The document summarizes key topics discussed at a journal club meeting for medical oncology residents. It includes questions about prognostic factors in breast cancer, genomic analysis technologies for determining breast cancer risk and chemotherapy regimens, and hormonal therapies for ER-positive breast cancers. It also summarizes several research studies and guidelines on intrinsic breast cancer subtypes, prognostic and predictive factors for determining adjuvant systemic therapies, and the Oncotype DX recurrence score assay.
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
Tumour Markers are substances present in the tumour, produced by the tumour or by the host as a response to the presence of the tumour, providing information about biological characteristics of the tumour. these tumour markers may specific for the tissue but often get elevated in neoplastic as well non-neoplastic lesions, further Various analytical platforms available for serum tumour markers lack standardisation. These factors add to interpretative challenges in serum tumour markers
This document discusses immunohistochemistry (IHC), which is used to identify tissue antigens through antigen-antibody interactions. It provides details on the IHC process, common antibodies and their targets, and tumor markers. IHC is useful for tumor diagnosis, narrowing differential diagnoses, and detecting unexpected diagnoses. The antibody panels discussed can help determine the primary site of cancers and differentiate between tumor types.
Tumor markers are biochemical indicators of cancer that can be detected in higher than normal amounts in blood, urine, or tissues of some cancer patients. They are produced by tumors or the body's response to tumors, and can help support cancer diagnosis, determine response to treatment, and provide prognosis information. However, tumor marker levels have limitations due to lack of specificity or sensitivity. Common tumor markers include PSA for prostate cancer, CA125 for ovarian cancer, AFP for liver cancer, and CEA for gastrointestinal cancers.
This document discusses the use of immunohistochemistry in breast pathology. It covers several topics:
1. Analyzing prognostic markers like hormone receptors in breast cancer and their predictive value.
2. Using myoepithelial cell markers to help solve diagnostic dilemmas and distinguish lesions.
3. Identifying tumor subtypes and assessing diagnoses using markers like luminal vs basal.
4. Evaluating cell populations in proliferative breast lesions and assessing neoplasia vs hyperplasia.
The document discusses four major clinical trials investigating the use of Herceptin (trastuzumab) in the adjuvant setting for HER2-positive breast cancer: HERA, NSABP B-31, Intergroup N9831, and BCIRG 006. The HERA trial is randomly assigning over 3,000 patients to 1 or 2 years of Herceptin or observation after standard adjuvant therapy. The other trials are comparing Herceptin-containing regimens to standard chemotherapy alone. The goals are to establish Herceptin's efficacy, safety, and optimal duration in early-stage disease.
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.
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.
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
Tumour Markers are substances present in the tumour, produced by the tumour or by the host as a response to the presence of the tumour, providing information about biological characteristics of the tumour. these tumour markers may specific for the tissue but often get elevated in neoplastic as well non-neoplastic lesions, further Various analytical platforms available for serum tumour markers lack standardisation. These factors add to interpretative challenges in serum tumour markers
This document discusses immunohistochemistry (IHC), which is used to identify tissue antigens through antigen-antibody interactions. It provides details on the IHC process, common antibodies and their targets, and tumor markers. IHC is useful for tumor diagnosis, narrowing differential diagnoses, and detecting unexpected diagnoses. The antibody panels discussed can help determine the primary site of cancers and differentiate between tumor types.
Tumor markers are biochemical indicators of cancer that can be detected in higher than normal amounts in blood, urine, or tissues of some cancer patients. They are produced by tumors or the body's response to tumors, and can help support cancer diagnosis, determine response to treatment, and provide prognosis information. However, tumor marker levels have limitations due to lack of specificity or sensitivity. Common tumor markers include PSA for prostate cancer, CA125 for ovarian cancer, AFP for liver cancer, and CEA for gastrointestinal cancers.
This document discusses the use of immunohistochemistry in breast pathology. It covers several topics:
1. Analyzing prognostic markers like hormone receptors in breast cancer and their predictive value.
2. Using myoepithelial cell markers to help solve diagnostic dilemmas and distinguish lesions.
3. Identifying tumor subtypes and assessing diagnoses using markers like luminal vs basal.
4. Evaluating cell populations in proliferative breast lesions and assessing neoplasia vs hyperplasia.
The document discusses four major clinical trials investigating the use of Herceptin (trastuzumab) in the adjuvant setting for HER2-positive breast cancer: HERA, NSABP B-31, Intergroup N9831, and BCIRG 006. The HERA trial is randomly assigning over 3,000 patients to 1 or 2 years of Herceptin or observation after standard adjuvant therapy. The other trials are comparing Herceptin-containing regimens to standard chemotherapy alone. The goals are to establish Herceptin's efficacy, safety, and optimal duration in early-stage disease.
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.
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.
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 is a powerpoint presentation of Immunohistochemistry of lesions of prostate. This presentation will be helpful for postgraduate pathology students and practitioners alike. We are also on youtube. Please visit our channel at https://www.youtube.com/channel/UCwjkzK-YnJ-ra4HMOqq3Fkw
- 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.
Tumor markers can play roles in early detection, diagnosis, prognosis, monitoring treatment response, and detecting recurrence of certain cancers. This document discusses various tumor markers including their reference ranges, associated cancers, clinical applications, and methods of detection. Key points covered include the roles of AFP for liver cancer screening, CEA and CA19-9 for colorectal cancer monitoring, PSA for prostate cancer screening and follow up, and CA125 for ovarian cancer treatment assessment and recurrence detection. The document also provides recommendations for optimal use of tumor marker tests.
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.
This document discusses the Gleason grading system for prostate cancer. It provides details on the original Gleason patterns from 1 to 5 based on tumor architecture, with pattern 1 being the most differentiated and pattern 5 being undifferentiated. The Gleason score is determined by adding the primary and secondary patterns. The document reviews reporting of Gleason scores for different specimen types like biopsies and radical prostatectomies. It also discusses modifications to the Gleason system over time with new discoveries in prostate cancer.
