Invited Speaker Abstracts最新文献

{"title":"Abstract PL2: Neoadjuvant Endocrine Therapy: The Times They are A-Changing","authors":"I. Mayer","doi":"10.1158/1538-7445.SABCS18-PL2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-PL2","url":null,"abstract":"Neoadjuvant endocrine therapy (NET) in hormone-receptor positive breast cancers (HR+ BC) has been, in general, under-utilized, mostly because the majority of HR+ BC are diagnosed as stage I or II, and undergo surgical management as their first strategic step. However, NET is a suitable therapeutic choice for HR+ BC in cases where downsizing of the tumor is necessary (i.e. achievement of breast conservation). A seminal clinical trial comparing NET with neoadjuvant chemotherapy (NAC) in post-menopausal patients with HR+ BC revealed that the rates of overall response and breast conservation surgery were almost identical. NET also allows clinicians to infer prognosis based on simple pathologic characteristics: several clinical trials, including the phase III POETIC clinical trial (n=4486) showed that low Ki67 (less than 10%) at baseline and after 2 weeks had excellent long term outcome, whereas Ki67 larger than 10% at baseline and after 2 weeks had significantly worse long term outcome. Additionally, the Preoperative Endocrine Prognostic Index (PEPI), which is based on pathologic tumor size, node status, Ki67 level and ER status (Allred score) at the time of surgery, post NET, can accurately predict long term outcome. Interestingly, the early (about 2 weeks) Ki67 levels post NET has consistently predicted results of several phase III adjuvant or metastatic endocrine therapy trials (IMPACT - ATAC; Z1031 - MA-27) even in combination with targeted agents (LORELEI - SANDPIPER; NET + everolimus - BOLERO-2). Results of the ALTERNATE (A011106), a NET comparing AI with fulvestrant in post-menopausal patients with stage II and III HR+ BC is eagerly awaited, as it is bound to mimic the results of phase II and III trials comparing fulvestrant and AI in HR+ MBC (FIRST, FALCON, FACT, SWOG0226). Ultimately, these tools help clinicians decide if the addition of chemotherapy is necessary or not in patients with HR+ BC. Finally, NEC is an excellent tool in providing insights into the biologic basis of endocrine therapy efficacy (biomarkers of response and mechanisms of resistance studied in the post-treatment residual cancer). NET incorporating targeted therapies such as PI3K pathway inhibitors have yielded somewhat disappointing results compared to endocrine therapy alone (LORELEI, Neo-ORB), considering that PIK3CA mutations are the most common genomic alterations seen in HR+ BC. However, several ongoing trials of NET with CDK4/6 inhibitors were recently completed or are ongoing (NeoPalAna, NeoMONARCH, PALLET, PELOPS), and these trials may be instrumental not only in predicting the success of the large phase III adjuvant endocrine therapy with or without CDK4/6 inhibitors clinical trials. Ultimately, relatively small NET clinical trials could help with the design of more intelligent large clinical trials, providing the opportunity of residual tissue availability as a platform of discovery for biomarkers of sensitivity and resistance, an excellent platform for the de","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"54 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130400929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract ES11-3: Microsurgical treatment of lymphedema","authors":"D. Chang","doi":"10.1158/1538-7445.SABCS18-ES11-3","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES11-3","url":null,"abstract":"Lymphedema is a chronic, debilitating condition that causes physical and psychological morbidity, affecting up to 250 million people worldwide. In the United States and other developed countries, cancer and its treatments are the most common causes of lymphedema. Lymphedema can evolve into progressive swelling, fibrosis, functional deficits, and chronic infections, thus adversely affecting quality of life and health care costs. Unfortunately, no definitive treatment for lymphedema currently exists. The advents of microsurgery, and more recently supermicrosurgery, have had a major impact on the evolution of these physiologic procedures, which have gained popularity to help reduce the severity of lymphedema. Lymphatic Bypass LVB are typically performed through incisions 2-3 cm in length and the number of bypasses can vary depending on a patient as well as a surgeon. In our prospective study in 100 consecutive patients, we have found that LVB can be effective in reducing lymphedema severity, particularly in patients with early-stage, upper-extremity lymphedema with reasonable amount of intact functioning lymphatic vessels and minimal tissue fibrosis. One recent technological advance in lymphovenous bypass procedures is the use of indocyanine green (ICG) fluorescence lymphangiography to map lymphatic vessels. ICG fluorescence lymphangiography enables surgeons to locate and make incisions precisely over functional lymphatic vessels for the lymphovenous bypass, substantially reducing operating time and may significantly improve the outcomes of LVB surgeries. Vascularized Lymph Node Transfer This procedure aims to bring vascularized tissue and healthy lymph nodes into sites affected by lymphedema. A flap containing lymph nodes can then be harvested typically from either the cervical region, axillary region or from the inguinal region. One proposed theory for mechanism is that lymphangiogenesis occur via growth factors produced by the transplanted lymph nodes and thereby bridging lymphatic pathways. A second proposed theory of mechanism is that vascularized lymph node transfer act as a lymphatic pump. Recently, simultaneous breast reconstruction using the transverse lower abdominal flap harvested with inguinal lymph nodes have gained popularity as a convenient option for lymphedematous women who desire reconstruction after mastectomy. Conclusions Currently there is no cure for lymphedema. Worldwide interest in using microsurgical procedures to treat lymphedema is gaining momentum. However, there is no consensus on the indications for which procedure to perform, when to intervene, or how to comparatively grade outcomes. We need further research and better understanding of lymphatic anatomy and lymphedema pathophysiology. In addition, more prospective and controlled studies are needed to objectively evaluate the outcomes of various treatment methods. Citation Format: Chang D. Microsurgical treatment of lymphedema [abstract]. In: Proceedings of the 2018 San","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126040436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract