Lee P. Shulman is the Anna Ross Lapham Professor of Obstetrics and Gynecology and Chief of the Division of Clinical Genetics at Northwestern University. He discloses advisory roles and speaking engagements with several genetic testing companies. His research focuses on inherited cancer risk assessment and genetic testing for hereditary cancer syndromes. He provides an overview of the genetics of cancer including tumor suppressor genes and oncogenes, as well as specific hereditary cancer syndromes like BRCA1/2, Lynch syndrome, and Cowden syndrome that increase cancer risk, especially for women's cancers.
This document summarizes genetic changes in endometrial cancer and Lynch syndrome (HNPCC). It discusses two types of endometrial cancer (Type I and Type II), risk factors, molecular features, diagnosis of Lynch syndrome, cancer risks, pathogenesis, tests used for screening/diagnosis including immunohistochemistry and microsatellite instability testing. Lynch syndrome is an autosomal dominant condition associated with mutations in mismatch repair genes that increases risks of colorectal, endometrial and other cancers.
This document provides an overview of molecular genetics and cancer biology concepts. It begins with an introduction to basic molecular genetics topics like DNA, genes, chromosomes, and gene expression. It then discusses how normal cells can become cancerous through genetic mutations that disrupt processes like tumor suppressor genes, oncogenes, the cell cycle, and DNA repair. The document emphasizes how understanding molecular genetics advances has helped improve diagnosis and treatment of cancers like prostate and bladder cancer, but also highlights ongoing challenges. It provides context on cancer rates and the need for continued research.
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.
This document discusses genetic cancer risk assessment and precision therapy approaches. It provides information on genes associated with increased risks of breast and ovarian cancer like BRCA1 and BRCA2. It summarizes lifetime cancer risks for mutation carriers and risk-reducing strategies. The document also covers multigene panel testing, challenges in interpreting results, and implications for surveillance and treatment. Advances in sequencing technologies have improved genetic testing but also require specialized expertise to apply testing and counseling appropriately.
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.
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.
Genetic counselor, Heather Herrmann, will dive in to the topic of Lynch Syndrome & CRC. Heather has enjoyed working in both pediatric genetics and cancer genetics throughout her career. She has focused the last eight years in the area of hereditary cancer syndromes and hereditary cancer risk assessment.
Cancer biochemistry involves biochemical alterations in cancer cells. Specific objectives include listing protooncogenes and tumor suppressor genes, and explaining their roles and mechanisms of action. Protooncogenes become oncogenes through activation mechanisms like mutations. Tumor suppressor genes like p53 regulate cell proliferation and their mutation leads to cancer. Cyclins and cell cycle phases are also discussed. Standard cancer treatments include surgery, radiotherapy, and chemotherapy using antimetabolite drugs. Tumor markers can be used for cancer diagnosis, prognosis, localization, and treatment monitoring and are classified based on their type.
This document summarizes genetic changes in endometrial cancer and Lynch syndrome (HNPCC). It discusses two types of endometrial cancer (Type I and Type II), risk factors, molecular features, diagnosis of Lynch syndrome, cancer risks, pathogenesis, tests used for screening/diagnosis including immunohistochemistry and microsatellite instability testing. Lynch syndrome is an autosomal dominant condition associated with mutations in mismatch repair genes that increases risks of colorectal, endometrial and other cancers.
This document provides an overview of molecular genetics and cancer biology concepts. It begins with an introduction to basic molecular genetics topics like DNA, genes, chromosomes, and gene expression. It then discusses how normal cells can become cancerous through genetic mutations that disrupt processes like tumor suppressor genes, oncogenes, the cell cycle, and DNA repair. The document emphasizes how understanding molecular genetics advances has helped improve diagnosis and treatment of cancers like prostate and bladder cancer, but also highlights ongoing challenges. It provides context on cancer rates and the need for continued research.
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.
This document discusses genetic cancer risk assessment and precision therapy approaches. It provides information on genes associated with increased risks of breast and ovarian cancer like BRCA1 and BRCA2. It summarizes lifetime cancer risks for mutation carriers and risk-reducing strategies. The document also covers multigene panel testing, challenges in interpreting results, and implications for surveillance and treatment. Advances in sequencing technologies have improved genetic testing but also require specialized expertise to apply testing and counseling appropriately.
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.
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.
Genetic counselor, Heather Herrmann, will dive in to the topic of Lynch Syndrome & CRC. Heather has enjoyed working in both pediatric genetics and cancer genetics throughout her career. She has focused the last eight years in the area of hereditary cancer syndromes and hereditary cancer risk assessment.
Cancer biochemistry involves biochemical alterations in cancer cells. Specific objectives include listing protooncogenes and tumor suppressor genes, and explaining their roles and mechanisms of action. Protooncogenes become oncogenes through activation mechanisms like mutations. Tumor suppressor genes like p53 regulate cell proliferation and their mutation leads to cancer. Cyclins and cell cycle phases are also discussed. Standard cancer treatments include surgery, radiotherapy, and chemotherapy using antimetabolite drugs. Tumor markers can be used for cancer diagnosis, prognosis, localization, and treatment monitoring and are classified based on their type.
HEREDITARY BREAST and OVARY CANCER [HBOC] SYNDROME, Dr BUI DAC CHI.hungnguyenthien
The BRCA genes normally help repair DNA damage but mutations increase cancer risk. Hereditary Breast and Ovarian Cancer (HBOC) Syndrome is caused by mutations in the BRCA1 and BRCA2 genes, increasing risks for early-onset breast, ovarian, pancreatic, and other cancers. Genetic testing can identify BRCA mutations to diagnose HBOC and determine risks for family members. Referral for genetic testing should be considered for those with personal or family histories of certain cancers.
The document discusses the molecular pathology of breast carcinoma. It describes the cellular types in the mammary gland, identification of mammary stem cells, and the epithelial cell hierarchy model. It also covers molecular classification of breast cancer, luminal and basal-like phenotypes, mechanisms of E-cadherin inactivation in lobular carcinoma, breast cancer in hereditary diffuse gastric cancer patients, and morphological and immunohistochemical features of BRCA1 and BRCA2 breast carcinomas.
This document summarizes hereditary cancer syndromes and BRCA mutations. It discusses that most cancers are sporadic, but 5-10% are hereditary due to germline mutations passed down from relatives. Hereditary cancers often occur earlier and increase risk for multiple cancer types. Specific cancer susceptibility genes are discussed, including BRCA1 and BRCA2 mutations which increase lifetime risks of breast and ovarian cancers. Diagnostic testing and management strategies for individuals with BRCA mutations are outlined, including increased cancer screening, risk-reducing surgeries, and lifestyle modifications. Genetic counseling plays an important role in assessing cancer risks and managing hereditary cancer syndromes in families.
- Were you diagnosed with colon or rectal cancer before the age of 50?
- Was anyone in your family diagnosed with colon cancer before the age of 50?
- Was anyone in your family diagnosed with uterine (endometrial) cancer before the age of 50?
- Are there cancers across several generations on one side of your family?
If you answered YES to just one of these questions, it's time to talk turkey about Lynch syndrome.
Lynch syndrome is an inherited genetic mutation, and having it increases your chance of getting colorectal cancer to 80%. Unfortunately, nearly every person living with Lynch syndrome is completely unaware of it.
Lynch syndrome also puts you at higher risk for brain, breast, kidney, melanoma, ovarian, pancreas, small bowel, stomach, or uterine/endometrial cancers. Knowledge is power and will help your medical team act more aggressively with their screening measures.
Brian Mansfield, a music critic for USA Today, didn't know he had Lynch syndrome until he was diagnosed with colorectal cancer earlier this year at the age of 48. After his diagnosis, he began talking with his family about their health history, "then the family tree lit up like a Christmas tree." Brian is chronicling his journey through a weekly USA Today online column, "My Semicolon Life."
Join national patient advocacy group Fight Colorectal Cancer as we host Brian and his doctor, Dr. Bill Harb, a colorectal surgeon at Cumberland Surgical Associates, along with Associate Director of Human Genetics at Ohio State University Heather Hampel as they tell you more about Lynch syndrome and how to dig into the medical mystery that may be lurking within your family tree. With the holidays coming up, never has there been a more appropriate time to talk turkey...and Lynch syndrome.
**Fight Colorectal Cancer thanks Can't Stomach Cancer, the Colon Club, Kidney Cancer Association, Myriad Genetics, and Ovarian Cancer National Alliance for their assistance with this webinar.**
Tumour markers can play a crucial role in detecting cancer and assessing response to therapy. They are substances produced either by tumour cells or by the body in response to cancer. Oncoproteins are proteins encoded by oncogenes which normally maintain a fine balance between cell proliferation and differentiation but become permanently activated in cancer, stimulating cell growth. Elevated levels of various oncoproteins and other tumour markers can be detected in blood and other body fluids, serving as biomarkers for early cancer detection and prediction of prognosis. Common tumour markers discussed include AFP, CEA, CA19-9, CA15-3, CA125, and proteins associated with growth factors, receptors, and cellular signalling pathways.