Audio and slides for this presentation are also available on YouTube: http://youtu.be/ukXhuy5cXrE
Huma Q. Rana, MD, a cancer geneticist with Dana-Farber Cancer Institute, explains the cancer risk associated with BRCA1 and BRCA2 gene mutations. This presentation was originally given on July 23, 2013 as part of the "What Every Woman Should Know" event put on by Dana-Farber's Susan F. Smith Center for Women's Cancers.
Small round cell tumors are a group of highly aggressive cancers composed of small, undifferentiated cells. The diagnostic approach involves clinical findings, imaging, pathology, and molecular genetics testing. Key small round cell tumors in pediatric patients include Ewing sarcoma, neuroblastoma, nephroblastoma, rhabdomyosarcoma, medulloblastoma, retinoblastoma, and lymphoblastic lymphoma. Immunohistochemistry and genetic testing are used to determine the specific tumor type to help guide treatment.
Breast cancer is caused by heterogeneous tumor cells whose behavior depends on biological features. Molecular subtyping through gene expression profiling can classify tumor types, recognize hereditary implications, identify appropriate therapies, determine prognosis, and avoid unnecessary treatment. The major subtypes are luminal A/B, HER2-enriched, and basal-like, which differ in gene expression, sensitivity to therapies, and clinical outcomes. Understanding the molecular biology of breast cancer is crucial for precision medicine approaches to management.
This document discusses hormonal therapy for breast cancer. It notes that around 60-70% of breast cancer patients are estrogen receptor positive. Estrogen receptor positive tumors have a better survival rate than estrogen receptor negative tumors. The document discusses the molecular basis of estrogen receptor signaling and the genomic and non-genomic mechanisms of estrogen action. It describes the different types of hormonal therapies used in breast cancer including selective estrogen receptor modulators, aromatase inhibitors, antiestrogens, LHRH agonists, and progestins. It discusses the application of hormonal therapy in the adjuvant setting for premenopausal and postmenopausal patients.
1) Tumors exist within a complex microenvironment consisting of various cell types that influence tumor growth, progression, and metastasis.
2) Chronic inflammation can promote tumor development by increasing genetic mutations while also stimulating angiogenesis and tumor cell proliferation.
3) The tumor microenvironment interacts bidirectionally with cancer cells to encourage processes like angiogenesis, immune suppression, invasion, and metastasis through factors such as TGF-β, VEGF, and cytokines.
4) Therapies targeting the tumor microenvironment can impact its composition and make cancer cells more invasive, highlighting the need for combination treatments.
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 background information on microsatellite instability (MSI). It discusses how microsatellites are short repetitive sequences prone to mutations during DNA replication due to slipped strand mispairing or unequal crossing over. MSI occurs when mutations inactivate DNA mismatch repair genes, leading to length alterations in microsatellite regions. This causes microsatellite instability, which is seen in certain cancers like colorectal cancer and can be assessed through testing tumor DNA for instability in microsatellite markers. Immunohistochemistry for mismatch repair proteins or direct testing for MSI can help identify tumors associated with defective mismatch repair and microsatellite instability.
Tumor markers are substances produced by cancer cells or other cells in response to cancer that can be detected in bodily fluids or tissues. The ideal tumor marker would be highly sensitive and specific to a cancer, produced early in cancer progression, and correlated with tumor burden. Common tumor markers include AFP for liver and germ cell cancers, CEA for gastrointestinal cancers, PSA for prostate cancer, CA125 for ovarian cancer, and calcitonin for thyroid cancer. Tumor markers have applications in cancer screening, diagnosis, staging, determining prognosis, monitoring treatment response, and detecting recurrence.
This document provides guidelines for the management of endometrial cancer from several European medical societies. It covers epidemiology, risk assessment, surgery, lymph node staging, adjuvant therapy, and management of early, advanced, and recurrent disease. Key points include recommending total hysterectomy and bilateral salpingo-oophorectomy for staging without vaginal cuff resection for early-stage disease. It also supports consideration of sentinel lymph node biopsy for staging in select cases and ovarian preservation in certain low-risk premenopausal patients. Molecular testing is encouraged to further stratify prognosis, especially in high-grade tumors.
The document discusses the EGFR pathway in colorectal cancer. It notes that EGFR is overexpressed in 25-82% of colorectal cancers and is involved in cell proliferation pathways. While EGFR overexpression is sometimes associated with worse outcomes, the significance is unclear due to inconsistent measurement methods. Anti-EGFR therapies like cetuximab show promise for colorectal cancer, but EGFR expression levels alone do not predict response to treatment. EGFR gene amplification analysis is also an uncertain prognostic indicator due to varying definitions and guidelines. Overall the role of EGFR in colorectal cancer requires further standardized research.
The document discusses new drug developments in subsets of breast cancer. It describes how breast cancer is being segmented into rare molecular subtypes defined by specific molecular alterations. This molecular segmentation is important for optimally developing targeted agents by enriching clinical trials for patients with the relevant molecular alteration. Several new drugs for treating specific breast cancer subtypes are mentioned, including drugs targeting HER2, angiogenesis, hormone receptors, and DNA repair pathways in triple negative 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 is a powerpoint presentation of Immunohistochemistry of lesions of prostate. This presentation will be helpful for postgraduate pathology students and practitioners alike. We are also on youtube. Please visit our channel at https://www.youtube.com/channel/UCwjkzK-YnJ-ra4HMOqq3Fkw
- 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.
