This document summarizes breast cancer risk factors, etiology, pathogenesis, classification, and carcinogenesis. It notes that breast cancer is most common in women over 30 and risk increases with age. The majority are estrogen receptor positive. Risk factors include family history, age of first birth, obesity, and hormone exposure. Cancers arise from genetic mutations in cells like luminal cells and can follow hereditary or sporadic pathways. Cancers are classified as either carcinoma in situ, confined to ducts/lobules, or invasive carcinoma penetrating the basement membrane. Carcinogenesis is a multi-step process as cells acquire mutations driving proliferation.
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
Microsatellite instability testing is an important part in diagnostics in Metastatic cancer settings after the FDA has given approval for tissue agnostic indications in almost all solid cancers. MSI by PCR and MMR status by IHC is also helpful for evaluation of genetic risk in Colon and Endometrial cancers
Tumor markers are biological substances that are produced by cancer cells or the body's response to cancer. Ideal tumor markers should be highly specific, sensitive, correlate with tumor stage/mass, and predict prognosis. Recent advances include new genetic and viral biomarkers. Tumor markers can be classified as hormones, oncofetal antigens, enzymes, tumor-associated proteins, receptors, and genetic markers. Oncogenes like RAS and C-myc can also serve as markers when mutated or translocated. Establishing biomarkers requires understanding how small molecular changes disrupt cellular functions and cancer initiation.
This document discusses cancer genomics and tumor sequencing. It explains that tumor genotyping helps clinicians individualize cancer treatments by matching patients to the best treatment based on their tumor's DNA alterations. Next generation sequencing methods have made it possible to sequence entire cancer genomes and identify additional targets for new cancer therapies. Large-scale projects like The Cancer Genome Atlas and the International Cancer Genome Consortium are analyzing hundreds of cancer genomes to better understand the molecular changes driving different cancer types.
Tumor markers are substances produced by tumors or the body's response to tumors that can help detect and monitor cancer. Alpha-fetoprotein (AFP) is elevated in hepatocellular carcinoma and germ cell tumors. It is useful for diagnosis, staging, prognosis, and monitoring treatment response in HCC and germ cell tumors. Carcinoembryonic antigen (CEA) is elevated in various cancers including colorectal cancer. CEA levels correlate with tumor stage and burden and can help monitor treatment response and detect recurrence, though it lacks sensitivity and specificity for screening and diagnosis.
The document discusses molecular testing for breast cancer. It describes how molecular testing can provide insights into breast cancer subtypes, predict response to treatments, and assess recurrence risk. Several molecular tests are discussed, including Oncotype DX, Mammaprint, Prosigna, and tumor sequencing to identify actionable mutations. Molecular profiling is becoming increasingly important for personalized prevention, diagnosis, and treatment of breast cancer.
The document discusses several gene expression profiling tests for early breast cancer, including OncotypeDX, MammaPrint, and TAILORx. OncotypeDX analyzes the expression of 21 genes to calculate a recurrence score that predicts the likelihood of distant recurrence within 10 years for tamoxifen-treated patients. MammaPrint analyzes 70 genes to classify patients into low or high risk groups. The TAILORx clinical trial aims to determine which patients with early breast cancer and OncotypeDX scores of 11-25 benefit from chemotherapy using a randomized design.
This document summarizes breast cancer risk factors, etiology, pathogenesis, classification, and carcinogenesis. It notes that breast cancer is most common in women over 30 and risk increases with age. The majority are estrogen receptor positive. Risk factors include family history, age of first birth, obesity, and hormone exposure. Cancers arise from genetic mutations in cells like luminal cells and can follow hereditary or sporadic pathways. Cancers are classified as either carcinoma in situ, confined to ducts/lobules, or invasive carcinoma penetrating the basement membrane. Carcinogenesis is a multi-step process as cells acquire mutations driving proliferation.
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
Microsatellite instability testing is an important part in diagnostics in Metastatic cancer settings after the FDA has given approval for tissue agnostic indications in almost all solid cancers. MSI by PCR and MMR status by IHC is also helpful for evaluation of genetic risk in Colon and Endometrial cancers
Tumor markers are biological substances that are produced by cancer cells or the body's response to cancer. Ideal tumor markers should be highly specific, sensitive, correlate with tumor stage/mass, and predict prognosis. Recent advances include new genetic and viral biomarkers. Tumor markers can be classified as hormones, oncofetal antigens, enzymes, tumor-associated proteins, receptors, and genetic markers. Oncogenes like RAS and C-myc can also serve as markers when mutated or translocated. Establishing biomarkers requires understanding how small molecular changes disrupt cellular functions and cancer initiation.
This document discusses cancer genomics and tumor sequencing. It explains that tumor genotyping helps clinicians individualize cancer treatments by matching patients to the best treatment based on their tumor's DNA alterations. Next generation sequencing methods have made it possible to sequence entire cancer genomes and identify additional targets for new cancer therapies. Large-scale projects like The Cancer Genome Atlas and the International Cancer Genome Consortium are analyzing hundreds of cancer genomes to better understand the molecular changes driving different cancer types.