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...Adonis Guancia
This document summarizes a presentation on rational options in breast cancer treatment informed by molecular understanding. It discusses the complexity of breast cancer at the molecular level, with every cancer being genetically unique and composed of multiple evolving clones. Standard adjuvant therapies do not fully address all the hallmarks of cancer. For HER2-positive breast cancer, the BCIRG 006 trial showed the TCH regimen of docetaxel, carboplatin and trastuzumab resulted in superior disease-free survival and fewer adverse effects compared to the AC→TH and AC→T regimens, suggesting TCH provides the best risk-benefit ratio.
Human cancer development, or oncogenesis, results from genetic changes in oncogenes and tumor suppressor genes. Oncogenes like Ras, Myc, and EGFR promote cancer when overexpressed, while tumor suppressors like p53 and Rb inhibit cancer when functioning normally. Genetic changes from carcinogens, radiation, viruses, or other sources can delete or mutate these genes, altering the control of mitosis and apoptosis and leading to uncontrolled cell growth and the multi-step development of tumors over time. Tumor markers in the blood can indicate the presence, severity, or progression of cancers and help guide treatment responses.
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
1. Breast cancer is a heterogeneous disease caused by genetic and environmental factors. Global gene expression profiling can classify breast cancers into biological classes associated with survival.
2. Genetic mutations in high, moderate, and low penetrance genes like BRCA1, BRCA2, CHEK2, p53 contribute to hereditary breast cancers.
3. Molecular subtypes including luminal A/B, HER2-enriched, and basal-like have distinct gene expression patterns, responses to treatment, and clinical behaviors.
85% of gastric cancers are adenocarcinomas which can be diffuse or intestinal type. Diffuse cancers have worse prognosis and lack cell cohesion. Risk factors include dried foods, nitrates, H. pylori infection, and pernicious anemia. Symptoms include abdominal pain, weight loss, and anemia. Treatment involves surgery with D1 or D2 lymph node dissection and chemotherapy or chemoradiation for advanced or high risk cancers.
This document summarizes genetics of hereditary breast cancer. About 5-10% of breast cancers are hereditary, with 40-50% caused by mutations in the BRCA1 and BRCA2 genes. Genetic testing is recommended for patients with a family history suggesting over 20-25% risk of a BRCA mutation. A positive test result increases cancer surveillance and treatment options like prophylactic surgeries, while laws protect against genetic discrimination in health insurance.
Tumor markers are proteins detected in blood that can indicate certain cancers. They are most useful for monitoring response to treatment and detecting early recurrence of cancer. With the exception of PSA, tumor markers lack sufficient accuracy for cancer screening. Some common tumor markers include CA 27.29 for breast cancer, CEA for colorectal cancer, and AFP and beta-hCG for germ cell tumors and liver cancer. While tumor markers can help manage cancer patients, no marker alone guarantees cure or determines treatment; clinical evaluation is also needed.
This document discusses cancer epidemiology and statistics globally, nationally, and locally. It provides data on the most common types of cancer worldwide, in the United States, and in Colombia in terms of incidence and mortality. It also discusses trends in cancer rates and risk factors for cancer such as obesity, tobacco use, diet, physical activity, and more. Graphics show cancer statistics for specific countries and populations.
- Tumor markers are glycoproteins detected by monoclonal antibodies that are produced by tumors or the body's response to cancer.
- Cancer antigen 125 (CA-125) is an important tumor marker used for ovarian cancer screening, diagnosis, treatment monitoring and recurrence detection, though it can be elevated in some non-cancerous conditions.
- For screening, CA-125 levels above 35 U/mL in postmenopausal women or 200 U/mL in premenopausal women should be further evaluated. Monitoring CA-125 after treatment can indicate response or recurrence of ovarian 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.
This document discusses newer tumor markers that can be used for cancer diagnosis, prognosis, and monitoring treatment. It describes various types of biochemical entities that serve as tumor markers, including nucleic acids, proteins, sugars, lipids, and whole tumor cells. Specific examples of tumor markers are discussed, such as enzymes, hormones, oncofetal antigens, tumor-associated proteins, carbohydrate antigens, and genetic markers. The ideal properties of tumor markers and their clinical applications are also summarized.
Tumor markers
Many cancers are associated with the abnormal production of some molecules which can be measured in plasma. These molecules are known as tumor markers.
A good tumor maker should have those properties:
1. A tumor marker should be present in or produced by tumor itself.
2. A tumor marker should not be present in healthy tissues.
3. Plasma level of a tumor marker should be at a minimum level in healthy subjects and in benign conditions.
4. A tumor marker should be specific for a tissue, it should have different immunological properties when it is synthesized in other tissues.
5. Plasma level of the tumor marker should be in proportion to the both size of the tumor and the activity of the tumor.
6. Half-life of a tumor should not be very long
7. A tumor marker should be present in plasma at a detectable level, even though tumor size is very small
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
Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected and measured in bodily fluids or tissues. They can help diagnose certain cancers, distinguish between benign and malignant tumors, monitor treatment response and detect recurrence. However, no single tumor marker is perfect as tumor marker levels can also be elevated in some non-cancerous conditions.
<마더리스크라운드> Hyperthermia and pregnancy mothersafe
Hyperthermia during pregnancy can cause developmental defects in embryos and fetuses. A body temperature of at least 38.3°C or higher is considered hyperthermia. Critical periods of susceptibility are during the first 8 weeks of pregnancy when organogenesis occurs. Hyperthermia has been associated with defects of the brain, heart, limbs and facial structures in both animal and human studies. Sustained fevers over 38.9°C for more than 24 hours during the first trimester appear to increase the risk of birth defects in humans. Strict limits on hot tub and sauna use are recommended during early pregnancy to avoid hyperthermia.
Smoking during pregnancy can have negative effects on both the mother and baby. It is associated with complications like miscarriage, preterm birth, low birth weight, and fetal growth restriction. The babies of mothers who smoke are also at higher risk for health issues later in life such as intellectual and behavioral problems. Nicotine and other chemicals in cigarette smoke can negatively impact the placenta and fetal development by disrupting nutrient transfer, oxygen delivery, and cell growth and differentiation. Maternal smoking is also linked to potential epigenetic changes that may influence fetal brain development and long-term health outcomes. Quitting smoking before or during pregnancy can help mitigate many of these risks.
HEREDITARY BREAST and OVARY CANCER [HBOC] SYNDROME, Dr BUI DAC CHI.hungnguyenthien
The BRCA genes normally help repair DNA damage but mutations increase cancer risk. Hereditary Breast and Ovarian Cancer (HBOC) Syndrome is caused by mutations in the BRCA1 and BRCA2 genes, increasing risks for early-onset breast, ovarian, pancreatic, and other cancers. Genetic testing can identify BRCA mutations to diagnose HBOC and determine risks for family members. Referral for genetic testing should be considered for those with personal or family histories of certain cancers.
The document discusses the molecular pathology of breast carcinoma. It describes the cellular types in the mammary gland, identification of mammary stem cells, and the epithelial cell hierarchy model. It also covers molecular classification of breast cancer, luminal and basal-like phenotypes, mechanisms of E-cadherin inactivation in lobular carcinoma, breast cancer in hereditary diffuse gastric cancer patients, and morphological and immunohistochemical features of BRCA1 and BRCA2 breast carcinomas.
This document summarizes hereditary cancer syndromes and BRCA mutations. It discusses that most cancers are sporadic, but 5-10% are hereditary due to germline mutations passed down from relatives. Hereditary cancers often occur earlier and increase risk for multiple cancer types. Specific cancer susceptibility genes are discussed, including BRCA1 and BRCA2 mutations which increase lifetime risks of breast and ovarian cancers. Diagnostic testing and management strategies for individuals with BRCA mutations are outlined, including increased cancer screening, risk-reducing surgeries, and lifestyle modifications. Genetic counseling plays an important role in assessing cancer risks and managing hereditary cancer syndromes in families.
- Were you diagnosed with colon or rectal cancer before the age of 50?
- Was anyone in your family diagnosed with colon cancer before the age of 50?
- Was anyone in your family diagnosed with uterine (endometrial) cancer before the age of 50?
- Are there cancers across several generations on one side of your family?
If you answered YES to just one of these questions, it's time to talk turkey about Lynch syndrome.
Lynch syndrome is an inherited genetic mutation, and having it increases your chance of getting colorectal cancer to 80%. Unfortunately, nearly every person living with Lynch syndrome is completely unaware of it.
Lynch syndrome also puts you at higher risk for brain, breast, kidney, melanoma, ovarian, pancreas, small bowel, stomach, or uterine/endometrial cancers. Knowledge is power and will help your medical team act more aggressively with their screening measures.
