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167. Immune checkpoints in breast cancer surgery
ABSTRACTS In 2011, there were 3 hospitals in which NAC was administered in <10% of patients, in 5 hospitals 10-15% received NAC and in 2 hospitals the proportion of patients receiving NAC was >20% (P<0.001). 495 of the 1,402 patients with NAC underwent a SNB, 91.5% of which prior to NAC. Of the patients who underwent a SNB prior to NAC (N¼453), 59.4% were N+ and 46.8% underwent ALND. Discussion: The administration of NAC has strongly increased over the past decade, especially in T2 tumours. Presently, in the Netherlands up to 1 in 8 patients receive NAC. Considerable variation exists in the administration of NAC between hospitals. 91.5% Of the patients underwent SNB before the NAC. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.161
167. Immune checkpoints in breast cancer surgery A. Kolacinska1, L. Pakula2, B. Cebula3, J. Chalubinska4, W. Fendler5, A. Morawiec Sztandera6, Z. Morawiec7, P. Smolewski3 1 Medical University of Lodz, Lodz, Poland 2 Copernicus Memorial Hospital, Dept of Anesthesiology, Lodz, Poland 3 Medical University of Lodz, Dept of Experimental Hematology, Lodz, Poland 4 Medical University of Lodz, Dept of Radiotherapy, Lodz, Poland 5 Medical University of Lodz, Dept of Pediatrics Hematology Oncology and Diabetology, Lodz, Poland 6 Medical University of Lodz, Dept of Head and Neck Cancer Surgery, Lodz, Poland 7 Copernicus Memorial Hospital, Dept of Surgical Oncology, Lodz, Poland Background: Immune checkpoints refer to a plethora of inhibitory pathways built into the immune system that are crucial for maintaining self-tolerance, but recent research has underlined their role in carcinogenesis. The aim of our study was to evaluate two major immune checkpoints (CTLA-4, PD-1) perioperatively in the serum of breast cancer patients undergoing breast conserving surgery (BCS) and sentinel node biopsy (SNB). Material and methods: We enrolled 35 patients with stage I and II breast cancer, aged between 28- and 81-years-old, mean age 61.2 years.2.7 ml of blood was collected from the patients to determine serum concentrations of CTLA-4 and PD-1 at three time points i.e. preoperatively, during anesthesia after harvesting of SN and 24 hours after BCS and SNB (105 blood samples). Control blood samples were taken from 25 healthy agematched women (after obtaining Ethics Committee approval). Assessment of CTLA-4 and PD-1 levels by flow cytometry was carried out by a dedicated hematologist using CD 152PE-labeled anti-human CTLA-4 and HU CD279 anti-PD-1 antibodies (Becton Dickinson). A dedicated breast pathologist, blinded towards laboratory results, examined all postoperative specimens. Results: A statistically significant difference was found between PD1 expression in breast cancer patients preoperatively and healthy controls (26.31+/-11.87 vs 12.72+/-8.15; p<0.0001). A statistically significant correlation was found between CTLA4 and PD1 levels before surgery (r¼0.43; p¼0.0084) but disappeared in the two subsequent measurements during (r¼0.08; p¼0.62) and after surgery (r¼0.14; p¼0.43). CTLA4 expression was associated with age (r¼0.33, p¼0.0453). Elevated levels of CTLA4 were present in older breast cancer patients. There was a trend towards significance between PD1 levels and tumor size before surgery and intraoperatively (T2¼31.41+/-14.14vs T1¼22.47+/-8.28; p¼0.07 and T2¼32.81+/-13.21 vs T1¼24.61+/-10.68 p¼0.08, respectively). A decrease in PD1 levels was observed after harvesting SN with metastasis, but not in SN- negative patients (p¼0.05). There was a negative correlation between PD1 expression and progesterone receptor (PR) status after BCS and SNB (r¼-0.39; p¼0.024). Conclusions: The results provide an essential basis for further studies to investigate the potential role of immune checkpoints in breast cancer and provide an immunological justification for purely surgical procedures,
S73 particularly axillary lymph node surgery, and enrich the already well-established position of chemotherapy, endocrine therapy and anti- HER2 therapy, with the option of fine-tuning of the immune system. Breast cancer patients show an altered profile of immune checkpoints markers, with higher concentrations of PD1 noted in larger tumors. Surgical removal of lymph nodes containing tumor cells alters the immunologic response by diminishing PD1 levels. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.162