Tumor markers are substances produced by tumors or the body's response to tumors that can help detect and monitor cancer. Alpha-fetoprotein (AFP) is elevated in hepatocellular carcinoma and germ cell tumors. It is useful for diagnosis, staging, prognosis, and monitoring treatment response in HCC and germ cell tumors. Carcinoembryonic antigen (CEA) is elevated in various cancers including colorectal cancer. CEA levels correlate with tumor stage and burden and can help monitor treatment response and detect recurrence, though it lacks sensitivity and specificity for screening and diagnosis.
The document discusses molecular testing for breast cancer. It describes how molecular testing can provide insights into breast cancer subtypes, predict response to treatments, and assess recurrence risk. Several molecular tests are discussed, including Oncotype DX, Mammaprint, Prosigna, and tumor sequencing to identify actionable mutations. Molecular profiling is becoming increasingly important for personalized prevention, diagnosis, and treatment of breast cancer.
The document discusses several gene expression profiling tests for early breast cancer, including OncotypeDX, MammaPrint, and TAILORx. OncotypeDX analyzes the expression of 21 genes to calculate a recurrence score that predicts the likelihood of distant recurrence within 10 years for tamoxifen-treated patients. MammaPrint analyzes 70 genes to classify patients into low or high risk groups. The TAILORx clinical trial aims to determine which patients with early breast cancer and OncotypeDX scores of 11-25 benefit from chemotherapy using a randomized design.
This document discusses molecular profiling of breast cancer. It begins by introducing breast cancer as the most common cancer in women. It then discusses traditional classifications based on histological and clinical features. However, up to half of hormone receptor positive cancers do not respond to treatment, showing clinical classifications are insufficient. Molecular profiling uses high-throughput techniques to better understand breast cancer biology and refine classifications. Gene expression profiling has identified major molecular subtypes, like luminal A/B, HER2-positive, and basal-like. Multigene assays provide prognostic and predictive information beyond traditional clinics-pathological factors. Several common assays are discussed, including Oncotype DX, Mammaprint, and PAM50. Next generation sequencing is also discussed for
Molecular profiling of breast cancer can classify tumor types, identify appropriate therapeutic targets, determine prognosis, and predict treatment response. Techniques include immunohistochemistry, fluorescence in situ hybridization, reverse transcription PCR, microarrays, and next generation sequencing to analyze protein expression, gene copy number, mutations, and gene expression levels. Breast cancers are classified into intrinsic subtypes including luminal A/B, HER2-enriched, basal-like, and claudin-low based on distinct gene expression patterns that predict clinical behavior and response to therapy.
Gene expression profiling in breast carcinomaghoshparthanrs
This document discusses gene expression profiling in breast cancer and its use in classifying tumor subtypes. It describes how gene expression profiling analyzes thousands of genes simultaneously to more accurately classify tumors. Breast cancer is classified into clinical subtypes based on receptor expression, including luminal, HER2-enriched, and basal subtypes. Gene signatures can provide prognostic information to help guide treatment decisions for early-stage breast cancer patients. Tests like Oncotype DX and Mammaprint analyze gene expression from tumor samples to predict the risk of recurrence.
Biomarkers can be used for screening, diagnosis, prognosis, and predicting response to treatment for cancer. In bladder cancer, screening biomarkers could identify high-risk groups but population screening may lead to many false positives. Diagnostic biomarkers are needed because hematuria is non-specific, and cystoscopy is expensive. Prognostic biomarkers help determine disease course as response can vary between patients with similar pathology. Predictive biomarkers identify subgroups likely to benefit from specific therapies.
Next-generation DNA sequencing (NGS) provides high-throughput sequencing of DNA fragments in parallel to determine sequences exponentially faster and cheaper than Sanger sequencing. NGS can be used for whole genome, whole exome, or targeted gene panel sequencing. It has various clinical applications including cancer screening and management, diagnosis of complex genetic diseases, and identification of pathogenic variants. Tumor mutation burden (TMB) quantifies total mutations per tumor genome and higher TMB may predict better response to immunotherapy by expressing more neoantigens.
Biomarkers have a diversified role in diagnosis, prognostication and risk stratification. This presentation aims to compile the basic information and new literature on various biomarkers pertaining to cancer care.
This document provides an overview of molecular testing in breast cancer. It discusses several tests including hormone receptor testing for ER and PR, HER2 testing, Ki67 proliferation index testing, next-generation sequencing, multi-analyte assays, and germline testing. These tests help classify breast cancer into molecular subtypes, provide prognostic information, predict response to therapies, and identify genetic predispositions. The tests utilize various methodologies like IHC, FISH, gene expression profiling, and DNA sequencing. The results of molecular testing guide treatment decisions and clinical management of breast cancer patients.
It contains introduction on basic molecular biology followed by detailed description on discovery , mechanism of oncogene activation, their effect on tumerogenesis , name of important oncogenes , their detection and targeted therapies against oncogenes in treating cancer
The document discusses immunotherapy and the role of pathologists in assessing tumor samples. It describes how certain tumors express PD-L1 antigens that can be recognized by the immune system, but the tumors also engage immune checkpoint pathways like PD-1 and CTLA-4 to evade the immune response. Immunotherapy drugs target these checkpoint pathways to enhance the immune response. The document outlines the FDA-approved PD-L1 immunohistochemistry assays and biomarkers used to identify cancer patients most likely to respond to immune checkpoint inhibitors for various cancer types including NSCLC, melanoma, bladder cancer, and colorectal cancer.