Brian Mansfield, a music critic for USA Today, didn't know he had Lynch syndrome until he was diagnosed with colorectal cancer earlier this year at the age of 48. After his diagnosis, he began talking with his family about their health history, "then the family tree lit up like a Christmas tree." Brian is chronicling his journey through a weekly USA Today online column, "My Semicolon Life."
Join national patient advocacy group Fight Colorectal Cancer as we host Brian and his doctor, Dr. Bill Harb, a colorectal surgeon at Cumberland Surgical Associates, along with Associate Director of Human Genetics at Ohio State University Heather Hampel as they tell you more about Lynch syndrome and how to dig into the medical mystery that may be lurking within your family tree. With the holidays coming up, never has there been a more appropriate time to talk turkey...and Lynch syndrome.
**Fight Colorectal Cancer thanks Can't Stomach Cancer, the Colon Club, Kidney Cancer Association, Myriad Genetics, and Ovarian Cancer National Alliance for their assistance with this webinar.**
Tumour markers can play a crucial role in detecting cancer and assessing response to therapy. They are substances produced either by tumour cells or by the body in response to cancer. Oncoproteins are proteins encoded by oncogenes which normally maintain a fine balance between cell proliferation and differentiation but become permanently activated in cancer, stimulating cell growth. Elevated levels of various oncoproteins and other tumour markers can be detected in blood and other body fluids, serving as biomarkers for early cancer detection and prediction of prognosis. Common tumour markers discussed include AFP, CEA, CA19-9, CA15-3, CA125, and proteins associated with growth factors, receptors, and cellular signalling pathways.
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...Adonis Guancia
This document summarizes a presentation on rational options in breast cancer treatment informed by molecular understanding. It discusses the complexity of breast cancer at the molecular level, with every cancer being genetically unique and composed of multiple evolving clones. Standard adjuvant therapies do not fully address all the hallmarks of cancer. For HER2-positive breast cancer, the BCIRG 006 trial showed the TCH regimen of docetaxel, carboplatin and trastuzumab resulted in superior disease-free survival and fewer adverse effects compared to the AC→TH and AC→T regimens, suggesting TCH provides the best risk-benefit ratio.
Human cancer development, or oncogenesis, results from genetic changes in oncogenes and tumor suppressor genes. Oncogenes like Ras, Myc, and EGFR promote cancer when overexpressed, while tumor suppressors like p53 and Rb inhibit cancer when functioning normally. Genetic changes from carcinogens, radiation, viruses, or other sources can delete or mutate these genes, altering the control of mitosis and apoptosis and leading to uncontrolled cell growth and the multi-step development of tumors over time. Tumor markers in the blood can indicate the presence, severity, or progression of cancers and help guide treatment responses.
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
1. Breast cancer is a heterogeneous disease caused by genetic and environmental factors. Global gene expression profiling can classify breast cancers into biological classes associated with survival.
2. Genetic mutations in high, moderate, and low penetrance genes like BRCA1, BRCA2, CHEK2, p53 contribute to hereditary breast cancers.
3. Molecular subtypes including luminal A/B, HER2-enriched, and basal-like have distinct gene expression patterns, responses to treatment, and clinical behaviors.
85% of gastric cancers are adenocarcinomas which can be diffuse or intestinal type. Diffuse cancers have worse prognosis and lack cell cohesion. Risk factors include dried foods, nitrates, H. pylori infection, and pernicious anemia. Symptoms include abdominal pain, weight loss, and anemia. Treatment involves surgery with D1 or D2 lymph node dissection and chemotherapy or chemoradiation for advanced or high risk cancers.
This document summarizes genetics of hereditary breast cancer. About 5-10% of breast cancers are hereditary, with 40-50% caused by mutations in the BRCA1 and BRCA2 genes. Genetic testing is recommended for patients with a family history suggesting over 20-25% risk of a BRCA mutation. A positive test result increases cancer surveillance and treatment options like prophylactic surgeries, while laws protect against genetic discrimination in health insurance.
Tumor markers are proteins detected in blood that can indicate certain cancers. They are most useful for monitoring response to treatment and detecting early recurrence of cancer. With the exception of PSA, tumor markers lack sufficient accuracy for cancer screening. Some common tumor markers include CA 27.29 for breast cancer, CEA for colorectal cancer, and AFP and beta-hCG for germ cell tumors and liver cancer. While tumor markers can help manage cancer patients, no marker alone guarantees cure or determines treatment; clinical evaluation is also needed.
This document discusses cancer epidemiology and statistics globally, nationally, and locally. It provides data on the most common types of cancer worldwide, in the United States, and in Colombia in terms of incidence and mortality. It also discusses trends in cancer rates and risk factors for cancer such as obesity, tobacco use, diet, physical activity, and more. Graphics show cancer statistics for specific countries and populations.
- Tumor markers are glycoproteins detected by monoclonal antibodies that are produced by tumors or the body's response to cancer.
- Cancer antigen 125 (CA-125) is an important tumor marker used for ovarian cancer screening, diagnosis, treatment monitoring and recurrence detection, though it can be elevated in some non-cancerous conditions.
- For screening, CA-125 levels above 35 U/mL in postmenopausal women or 200 U/mL in premenopausal women should be further evaluated. Monitoring CA-125 after treatment can indicate response or recurrence of ovarian 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.
This document discusses newer tumor markers that can be used for cancer diagnosis, prognosis, and monitoring treatment. It describes various types of biochemical entities that serve as tumor markers, including nucleic acids, proteins, sugars, lipids, and whole tumor cells. Specific examples of tumor markers are discussed, such as enzymes, hormones, oncofetal antigens, tumor-associated proteins, carbohydrate antigens, and genetic markers. The ideal properties of tumor markers and their clinical applications are also summarized.
Tumor markers
Many cancers are associated with the abnormal production of some molecules which can be measured in plasma. These molecules are known as tumor markers.
A good tumor maker should have those properties:
1. A tumor marker should be present in or produced by tumor itself.
2. A tumor marker should not be present in healthy tissues.
3. Plasma level of a tumor marker should be at a minimum level in healthy subjects and in benign conditions.
4. A tumor marker should be specific for a tissue, it should have different immunological properties when it is synthesized in other tissues.
5. Plasma level of the tumor marker should be in proportion to the both size of the tumor and the activity of the tumor.
6. Half-life of a tumor should not be very long
7. A tumor marker should be present in plasma at a detectable level, even though tumor size is very small
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
Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected and measured in bodily fluids or tissues. They can help diagnose certain cancers, distinguish between benign and malignant tumors, monitor treatment response and detect recurrence. However, no single tumor marker is perfect as tumor marker levels can also be elevated in some non-cancerous conditions.
<마더리스크라운드> Hyperthermia and pregnancy mothersafe
Hyperthermia during pregnancy can cause developmental defects in embryos and fetuses. A body temperature of at least 38.3°C or higher is considered hyperthermia. Critical periods of susceptibility are during the first 8 weeks of pregnancy when organogenesis occurs. Hyperthermia has been associated with defects of the brain, heart, limbs and facial structures in both animal and human studies. Sustained fevers over 38.9°C for more than 24 hours during the first trimester appear to increase the risk of birth defects in humans. Strict limits on hot tub and sauna use are recommended during early pregnancy to avoid hyperthermia.
Smoking during pregnancy can have negative effects on both the mother and baby. It is associated with complications like miscarriage, preterm birth, low birth weight, and fetal growth restriction. The babies of mothers who smoke are also at higher risk for health issues later in life such as intellectual and behavioral problems. Nicotine and other chemicals in cigarette smoke can negatively impact the placenta and fetal development by disrupting nutrient transfer, oxygen delivery, and cell growth and differentiation. Maternal smoking is also linked to potential epigenetic changes that may influence fetal brain development and long-term health outcomes. Quitting smoking before or during pregnancy can help mitigate many of these risks.
The document discusses an oncogenomics explorer tool for analyzing ovarian serous carcinoma data. It describes analyzing samples to identify the most frequently mutated genes (TP53, BRCA1, BRCA2). Most high-grade tumors are characterized by TP53 mutations and lack mutations in other genes. The tool allows viewing mutations in genes like NF1 and correlating genetic data with clinical variables. It identifies genes with correlations between copy number and expression, and allows comparing expression between amplified and unamplified gene regions. The tool facilitates in-depth exploration of genetic datasets.
Trisomy 8, Turners syndrome, Triple X: A Case ReportDominick Maino
This case report describes a 13-year-old female patient with three rare genetic conditions: Trisomy 8, Turner Syndrome, and Triple X Syndrome. She presented with refractive errors, oculomotor dysfunction, and impaired vision information processing. After 27 optometric vision therapy sessions targeting these issues, her visual skills improved to age-appropriate levels. This is the first reported case of a patient with all three syndromes, demonstrating that vision therapy can effectively treat visual problems in individuals with genetic anomalies.
