Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these...Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.展开更多
Breast cancer(BC)is the most common malignant tumor and one of the top causes of cancer-related death worldwide(Sung et al.,2021).The recent advances in early tumor diagnosis coupled with more effective treatment stra...Breast cancer(BC)is the most common malignant tumor and one of the top causes of cancer-related death worldwide(Sung et al.,2021).The recent advances in early tumor diagnosis coupled with more effective treatment strategies resulted in a steady increase of long-term survivors(Nardin et al.,2020;Invernizzi et al.,2022).These improved survival rates led to a significantly higher incidence of disabling complications related to breast cancer and/or its treatment(Invernizzi et al.,2020a;D’Egidio et al.,2017;Zhong et al.,2020).展开更多
Digital Pathology is becoming more and more important to achieve the goal of precision medicine.Advances in whole-slide imaging,software integration,and the accessibility of storage solutions have changed the patholog...Digital Pathology is becoming more and more important to achieve the goal of precision medicine.Advances in whole-slide imaging,software integration,and the accessibility of storage solutions have changed the pathologists’clinical practice,not only in terms of laboratory workflow but also for diagnosis and biomarkers analysis.In parallel with the pathology setting advancement,translational medicine is approaching the unprecedented opportunities unrevealed by artificial intelligence(AI).Indeed,the increased usage of biobanks’datasets in research provided new challenges for AI applications,such as advanced algorithms,and computer-aided techniques.In this scenario,machine learning-based approaches are being propose in order to improve biobanks from biospecimens collection repositories to computational datasets.To date,evidence on how to implement digital biobanks in translational medicine is still lacking.This viewpoint article summarizes the currently available literature that supports the biobanks’role in the digital pathology era,and to provide possible practical applications of digital biobanks.展开更多
HER2 is a pillar biomarker in breast cancer,and it is assessed by immunohistochemistry(IHC)using a three-tier scoring system and reflex in situ hybridization(ISH)for IHC score 2+.Novel HER2-directed antibody-drug conj...HER2 is a pillar biomarker in breast cancer,and it is assessed by immunohistochemistry(IHC)using a three-tier scoring system and reflex in situ hybridization(ISH)for IHC score 2+.Novel HER2-directed antibody-drug conjugates have demonstrated significant antitumor activity in breast cancers with low levels of HER2 expression,i.e.IHC score 1+or ISH-negative IHC score 2+.Both primary and acquired resistance to anti-HER2 therapies remains a challenge in the treatment of breast cancers according to the HER2 positivity continuum.Thus,the ability to precisely discriminate among HER2-zero,HER2-low,and HER2-positive breast cancers is no longer a mere academic exercise.HER2 testing criteria,guidelines,and quality controls are re-gaining momentum for this new clinical need.Therefore,all preanalytical and analytical variables that might trouble the sensitivity and reproducibility of this test should be carefully considered to address all possible issues and open all possible therapeutic opportunities for breast cancer patients.展开更多
Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers;however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER...Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers;however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER2 afterneoadjuvant therapy and at metastatic relapse and identified clinicopathological variables more frequentlyassociated with this event. Nevertheless, the biological mechanisms underlying HER2 loss are still poorlyunderstood. HER2 downregulation, intratumoral heterogeneity, clonal selection, and true subtype switch have beensuggested as potential causes of HER2 loss, but translational studies specifically investigating the biology behindHER2 loss are virtually absent. On the other side, technical pitfalls may justify HER2 loss in some of these samples.The best treatment strategy for patients with HER2 loss is currently unknown. Considering the prevalence of thisphenomenon and its apparent correlation with worse outcomes, we believe that correlative studies specificallyaddressing HER2 loss are warranted.展开更多
文摘Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.
文摘Breast cancer(BC)is the most common malignant tumor and one of the top causes of cancer-related death worldwide(Sung et al.,2021).The recent advances in early tumor diagnosis coupled with more effective treatment strategies resulted in a steady increase of long-term survivors(Nardin et al.,2020;Invernizzi et al.,2022).These improved survival rates led to a significantly higher incidence of disabling complications related to breast cancer and/or its treatment(Invernizzi et al.,2020a;D’Egidio et al.,2017;Zhong et al.,2020).
文摘Digital Pathology is becoming more and more important to achieve the goal of precision medicine.Advances in whole-slide imaging,software integration,and the accessibility of storage solutions have changed the pathologists’clinical practice,not only in terms of laboratory workflow but also for diagnosis and biomarkers analysis.In parallel with the pathology setting advancement,translational medicine is approaching the unprecedented opportunities unrevealed by artificial intelligence(AI).Indeed,the increased usage of biobanks’datasets in research provided new challenges for AI applications,such as advanced algorithms,and computer-aided techniques.In this scenario,machine learning-based approaches are being propose in order to improve biobanks from biospecimens collection repositories to computational datasets.To date,evidence on how to implement digital biobanks in translational medicine is still lacking.This viewpoint article summarizes the currently available literature that supports the biobanks’role in the digital pathology era,and to provide possible practical applications of digital biobanks.
文摘HER2 is a pillar biomarker in breast cancer,and it is assessed by immunohistochemistry(IHC)using a three-tier scoring system and reflex in situ hybridization(ISH)for IHC score 2+.Novel HER2-directed antibody-drug conjugates have demonstrated significant antitumor activity in breast cancers with low levels of HER2 expression,i.e.IHC score 1+or ISH-negative IHC score 2+.Both primary and acquired resistance to anti-HER2 therapies remains a challenge in the treatment of breast cancers according to the HER2 positivity continuum.Thus,the ability to precisely discriminate among HER2-zero,HER2-low,and HER2-positive breast cancers is no longer a mere academic exercise.HER2 testing criteria,guidelines,and quality controls are re-gaining momentum for this new clinical need.Therefore,all preanalytical and analytical variables that might trouble the sensitivity and reproducibility of this test should be carefully considered to address all possible issues and open all possible therapeutic opportunities for breast cancer patients.
文摘Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers;however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER2 afterneoadjuvant therapy and at metastatic relapse and identified clinicopathological variables more frequentlyassociated with this event. Nevertheless, the biological mechanisms underlying HER2 loss are still poorlyunderstood. HER2 downregulation, intratumoral heterogeneity, clonal selection, and true subtype switch have beensuggested as potential causes of HER2 loss, but translational studies specifically investigating the biology behindHER2 loss are virtually absent. On the other side, technical pitfalls may justify HER2 loss in some of these samples.The best treatment strategy for patients with HER2 loss is currently unknown. Considering the prevalence of thisphenomenon and its apparent correlation with worse outcomes, we believe that correlative studies specificallyaddressing HER2 loss are warranted.
