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Ehealth: Friend or FOE
Abstracts / The Breast 36 S1 (2017) S19–S76
Ann Oncol. 2016 Aug;27(8):1423–43. doi: 10.1093/annonc/ mdw213 [2] http://www.who.int/medicines/publications/essentialmedici nes/en/ accessed May 2017
IN29 EHEALTH: FRIEND OR FOE Timo Schinköthe CANKADO, Munich, Germany Modern communication technologies provide new ways of cooperation and interaction. Companies do have teams spread out over continents and working together via the internet. The process of digitalisation and remote cooperation is unstoppable in each industry and service. Simply put, eHealth is the digital change in medicine and will also become the standard in near future. As in all other industries, a lot of work processes can be optimised using internet driven tools and services. On the other hand, medicine is not like all other professions. Patients, their disease, their needs, their care and their fears cannot be simply converted into a digital data. Taking care of a patient, analysing and understanding his situation, needs the use of all five senses and frequently demand empathy. It is, therefore, important to keep an eye on where and how the use of eHealth is beneficial and where perhaps medical skills are curtailed.
IN30 WHAT’S NEW IN BIOLOGY Aleix Prat Hospital Clinic, Medical Oncology Department, Barcelona, Spain Triple-negative breast cancer (TNBC) is a complex entity from a biological point of view; actually, TNBC is comprised of many different disease entities [1]. In this presentation, I will review the most up-to-date data on TNBC from a molecular perspective, with a special focus on the association of many of these biological alterations with clinical outcome and the most promising therapeutic strategies. At the somatic DNA level, the 2 most frequent mutations are TP53 (60–70%) and PIK3CA (∼10%) [2]. Additionally, loss of PTEN occurs in 9% of TNBC and, in general, is mutually exclusive with PIK3CA hotspot mutations. At the germline DNA level, the most frequent mutation is BRCA1 (∼10%) [3,4]. At the RNA and protein level, the most notable biological feature is an increase in proliferation, most likely due to loss-of-function of DNA-repair genes, retinoblastoma or amplification of cyclin E1. In this scenario, different gene expression-based classifications exist such as intrinsic subtype (Basal-like, Luminal A, Luminal B and HER2-enriched) [5–7] and the 7 TNBC-type subtype (BL1, BL2, M, MSL, IM and Luminal Androgen Receptor [LAR]) [8] have been reported. Although different, they are somewhat concordant in identifying a subgroup of TNBCs, which represent up to 20%, as nonBasal-like or LAR. From a biological perspective, Basal-like tumors should be considered a cancer-type by itself, as suggested by the PanCancer TCGA project across 12 cancer-types, despite having the same tissue of origin as estrogen receptor (ER) positive tumours [9]. Interestingly, nonBasal-like or LAR subtype can be defined as TNBCs but histologically and genetically resemble luminal-like ER-positive breast cancer. LAR tumors are enriched for PIK3CA mutations (∼46%) and are less sensitive to chemotherapy. In addition, non-Basal-like tumors might benefit more from
S29