Tumor markers can play roles in early detection, diagnosis, prognosis, monitoring treatment response, and detecting recurrence of certain cancers. This document discusses various tumor markers including their reference ranges, associated cancers, clinical applications, and methods of detection. Key points covered include the roles of AFP for liver cancer screening, CEA and CA19-9 for colorectal cancer monitoring, PSA for prostate cancer screening and follow up, and CA125 for ovarian cancer treatment assessment and recurrence detection. The document also provides recommendations for optimal use of tumor marker tests.
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.
This document discusses the Gleason grading system for prostate cancer. It provides details on the original Gleason patterns from 1 to 5 based on tumor architecture, with pattern 1 being the most differentiated and pattern 5 being undifferentiated. The Gleason score is determined by adding the primary and secondary patterns. The document reviews reporting of Gleason scores for different specimen types like biopsies and radical prostatectomies. It also discusses modifications to the Gleason system over time with new discoveries in prostate cancer.
Audio and slides for this presentation are also available on YouTube: http://youtu.be/ukXhuy5cXrE
Huma Q. Rana, MD, a cancer geneticist with Dana-Farber Cancer Institute, explains the cancer risk associated with BRCA1 and BRCA2 gene mutations. This presentation was originally given on July 23, 2013 as part of the "What Every Woman Should Know" event put on by Dana-Farber's Susan F. Smith Center for Women's Cancers.
Small round cell tumors are a group of highly aggressive cancers composed of small, undifferentiated cells. The diagnostic approach involves clinical findings, imaging, pathology, and molecular genetics testing. Key small round cell tumors in pediatric patients include Ewing sarcoma, neuroblastoma, nephroblastoma, rhabdomyosarcoma, medulloblastoma, retinoblastoma, and lymphoblastic lymphoma. Immunohistochemistry and genetic testing are used to determine the specific tumor type to help guide treatment.
Breast cancer is caused by heterogeneous tumor cells whose behavior depends on biological features. Molecular subtyping through gene expression profiling can classify tumor types, recognize hereditary implications, identify appropriate therapies, determine prognosis, and avoid unnecessary treatment. The major subtypes are luminal A/B, HER2-enriched, and basal-like, which differ in gene expression, sensitivity to therapies, and clinical outcomes. Understanding the molecular biology of breast cancer is crucial for precision medicine approaches to management.
This document discusses hormonal therapy for breast cancer. It notes that around 60-70% of breast cancer patients are estrogen receptor positive. Estrogen receptor positive tumors have a better survival rate than estrogen receptor negative tumors. The document discusses the molecular basis of estrogen receptor signaling and the genomic and non-genomic mechanisms of estrogen action. It describes the different types of hormonal therapies used in breast cancer including selective estrogen receptor modulators, aromatase inhibitors, antiestrogens, LHRH agonists, and progestins. It discusses the application of hormonal therapy in the adjuvant setting for premenopausal and postmenopausal patients.
1) Tumors exist within a complex microenvironment consisting of various cell types that influence tumor growth, progression, and metastasis.
2) Chronic inflammation can promote tumor development by increasing genetic mutations while also stimulating angiogenesis and tumor cell proliferation.
3) The tumor microenvironment interacts bidirectionally with cancer cells to encourage processes like angiogenesis, immune suppression, invasion, and metastasis through factors such as TGF-β, VEGF, and cytokines.
4) Therapies targeting the tumor microenvironment can impact its composition and make cancer cells more invasive, highlighting the need for combination treatments.
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 background information on microsatellite instability (MSI). It discusses how microsatellites are short repetitive sequences prone to mutations during DNA replication due to slipped strand mispairing or unequal crossing over. MSI occurs when mutations inactivate DNA mismatch repair genes, leading to length alterations in microsatellite regions. This causes microsatellite instability, which is seen in certain cancers like colorectal cancer and can be assessed through testing tumor DNA for instability in microsatellite markers. Immunohistochemistry for mismatch repair proteins or direct testing for MSI can help identify tumors associated with defective mismatch repair and microsatellite instability.
Tumor markers are substances produced by cancer cells or other cells in response to cancer that can be detected in bodily fluids or tissues. The ideal tumor marker would be highly sensitive and specific to a cancer, produced early in cancer progression, and correlated with tumor burden. Common tumor markers include AFP for liver and germ cell cancers, CEA for gastrointestinal cancers, PSA for prostate cancer, CA125 for ovarian cancer, and calcitonin for thyroid cancer. Tumor markers have applications in cancer screening, diagnosis, staging, determining prognosis, monitoring treatment response, and detecting recurrence.
This document provides guidelines for the management of endometrial cancer from several European medical societies. It covers epidemiology, risk assessment, surgery, lymph node staging, adjuvant therapy, and management of early, advanced, and recurrent disease. Key points include recommending total hysterectomy and bilateral salpingo-oophorectomy for staging without vaginal cuff resection for early-stage disease. It also supports consideration of sentinel lymph node biopsy for staging in select cases and ovarian preservation in certain low-risk premenopausal patients. Molecular testing is encouraged to further stratify prognosis, especially in high-grade tumors.
The document discusses the EGFR pathway in colorectal cancer. It notes that EGFR is overexpressed in 25-82% of colorectal cancers and is involved in cell proliferation pathways. While EGFR overexpression is sometimes associated with worse outcomes, the significance is unclear due to inconsistent measurement methods. Anti-EGFR therapies like cetuximab show promise for colorectal cancer, but EGFR expression levels alone do not predict response to treatment. EGFR gene amplification analysis is also an uncertain prognostic indicator due to varying definitions and guidelines. Overall the role of EGFR in colorectal cancer requires further standardized research.
The document discusses new drug developments in subsets of breast cancer. It describes how breast cancer is being segmented into rare molecular subtypes defined by specific molecular alterations. This molecular segmentation is important for optimally developing targeted agents by enriching clinical trials for patients with the relevant molecular alteration. Several new drugs for treating specific breast cancer subtypes are mentioned, including drugs targeting HER2, angiogenesis, hormone receptors, and DNA repair pathways in triple negative breast cancer.