La ataxia telangiectasia es un síndrome autosómico recesivo causado por mutaciones en el gen ATM en el cromosoma 11q22-23 que afecta el ciclo celular. Provoca una marcha atáxica a los dos años, telangiectasias a los 4-8 años, inmunodeficiencia que lleva a neumonías y linfomas, y una esperanza de vida de 20 a 39 años.
Turner's syndrome is a genetic condition that affects development in females caused by a missing or partial X chromosome. Common symptoms include short stature, broad chest, increased weight, and reproductive sterility. While there is no cure, treatment options focus on hormone therapy to promote growth and reduce osteoporosis risks, as well as modern reproductive technologies. Turner's syndrome is usually inherited from the father and patients can live normal lives with close medical monitoring.
Turner syndrome is a genetic condition that affects females, caused by missing or structural abnormalities of an X chromosome. It can cause short stature, lack of sexual development at puberty, infertility, and other health issues. Klinefelter syndrome is a condition in males caused by at least one extra X chromosome, resulting in enlarged breasts and reduced facial/body hair. Fragile X syndrome is caused by a gene on the X chromosome shutting down, leading to intellectual disabilities, large ears, joint issues, and other traits.
This document discusses cancer risks associated with hereditary cancer syndromes like BRCA1/2 mutations and HNPCC. It provides lifetime risk percentages for various cancers in mutation carriers compared to the general population. It describes screening and prevention strategies like surveillance, chemoprevention, and prophylactic surgery that can reduce cancer risk. Genetic testing considerations and the importance of informing at-risk relatives is also covered.
Turner syndrome is a genetic condition where females are missing an X chromosome. It affects about 1 in 2,500 baby girls. Common characteristics include short stature and lack of ovarian development leading to infertility. While it cannot be passed down from parent to child, it is typically caused by a failure of chromosomes to separate during egg formation. Diagnosis is often made based on physical characteristics, and can be confirmed with a blood test. Hormone replacement therapy is the primary treatment.
Hereditary breast and ovarian cancer clinic visit visual aids (Mayo Clinic Fl...Douglas Riegert-Johnson
The document summarizes information about hereditary breast and ovarian cancer syndrome (HBOC). It finds that 10-25% of breast cancer and 5-10% of ovarian cancer is considered hereditary. The majority of HBOC cases, around 84%, are caused by mutations in the BRCA1 and BRCA2 genes. Carriers of BRCA1 and BRCA2 mutations have significantly increased lifetime risks of developing breast cancer (56-87% for both genes) and ovarian cancer (44% for BRCA1, 27% for BRCA2) compared to the general population. Genetic testing for BRCA1 and BRCA2 mutations is available to assess cancer risk and guide risk-reducing medical or
Chapter 5 hereditary cancer syndrome next generationNilesh Kucha
This document provides an overview of hereditary cancers and genetic testing. It discusses:
- The difference between sporadic and hereditary cancers, with hereditary cancers making up 10% of cases and being caused by germline mutations passed down from a parent.
- Several hereditary cancer syndromes are described in detail, including BRCA1/2 associated with breast and ovarian cancer, Li-Fraumeni syndrome, Cowden syndrome, and Lynch syndrome.
- Surveillance recommendations are provided for each syndrome to enable early cancer detection.
- The role of genetic testing is discussed to identify mutations that cause hereditary cancer syndromes and guide patient management.
Use of Autoantibodies to detect the onset of breast cancerIsabelle Chiu
This document discusses using autoantibodies to detect the early onset of breast cancer. It begins by introducing breast cancer and some of the common screening and testing methods like mammograms, MRI, and biopsies. It then discusses how tumors produce tumor-associated antigens that the immune system recognizes through autoantibodies. The document analyzes several studies using techniques like Luminex bead arrays to test for autoantibodies against tumor antigens in breast cancer patients, finding autoantibodies against antigens like p53, HER2, and NY-ESO-1. It concludes that monitoring autoantibody profiles could help detect cancers patients are predisposed to before symptoms appear.
This document discusses genetics implications for survivorship programs. It highlights identifying patients who were previously missed for genetic testing and may benefit from re-testing given advances in panel testing. It also reviews managing hereditary cancer risks and addressing the psychosocial issues patients face, such as making difficult medical decisions, informing relatives, and dealing with feelings of guilt. Survivorship programs can help such patients navigate these medical and familial implications.
Genetics and "Genomics" Dr. Roisin O’Cearbhaill slidesbkling
The words genetics and “genomics” are sometimes used interchangeably, but what exactly do these two terms mean and how are they different?
This program will help unpack the confusion surrounding these very different forms of testing. Join Peggy Cottrell, MS, CGC, board certified genetic counselor at Sharsheret and Dr. Roisin O’Cearbhaill, Research Director of the Gynecologic Medical Oncology Service at Memorial Sloan Kettering Cancer Center (MSKCC), as they explain the types of tests you may have had and what tests you should consider.
This document discusses hereditary breast and ovarian cancer and the role of genetics in cancer risk. It provides an overview of BRCA1 and BRCA2 genes which are known to increase the risk of breast and ovarian cancers when mutated. Individuals with mutations in these genes have a high lifetime risk, up to 85%, of developing breast cancer and 16-44% risk for ovarian cancer. Referral to a cancer genetics clinic is recommended for those with a strong family history or personal history of related cancers to determine risk and recommend screening and management options.
This document discusses benign breast disease, risk factors for breast cancer, hereditary breast cancer syndromes, screening and surveillance for breast cancer, evaluation of breast symptoms such as lumps, nipple discharge, and abnormal mammogram findings. It provides guidelines for managing increased risk and evaluating various breast abnormalities to determine if biopsy or other follow up is needed.
BRCA – Importance in Hereditary Breast & Ovarian CancerLifecare Centre
BRCA – Importance in Hereditary
Breast & Ovarian Cancer
DGF & WOW India
presentation was made by
Dr Sharda Jain
based on presentation made by
Dr Sunil Tadepalli
All in the Family: Hereditary Risk for Gynecologic Cancerbkling
Knowing and understanding your inherited genetics is important for ovarian and uterine cancer patients. Dr. Melissa Frey, gynecologic oncologist at Weill Cornell Medicine, discusses how genetic factors affect women with ovarian and uterine cancer and influence treatment decisions, with a particular focus on BRCA1 & 2 and Lynch Syndrome.
This webinar was being put on in partnership with FORCE.
It contains details about breast carcinoma-pathology,investigations and diagnosis,NACT,surgery and adjuvant therapy. Hope you will find it helpful.....
Cancer susceptibility syndromes dr. varunVarun Goel
All cancer involves genetic changes in cells. Normally DNA repair mechanisms correct mutations, but if too many mutations accumulate it can lead to tumor development. Mutations can be inherited (germline) and increase cancer risk, or somatic and only affect one cell. The "two-hit" model explains that two mutations are typically needed - one inherited and one somatic - to cause cancer like in Lynch syndrome. Screening recommendations exist for hereditary cancer syndromes like starting colonoscopy at age 20-25 for Lynch syndrome due to the high risk of colon cancer.
Cancer is characterized by uncontrolled cell growth and the spread of abnormal cells. It is caused by somatic mutations and disruptions to oncogenes and tumor suppressor genes. Many factors like environment, diet, smoking, and alcohol consumption can influence cancer risk. Researchers are studying the cancer genome to better understand carcinogenesis at the molecular level and identify new targeted therapies.
Colorectal cancer results from the accumulation of genetic mutations that progress from normal tissue to dysplastic adenomas to carcinoma over approximately 15 years. Patients with certain hereditary syndromes like familial adenomatous polyposis and hereditary non-polyposis colorectal cancer are at very high risk and require aggressive screening. Screening options for average risk patients include fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy which can detect and remove precancerous polyps, reducing colorectal cancer incidence and mortality.
Cancer is the second leading cause of death worldwide after cardiovascular disease. In India, an estimated 2.25 million people are living with cancer, with over 11 lakh new cases registered annually. Some key statistics for India include one woman dying of cervical cancer every 8 minutes and two women dying of breast cancer for every one diagnosed. Tumor markers are substances produced by cancerous tissues or the body in response to cancer that can help detect or monitor cancer. Some common tumor markers are CEA, AFP, CA125, and PSA. Tumor markers can be used for screening, diagnosis, staging, prognosis, and monitoring treatment effectiveness and recurrence. Characteristics of ideal tumor markers include cancer specificity, high sensitivity and specificity for detection
Audio and slides for this presentation are available on YouTube: http://youtu.be/e_KVYJX2GTs
Have you ever wondered about your genetic predisposition to cancer? How cancer evolves in families? Or how cancer cells differ from normal cells in your body? Join Judy Garber, MD, MPH, director of the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute, as she explores the basics of cancer genetics, DNA mutations, genetic screening, management, and more.