Cancer is caused by genetic mutations in somatic cells. Whole genome sequencing can identify all genetic alterations in cancer including single nucleotide mutations, small insertions/deletions, copy number changes, and chromosomal rearrangements. Earlier methods focused on sequencing protein kinase genes known to be involved in cancer signaling pathways. Current methods like whole exome sequencing focus on coding exons to identify damaging mutations at lower cost compared to whole genome sequencing. Non-coding mutations in regulatory regions and microRNAs are also important in cancer development.
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...QIAGEN
A liquid biopsy is often described as a sensitive and specific blood test to detect circulating tumor cells (CTCs). CTCs, shed by both the primary and metastasized tumors, carry specific information about their origins and markers that will enable us to discover new diagnosis, prognosis and therapeutic targets. This slidedeck gives an overview of the recent progress in exploring the predictive potential of circulating biomarkers, including circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs (lncRNAs) and exosomes. Addressing both biological and technical aspects, we detail the isolation and characterization of circulating biomarkers. Challenges and solutions are also featured.
Genetic testing and counseling can help determine cancer risk based on family history and genetic mutations. Most cancers are sporadic but 5-10% are hereditary due to inherited gene mutations. Genetic counselors use family histories and genetic tests to assess cancer risks, recommend screening, and provide counseling to relatives. While some cancers have clear high-risk genes, most have contributions from multiple common and rare variants, so interpretation requires expertise.
This document discusses microsatellite instability (MSI), which refers to changes in repeated sequences of DNA called microsatellites during DNA replication due to defects in the DNA mismatch repair system. The key mechanisms, detection methods, clinical significance and applications of MSI in various cancers are described. MSI is an important factor in tumor development and progression. Detection of MSI using techniques such as PCR and immunohistochemistry can aid in cancer diagnosis and predict response to immunotherapy. Cancers with high MSI (MSI-H) often respond well to immune checkpoint inhibitors.
Tumor markers are biomarkers found in blood, urine, or tissues that can indicate the presence of cancer when elevated. They can be produced directly by tumors or other cells in response to tumors. While tumor marker assays help with cancer staging and treatment, they are usually not definitive diagnostic tests and biopsy is required for diagnosis. Tumor markers include proteins, peptides, and carbohydrates and can be used for cancer screening, monitoring recurrence, diagnosis, staging, prognosis, evaluating treatment effectiveness, and as companion diagnostics. Commonly used tumor markers include alpha fetoprotein, CA15-3, CA27-29, CA19-9, and CA-125.
- Three major molecular assays have been developed for prognostic assessment of breast cancer: Oncotype DX, Mammaprint, and Prosigna.
- Oncotype DX uses a 21-gene signature to predict recurrence risk in ER+ breast cancer. Mammaprint uses a 70-gene signature and Prosigna uses the PAM50 intrinsic subtyping algorithm.
- Clinical trials have validated the use of these assays in lymph node positive and negative disease to predict chemotherapy benefit and guide treatment decisions. Ongoing research aims to further refine risk assessment and subclassify breast cancer.
This document discusses biomarkers in cancer detection and diagnosis. It defines biomarkers as molecules that indicate normal or abnormal biological processes and may signal diseases like cancer. Biomarkers can be found in tissues, blood, or other bodily fluids and include proteins, genes, RNA, carbohydrates, or viruses associated with certain cancers. Biomarkers are useful for early cancer detection, diagnosis, assessing prognosis, predicting treatment effectiveness, and identifying molecular drug targets. Several protein, DNA, and RNA biomarkers for cancers of the breast, ovary, prostate, bladder, oral cavity, colon, and HIV-associated cancers are discussed. Imaging techniques can also serve as cancer biomarkers by aiding screening, diagnosis, and monitoring treatment response.
Molecular methods such as polymerase chain reaction (PCR), real-time PCR, fragment analysis, high-resolution melting analysis, Sanger sequencing, pyrosequencing, and fluorescence in situ hybridization (FISH) are increasingly used in cancer care for diagnosis, prognosis, predicting therapy response, and monitoring minimal residual disease. These techniques detect various biomarkers including mutations, gene fusions, amplifications, and epigenetic changes from samples such as blood, tissue, and bone marrow. The molecular diagnostic tests must demonstrate high analytic validity, clinical validity, and utility to be clinically applicable.
Molecular classification breast carcinomassuser56f01e1
This document discusses the molecular classification of breast cancer and its role in patient management. It begins by explaining the need for molecular classification in diagnosis, prognosis, prediction, and management of breast cancer patients. It then covers various molecular alterations and genetic factors that contribute to breast cancer development, including growth factor receptors, signaling molecules, cell cycle regulators, and adhesion molecules. The major subtypes of breast cancer - luminal A/B, HER2-enriched, and basal-like - are identified based on expression of estrogen receptor, progesterone receptor, HER2, and Ki-67. Molecular classification is important for determining prognosis and guiding treatment decisions.
Not All Uterine Cancer is the Same: What to Know About Rare Uterine Cancersbkling
This document discusses rare types of uterine cancers and their treatment strategies. It begins by reviewing trends in uterine cancer in the US, noting that endometrioid cancers make up 80% of cases while rare high risk types like serous carcinoma account for 20%. It then discusses the different rare types in more detail like leiomyosarcomas, carcinosarcomas, and clear cell carcinomas. Molecular testing results and targeted therapies are explored. Treatment approaches for each rare type are provided, including chemotherapy regimens, radiation, immunotherapy, and targeted therapies. Clinical trials are encouraged. Overall survival benefits of immunotherapy and targeted therapies are shown for certain rare uterine cancer patients.