The document discusses new drug developments in subsets of breast cancer. It describes how breast cancer is being segmented into rare molecular subtypes defined by specific molecular alterations. This molecular segmentation is important for optimally developing targeted agents by enriching clinical trials for patients with the relevant molecular alteration. Several new drugs for treating specific breast cancer subtypes are discussed, including drugs targeting HER2, angiogenesis, hormone receptors, and DNA repair pathways in triple negative breast cancer.
This document discusses individual prognosis and predictive biomarkers in breast cancer. It covers classical prognostic factors like age, grade, histological subtypes, hormone receptor status, Ki67, and more. It also discusses intrinsic subtypes defined by gene expression profiling that can be translated to immunohistochemistry. Several gene expression signatures are mentioned, including MammaPrint, OncotypeDX, EndoPredict, and Prosigna, which provide prognostic and predictive information. Accurate pathology testing is essential for treatment decisions, and gene signatures may increase confidence, though some cases will still be challenging.
1) Triple negative breast cancer (TNBC) lacks expression of estrogen receptor, progesterone receptor, and HER2, making targeted therapy difficult.
2) Researchers are working to identify molecular targets in TNBC to develop new targeted therapies through preclinical studies and clinical trials.
3) New potential targets being studied in clinical trials include BRCA mutations, EGFR, AR, SRC kinases, and nuclear receptors. Identification of targets what TNBC "does have" offers hope for improved treatments.
This document summarizes several studies on immunotherapy for ovarian cancer. It finds that the presence of tumor infiltrating lymphocytes (TILs) predicts better prognosis. Anti-PD-1/PD-L1 therapies such as nivolumab, pembrolizumab, and avelumab have shown response rates of 11.5-17% in ovarian cancer. Combining PARP inhibitors with immunotherapy may increase response rates to 45% in patients with BRCA mutations. Ongoing studies are combining anti-angiogenic therapies like bevacizumab with immunotherapies and exploring these combinations as adjuvant therapies or in platinum-resistant disease.
This document summarizes systemic treatment approaches for breast cancer, including chemotherapy, hormonal therapy, targeted therapy, and bisphosphonates. It discusses neoadjuvant and adjuvant treatment given before or after surgery to cure cancer or kill remaining micrometastases, as well as palliative treatment for metastatic disease aimed at prolonging survival and controlling symptoms. Key points covered include common drugs and regimens, treatment according to risk level, and adjuvant trials supporting targeted therapies like trastuzumab.
1) The document discusses a symposium on trastuzumab in early breast cancer treatment.
2) Trastuzumab requires HER2 overexpression for efficacy and is associated with improved overall survival when used in the adjuvant setting for breast cancers that overexpress HER2.
3) The symposium included a question and answer session on the appropriate use and efficacy of trastuzumab in breast cancer treatment.
This document discusses personalized cancer therapy for ovarian cancer. It summarizes that high grade serous ovarian cancer (HGSOC) is the most common and aggressive form of ovarian cancer. HGSOC often has defects in the BRCA1/2 pathway involved in DNA repair. This makes HGSOC sensitive to PARP inhibitors, which have been FDA approved. The document also discusses developing biomarkers like the homologous recombination deficiency (HRD) score to predict which patients will respond to PARP inhibitors based on their tumor's DNA repair capabilities. Combination therapies targeting multiple pathways like the PI3K and PARP pathways are presented as a strategy to overcome resistance to targeted therapies.
This document discusses epidermal growth factor receptor (EGFR) inhibitors for the treatment of non-small cell lung cancer. It provides background on EGFR expression in various cancers and the role of EGFR in tumor growth. It describes various EGFR inhibitors including cetuximab, gefitinib and erlotinib. It summarizes several clinical trials that evaluated these drugs as monotherapy or in combination with chemotherapy. It discusses ongoing research questions around patient selection, combination/sequencing of therapies, and use of EGFR inhibitors in other cancer types.
PROGNOSTIC AND PREDICTIVE FACTORS FOR METASTATIC CARCINOMA BREASTDrAnkitaPatel
This document discusses various prognostic and predictive factors in breast cancer. It is divided into three categories:
Category I factors that are proven to be prognostically important and useful in clinical management, including tumor size, lymph node status, histological grade, and hormone receptor status.
Category II factors that are extensively studied biologically but require further validation, such as HER2 status, p53 mutation, and lymphovascular invasion.
Category III factors that are not sufficiently studied to demonstrate prognostic value, including tumor angiogenesis and EGFR. Various biomarkers and assays used to evaluate these factors are also described.
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.
Prognostic & predictive factors of breast cancerMohammed Fathy
1) Prognostic factors provide information about a patient's outcome without treatment, while predictive factors provide information about how a patient may respond to a specific treatment.
2) Many clinical factors, pathological features, tissue markers, and genomic expression profiles can provide prognostic and predictive information for breast cancer patients.
3) Key prognostic factors include age, tumor stage, tumor size, nodal involvement, histological grade, hormone receptor status, and intrinsic subtypes. Predictive factors include hormone receptor and HER2 status.
This document discusses predictive factors for the effects of adjuvant systemic treatments in breast cancer. It mentions that hormonal receptor status and HER2 status are useful predictive factors, but explain only part of the variability in treatment responses. It also discusses genomic signatures as promising predictive tools, but notes they require further validation before clinical application. Overall, the document examines current predictive markers and new areas of research into personalized treatment approaches using multi-gene profiles.
Adjuvant Systemic Therapy | Lunch and Learn - Dec 2014 | Dr. Caroline LohrischCBCFBCYukon
Dr. Lohrisch's research presentation is about a multi-disciplinary approach to treatment therapies that will assist oncologists in choosing the right treatment, for the right woman, for the right disease.