168. A systematic review of the clinical impact of the PIP breast implants U. Wazir1, A. Kasem1, K. Mokbel1 1 London Breast Institute, Breast and Endocrine Surgery, London, United Kingdom Background: The recent controversy regarding the use of industrial silicone in mammary implants marketed by Poly Implant Prothese (PIP) raised serious questions regarding their safety in humans. The implants from PIP were used extensively worldwide for augmentation or breast reconstruction. In this systematic review, we intend to examine the evidence pertaining to the clinical impact of mammary implants manufactured by PIP. Materials and methods: Articles were identified by searches of Medline, PubMed, Embase and Google Scholar databases up to March 2014 using the terms: ’PIP’, ’Poly Implant Prothese’, breast implants’ and ’augmentation mammoplasty’ or ’silicone’. In addition the websites of regulating bodies in Europe, USA and Australia were searched for reports related to PIP mammary implants. Results: PIP mammary implants are more likely to rupture than other implants and can cause adverse effects in the short to the medium term related to the symptoms of rupture such as pain, lumps in the breast and axilla and anxiety. Conclusions: There is no evidence that PIP implant rupture causes long-term adverse health effects in humans so far. The long-term adverse effects usually arise from inappropriate extensive surgery, such as axillary lymph node dissection or extensive resection of breast tissue due to silicone leakage. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.163
169. Can lymphovascular invasion detected in preoperative core biopsy predict sentinel node positivity in early breast cancer? S. Abeysiri1, F. Mihaimeed1, L. Jones2 1 Newham University Hospital, London, United Kingdom 2 Barts Health NHS Trust, London, United Kingdom Background: Sentinel node biopsy is accepted gold standard care in early breast cancer with normal axillary lymph nodes assessed with preoperative ultrasound or fine needle aspirate. About 30% of these patients require further operative intervention for completion node clearance. Preoperative predicting factors may further reduce the number of patients who may require second axillary procedures. Aims: To retrospectively study the correlation between lymphovascular invasion (LVI) detected in preoperative breast core biopsy and post operative sentinel node positivity. Materials and Methods: All patients undergoing core biopsy and sentinel node biopsy for invasive breast cancer processed in a regional central laboratory, were identified over a period of 14 months. Data collected included the LVI status reported on core biopsy sample, sentinel node status and histopathology details on post operative tissue specimens (including type, size and grade of tumour).
167. Immune checkpoints in breast cancer surgery A. Kolacinska1, L. Pakula2, B. Cebula3, J. Chalubinska4, W. Fendler5, A. Morawiec Sztandera6, Z. Morawiec7, P. Smolewski3 1 Medical University of Lodz, Lodz, Poland 2 Copernicus Memorial Hospital, Dept of Anesthesiology, Lodz, Poland 3 Medical University of Lodz, Dept of Experimental Hematology, Lodz, Poland 4 Medical University of Lodz, Dept of Radiotherapy, Lodz, Poland 5 Medical University of Lodz, Dept of Pediatrics Hematology Oncology and Diabetology, Lodz, Poland 6 Medical University of Lodz, Dept of Head and Neck Cancer Surgery, Lodz, Poland 7 Copernicus Memorial Hospital, Dept of Surgical Oncology, Lodz, Poland Background: Immune checkpoints refer to a plethora of inhibitory pathways built into the immune system that are crucial for maintaining self-tolerance, but recent research has underlined their role in carcinogenesis. The aim of our study was to evaluate two major immune checkpoints (CTLA-4, PD-1) perioperatively in the serum of breast cancer patients undergoing breast conserving surgery (BCS) and sentinel node biopsy (SNB). Material and methods: We enrolled 35 patients with stage I and II breast cancer, aged between 28- and 81-years-old, mean age 61.2 years.2.7 ml of blood was collected from the patients to determine serum concentrations of CTLA-4 and PD-1 at three time points i.e. preoperatively, during anesthesia after harvesting of SN and 24 hours after BCS and SNB (105 blood samples). Control blood samples were taken from 25 healthy agematched women (after obtaining Ethics Committee approval). Assessment of CTLA-4 and PD-1 levels by flow cytometry was carried out by a dedicated hematologist using CD 152PE-labeled anti-human CTLA-4 and HU CD279 anti-PD-1 antibodies (Becton Dickinson). A dedicated breast pathologist, blinded towards laboratory results, examined all postoperative