Douglas Riegert-Johnson discusses screening and referral for genetic diseases. Primary care providers should obtain a detailed cancer family history including cancer types and ages of diagnosis. Patients meeting certain criteria like breast cancer under age 50 or multiple primaries should be referred for genetic counseling. All colon cancer patients should now undergo tumor testing for Lynch syndrome. Genetic counselors can be located through the National Society of Genetic Counselors website. While genetic testing is advancing, randomized controlled trials are needed to establish clinical utility.
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.
The document discusses classification and treatment of triple negative breast cancer (TNBC). It begins with an overview of TNBC classification including molecular subtypes. It then describes the clinical characteristics and prognosis of TNBC compared to other breast cancer types. Treatment options discussed include chemotherapy with taxanes and platinum agents shown to be effective. Other potential targeted therapies mentioned include PARP inhibitors, EGFR inhibitors, angiogenesis inhibitors, and tyrosine kinase inhibitors.
1. cancer care.pdf medical surgical nursing 1akoeljames8543
This document provides an overview of cancer principles and concepts in Kenya. It discusses Kenya's health policy goals to address rising non-communicable diseases like cancer. Cancer arises due to uncontrolled cell growth and can spread through the body. Risk factors include genetics, behaviors, age, and environmental exposures. Diagnosis relies on tissue biopsy. Cancer management involves multidisciplinary teams. Prevention strategies include screening and avoiding risk factors. Genetic testing can assess cancer risk in families with predispositions. The cell cycle is important to understand cancer development.
The document discusses testicular anatomy and germ cell tumors. It describes the following key points:
1) The testis is the male gonad homologous to the female ovary. The primary lymphatic drainage of the testis is to the retroperitoneal lymph nodes.
2) Germ cell tumors are the most common testicular cancers. They include seminomas and non-seminomas such as embryonal carcinoma, yolk sac tumor, teratoma, and choriocarcinoma.
3) Diagnostic workup involves tumor markers such as AFP, beta-HCG, LDH, and radical inguinal orchiectomy for tissue diagnosis and staging. Biopsy
This document provides an overview of sexually transmitted infections (STIs) for clinicians. It discusses the most common bacterial, viral and parasitic STIs including their epidemiology, diagnosis and treatment recommendations. Screening and prevention strategies are also reviewed, including behavioral counseling, vaccination, condom use and expedited partner therapy. The impacts of STIs on women's reproductive health are highlighted.
This document discusses the differential diagnosis and management of vulvovaginal disorders. It begins by categorizing common conditions into infections (trichomoniasis, bacterial vaginosis, vulvovaginal candidiasis), skin conditions (fungal vulvitis, contact dermatitis, vulvar dermatoses), and psychogenic causes. It then provides detailed guidelines on evaluating, diagnosing, and treating specific infections like trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. It also reviews vulvar conditions like lichen sclerosus, contact dermatitis, and classifications of vulvar dermatoses.
This document provides information about migraine in women. Some key points:
- Migraine is 3 times more common in women than men. Hormonally-associated migraines affect 12 million women in the US.
- Migraines are often associated with changes in hormone levels, such as during menstruation, pregnancy, use of oral contraceptives, and menopause.
- Diagnosis of migraine involves evaluating symptoms such as headache duration/intensity, nausea, light/sound sensitivity, visual/sensory disturbances (aura).
- Treatment involves both acute symptomatic relief and preventive medications, though choices are more limited during pregnancy/breastfeeding due to safety.
This document discusses 5 case studies involving GI disorders in women. The first case involves a 32-year-old woman with 5 years of diarrhea and abdominal pain. The next best step is reassurance without further testing, as her symptoms are consistent with irritable bowel syndrome. The second case involves a 38-year-old woman with vomiting after gastric bypass surgery, where an internal hernia is the most likely cause. The third case involves a pregnant woman referred for irritable bowel syndrome, where testing her for celiac disease is the next best step. The fourth case involves constipation, where pelvic floor dysfunction is the most likely diagnosis given her exam findings. The fifth case involves a 58-year-old woman with diarrhea
Here are my recommendations for the 56 year old woman with subclinical hypothyroidism:
1. Her diagnosis is subclinical hypothyroidism based on an elevated TSH of 7.1 and normal free T4.
2. Given her age (56), fatigue, and 3-4 lb weight gain, I would recommend a trial of levothyroxine therapy. Treatment is reasonable for patients with TSH >10 or positive thyroid antibodies, which she does not have data for. However, treatment may modestly improve her lipids and symptoms.
3. She should be monitored every 6 months with TSH checks to ensure her TSH is maintained between 0.5-2.0 and that she does not
The document announces the Women's Health 2012 Congress hosted by the NIH Office of Research on Women's Health. It will feature scientific poster awards for Women's Health and Sex Differences Research. The congress focuses on women's health issues and research.
The document discusses how the Affordable Care Act (ACA) aims to improve access to preventive health services for women by requiring new health plans to cover recommended preventive services without cost sharing. This includes services for cancer screening, chronic disease prevention and management, vaccinations, healthy behaviors counseling, pregnancy-related care, and reproductive health services. The new rules apply to new private health plans starting in 2010 and 2012, with some exemptions for grandfathered and religious plans. Implementation will consider factors like network restrictions, separate billing for visits and services, and ensuring adequate provider training and capacity.
The document summarizes the charge given by the Institute of Medicine to convene a committee of experts to review women's preventive health services and identify gaps. The committee was tasked with recommending services to be included in comprehensive national guidelines. After reviewing evidence, the committee made 8 recommendations, including screening for gestational diabetes, HPV testing, counseling on STIs and HIV, contraception services, lactation support, interpersonal violence screening, and annual well-woman visits.
This document summarizes key aspects of the Affordable Care Act (ACA) and how it benefits women's health and preventive care. It discusses how the ACA expands insurance coverage to over 34 million Americans, strengthens consumer protections, and requires insurers to cover preventive services for women at no additional cost. Specifically, it outlines services that must be covered for pregnant women, various cancer and disease screenings, counseling services, contraception and sterilization coverage, lactation support, and violence screening. It also notes that some existing "grandfathered" health plans are exempt from some ACA requirements but still must cover certain new benefits.
Dr. Iglesia has no conflicts of interest to disclose. The objectives of the document are to develop effective treatment plans, communicate treatment goals, minimize medication side effects, and describe new therapies for overactive bladder in women. Overactive bladder affects millions of Americans, especially women, and prevalence increases with age. New therapies aim to change stereotypes about overactive bladder and provide realistic information about prevalence and severity. Behavioral interventions like pelvic floor exercises and bladder training can be effective treatment approaches.
The document discusses cervical cancer screening guidelines and strategies, comparing the use of Pap tests, HPV tests, and primary HPV screening. It provides information on the epidemiology of HPV and progression to cervical cancer, as well as data from studies showing that primary HPV screening can detect more high-grade cervical lesions than cytology alone.
The document discusses depression in women and improving outcomes. Major depression has a significant public health impact and is the leading cause of disability among women worldwide. Women experience depression rates 1.5-2.5 times higher than men ages 15-54. Key ways to improve outcomes include considering differential diagnoses, treating to remission, measuring symptom improvement, using evidence-based interventions personalized to the individual woman, and providing self-help resources.
This document discusses strategies for managing obesity in women. It notes that obesity is influenced by multiple factors including genetics, environment, diet, physical activity, and life events. Key life events that can influence weight gain include pregnancy, menopause, and aging. Maternal obesity increases health risks for both mother and child during pregnancy and the child's future obesity risk. Abdominal obesity, as measured by waist circumference, is a better predictor of health risks than BMI alone. Managing obesity requires addressing its underlying causes through lifestyle changes.
This document is an in memoriam for Trudy L Bush, a professor of epidemiology and preventive medicine at the University of Maryland who passed away in 2001. It summarizes her landmark research on the effects of hormones on various body systems, her trailblazing leadership in the field of women's health, and her tireless commitment to medical education relating to women's health and menopause. The document honors her memory with an annual lecture series.
Evidence based management of cardiovascular disease in women plmiami
1. Evidence Based Management of Cardiovascular Disease in Women discusses the leading causes of death in Americans and how cardiovascular disease is the number one killer of women.
2. The document reviews gender differences in atherosclerosis, such as plaque erosion being more common in women than plaque rupture seen in men, making diagnosis of cardiovascular disease more difficult in women.
3. Prevention strategies discussed include reducing atherosclerosis, preventing plaque rupture and erosion, limiting thrombosis, and recognizing the presence of cardiovascular disease in women.
This document discusses care of cancer survivors and outlines the following key points in 3 sentences:
1) Approximately 3% of the population are cancer survivors, with many being elderly and having multiple comorbidities. 2) Both cancer-related and general medical needs must be addressed in cancer survivors, including surveillance for recurrence, late effects of treatment, and new primary cancers as well as screening and management of comorbidities. 3) The role of primary care physicians in providing ongoing care for cancer survivors along with survivorship care plans is reviewed.