Learn more about her research http://ow.ly/Fzfdt
Acquired Disorders of Spermatogenesis By Paul J. Turek MD, Emeritus Professor...The Turek Clinics
Lecture on Acquired Disorders of Spermatogenesis written and presented by Paul J. Turek MD, Emeritus Professor and Endowed Chair in Urology Education, Department of Urology, University of California San Francisco and current Director of the The Turek Clinic, in San Francisco, California.
Correlation of Her-2 neu over-expression with clinico pathological features o...Apollo Hospitals
The classical clinico pathological features such as tumour
size, axillary node status, histological type and grade have a
well-established prognostic role in breast cancer.
Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinibseayat1103
This document discusses a clinical trial comparing the efficacy of erlotinib and gefitinib for the treatment of non-small cell lung cancer. The trial found that both erlotinib and gefitinib showed efficacy in NSCLC patients with EGFR mutations, with erlotinib demonstrating a median progression-free survival of 10.8 months compared to 5.4 months for standard chemotherapy in EGFR mutation-positive patients. Subsequent studies confirmed the superior efficacy of both erlotinib and gefitinib in NSCLC patients with EGFR mutations, particularly those with exon 19 deletions or L858R mutations. The document concludes by discussing the current NCCN guidelines for use of erlotinib and
This document discusses personalized medicine in the Czech Republic and the BIOMEDREG project. It provides background on Palacky University in Olomouc, Czech Republic and its role in molecular and translational medicine. It then discusses the history and current state of personalized medicine in oncology in the Czech Republic, including predictive cancer biomarkers routinely used in clinical practice and specialized molecular diagnostic laboratories. Finally, it introduces the BIOMEDREG project as a new research platform for advancing personalized medicine through molecular diagnostics, clinical registries, and predictive modeling.
Tumor markers are biological substances released by tumor cells or the body in response to tumors. They can be detected in bodily fluids and indicate the presence or progression of cancer. While no single tumor marker is perfect, they can be useful for screening, diagnosis, staging, prognosis, monitoring treatment response, and detecting recurrence. Common tumor markers include CEA, AFP, CA19-9, PSA, CA125, and hormone receptors. A variety of detection methods exist. While beneficial, tumor markers also have limitations like elevated levels in benign conditions and lack of presence in some cancer types. Continual research aims to improve tumor marker tests and discover new markers.
This document discusses recent updates in lung cancer. It begins by noting that lung cancer is the leading cause of cancer death in the US and is often diagnosed at an advanced stage. Screening with low-dose CT scans can detect lung cancer earlier and has been shown to decrease lung cancer mortality by 20% compared to chest x-rays. The National Lung Screening Trial established low-dose CT screening as an effective screening method for those at high risk. Biomarker testing is important to identify driver mutations and guide targeted therapy options, though barriers like tissue availability and turnaround time exist. Osimertinib has demonstrated superior progression-free survival compared to earlier EGFR TKIs for patients with EGFR-mut
This document discusses biomarkers in cancer immunotherapy. It begins by defining an immuno-biomarker as a measurable indicator of the immune system's response to cancer or its treatment. Biomarkers can be used to predict response, resistance, toxicity, and hyperprogression to immunotherapy. Popular biomarkers discussed include PD-L1 expression, tumor mutational burden (TMB), and T-cell receptor (TCR) repertoire. The predictive value of these biomarkers is explored for various cancer types. Limitations and heterogeneity of PD-L1 expression are also noted. The document examines ongoing efforts to standardize the measurement and clinical application of biomarkers to optimize immunotherapy.
This document provides a pathology report for a 34-year-old female patient. It summarizes the findings from biopsies of the right and left breast. For the right breast, it finds an invasive ductal carcinoma measuring 1.5 x 1.3 x 1 cm. Three of 39 lymph nodes from the right axilla showed metastatic carcinoma. The left breast tissue showed benign findings with no evidence of malignancy. The conclusion is infiltrating ductal carcinoma of the right breast with metastasis to 3 lymph nodes, classified as T1c/N1a.
The document discusses several antibody-drug conjugates (ADCs) that are being studied or developed for the treatment of non-small cell lung cancer (NSCLC). It summarizes clinical trial results of trastuzumab emtansine and trastuzumab deruxtecan for HER2-positive NSCLC, and sacituzumab govitecan and datopotamab deruxtecan for Trop-2 positive NSCLC. It also briefly mentions ADCs in development that target HER3, c-MET, CEACAM5, Axl, PTK7, NaPi2b, and Nectin-4 for lung cancer. The document concludes by reviewing a phase 1 clinical trial of
Indian women are more likely to have certain types of cancer according to Dr. R. Rajkumar. Over the last 25 years, large cancer trials have led to better outcomes for patients. Current research focuses on understanding cancer genes and cell growth to develop more targeted individualized treatments.
This document discusses treatment options for triple negative breast cancer (TNBC). It begins with a case study of a 56-year-old female patient diagnosed with TNBC. It then provides details on the characteristics and subtypes of TNBC, noting that it is an aggressive disease with poor prognosis. Current treatment approaches for metastatic TNBC are discussed, including sequential single-agent chemotherapy with taxanes, anthracyclines, antimetabolites, and platinum agents. Several key clinical trials comparing different chemotherapy regimens for TNBC are summarized, such as the TNT trial comparing carboplatin and docetaxel, and the TNACITY trial evaluating nab-paclitaxel plus carboplatin
This document provides guidelines for the management of gestational trophoblastic neoplasia (GTN). It outlines recommendations for initial treatment, monitoring, diagnosis of persistent postmolar GTN, and treatment approaches depending on the risk level and response. For low-risk GTN, single-agent chemotherapy such as methotrexate or dactinomycin is recommended. For high-risk or relapsed GTN, more intensive regimens including EMA/CO are used. Treatment is monitored closely with hCG assays and adjusted based on the tumor response.