ES7-2: Practical approach to the axilla after neoadjuvant chemotherapy: What the clinical trials don't address","authors":"A. Barrio","doi":"10.1158/1538-7445.SABCS18-ES7-2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES7-2","url":null,"abstract":"Neoadjuvant chemotherapy (NAC) was initially used in patients with inoperable breast cancer to improve resectability, but it is also beneficial in women with operable breast cancer, particularly with respect to the axilla. Nodal pathologic complete response (pCR) rates among clinically node-positive patients treated with modern systemic therapy range from 35-49%. The ability to downstage the axilla and potentially avoid axillary lymph node dissection (ALND) is one of the greatest surgical advantages of NAC. The optimal approach to the axilla after NAC varies based on the clinical nodal stage prior to NAC. In clinically node-negative patients, the use of sentinel lymph node biopsy (SLNB) after NAC has been well studied, with high identification rates and false-negative rates that are similar to the upfront surgery setting. In addition, regional recurrence rates are no different between clinically node-negative patients treated with SLNB alone after NAC, or those treated with upfront SLNB. In clinically node-positive patients, 3 single-arm prospective trials have demonstrated that SLNB after NAC results in a false-negative rate As all patients in the prospective trials had an ALND, the frequency with which ALND could be avoided with the use of NAC in clinically node-positive patients was not addressed, although more recent data have demonstrated that approximately 50% will achieve a nodal pCR and avoid ALND. Indications for ALND after NAC include any positive SLN (including micrometastases and isolated tumor cells), failed mapping, or patients presenting with inoperable breast cancer. Nodal recurrence rates among clinically node-positive patients treated with SLNB alone after NAC are largely unknown, with only one small study demonstrating low regional recurrence rates. Ultimately, the optimal treatment strategy to avoid ALND in patients with operable breast cancer is complex and based on a combination of tumor subtype, clinical nodal status, and type of breast surgery performed. With the continued use of modern systemic therapy and improved radiation techniques for breast cancer, our ability to de-escalate surgical care and reduce the morbidity of surgery, while still maintaining excellent disease control, has become our new standard of care. Citation Format: Barrio A. Practical approach to the axilla after neoadjuvant chemotherapy: What the clinical trials don9t address [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES7-2.","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"301 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131736089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract ES2-2: Breast cancer's metastatic moment: How postpartum tissue involution facilitates progression","authors":"P. Schedin","doi":"10.1158/1538-7445.SABCS18-ES2-2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES2-2","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128339428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract ES9-3: Triple negative breast cancer: Current and future directions in metastatic patients","authors":"Jenny C. Chang","doi":"10.1158/1538-7445.SABCS18-ES9-3","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES9-3","url":null,"abstract":"Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) with both early and metastatic disease. The poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets and other approaches to treat these patients. Massively parallel sequencing and other 9omics9 technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 9BRCAness9, as well as a subgroup with a high degree of tumor-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. Additional data from trials with antibody drug conjugates have yielded promising results. We discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities. Citation Format: Chang J. Triple negative breast cancer: Current and future directions in metastatic patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES9-3.","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"170 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134334691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract ES3-2: Multidisciplinary management of breast cancer brain metastases","authors":"C. Tsien","doi":"10.1158/1538-7445.SABCS18-ES3-2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES3-2","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123430915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract BS1-2: Neutrophil extracellular traps promote breast cancer metastasis","authors":"M. Egeblad","doi":"10.1158/1538-7445.SABCS18-BS1-2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-BS1-2","url":null,"abstract":"Cancer cells from a primary tumor can disseminate to other tissues, but remain dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to “awaken”, resume proliferation, and develop into metastases. Using mouse models, we have found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Using intravital imaging techniques, which allow for long-term time-lapse imaging of cancer cells and surrounding host cells in living mice, we observed that sustained inflammation induced the formation of neutrophil extracellular traps (NETs). NETs are pathogen-trapping structures generated by expulsion of the neutrophil9s DNA with associated proteolytic enzymes in response to e.g., infections. We confirmed that NETs were present in clinical samples of breast cancer lung metastases. Mechanistic analysis revealed that NETs were required for awakening dormant cancer and specifically that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin alpha-3 beta-1 signaling. We generated antibodies against NET-remodeled laminin and these prevented awakening of dormant cells in mice. In addition, pharmacological inhibition of NET formation or digestion of NETs with DNase I-coated nanoparticles also markedly reduced awakening and lung metastases in mice. Our data suggest that induction of NETs is an important host-mediated mechanism of promoting metastasis and a potential therapeutic target to prevent preventing dormant cell awakening and prolong the survival of cancer patients. Citation Format: Egeblad M. Neutrophil extracellular traps promote breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr BS1-2.","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132109150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}