This document discusses factors that influence peak bone mass attained during adolescence and young adulthood. It notes that genetics account for 80% of variability in peak bone mass, and lists several genes associated with bone mineral density and fracture risk. Nutrition, physical activity, body composition, endocrine status like age of menarche, and use of birth control also impact peak bone mass. Regular weight-bearing exercise and adequate calcium, vitamin D, and protein intake during growth can help increase bone mass accrual and attain a higher peak.
This document summarizes best practices in lesbian health based on a presentation by Dr. Patricia Robertson. It finds that lesbians have higher rates of smoking, childhood abuse, obesity, and certain STIs. They have lower rates of Pap smears and mammograms due to cost and prior adverse experiences. The document recommends screening lesbians appropriately, discussing family planning options, ensuring legal protections for partners, and advocating for lesbian health in the community. Providers should encourage disclosure of sexual orientation to provide culturally competent care.
This document summarizes evidence-based care of women with rheumatoid arthritis (RA). It discusses that RA is a chronic inflammatory disorder that principally affects the synovial joints. It is characterized by a proliferative response in the synovium leading to bone and cartilage destruction. The document reviews who is affected by RA, common articular features, characteristic deformities, and extra-articular manifestations. It also discusses the natural history of RA and whether there are any gender differences. Current management approaches from 2012 are presented, including early diagnosis, prompt initiation of traditional DMARDs, and appropriate use of biological DMARDs.
This document discusses gender differences in substance abuse. It finds that while males have higher rates of substance use, females are at least as vulnerable to substance abuse and may become dependent more rapidly if given the opportunity. Specifically, females are more likely than males to become dependent on sedatives, anxiolytics, and opioids. Animal studies also show females self-administer more of several substances and acquire drug conditioning faster. Overall, the document suggests the vulnerability to substance abuse is similar between males and females.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
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Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...
Am 7.15 shulman
1. Lee P. Shulman MD
The Anna Ross Lapham Professor of Obstetrics and Gynecology and Chief
Division of Clinical Genetics
Director, Northwestern Ovarian Cancer Early Detection and Prevention
Program
Co-Director, Cancer Genetics Program
The Robert S. Lurie Comprehensive Cancer Center
Feinberg School of Medicine of Northwestern University
Chicago, Illinois
3. Inherited Cancer
Earlier age of onset
Higher rate of bilaterality
Associated tumors
Not distinguished by pathology, metastatic
pattern or survival characteristics
4. KNUDSON
Two-step process
First: germinal or somatic mutation
Second: somatic mutation
5. The Genetics of Cancer
Intact Tumor Suppressor Gene X
XX Killed Cell
XXX
Normal Cell
Tumor Suppressor Gene Mutation
X
XXX
XX
XXX
XX
XX
Cancerous Cell
6. Comparison of Oncogenes and Tumor-
Suppressing Genes
ONCOGENES TUMOR-SUPPRESSING
Gene active Gene inactive
Specific translocations Deletions or mutations
Translocations somatic Mutations auto dominant or
nonhereditary
Dominant at cell level Recessive at cell level
Leukemia/lymphoma Solid tumors
7. Why do cancer risk assessment and genetic
testing for hereditary cancer syndromes?
Our best opportunity to determine risk for
cancer development
For carriers, positive status will impact
surveillance/prevention recommendations
For non-carriers in families with
mutation, avoids unnecessary interventions
For non-carriers in families without a delineated
mutations, may not alter risk
Offer risk-reducing surgery
Information for family members
Reproductive decision-making
9. Genetic cancer syndromes in
women’s health
Hereditary Breast Ovary Cancer Syndrome
BRCA1/BRCA2 (HBOC: 17q21/13q12-13)
Breast
Ovarian Epithelial (OEC)
Lynch Syndrome (HNPCC)
Multiplex mismatch repair (MMR) genes
Colorectal
Endometrial
OEC
10. Genetic cancer syndromes in women’s
health
Cowden syndrome (10q23.3)
Multiple hamartomas
Thyroid cancer
Male and female breast cancer
Endometrial cancer
Li-Fraumeni syndrome (TP53)
Early onset breast cancer
Childhood malignancies:
brain, stomach, lung, pancreas, ovary, melanoma
50% risk fo cancer by age 40, 90% by age 60
11. BRCA1/2
Tumor suppressing genes
Role in cell cycle regulation
Dominant inheritance with relatively
high penetrance
12. BRCA1/2
Tumor suppressing genes
Role in cell cycle regulation
Dominant inheritance with relatively
high penetrance
13. BRCA1
17q21
Female mutation carriers
85% lifetime risk of breast CA
○ 20% develop by age 40
○ 51% by age 50
○ 85% by age 70
10% of women with breast CA under the age of
35 are mutation carriers
40-60% lifetime risk of ovarian CA
Shulman LP. Obstet Gynecol Clin N Am 2010
14. Breast & Ovarian Cancer Risks Associated with BRCA1 Alterations
90
80
70
60
50
40
30
20
10
0
AGE020406080
BRCA 1 - Breast
General Population - Breast
BRCA 1 - Ovarian
General Population - Ovarian
15. BRCA2
13q12-13
Lifetime breast cancer risk: 80%
Lifetime ovarian cancer risk: 12-15%
Lifetime male breast cancer risk: 6%
100-fold increase in male breast cancer risk
compared to general population
Shulman LP. Obstet Gynecol Clin N Am 2010
16. Breast & Ovarian Cancer Risks Associated with BRCA2 Alterations
90
80
70
60
50
40
30
20
10
0
AGE020406080
BRCA 2 - Breast
General Population - Breast
BRCA 2 - Ovarian
General Population - Ovarian
17. BRCA1/2 Founder Mutations
Frequency of BRCA1/2 mutations in general
population approximately 1/500
Frequency of BRCA1/2 mutations in Ashkenazi
Jewish community approximately 1/40
3 mutations comprise 98% of mutations detected in AJ
community
○ BRCA1: 185delAG, 5382insC
○ BRCA2: 6174delT
Icelandic founder mutation in BRCA2: 999delG
accounts for 7% of all EOC cases in Iceland
Shulman LP. Obstet Gynecol Clin N Am 2010
18. Ovarian Cancer
Lynch (HNPCC)
Colon
Endometrial
Breast
8-10% lifetime risk for developing OEC
Specific criteria for genetic screening:
microsatellite instability (MSI genes) per Bethesda
criteria
Colonoscopy and endometrial surveillance remain
the main screening modalities
Shulman LP. Obstet Gynecol Clin N Am 2010
19. Lynch syndrome – Genetics
Multistep mismatch repair (MMR) system
Gene products are involved in correcting
single base pair mistakes that can occur
during DNA replication
○ MLH1cloned in 1994 (3p21)
○ MSH2cloned in 1993 (2p21-22)
○ MSH6cloned in 1997 (2p15)
○ PMS2cloned in 1994 (7p22)
Shulman LP. Obstet Gynecol Clin N Am 2010
20. Mismatch Repair Genes
MSH6
MLH1
MSH2
PMS2
PMS1?
Chr 7
Chr 3
Chr 2
HNPCC is associated with germline mutations
in any one of four mismatch repair genes
21. Lynch
Syndrome
Few adenomas
80% CRC risk, mean 44 yrs
More proximal colonic
Frequent synchronous and
metachronous CRC
MMR mutations:
MLH1, MSH2, MSH6, PMS2
Burt, J Natl Compr Canc Netw 2010; 8:8-61
Jasperson, Burt, Gastroenterol, 2010; 138:2044
23. Other Cancer Predisposition
Genes: KRAS?
Ratner et al 2010
○ Genetic marker for non-small-cell lung cancer
○ Present in fewer than 18% of other solid tumors
○ KRAS-variant associated with more than 25% of nonselectedOEC
cases.
○ Marker for significant increased risk of developing OC
○ KRAS-variant present in 61% of HBOC patients without BRCA1 or
BRCA2mutations
○ KRAS-variant may be a new genetic marker of cancer risk for
HBOC families without other known genetic abnormalities.
