs infratentorial +/-supratentorial) is not associated with the relapse after radiosurgical treatment. The aim of this study was to analyze the influence of brain tumor location on the prognosis in breast cancer patients mainly treated by WBRT+/- radiosurgery. Material and Methods: The group of patients was retrospectively selected from the population of breast cancer patients treated due to brain metastases by radiation therapy in MSC Memorial Cancer Center and Institute of Oncology in Gliwice. By the analysis of patient’s records we identified 315 pts treated between 2005-2014. Patients’ median age at BM diagnosis was 56 years (range 28-83). The majority (51.7%) presented good performance status (ECOG 0-1). BM co-occuring with active disease outside the brain were diagnosed in 218 pts (69.2%). Eighty seven pts (27,6%) presented with a single metastatis, 68 pts (21,6%) with 2-3, and 160 pts (50,8%) with multiple BM. Supratentorially located disease was found in 133 pts (42.2%), 37 pts (11,7%) have had infratentorial BM, while in 145 pts (46%) they were located in both compartments. More detailed analysis of tumor location (lobes, deep brain structures) was also carried out. All BM were treated with radiotherapy, 89.8% underwent WBRT, 19.7% of patients underwent additional metastasectomy, 39.7% stereotactic irradiation: in combination with WBRT 29.5% or alone 10.2%. One hundred twenty two pts (38.7%) underwent systemic treatment after BM diagnosis. Statistical analysis was carried out by the use uni-and multivariate Cox regression, with overall survival from the diagnosis of brain metastases as the major endpoint in the study. Results: Median OS from BM diagnosis was 6 months (0-119 months ). The survival time was highly associated with the number of metastases (p<0.05), and associated with the biological subtype of the tumor (longest for luminal subtype, intermediate in HER2-positive disease, shortest in triple negative disease, p<0.05). The presence of extracranial disease and poor performance status were negatively impacting OS (p<0.05). In the comparison of limited number of metastases (1-3) located supratentorially, infratentorially and in both locations there were no differences in the overall survival time (n.s.). The similar pattern was observed in multiple metastases group (n.s.), although in both strata the number of BM was stronger factor than their location. Conclusion: Metastasis location in brain appears not to determine prognosis in patients treated by radiation therapy.
PO99 TREATMENT OUTCOMES OF BREAST CANCER BRAIN METASTASES Ivica Ratosa, Tanja Marinko, Andreja Gojkovic Horvat, Jasenka Gugic, Manja Sesek, Mateja Bozic, Marija Snezna Paulin Kosir, Elga Majdic Institute of Oncology Ljubljana, Department of Radiation Oncology, Ljubljana, Slovenia Background: Breast cancer (BC) brain metastases (BM) influence quality of life and survival in metastatic BC. The purpose of this retrospective study is to evaluate treatment outcomes in patients with BM, treated with whole brain radiotherapy (WBRT) regarding to molecular subtypes, clinical characteristics and available prognostic indexes (PI). Methods: We retrospectively reviewed medical records of 133 metastatic BC patients treated with WBRT from April 2005 to December 2012 at Institute of Oncology Ljubljana. Intrinsic subtypes of BC were defined as luminal A (ER+, HER2-, low Ki67, high PR+), luminal B HER2-