This document discusses molecular profiling of breast cancer. It begins by introducing breast cancer as the most common cancer in women. It then discusses traditional classifications based on histological and clinical features. However, up to half of hormone receptor positive cancers do not respond to treatment, showing clinical classifications are insufficient. Molecular profiling uses high-throughput techniques to better understand breast cancer biology and refine classifications. Gene expression profiling has identified major molecular subtypes, like luminal A/B, HER2-positive, and basal-like. Multigene assays provide prognostic and predictive information beyond traditional clinics-pathological factors. Several common assays are discussed, including Oncotype DX, Mammaprint, and PAM50. Next generation sequencing is also discussed for
Molecular profiling of breast cancer can classify tumor types, identify appropriate therapeutic targets, determine prognosis, and predict treatment response. Techniques include immunohistochemistry, fluorescence in situ hybridization, reverse transcription PCR, microarrays, and next generation sequencing to analyze protein expression, gene copy number, mutations, and gene expression levels. Breast cancers are classified into intrinsic subtypes including luminal A/B, HER2-enriched, basal-like, and claudin-low based on distinct gene expression patterns that predict clinical behavior and response to therapy.
Gene expression profiling in breast carcinomaghoshparthanrs
This document discusses gene expression profiling in breast cancer and its use in classifying tumor subtypes. It describes how gene expression profiling analyzes thousands of genes simultaneously to more accurately classify tumors. Breast cancer is classified into clinical subtypes based on receptor expression, including luminal, HER2-enriched, and basal subtypes. Gene signatures can provide prognostic information to help guide treatment decisions for early-stage breast cancer patients. Tests like Oncotype DX and Mammaprint analyze gene expression from tumor samples to predict the risk of recurrence.
Biomarkers can be used for screening, diagnosis, prognosis, and predicting response to treatment for cancer. In bladder cancer, screening biomarkers could identify high-risk groups but population screening may lead to many false positives. Diagnostic biomarkers are needed because hematuria is non-specific, and cystoscopy is expensive. Prognostic biomarkers help determine disease course as response can vary between patients with similar pathology. Predictive biomarkers identify subgroups likely to benefit from specific therapies.
Next-generation DNA sequencing (NGS) provides high-throughput sequencing of DNA fragments in parallel to determine sequences exponentially faster and cheaper than Sanger sequencing. NGS can be used for whole genome, whole exome, or targeted gene panel sequencing. It has various clinical applications including cancer screening and management, diagnosis of complex genetic diseases, and identification of pathogenic variants. Tumor mutation burden (TMB) quantifies total mutations per tumor genome and higher TMB may predict better response to immunotherapy by expressing more neoantigens.
Biomarkers have a diversified role in diagnosis, prognostication and risk stratification. This presentation aims to compile the basic information and new literature on various biomarkers pertaining to cancer care.
This document provides an overview of molecular testing in breast cancer. It discusses several tests including hormone receptor testing for ER and PR, HER2 testing, Ki67 proliferation index testing, next-generation sequencing, multi-analyte assays, and germline testing. These tests help classify breast cancer into molecular subtypes, provide prognostic information, predict response to therapies, and identify genetic predispositions. The tests utilize various methodologies like IHC, FISH, gene expression profiling, and DNA sequencing. The results of molecular testing guide treatment decisions and clinical management of breast cancer patients.
It contains introduction on basic molecular biology followed by detailed description on discovery , mechanism of oncogene activation, their effect on tumerogenesis , name of important oncogenes , their detection and targeted therapies against oncogenes in treating cancer
The document discusses immunotherapy and the role of pathologists in assessing tumor samples. It describes how certain tumors express PD-L1 antigens that can be recognized by the immune system, but the tumors also engage immune checkpoint pathways like PD-1 and CTLA-4 to evade the immune response. Immunotherapy drugs target these checkpoint pathways to enhance the immune response. The document outlines the FDA-approved PD-L1 immunohistochemistry assays and biomarkers used to identify cancer patients most likely to respond to immune checkpoint inhibitors for various cancer types including NSCLC, melanoma, bladder cancer, and colorectal cancer.
Cancer is caused by genetic mutations in somatic cells. Whole genome sequencing can identify all genetic alterations in cancer including single nucleotide mutations, small insertions/deletions, copy number changes, and chromosomal rearrangements. Earlier methods focused on sequencing protein kinase genes known to be involved in cancer signaling pathways. Current methods like whole exome sequencing focus on coding exons to identify damaging mutations at lower cost compared to whole genome sequencing. Non-coding mutations in regulatory regions and microRNAs are also important in cancer development.
Liquid Biopsy Overview, Challenges and New Solutions: Liquid Biopsy Series Pa...QIAGEN
A liquid biopsy is often described as a sensitive and specific blood test to detect circulating tumor cells (CTCs). CTCs, shed by both the primary and metastasized tumors, carry specific information about their origins and markers that will enable us to discover new diagnosis, prognosis and therapeutic targets. This slidedeck gives an overview of the recent progress in exploring the predictive potential of circulating biomarkers, including circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs (lncRNAs) and exosomes. Addressing both biological and technical aspects, we detail the isolation and characterization of circulating biomarkers. Challenges and solutions are also featured.