Ratner et al. Cancer Res 2010
24. Other Putative Genetic Etiologies for OEC
RAD15C germline mutations
Clague et al PLoS ONE 6(9) 2011
Genome-wide Association Studies
19p13 (Bolton et al, Nat Genet 2010)
2q31 (Goode et al, Nat Genet 2010)
8q24 (Goode et al, Nat Genet 2010)
Telomeres
Structures at end of chromosomes that contribute to genomic
stability
Shortening with repeated cell divisions may lead to genomic
instability and carcinogenesis
Women with serous OEC had shorter telomeres than age-matched
controls (Mirabello et al Cancer Causes Control 2010)
25. BRCA1/2 Counseling
Family/personal history is the primary method
to determine risk for cancer predisposition
syndrome, likelihood of mutation and risk for
cancer development
Advise of current limitations of screening
Negative results IN NO WAY guarantee
protection
Positive results do not guarantee malignancy
Implications of negative/positive results with
regard to screening/diagnostic and therapeutic
options
26. Criteria for Further Risk Evaluation
Affected individual with one or more of the following:
Early-age-onset breast cancer
Triple negative (ER-, PR-, HER2-) breast cancer ·
Two breast cancer primaries
Breast cancer at any age, with
○ > 1 close blood relative with breast cancer < 50 y
○ > 1 close blood relative with OEC/FT cancer at any age
○ >2 close blood relatives with breast cancer/pancreatic cancer at any age
A combination of breast cancer with one or more of the following: thyroid cancer, sarcoma,
adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain tumors, diffuse gastric
cancer,dermatologic manifestations or leukemia/lymphoma on the same side of family
Ovarian/fallopian tube/primary peritoneal cancer
Male breast cancer
An unaffected individual with a family history of one or more of the following:
○ > 2 breast primaries from the same side of family (maternal or paternal)
○ >1 ovarian primary from the same side of family (maternal or paternal)
○ A combination of breast cancer with one or more of the following: thyroid cancer, sarcoma,
adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain tumors, diffuse gastric
cancer, dermatologic manifestations or leukemia/lymphoma on the same side of family
A known mutation in a breast cancer susceptibility gene ·
From a population at risk
Male breast cancer
NCCN Guidelines, Version 1.2011
27. Assessment
Patient needs and concerns: ·
Knowledge of genetic testing for cancer risk, including benefits, risks, and limitations
Goals for cancer family risk assessment
Detailed family history
Expanded pedigree to include first-, second-, and third- degree relatives (parents, children,
siblings, aunts, uncles, nieces, nephews, grandparents, grandchildren, half-siblings, great-
grandparents, great-aunts, great-uncles, great-grandchildren, first-cousins
Types of cancer
Bilaterality
Age at diagnosis
History of chemoprevention and/or risk-reducing surgery
Medical record documentation, particularly pathology reports of primary cancers
Detailed medical and surgical history
Any personal cancer history
Carcinogen exposure (eg, history of radiation therapy)
Reproductive history
Hormone use
Previous breast biopsies
Focused physical exam (refer to specific syndrome)
Breast/ovarian
Dermatologic,f including oral mucosa
Head circumference
Thyroid
NCCN Guidelines, Version 1.2011
28. Hereditary Breast/Ovarian Genetic
Testing Criteria
Individual from a family with a known deleterious BRCA1/BRCA2
mutation
Personal history of breast cancer + one or more of the following:
Diagnosed age <45 y
Diagnosed age <50 y with >1 close blood relative with breast cancer <50 y and/or >1
close blood relative with epithelial ovarian/fallopian tube/primary peritoneal cancer at
any age
Two breast primaries when first breast cancer diagnosis occurred prior to age 50 y
Diagnosed age < 60 y with a triple negative breast cancer
Diagnosed age < 50 y with a limited family history (e.g., adoption)
Diagnosed at any age, with >2 close blood relatives with breast and/or epithelial
ovarian/ fallopian tube/ primary peritoneal cancer at any age
Close male blood relative with breast cancer
Personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer
For an individual of ethnicity associated with higher mutation frequency (e.g., Ashkenazi
Jewish, Icelandic), no additional family history may be required.
NCCN Guidelines, Version 1.2011
29. Hereditary Breast/Ovarian Genetic
Testing Criteria (cont’d)
Personal history of epithelial ovarian g/fallopian tube/ primary peritoneal
cancer
Personal history of male breast cancer
Personal history of breast and/or ovarian cancer at any age with >2 close
blood relatives with pancreatic cancer at any age
Personal history of pancreatic cancer at any age with >2 close blood
relatives with breast and/or ovarian and/or pancreatic cancer at any age
Family history only:
First- or second-degree blood relative meeting any of the above criteria
Third-degree blood relative with breast cancer and/or ovarian/fallopian tube/ primary
peritoneal cancer with >2 close blood relatives with breast cancer (at least one with
breast cancer <50 y) and/or ovarian cancer
NCCN Guidelines, Version 1.2011
30. BRCA1/2 Testing
Bestto first assess affected
family members whenever
possible (insurance
issues, costs), especially in cases
of sporadic disease
31. Variant of Uncertain Significance (VUS)
A sequence within a gene not typically
found in the general population and not
consistently associated with disease
VUS found in approximately 12% of
women tested for BRCA1/2 status1
VUS should be discussed in all genetic
counseling sessions for individuals
considering genetic testing2
1. Domchek et al. J Clin Oncol 2008
2. Miller-Samuel et al. Semin Oncol 2011
32. Variant of Uncertain Significance (VUS)
Clinical response to VUS is based on the
reason for undergoing testing
Clinical response also based on
ethnic/racial background if gene mutations
are found in certain ethnic/racial groups
More detailed family history (e.g., medical
records) will help to better delineate risk if
VUS is found
Testing of other family members, especially
those with cancer, is invaluable to
determine the clinical implication of VUS
Miller-Samuel et al. Semin Oncol 2011
33. Variant of Uncertain Significance (VUS)
Over time, the status of some VUS will
change based on studies of the
sequence in other individuals.
Deleterious mutation
Polymorphism
Favor deleterious
Favor polymorphism
Miller-Samuel et al. Semin Oncol 2011
34. Genetic predisposition to gynecologic
cancer syndromes
Summary
Family/personal history-taking remains THE
vital component of cancer risk assessment
At-risk women should be offered genetic
testing when appropriate
“If you have a hammer, everything is a nail”
Not every woman at increased for OEC is at risk for
BRCA1/2; consider associated malignancies in family
Surveillance and conservative prevention
strategies available
Effective surveillance for breast cancer
Effective prevention for ovarian cancer
35.
36. Breast and Ovarian Cancer
Epidemiology
Estimates for 2012
Breast cancer
226,870 new cases (26% of all cancer)
○ Up from 212,920 (31%) in 2006
39,920 deaths (15% of all cancer deaths)
○ Down from 40,970 (15%) in 2006
1975 to 2002 – survival improved 75 to 89%
Second behind lung cancer as a cause of cancer
death in women
Ovarian cancer
22,280 new cases (3% of all cancers)
○ Up from 20,180 in 2006
15,500 deaths (6% of all cancer deaths)
○ Up from 15,310 in 2006
Causes most deaths from cancers of the female
reproductive system
Data from http://www.cancer.org, 2 February 2012
37. Clinical Implications
Improved ability to assess risk
Limited ability to provide clinically useful
interventions
Little information regarding interaction
of multiple risk factors
Few options for women at increased risk
for breast cancer – increased
surveillance but few conservative
preventative options
39. Patients with 5-10% chance of being in
HBOC family
Breast cancer ≤40
Bilateral breast cancer (esp. if 1st occurred
<50)
Breast cancer ≤50 and close relative with
breast cancer ≤50
Jewish women with breast cancer ≤50
2 or more close relatives with any of these
criteria
SGO Committee Statement, 2007
40. Patients with > 25% chance of being in
HBOC family
Personal hx of both breast and ovarian cancer
Have ovarian cancer AND close relative with
ovarian cancer (any age) or breast cancer
(<50)
Jewish women with ovarian cancer (any age)
or breast cancer (<40)
Have breast cancer (<50) and close relative
with ovarian cancer (any age) or male with
breast ca
1° or 2° relative with known BRCA1 or BRCA2
mutation
SGO Committee Statement, 2007
41. 2007 ACS Guidelines for MRI
Women at high risk (> 20% lifetime
risk)
MRI plus mammogram every year
Women at moderately increased risk
(15-20%)
Consult with their doctors about benefits
and limitations of adding MRI to yearly
mammograms
Women with lifetime risk < 15%
Yearly MRI screening is not recommended
42. Recommendations for TamoxifenCandidates
Women with 5-year risk of breast cancer >
1.66% should be offered option of tamoxifen
Greatest benefit seen with least side effects
Premenopausal women
Women without a uterus
Women > 5% 5-year risk
Chlebowski RT, et al. J Clin Oncol. 2002;20(15):3328-43
IBIS Investigators. Lancet. 2002;360:817-24
43. Prophylactic Mastectomy
Total (simple) mastectomy appears more
effective than subcutaneous mastectomy
Shown to reduce risk of breast cancer in
women with BRCA mutations by 90-94%
New Engl J Med 2001;345:159-64
44. Typical Intraoperative Appearance of Stage III Epithelial Ovarian Cancer
Advanced epithelial ovarian cancer
No “precursor
lesion”
Most diagnosed in
Stage 3 or 4
Mortality rates
directly correlated
with stage at
diagnosis
Cannistra, S. A. N Engl J Med 2004;351:2519-2529
45. Lifetime
Family History of Ovarian Cancer Risk
None 1.5%
1 first-degree relative 5%
2 first-degree relatives 7%
Hereditary ovarian cancer
40%
syndrome
Known BRCA1, BRCA2, Lynch
10-50%
mutation
Shulman LP. Obstet Gynecol N Am 2010
46. Ovarian Cancer: Risk Reduction
Birth control pills
First full-term pregnancy < age 25;
number of pregnancies
Breast-feeding
BTL/hysterectomy RR 0.33/0.67
Prophylactic salpingo-oophorectomy
Reduced risk of primary peritoneal cancer
remains
Shulman LP. Obstet Gynecol N Am 2010
47. Chemoprevention of Ovarian
Cancer
Oral Contraceptives
The risk of ovarian cancer was 60% lower
among women with mutations in BRCA1 and
BRCA2 who used oral contraceptives for > 6
years
New Engl J Med 1998; 339:424-8
New Engl J Med 2001;345:235-40
48. Chemoprevention of Ovarian
Cancer
RCGP Oral Contraception Study
• 339,000 wy never users compared to
744,000 wy ever users
• Relative Risks
• Breast 0.98
• Uterine Body 0.58*
• Ovary 0.54*
Hannaford et al. BMJ 2007;335:651.