specimens. Results: A statistically significant difference was found between PD1 expression in breast cancer patients preoperatively and healthy controls (26.31+/-11.87 vs 12.72+/-8.15; p<0.0001). A statistically significant correlation was found between CTLA4 and PD1 levels before surgery (r¼0.43; p¼0.0084) but disappeared in the two subsequent measurements during (r¼0.08; p¼0.62) and after surgery (r¼0.14; p¼0.43). CTLA4 expression was associated with age (r¼0.33, p¼0.0453). Elevated levels of CTLA4 were present in older breast cancer patients. There was a trend towards significance between PD1 levels and tumor size before surgery and intraoperatively (T2¼31.41+/-14.14vs T1¼22.47+/-8.28; p¼0.07 and T2¼32.81+/-13.21 vs T1¼24.61+/-10.68 p¼0.08, respectively). A decrease in PD1 levels was observed after harvesting SN with metastasis, but not in SN- negative patients (p¼0.05). There was a negative correlation between PD1 expression and progesterone receptor (PR) status after BCS and SNB (r¼-0.39; p¼0.024). Conclusions: The results provide an essential basis for further studies to investigate the potential role of immune checkpoints in breast cancer and provide an immunological justification for purely surgical procedures,
S73 particularly axillary lymph node surgery, and enrich the already well-established position of chemotherapy, endocrine therapy and anti- HER2 therapy, with the option of fine-tuning of the immune system. Breast cancer patients show an altered profile of immune checkpoints markers, with higher concentrations of PD1 noted in larger tumors. Surgical removal of lymph nodes containing tumor cells alters the immunologic response by diminishing PD1 levels. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.162
168. A systematic review of the clinical impact of the PIP breast implants U. Wazir1, A. Kasem1, K. Mokbel1 1 London Breast Institute, Breast and Endocrine Surgery, London, United Kingdom Background: The recent controversy regarding the use of industrial silicone in mammary implants marketed by Poly Implant Prothese (PIP) raised serious questions regarding their safety in humans. The implants from PIP were used extensively worldwide for augmentation or breast reconstruction. In this systematic review, we intend to examine the evidence pertaining to the clinical impact of mammary implants manufactured by PIP. Materials and methods: Articles were identified by searches of Medline, PubMed, Embase and Google Scholar databases up to March 2014 using the terms: ’PIP’, ’Poly Implant Prothese’, breast implants’ and ’augmentation mammoplasty’ or ’silicone’. In addition the websites of regulating bodies in Europe, USA and Australia were searched for reports related to PIP mammary implants. Results: PIP mammary implants are more likely to rupture than other implants and can cause adverse effects in the short to the medium term related to the symptoms of rupture such as pain, lumps in the breast and axilla and anxiety. Conclusions: There is no evidence that PIP implant rupture causes long-term adverse health effects in humans so far. The long-term adverse effects usually arise from inappropriate extensive surgery, such as axillary lymph node dissection or extensive resection of breast tissue due to silicone leakage. No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2014.08.163
169. Can lymphovascular invasion detected in preoperative core biopsy predict sentinel node positivity in early breast cancer? S. Abeysiri1, F. Mihaimeed1, L. Jones2 1 Newham University Hospital, London, United Kingdom 2 Barts Health NHS Trust, London, United Kingdom Background: Sentinel node biopsy is accepted gold standard care in early breast cancer with normal axillary lymph nodes assessed with preoperative ultrasound or fine needle aspirate. About 30% of these patients require further operative intervention for completion node clearance. Preoperative predicting factors may further reduce the number of patients who may require second axillary procedures. Aims: To retrospectively study the correlation between lymphovascular invasion (LVI) detected in preoperative breast core biopsy and post operative sentinel node positivity. Materials and Methods: All patients undergoing core biopsy and sentinel node biopsy for invasive breast cancer processed in a regional central laboratory, were identified over a period of 14 months. Data collected included the LVI status reported on core biopsy sample, sentinel node status and histopathology details on post operative tissue specimens (including type, size and grade of tumour).