Genetic testing and counseling can help determine cancer risk based on family history and genetic mutations. Most cancers are sporadic but 5-10% are hereditary due to inherited gene mutations. Genetic counselors use family histories and genetic tests to assess cancer risks, recommend screening, and provide counseling to relatives. While some cancers have clear high-risk genes, most have contributions from multiple common and rare variants, so interpretation requires expertise.
This document discusses microsatellite instability (MSI), which refers to changes in repeated sequences of DNA called microsatellites during DNA replication due to defects in the DNA mismatch repair system. The key mechanisms, detection methods, clinical significance and applications of MSI in various cancers are described. MSI is an important factor in tumor development and progression. Detection of MSI using techniques such as PCR and immunohistochemistry can aid in cancer diagnosis and predict response to immunotherapy. Cancers with high MSI (MSI-H) often respond well to immune checkpoint inhibitors.
Tumor markers are biomarkers found in blood, urine, or tissues that can indicate the presence of cancer when elevated. They can be produced directly by tumors or other cells in response to tumors. While tumor marker assays help with cancer staging and treatment, they are usually not definitive diagnostic tests and biopsy is required for diagnosis. Tumor markers include proteins, peptides, and carbohydrates and can be used for cancer screening, monitoring recurrence, diagnosis, staging, prognosis, evaluating treatment effectiveness, and as companion diagnostics. Commonly used tumor markers include alpha fetoprotein, CA15-3, CA27-29, CA19-9, and CA-125.
- Three major molecular assays have been developed for prognostic assessment of breast cancer: Oncotype DX, Mammaprint, and Prosigna.
- Oncotype DX uses a 21-gene signature to predict recurrence risk in ER+ breast cancer. Mammaprint uses a 70-gene signature and Prosigna uses the PAM50 intrinsic subtyping algorithm.
- Clinical trials have validated the use of these assays in lymph node positive and negative disease to predict chemotherapy benefit and guide treatment decisions. Ongoing research aims to further refine risk assessment and subclassify breast cancer.
This document discusses biomarkers in cancer detection and diagnosis. It defines biomarkers as molecules that indicate normal or abnormal biological processes and may signal diseases like cancer. Biomarkers can be found in tissues, blood, or other bodily fluids and include proteins, genes, RNA, carbohydrates, or viruses associated with certain cancers. Biomarkers are useful for early cancer detection, diagnosis, assessing prognosis, predicting treatment effectiveness, and identifying molecular drug targets. Several protein, DNA, and RNA biomarkers for cancers of the breast, ovary, prostate, bladder, oral cavity, colon, and HIV-associated cancers are discussed. Imaging techniques can also serve as cancer biomarkers by aiding screening, diagnosis, and monitoring treatment response.
Molecular methods such as polymerase chain reaction (PCR), real-time PCR, fragment analysis, high-resolution melting analysis, Sanger sequencing, pyrosequencing, and fluorescence in situ hybridization (FISH) are increasingly used in cancer care for diagnosis, prognosis, predicting therapy response, and monitoring minimal residual disease. These techniques detect various biomarkers including mutations, gene fusions, amplifications, and epigenetic changes from samples such as blood, tissue, and bone marrow. The molecular diagnostic tests must demonstrate high analytic validity, clinical validity, and utility to be clinically applicable.
Molecular classification breast carcinomassuser56f01e1
This document discusses the molecular classification of breast cancer and its role in patient management. It begins by explaining the need for molecular classification in diagnosis, prognosis, prediction, and management of breast cancer patients. It then covers various molecular alterations and genetic factors that contribute to breast cancer development, including growth factor receptors, signaling molecules, cell cycle regulators, and adhesion molecules. The major subtypes of breast cancer - luminal A/B, HER2-enriched, and basal-like - are identified based on expression of estrogen receptor, progesterone receptor, HER2, and Ki-67. Molecular classification is important for determining prognosis and guiding treatment decisions.
Not All Uterine Cancer is the Same: What to Know About Rare Uterine Cancersbkling
This document discusses rare types of uterine cancers and their treatment strategies. It begins by reviewing trends in uterine cancer in the US, noting that endometrioid cancers make up 80% of cases while rare high risk types like serous carcinoma account for 20%. It then discusses the different rare types in more detail like leiomyosarcomas, carcinosarcomas, and clear cell carcinomas. Molecular testing results and targeted therapies are explored. Treatment approaches for each rare type are provided, including chemotherapy regimens, radiation, immunotherapy, and targeted therapies. Clinical trials are encouraged. Overall survival benefits of immunotherapy and targeted therapies are shown for certain rare uterine cancer patients.
Tumor markers are substances found in blood, urine, or tissue that can indicate the presence of cancer. They include proteins, mutations, and DNA patterns from cancer cells. Ideal tumor markers are cancer-specific, correlate with tumor size, and predict recurrences before clinical detection. Common tumor markers include CEA for colorectal cancer, CA125 for ovarian cancer, PSA for prostate cancer, and HER2/neu for breast cancer response to targeted therapies. While tumor markers can help monitor cancer, they have limitations as cancer may not produce markers and benign conditions can elevate levels. Tumor marker tests alone cannot diagnose cancer.