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Pictorial and detailed description of patellar instability with sign and symptoms and how to diagnose , what investigations you should go with and how to approach with treatment options . I have presented this slide in my 2nd year junior residency in orthopedics at LLRM medical college Meerut and got good reviews for it
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Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga
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Osvaldo Bernardo Muchanga
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How to Control Your Asthma Tips by gokuldas hospital.
Er pos and pr neg breast cancer
1. JOURNAL CLUB
13/09/2012
DR. R. RAJKUMAR
III YR POST GRADUATE
DEPARTMENT OF MEDICAL ONCOLOGY
2. Question 1
• Important prognostic factors in breast
cancer include:
– A. Lymph node status, hormone receptor
status, and TNM stage
– B. Histologic subtype
– C. Family History
– D. Age at diagnosis
3. Question 2
• Genomic Analysis:
– A. Determines familial breast cancer risk
– B. Oncotype DX technology is useful in
ER+ and ER- breast cancers
– C. Helps determine the best adjuvant
chemotherapy regimen
– D. Has been validated in retrospective
studies
4. Question 3
HORMONAL THERAPY FOR ER+ PR –
BREAST CANCER
• 1.TAMOXIFEN
• 2.AROMATASE INHIBITORS
• 3.NOVEL TARGETED AGENTS
• 4.DONT KNOW
8. Adjuvant Systemic Therapy for
Breast Cancer: Decision Making
Prognostic Factors
– Estimate outcome independent of systemic
treatment
– Reflect tumor biology: Who should be treated?
Predictive Factors
– Reflect a relative resistance or sensitivity to
specific therapy
– What specific treatment(s) should be offered to
an individual?
9. Breast Cancer Prognostic Factors
Accepted
– TNM Stage
– Axillary Nodal Status
– Tumor Size
– Tumor Grade
– ER Content
– Oncotype DX (?)
Investigational
– Gene expression arrays
– Proteomics
– Pharmacogenetics
– Novel imaging
– Other
10. Breast Cancer Predictive Factors
Accepted
– ER status
– Grade
– HER 2 overexpression
– Oncotype DX (?)
Investigational
– Gene expression arrays
– Proteomics
– Pharmacogenetics
– Novel imaging
– Other
11. Intrinsic Breast Cancer
Subtypes described by
Perou et al.
Luminal A
Luminal B
HER2+
Basal-like
Express ↑ amounts
Express ↑ levels of EGFR,
Of luminal cyto-
c-kit, & growth factors like
Keratins & genetic
hepatocyte growth factor
Markers of luminal
and IGF
Epithelial cells of
Normal tissue
Sotiriou, C. et al. NEJM, 2009.
11
12. Figure 1a.
Sorlie T, Tibshirani R, Parker J, et al: Repeated observation of
breast tumor subtypes in independent gene expression data
sets. Proc Natl Acad Sci U S A 100:8418-23, 2003 12
13. St. Gallen 2007
Highly Endocrine Non–endocrine Incompletely
Responsive Responsive Endocrine Responsive
High ER and PgR ER and PgR Low ER and PgR
and both absent or
No HER2 PgR absent
overexpression or
and
Low Ki-67 HER2 overexpression
or
High Ki-67
ER = estrogen receptor; PgR = progesterone receptor.
Goldhirsch et al. Ann Oncol. 2007;18:1133.
13
14. St. Gallen – Endocrine Responsiveness
“Practical” Clinical Subgroups
Endocrine-
responsiveness
Absent Uncertain Sure
ER and PR absent ER and PR low/int Both receptors
and/or any of these high levels
• PgR absent No
• UPA/PAI-1 high No
• HER-2 overexpressed No
• Increased proliferation No
• High grade No
Chemo only options Chemo adds Chemo doesn’t work
to hormonal
14
15. The Level of ER Expression Is
Predictive
The higher the level of expression, the greater the benefit
from endocrine treatment
The higher the level of expression, the lesser the added
benefit of chemotherapy
15
16. Added Value of PgR Status in
Assessing Endocrine Responsiveness
Estrogens ER
Estrogen-responsive elements
Cell cycle PgR synthesis
16
17. Added Value of PgR Status Assessment
Quality control of ER status assessment
– ER-/PgR+ tumors do not exist (almost!)
– ER 10%/PgR 90% is very unusual (and likely related to poor
sensitivity of ER staining)
Prognosis (among ER+ tumors)
Effectiveness of endocrine therapies (and chemotherapy
in premenopausal patients)
Response to AI?
AI = aromatase inhibitor.
Viale et al. J Clin Oncol. 2007;25:3846.
17
18. STEPP for Central PgR
(ER-Expressing) in the BIG 1-98 Trial
100
80
4-y DFS (%)
Tamoxifen
60 Letrozole
40
20
0
0 10 30 40 50 60 75 90 99
Subpopulation by PgR%
STEPP = subpopulation treatment effect pattern plot.
19
19. Is ER/PgR Status Assayed Well in
Clinical Practice?
Inconsistent allocation to “ER/PgR-negative”
– No immunoreactive cells?
– Less than 10% immunoreactive cells?
– Less than 20% immunoreactive cells?
– A different threshold for different clinical questions/settings?