docetaxel than carboplatin (in the TNT trial), and might benefit in the future from anti-androgen therapies, like enzalutamide. In the other hand, in addiction to BRCA, ATM and TP53 are other critical genes in the DNA-damage response signalling pathway, which might have a role in basal-like tumorigenesis [10]. With this rational, several clinical trials exploring the role of chemotherapy and biological agents targeting defective DNA-repair pathways. Finally, one important biological process in TNBC is immune infiltration. Indeed, the increase of tumor-infiltrating lymphocytes (TILs) in TNBC is associated with a higher likelihood of achieving a pCR, and better survival outcomes in the adjuvant setting than TNBCs with low degree of TILs [11]. In the metastatic setting, a subgroup of TNBCs, representing 18.5% of all TNBC with PDL1 IHC >1%, benefit from anti-PD1 monotherapy [12]. Whether these tumors are the ones with higher number of TILs is currently unknown. Further studies are need to show how classifying TNBC into distinct molecular entities improve patient outcomes. References [1] Prat A., et al., Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer, 2014. 111(8): p. 1532–41.2. [2] Cancer Genome Atlas N., Comprehensive molecular portraits of human breast tumours. Nature, 2012. 490(7418): p. 61–70. [3] Chen S. and Parmigiani G., Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol, 2007. 25(11): p. 1329–33. [4] Mafficini A., et al., BRCA somatic and germline mutation detection in paraffin embedded ovarian cancers by nextgeneration sequencing. Oncotarget, 2016. 7(2): p. 1076–83. [5] Parker J.S., et al., Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol, 2009. 27(8): p.1160–7. [6] Prat A., et al., Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist, 2013. 18(2): p. 123–33. [7] Perou C.M., et al., Molecular portraits of human breast tumours. Nature, 2000. 406(6797): p. 747–52. [8] Lehmann B.D., et al., Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011. 121(7): p. 2750–67. [9] Hoadley K.A., et al., Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell, 2014. 158(4): p. 929–44. [10] Konstantinopoulos P.A., et al., Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol, 2010. 28(22): p. 3555–61. [11] Disis M.L. and Stanton S.E., Immunotherapy in breast cancer: An introduction. Breast, 2017. [12] Nanda R., et al., Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol, 2016. 34(21): p. 2460–7.
IN31 THE ROLE OF IMMUNOTHERAPY IN THE TREATMENT OF TRIPLE NEGATIVE BREAST CANCER (TNBC) Hope S. Rugo University of California San Francisco Comprehensive Cancer Center, San Francisco, USA Recent and emerging data have generated great excitement about manipulating the patient’s own immune system to attack and eliminate malignant tumors. Although the majority of success has not been in breast cancer, recent studies have increased enthusiasm about this therapeutic modality. A series of immune checkpoints are hardwired into the immune system in order to modulate the duration and amplitude of the immune response, reducing
Ann Oncol. 2016 Aug;27(8):1423–43. doi: 10.1093/annonc/ mdw213 [2] http://www.who.int/medicines/publications/essentialmedici nes/en/ accessed May 2017
IN29 EHEALTH: FRIEND OR FOE Timo Schinköthe CANKADO, Munich, Germany Modern communication technologies provide new ways of cooperation and interaction. Companies do have teams spread out over continents and working together via the internet. The process of digitalisation and remote cooperation is unstoppable in each industry and service. Simply put, eHealth is the digital change in medicine and will also become the standard in near future. As in all other industries, a lot of work processes can be optimised using internet driven tools and services. On the other hand, medicine is not like all other professions. Patients, their disease, their needs, their care and their fears cannot be simply converted into a digital data. Taking care of a patient, analysing and understanding his situation, needs the use of all five senses and frequently demand empathy. It is, therefore, important to keep an eye on where and how the use of eHealth is beneficial and where perhaps medical skills are curtailed.