Triple negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks estrogen receptors, progesterone receptors, and excess HER2 protein. It tends to be more common in younger women, Black women, and those with BRCA1 mutations. Diagnosis involves biopsy and testing for ER, PR, and HER2 biomarkers. Treatment typically involves chemotherapy since hormone therapies and HER2-targeted drugs are ineffective. New drugs like PARP inhibitors and immunotherapy are showing promise, with one PARP inhibitor recently approved to reduce the risk of death from early-stage HER2-negative breast cancer. While treatments are advancing, TNBC remains a difficult form of breast cancer to treat due to its resistance to many therapies.
This document summarizes a presentation on personalized medicine approaches for ovarian cancer patients. It discusses how inherited mutations, molecular abnormalities in tumors, and components in blood can be used to design personalized treatment plans. It provides examples of clinical trials targeting BRCA mutations, p53 pathways, folate receptors, and immunotherapy. While personalized medicine holds promise, challenges remain due to tumor heterogeneity, redundant pathways, and limitations of current methods like xenografts. Improved validation of genetic risk loci and minimizing toxicity are areas for future work.
Tumor markers are proteins or mutated proteins that can indicate the presence of cancer. They are useful for screening, diagnosis, monitoring treatment and detecting recurrence, though none are sufficiently sensitive and specific for screening alone. Tumor markers associated with cell proliferation, differentiation, metastasis and other tumor events can provide information about cancer. While not diagnostic, they are helpful for treatment monitoring given their limitations. Proper use requires understanding their sensitivity, specificity and potential causes of false positives.
There are a variety of tests that you may face during the process of your diagnosis which will likely affect your treatment decision making. Join this informative webinar where Scott Weissman, MS, CGC, will explain the difference between tumor and germline testing so that you can better understand the tests you receive and what they mean for you.
Breast Cancer Treatment: Where we are, Where we're going - April 24th, 2018Summit Health
This document summarizes a presentation on breast cancer treatment. It discusses:
1) The current state of breast cancer treatment including molecular classification, adjuvant therapies, neoadjuvant therapies, and treatments for metastatic disease.
2) Surgical options for breast cancer including lumpectomy, mastectomy, and breast reconstruction techniques.
3) Radiation therapy techniques including reducing heart dose using deep inspiration breath hold and shorter treatment schedules.
This document discusses the importance of cancer biomarkers for selecting effective targeted drug therapies. It provides examples of predictive biomarkers such as BCR-ABL for CML treated with tyrosine kinase inhibitors, EGFR mutations for NSCLC treated with EGFR inhibitors, and HER2 overexpression for breast cancer treated with trastuzumab. The use of predictive biomarkers can help personalize cancer treatment by identifying patients most likely to respond to a specific drug and avoid unnecessary toxicity for those who will not benefit.
Cellular and Molecular Tumor Markers by Prof. Mohamed Labib Salem, PhD (Lux...Prof. Mohamed Labib Salem
This document provides an overview of cellular and molecular tumor markers. It discusses what cancer and tumors are, different types of tumor markers including cellular markers, and applications of tumor markers such as detection, diagnosis and monitoring treatment response. Evaluation criteria for tumor markers like sensitivity and specificity are covered. Common tumor markers used for specific cancer types are listed. Methods for measuring tumor markers like ELISA, PCR, immunohistochemistry and mass spectrometry are described. Limitations of tumor markers are also noted.
Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 receptors. It represents 15% of breast cancers and has a higher sensitivity to chemotherapy than other subtypes. New targeted therapies are being developed and tested in clinical trials based on TNBC's defective DNA repair pathways. These include PARP inhibitors, platinum chemotherapy, and angiogenesis inhibitors. TNBC is a heterogeneous disease with multiple molecular subtypes, each with different treatment responses. Participation in clinical trials is important to advance new targeted therapies for TNBC.
This document provides an overview of cancer including:
- Cancer is caused by abnormal cell proliferation without control and the ability to invade other tissues. The cardinal features of cancer are growth, invasion and metastasis.
- Carcinogenesis is a multi-step process involving genetic changes like mutations in proto-oncogenes, tumor suppressor genes, genes regulating apoptosis and DNA repair.
- Environmental risk factors for cancer include tobacco, radiation, alcohol, bacteria/viruses, diet and obesity. Cancer etiology involves non-lethal genetic damage to proto-oncogenes and tumor suppressor genes from inherited or environmental factors.
- In breast cancer, adjuvant chemotherapy improves outcomes. Regimens include anthracyclines
Mike Janicek, MD, and Bradley J. Monk, MD, FACS, FACOG, prepared useful Practice Aids pertaining to DDR-mutant cancers and PARP inhibitors for this CME activity titled, "Targeting Pathogenic Mutations in the DNA Damage Response Pathway: Genetic Testing and Counseling in the Era of Precision Medicine and Next-Generation Sequencing." For the full presentation, complete CME information, and to apply for credit, please visit us at https://bit.ly/2T8MPzj. CME credit will be available until May 26, 2021.