Conflicting results
– >15% disagreement between different laboratories (false negative)
20
21. Oncotype DX 21-Gene
Recurrence Score (RS) Assay
16 Cancer and 5 Reference Genes From 3 Studies
PROLIFERATION ESTROGEN RS = + 0.47 x HER2 Group Score
Ki-67 ER - 0.34 x ER Group Score
STK15 PR + 1.04 x Proliferation Group Scor
Survivin Bcl2 + 0.10 x Invasion Group Score
Cyclin B1 SCUBE2 + 0.05 x CD68
MYBL2 - 0.08 x GSTM1
GSTM1 BAG1 - 0.07 x BAG1
INVASION
Stromelysin 3 CD68 Category RS (0-100)
Cathepsin L2 REFERENCE
Low risk RS <18
Beta-actin Int risk RS ≥18 and <31
HER2 GAPDH
GRB7 RPLPO High risk RS ≥31
HER2 GUS
TFRC
Paik et al. N Engl J Med. 2004;351:2817- 22
22. Standardized Quantitative
Oncotype DX Assay
Recurrence Score in N-, ER+ patients
40%
Intermediate
Low Risk Group High Risk Group
Risk Group
35%
Distant Recurrence at 10 Years
30%
25%
20%
15%
10%
5%
0%
0 5 10 15 20 25 30 35 40 45 50
Recurrence Score
Lower RS’s Higher RS’s
•Lower likelihood of recurrence •Greater likelihood of recurrence
•Greater magnitude of TAM benefit •Lower magnitude of TAM benefit
•Minimal, if any, chemotherapy benefit •Clear chemotherapy benefit
1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research 2006 23
3) Paik et al JCO 2006, 4) Gianni et al JCO 2005 23
23. Oncotype DX Extensively Studied:
Study Experience in >3700 Patients
Study Type No. Pts
Providence Exploratory 136
Rush* Exploratory 78
NSABP B-20 Exploratory 233
NSABP B-14* Prospective 668
MD Anderson* Prospective 149
Kaiser Permanente* Prospective Case-Control 790 Cases/Controls
NSABP B-14 Prospective Placebo vs Tam 645
Milan* Exploratory 89
NSABP B-20* Prospective Tam vs Tam+Chemo 651
ECOG 2197* Exploratory and Prospective 776
SWOG 8814 Prospective Tam vs Tam+Chemo 367
*Published studies24
24. Schema: TAILORx
Node-Neg, ER-Pos Breast Cancer
Register
Specimen
Oncotype DX Assay
banking
RS 11-25
RS <10 Randomize RS >25
Hormone Hormone Rx Chemotherapy
Therapy vs +
Registry Chemotherapy Hormone Rx
+ Hormone Rx
Primary study group
25
25. Mammaprint: Development of the 70-
Gene Signature
DNA microarray analysis of 78 breast primary tumors (untreated)
– Pts were <55 years of age with T1-2/N0 disease
– Pts selected based on outcome: Distant metastases within 5
years
Statistical analysis, “supervised classification,” identified 231
genes correlated with disease outcome Top 70 genes selected
Genes that regulate cell cycle, invasion, metastasis, &
angiogenesis
Patients categorized as “good prognosis” or “poor prognosis.”
Found to be a better predictor of distant metastases within 5
years than all clinical variables in this study
Van ’t Veer, L. Nature, 2002.
26
26. EORTC-BIG MINDACT TRIAL DESIGN
6,000 Node negative women
Evaluate Clinical-Pathological risk and 70-gene signature risk
N=3300 (55%) N=2100 (35%) N=600 (10%)
Clinical-pathological Discordant cases Clinical-pathological
and 70-gene both Clin-Path LOW Clin-Path HIGH and 70-gene both
HIGH risk 70-gene HIGH 70-gene LOW LOW risk
Randomize
Use Clin-Path risk to Use 70-gene risk to decide
decide Chemo or not Chemo or not
Adjuvant
Adjuvant Endocrine
Chemotherapy
therapy only
(+ endocrine Tx if ER+)
The goal of this trial is to show that MammaPrint can
spare 20-30% of patients from adjuvant chemo
Dr Martine Piccart-Gephart JBI, Brussels 27
27. 70-gene 21-gene 2-Gene Intrinsic
Signature Signature Ratio Subtypes
Analysis Supervised Supervised Supervised Unsupervised
Approach
Formalin-Fixed, Formalin-Fixed, Formalin-Fixed,
Tissue Type Fresh or Frozen Parafin- Parafin- Parafin-
embedded embedded embedded
Technique DNA microarrays Q-RT-PCR Q-RT-PCR Q-RT-PCR
Prognostic Untreated pts Untreated & TAM-treated, TAM-treated
age<60, T1-2, LN- TAM-treated ER+/LN-
ER+/LN- untreated
Predictive Benefit to TAM Response to TAM
NO +/- CMF/MF NO
Validation Retrospective Retrospective Retrospective Retrospective
Prospective
Trials MINDACT TAILORX NONE NONE
28
28. Steroid Hormone Receptor Signaling
Reading:
Handbook of cell signaling, Ed RA Bradshaw and EA Dennis, 2003.
Chapter 275
Cheskis, BJ, 2004. Regulation of cell signaling cascades by steroid
hormones
Steroid hormones are produced by endocrine glands
Essential regulators of: reproduction, secondary sex
characteristics
Development, differentiation
Glucose metabolism
Response to stress and salt balance
29. Nuclear Receptor Superfamily
large family of structurally related ligand-inducible
transcription factors, including:
steroid receptors (SRs),
thyroid/retinoids receptors (TR, RARs and RXRs),
vitamin D receptors (VDR),
estrogen receptors (ERa and ERb),
and orphan receptors for which no ligand has
been yet identified.
While having in common a modular structure, they
are activated by distinct lipophilic small molecules
such as glucocorticoids, progesterone, estrogens,
retinoids, and fatty acid derivatives
30.
31. Estrogen Receptors
ER-
Uterus, testis, pituitary, ovary, epididymis, and adrenal
gland.
ER- (Kuiper et al. 1996)
brain, kidney, prostrate, ovary, lung, bladder, intestine,
and epididymis.
88% identity with rat ER-b;
47% identity with human ER-a
Both ERs are localized to membrane, cytosol, and
nucleus.