IN30 WHAT’S NEW IN BIOLOGY Aleix Prat Hospital Clinic, Medical Oncology Department, Barcelona, Spain Triple-negative breast cancer (TNBC) is a complex entity from a biological point of view; actually, TNBC is comprised of many different disease entities [1]. In this presentation, I will review the most up-to-date data on TNBC from a molecular perspective, with a special focus on the association of many of these biological alterations with clinical outcome and the most promising therapeutic strategies. At the somatic DNA level, the 2 most frequent mutations are TP53 (60–70%) and PIK3CA (∼10%) [2]. Additionally, loss of PTEN occurs in 9% of TNBC and, in general, is mutually exclusive with PIK3CA hotspot mutations. At the germline DNA level, the most frequent mutation is BRCA1 (∼10%) [3,4]. At the RNA and protein level, the most notable biological feature is an increase in proliferation, most likely due to loss-of-function of DNA-repair genes, retinoblastoma or amplification of cyclin E1. In this scenario, different gene expression-based classifications exist such as intrinsic subtype (Basal-like, Luminal A, Luminal B and HER2-enriched) [5–7] and the 7 TNBC-type subtype (BL1, BL2, M, MSL, IM and Luminal Androgen Receptor [LAR]) [8] have been reported. Although different, they are somewhat concordant in identifying a subgroup of TNBCs, which represent up to 20%, as nonBasal-like or LAR. From a biological perspective, Basal-like tumors should be considered a cancer-type by itself, as suggested by the PanCancer TCGA project across 12 cancer-types, despite having the same tissue of origin as estrogen receptor (ER) positive tumours [9]. Interestingly, nonBasal-like or LAR subtype can be defined as TNBCs but histologically and genetically resemble luminal-like ER-positive breast cancer. LAR tumors are enriched for PIK3CA mutations (∼46%) and are less sensitive to chemotherapy. In addition, non-Basal-like tumors might benefit more from
S29
docetaxel than carboplatin (in the TNT trial), and might benefit in the future from anti-androgen therapies, like enzalutamide. In the other hand, in addiction to BRCA, ATM and TP53 are other critical genes in the DNA-damage response signalling pathway, which might have a role in basal-like tumorigenesis [10]. With this rational, several clinical trials exploring the role of chemotherapy and biological agents targeting defective DNA-repair pathways. Finally, one important biological process in TNBC is immune infiltration. Indeed, the increase of tumor-infiltrating lymphocytes (TILs) in TNBC is associated with a higher likelihood of achieving a pCR, and better survival outcomes in the adjuvant setting than TNBCs with low degree of TILs [11]. In the metastatic setting, a subgroup of TNBCs, representing 18.5% of all TNBC with PDL1 IHC >1%, benefit from anti-PD1 monotherapy [12]. Whether these tumors are the ones with higher number of TILs is currently unknown. Further studies are need to show how classifying TNBC into distinct molecular entities improve patient outcomes. References [1] Prat A., et al., Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer, 2014. 111(8): p. 1532–41.2. [2] Cancer Genome Atlas N., Comprehensive molecular portraits of human breast tumours. Nature, 2012. 490(7418): p. 61–70. [3] Chen S. and Parmigiani G., Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol, 2007. 25(11): p. 1329–33. [4] Mafficini A., et al., BRCA somatic and germline mutation detection in paraffin embedded ovarian cancers by nextgeneration sequencing. Oncotarget, 2016. 7(2): p. 1076–83. [5] Parker J.S., et al., Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol, 2009. 27(8): p.1160–7. [6] Prat A., et al., Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist, 2013. 18(2): p. 123–33. [7] Perou C.M., et al., Molecular portraits of human breast tumours. Nature, 2000. 406(6797): p. 747–52. [8] Lehmann B.D., et al., Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011. 121(7): p. 2750–67. [9] Hoadley K.A., et al., Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell, 2014. 158(4): p. 929–44. [10] Konstantinopoulos P.A., et al., Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol, 2010. 28(22): p. 3555–61. [11] Disis M.L. and Stanton S.E., Immunotherapy in breast cancer: An introduction. Breast, 2017. [12] Nanda R., et al., Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol, 2016. 34(21): p. 2460–7.
IN31 THE ROLE OF IMMUNOTHERAPY IN THE TREATMENT OF TRIPLE NEGATIVE BREAST CANCER (TNBC) Hope S. Rugo University of California San Francisco Comprehensive Cancer Center, San Francisco, USA Recent and emerging data have generated great excitement about manipulating the patient’s own immune system to attack and eliminate malignant tumors. Although the majority of success has not been in breast cancer, recent studies have increased enthusiasm about this therapeutic modality. A series of immune checkpoints are hardwired into the immune system in order to modulate the duration and amplitude of the immune response, reducing