Carcinoma of unknown primary (CUP) accounts for 3-5% of all cancers. It is defined as a biopsy-proven malignancy without an identified primary site despite extensive evaluation. The median overall survival is typically 9 months. However, certain favorable subsets have been identified including women with peritoneal carcinomatosis or axillary lymph node metastases, men with skeletal metastases and elevated PSA, and extragonadal germ cell tumor syndrome patients. Molecular tumor profiling and next-generation sequencing can help identify targets for personalized treatment. While most CUP patients receive empirical platinum-based chemotherapy, evolving treatment options include targeted therapies, immunotherapy, and stereotactic radiotherapy for limited metastases. Identifying the primary site
Report Back from SGO: What’s the Latest in Uterine Cancer?bkling
Dr. Jeannine Villella, Chief of Gynecologic Oncology at Lenox Hill Hospital, provides a comprehensive update from the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer. Dr. Villella breaks down what the research presented at the conference means for you and discusses new developments.
This document discusses treatment approaches for metastatic triple negative breast cancer. It notes that chemotherapy is currently the standard treatment but that the disease is heterogeneous. Several new targeted treatment approaches are discussed that are being explored in clinical trials, including PARP inhibitors targeting DNA repair, platinum agents, anti-androgens targeting the androgen receptor, immune checkpoint inhibitors, and antibody-drug conjugates. Ongoing research aims to improve outcomes by identifying biomarkers to match patients to effective targeted therapies.
1. Several molecular pathways are involved in breast cancer pathogenesis, including steroid hormone receptors, HER2/neu, cell cycle proteins, and growth factors.
2. Risk factors for breast cancer include increasing age, female gender, family history, genetic mutations, personal history of breast cancer or other breast diseases, reproductive factors, and hormone use.
3. High risk patients are identified using tools like the Gail model and managed through increased screening including breast self-exams, clinical exams, mammograms, and MRI. Preventive options include tamoxifen, raloxifen, and prophylactic surgeries.
This document discusses the role of surgery in preventing hereditary cancers. It describes several hereditary cancer syndromes where prophylactic surgery can significantly reduce cancer risk, including breast cancer associated with BRCA1/2 mutations and diffuse gastric cancer associated with CDH1 mutations. For these high-risk conditions, the document reviews cancer risks, genetic testing approaches, screening options, and evidence regarding risk-reducing surgeries such as mastectomy and gastrectomy. It provides guidance on identifying appropriate candidates and timing for preventive surgical interventions.
Rare cancers account for approximately 22% of all cancer diagnoses and 24% of all cancer cases. While individual rare cancers are individually rare, collectively they are not uncommon. Recent advances in genetic and genomic testing have enabled more precise diagnosis and targeting of treatments for rare cancers based on genetic abnormalities. However, rare cancers still face challenges including a lack of information and support organizations, limited clinical trials and reimbursement options, and difficulties in drug development and regulatory approval due to small patient populations.
Similar to Molecular diagnosis in breast cancer (20)
This document discusses post-mastectomy breast reconstruction options. It begins with an overview of surgical options for breast cancer treatment, including breast-conserving therapy and mastectomy. It then discusses the reasons for and goals of breast reconstruction. The document outlines the anatomy of the breast and techniques for immediate and delayed breast reconstruction using implants, pedicled flaps like latissimus dorsi flaps and TRAM flaps, and free flaps like DIEP flaps. It also discusses nipple-areolar complex reconstruction and procedures to achieve symmetry in the contralateral breast.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
2. • Molecular pathology techniques used commonly in hematological
malignancies and soft tissue sarcomas
• Paradigm shift in classification : Histopathological molecular
• Among epithelial malignancies breast cancer is most extensively
studied
• Led to the concept that breast cancer is a heterogenous disease
3. Molecular classification
• Research by Stanford group classified breast cancer into four subtypes
• Luminal A
• Luminal B
• HER 2 enriched
• Basal like
• Different biological and clinical behaviour and response to therapy
4. • ER positive group :
• Luminal A( ER/PR +ve, Ki67 <14%)
•
• Luminal B ( ER/PR +ve, Ki67 >14%)
• Prognosis of luminal B worse than luminal A
5. • ER negative group :
• Her 2 enriched group : high level of her2
• Basal like : ER/PR/Her -ve, express basal cytokeratins
• Claudin –low tumors : epithelial to mesenchymal transition
• Molecular apocrine subgroup : increased androgen signalling and molecular
apocrine gene profile
6. • Triple Negative Breast Cancer
• ER/PR/Her and CK –ve
• 7 distinct molecular subtypes
• Basal-like 1(BL1), basal-like 2 (BL2), mesenchymal (M), mesenchymal stem-like (MSL),
immunomodulatory (IM), luminal androgen receptor(LAR), and unstable subgroups
• Different TNBC subgroups have different response to NACT
• Rate of pathological complete response(pCR) is better for BL1 comparatively
7. Prognostic gene signatures
• To identify patients who will benefit from adjuvant chemotherapy