ER and differ in C-terminal ligand binding domains and
N-terminal transactivation domains. Highest homology in
DNA binding domain.
Estrogen-related orphan receptors (ERR)
36. Steroid receptor coactivators and
ER-dependent gene transcription
Histone
P/CAF Acetylase
CBP Activity
SRC
Family AIB1
Transcription
Estradiol-bound ER
37. Mode of Action of Estradiol
Estradiol AF2 Coactivator
FULLY
E + ER E E ACTIVATED
E RNA
E ERE TRANSCRIPTION
Receptor Nuclear POLII
Coactivator
(tumor cell
AF1dimerization localization of
AF1 division)
fully active ER
AF1 + to ERE AF1 and AF2
AF2 recruit
ACTIVE coactivators
ted from: Wakeling AE. Endocr-Relat Cancer 2000; 7: 17–28.
39. HREs are short cis-acting sequences located within the promoters or
enhancers of target genes.
HREs: inverted repeats of AGGTCA (ER and ERRs)
inverted repeats of AGAACA (for GR, MR, PR, and AR)
40.
41.
42.
43.
44.
45. Hall et al.
J. Biol. Chem., Vol. 276, Issue 40, 36869-36872, October 5, 2001
46.
47. Genomic versus Non-
genomic
changes in gene changes in existing
expression enzyme activity and/or
protein structure
delayed (hrs-days)
rapid (sec-min)
requires nuclear
unknown cytosolic
receptor
mechanisms
prevented by
not affected by
transcription and
transcription and
translation inhibitors
translation inhibitors
48.
49. Cross-talk between signal transduction
and endocrine pathways
Growth factor
Estrogen IGFR
HER2 Trastuzumab
Plasma
P P
membrane P P
P
AI P SOS
PI3-K RAS
RAF
Cell
P
survival Akt MEK
P
ER
p90RSK P
MAPK
P
Cytoplasm Cell
P P P Basal growth
P transcription
ER p160 CBP machinery
ER
Nucleus ERE ER target gene transcription
Adapted from Johnston
50. Ligand
E
ErbB ErbB
P P
P E
p85
p110 Ras ER
Akt MAPK
P E
P ER
Transcription
ER-Responsive Element
51.
52.
53. CHARACTERISTICS OF ER+ PR-
BREAST CANCER
• MORE AGGRESSIVE PHENOTYPE
• LARGER IN SIZE
• OLDER PATIENTS >60 YRS
• HIGHER BMI
• HIGHER S PHASE FRACTION
• GREATER GENOMIC INSTABILITY
• HIGHER LEVELS OF EGFR & HER1 HER2
• TAMOXIFEN RESISTANCE
54.
55.
56.
57.
58. ER+/PR tumors are resistant to
tamoxifen (ATAC)
From Cui et al. JCO 23:7721, 2005
59. Negative PR is a marker of high HER1/HER2
levels and tamoxifen resistance
ER+/PR+
ER+/PR+
Arpino et al. JNCI 97:1254, 2005
60. Negative PR is a marker of high HER1/HER2
levels and tamoxifen resistance
ER+/PR+ ER+/PR
ER+/PR+ ER+/PR
Arpino et al. JNCI 97:1254, 2005
61.
62.
63. The Molecular Portrait Hypothesis
You can recognize the
Mona Lisa by her smile
and her nose and her eyes and even her hands – if you are really good,
but not the sky or the trees
64. The Promise of Personalized
Medicine in Breast Cancer
Tamoxifen
Postmenopausal
Women with HR+ Aromatase
breast Cancer Inhibitor
Chemotherapy
Biologic agents Anth, Taxane,
Platimun
Her2, EGFR, VEGF, Parp
65. Question 1
• Important prognostic factor in breast
cancer include lymph node status,
hormone receptor status, and TNM
staging
– Histologic subtype and family history have
not been independently validated
prognostically, and age at diagnosis is
neither prognostic nor predictive
Stearns et.al., BCRT 1998; 52: 239-259
Harris, L et.al., J Clin Oncol 2007 Nov 20; 25 (83) 5287-312
66. Question 2
• Genomic analysis has been validated in
retrospective studies
– Available genomic analytic assays
(Oncotype DX, Mammaprint) do not
determine familial risk. Oncotype DX has
been validated only in ER+ breast cancers.
Neither assay determines type of adjuvant
chemotherapy.
Paik, S et.al., N Eng J Med 2004 Dec 30; 351(27): 2817-26
Paik, S et.al., J Clin Oncol 2006 Aug 10; 24(23): 3726-34
Albain, K et.al., SABCS 2007 abstr #10
67. Question 3
• HORMONAL THERAPY FOR ER+ PR –
BREAST CANCER
1. AI - 52% lower risk for recurrence
2. EGFR INHIBITORS , m TOR INHIBITORS,
PI3K INHIBITORS, IGF INHIBITORS
anastrozole plus gefinitib- 49% clinical benefit.
Editor's Notes
Microarray studies show that luminal types express high amounts of luminal cytokeratins and genetic markers of luminal epithelial cell of normal breast tissueBasal-like no ER, PR, or ER related genes; high levels of EGFR, c-kit, and growth factors such as hepatocyte growth factor and IGF
34 with distant mets at <5 yrs, 44 disease-free at >5 years, and 18 BRCA1/2 BRCA2 germline mutations; 19 to validate signatureStatistical analysis called “supervised classification,” the expression of 231 genes seemed to be significantly correlated with disease outcome (distant mets within 5 years). They were ranked on the basis of their correlation coefficient with disease outcome; the top 70 genes were shown to most accurately classify tumors in either good or poor prognosis categories.Pts with correlation coefficient >0.4 were in the good prognosis groupOdds ratio of distant mets in the poor prognosis group compared to the good prognosis group = 15