• 1st Generation : Oncotype Dx and Mammaprint
• Better predictive power for early recurrences
• 2nd Generation : Prosigna/ Endopredict/ Breast Cancer Index
• Can predict both early and late recurrences
• Restricted to ER positive cancers, ER negative cases considered ‘high risk’
• Tests can be performed on formalin-fixed paraffin-embedded (FFPE)
samples
8. • Oncotype Dx
• RT- PCR assay, evaluates expression of
21 genes (16+5)
• Computes recurrence score from 0-
100 , low risk ( <18), intermediate risk
(18-30), high risk (>31)
• Validated by TAILORx study
• Benefit of addition of chemotherapy
to ER +ve, Her –ve, node –ve patients
treated with tamoxifen
9. • Mammaprint
• DNA microarray based test
• Evaluates expression of 70 genes
• Validated by MINDACT trial
• For patients < 61 yrs of age, with
stage 1/2 ER +ve, node –ve
breast cancer
10. • Prosigna
• RT-PCR based assay , using Nanostring technology
• Evaluates 50 genes
• Computes risk of recurrence (ROR) at 10 years
• Used in post menopausal women, Stage 1/2 , ER +ve on AI
• Endopredict
• RT-PCR
• Evaluates 8 cancer related genes
• Can be combined with tumor size and nodal status to give comprehensive risk
score Epclin
• Validated by ABCSG -6 trial
11. • Breast Cancer Index
• RT-PCR based
• Quantifies expression ratio of HOXB13 and IL17BR
• Integrated with Molecular Grade Index (MGI)
• Validated by Stockholm trial
• 8th edition of AJCC recommended to include Oncotype Dx in staging
patients with ER +ve, HER 2 –ve cancers
12. In situ hybridization (ISH)
• It’s a molecular technique that allows visualization of genes on a glass
slide
• Combines molecular genetics with traditional pathology
• Three methods of ISH
• Flourescent in situ hybridization (FISH)
• Chromogenic in situ hybridization (CISH)
• Silver in situ hybridization (SISH)
13. • In diagnostic breast pathology it enables
• HER 2 amplification
• Predicts response to anti HER 2 therapy and Chemotherapy in adjuvant, neoadjuvant
and metastatic settings
• FGFR1 amplification
• Predicts response to FGFR1 tyrosine kinase inhibitors
• Detection of fusion genes in rare histologic types
• MYB/MYBL1 amplification in Breast Adenoid cystic carcinoma
14. HER2 assesment
• HER2 , member of human epidermal growth factor
• Expressed in 15-20% of breast cancers
• Evolution of targeted therapy
• Trastuzumab/ pertuzumab : humanized monoclonal anti – HER2 antibody
• Lapatinib : HER2 tyrosine kinase inhibitor
• Trastuzumab Emtansine (T-DM1) : Drug delivery system
15. • ASCO/CAP guideline 2013
recommend
• Immunohistochemistry followed by
In situ hybridization in equivocal
cases
• Trastuzumab given to IHC 3+ and /or
ISH positive
16. • ‘HER2 double equivocal’ cancers are typically ER +ve and defined as
luminal B-like ( show high Ki67 indices)
• Oncologist may consider offering anti HER2 therapy based on patients
performance status and wish
• Caution :
• Residual carcinomas following taxane based chemotherapy may present giant
syncytial multinucleated looking cells harbouring abnormally high HER2
signals
• But HER2/CEP 17 ratio is normal
17. • Also , only a proportion of HER2 positive cases respond to anti HER2
therapy
• Most show progression within 1 year
• 15% patients receiving adjuvant therapy develop metastasis
• 50% patients receiving neoadjuvant therapy have residual diease following
treatment
18. Familial Breast Cancer
• Hereditary breast cancer < 10 % of all
• Half contain BRCA1 or BRCA2 mutations (tumor suppressor)
• BRCA1 : high grade features on histology
• Grade 3
• ductal NST
• medullary or atypical medullary
• pushing borders
• lymphocytic infiltrates
• Necrosis
• 80% are ER/PR/Her –ve , express basal markers ( CK5/6, p-cadherins, EGFR)
• BRCA testing should be offered to patients with above features
19. • BRCA2 have high grade features but are frequently ER +ve
• Inactivation of BRCA1 or BRCA2 leads to deficiency in homologous
recombination repair of DNA double-strand breaks and inter-strand
crosslinks
• More sensitive to cross linking agents (platinum salts) than spindle poisons
• Sensitive to PARP enzyme inhibitors ( block base excision repair pathway ) :
OLAPARIB
20. • BRCAness :
• tumours that have not arisen from a germline BRCA1 or BRCA2 mutation but
share certain molecular features, in particular a homologous recombination
defect
• TNBC
• Sensitive to PARP inhibitors
21. • PALB2 : partner and localizer of BRCA2
• Tumor suppressor
• 35% risk of breast cancer by age 70
• Increased susceptibility to PARP inhibitors
22.
23.
24. Intratumoral heterogeneity and liquid biosy
• Tumours are composed of multiple clones with distinct genetic alterations
• May result in the emergence of resistant cell populations upon therapeutic
pressure
• Metastatic outgrowths might stem from a minor cell subpopulation of the
primary tumour
• Traditional approaches in which DNA from the bulk of the tumour is
sequenced, do not have the power to detect minor subclones
25. • Liquid Biopsy : study of circulating tumor free DNA (cfDNA) and circulating
tumor cells (CTC)
• Can detect mutations present in metastatic foci and absent in primary
tumor
• ESR1 mutations : mediate resistance to oestrogen deprivation
• Found in higher frequency in metastatic breast cancer
• SoFEA trial : patients with ESR1 mutation showed better response to
fulvestrant (SERD) than exemestane (AI)
26. • cfDNA analysis can detect somatic reversion mutations in BRCA1 and
BRCA2 carriers with metastatic breast cancer treated with platinum
and/or PARP inhibitors
• Liquid biopsy can guide therapy in both early and metastatic breast
cancere.
27. References
• DeVita : principles of oncology (10th ed)
• Molecular diagnosis in breast cancer : F Pareja, C marchio