49. Breast Cancer in Women at High-
Risk for Ovarian Cancer Using OCs
Comparative study: 1,156 cases of invasive breast
cancer (47 BRCA1 and 36 BRCA2) and 815 controls
using low dose oral contraceptives
OC use for at least 12 months reduced risk of breast
cancer for BRCA1 (OR 0.22) and no change for BRCA
2 (1.02) or noncarriers (0.93)
OC use in women who are BRCA mutation carriers will
not increase the risk for breast cancer and will likely
reduce the risk for ovarian cancer
Milne et al 2005
50. Ovarian Cancer
OC use will reduce the risk of developing
ovarian cancer1
5 years of use: 27% reduction
15 years of use: 80% reduction
Average 5% risk reduction per year of OC use2
Protective effect diminishes 10 years after
cessation
Effects are associated with all combination OCs
Tubal ligation will reduce the risk of
developing ovarian cancer by 50%3
1. Cibula D et al Hum Reprod Update 2010
2. Lurie G et al Epidemiology 2008
3. Cibula D et al Hum Reprod Update 2011
51. Why Tubal Ligation?
Initially thought to be associated with reduced
blood flow to ovaries resulting from tubal
ligation1
Theories as to tubal ligation causing a
separation of the ovaries from the rest of the
genital tract to reduce ovarian inflammation2,3
Studies of inflammation and decreases in
estrogen levels and follicle numbers and activity
have failed to support the aforementioned
theories4,5
1. Hankinson SE et al. JAMA 1993
2. Green A et al. Int J Cancer 1997
3. Ness RB, et al. Epidemiology 2000
4. Merritt MA et al. Int J Cancer 2007
5. Carmona F, et al. AJOB 2003
52. Ovarian Cancer: Fallopian
Tube?
122 BRCA1/2 positive women undergoing
prophylactic BSO
7 early malignancies (5.7%)
All 7 originated in the fimbrial and ampullary
regions of the fallopian tubes
○ 2 with surface implants on the ovarian surface
○ 2 cases required more detailed sectioning of the FT
to detect malignancy
Callahan et al. J Clin Oncol 2007
53. Ovarian Cancer: Fallopian
Tube?
Serous tubal intraepithelial carcinomas (STICs)
Secretory cells showing significant atypia
By immunohistochemistry, STICs contain p53
mutations and are mostly highlighted by nuclear
accumulation of mutated p53 protein
Highly proliferative
p53 signature
Benign secretory outgrowth in fimbria and is a putative
cancer precursor
1. Crum CP. Mol Oncol 2009
2. Chen EY et al. J Pathol 2010
55. Population-Based Screening for
Ovarian Cancer: NO!
The Prostate, Lung, Colorectal and Ovarian
(PLCO) Cancer Screening Randomized
Controlled Trial
78,216 women 55-74
Annual screening vs. usual care
Annual screening: CA-125 for 6 years and TV-
USG for 4 years.
○ CA-125 > 35U/ml
○ Ovarian volume greater than 10 cm3
○ Cyst volume greater than 10 cm3
○ Any solid area or papillary projection extening into
the cavity of a cystic ovarian tumor of any size
○ Any mixed (solid and cystic) component
Buys SS et al. JAMA 2011
56. PLCO
OEC diagnosed
○ 5.7/10,000 person-years in intervention group
○ 4.7/10,000 person-years in routine care group
○ Rate ratio 1.21 (95% CI: 0.99-1.48)
Deaths
○ 3.1/10,000 person-years in intervention group
○ 2.6/10,000 person-years in routine care group
○ Rate ratio 1.18 (95% CI: 0.82-1.71)
Buys SS et al. JAMA 2011
57. Current Screening
Guidelines
“…annual screening for ovarian cancer,
as performed in the PLCO trial…does
not reduce disease-specific mortality in
women at average risk for ovarian
cancer but DOES (emphasis added)
increase invasive medical procedures
and assocaited harms.”
Buys SS, et al. JAMA 2011
58. Screening for Ovarian Cancer in a
High-Risk Community: Not Yet!
Increased surveillance
Serum biomarkers
Transvaginal ultrasound
59. Screening approaches
Genetic
Imaging
Biochemical
Symptom index
Combination/Multiplex
None have been shown to
consistently detect early lesions or
reduce mortality
60. Increased surveillance
No evidence to support a decrease in
mortality from increased surveillance
Genetic counseling and testing increased
surveillance and led to risk-reducing
surgeries that resulted in the prevention
of OEC and the detection of early-stage
tumors in women with BRCA1 and
BRCA2 mutations
Scheuer L et al. J Clin Oncol 2002
62. NOCEDPP
Ultrasound Screening in a high-risk population
12,709 scans in 4,526 “high-risk” women
Ultrasound screening alone ineffective for detecting
early stage ovarian cancer
Fishman, Cohen, Blank, Shulman et al. Am J Obstet Gynecol 2005
63. University of Kentucky Ovarian Cancer
Screening Project Update: 2009
31,748 women
22.8% with a positive family history
TVS better than Symptom Index (SI) for the detection of
malignancies
DR: 73.3% v. 20%
SI better than TVS for delineating benign lesions
91.3% v. 74.4%
Use of TVS and SI resulted in poor identification of
malignancies (16.7%) but improved distinguishing of benign
lesions (97.9%)
Pavlik EJ, et al. Cancer
Volume 115, Issue 16, pages 3689-3698, 14 JUL 2009 DOI: 10.1002/cncr.24407
64. Use of symptom index
Major associated symptoms
Pelvic pain
Abdominal pain
Increased abdominal size
Bloating
Feeling full early
Difficulty eating
Sensitivity: 56.7% early st
Screen “positive” if any symptoms
79.5% adv st
present for < 1yr, but occurred >12 times
2-3% of general population
per month
had positive screen
Goff et al, Cancer 2007
65. Ovarian cancer biomarkers
CA-125
Elevated in about 1% normal
women, 80% of epithelial ovarian
cancers (50% of St I disease)
PPV alone <10%, around 20% in combo
with sonography
May perform better as serial assay
66.
67. Lynch syndrome: Screening/Management
Annual colonoscopy
Colon initiated between 20-25
Endometrial/Ovarian Annual TVU w/ color
Doppler, CA-125 and
endometrial aspirate
beginning at age 25-35
Annual
Gastric esophagogastroduodenosc
opy (EGD) beginning at
age 30
Upper Epithelial Tract (also Annual urinanalysis w/
with MTS) cytology and renal
ultrasound beginning at
age 30
Liver Annual LFTs beginning at
age 30
Skin Tumors (MTS) Annual dermatologic exam
68.
69. Women with a Pelvic Mass are at Risk for
OEC
20% of women will be diagnosed with an
adnexal mass1
300,000 per annum in U.S.
5-10% of women will have surgery for an
ovarian neoplasm2
13-21% of these masses will be malignant2
1.Curtin JP. Gynecol Oncol. 1994;55:S42-S46.
2. NIH Consensus Development Conference Statement. Gynecol Oncol. 1994;55:S4-S14.
70. Work-up of Adnexal Mass
Must first categorize as functional, benign neoplastic
or potentially malignant
Diagnostic approach depends on:
Age Ultrasound configuration
Size of mass Color-flow Doppler flow
Unilateral vs. bilateral Presence of symptoms
CA-125 levels
71. ACOG and SGO Referral Guidelines
Newly Diagnosed Pelvic Mass
Premenopausal Postmenopausal
(<50 years of age) (≥50 years of age)
CA 125 >200U/ml) CA 125 >35U/ml
Ascites Ascites
Nodular or fixed pelvis mass
Evidence of abdominal or
Evidence of abdominal or
distant metastasis (by distant metastasis (by exam or
exam or imaging study) imaging study)
Family history of breast or Family history of breast or
OC(in a first-degree OC(in a first-degree relative)
relative)
ACOG Practice Bulletin No. 83. Obstet Gynecol. 2007;110:201-14.
Im SS, et al. Obstet Gynecol. 2005;105:35-41.
72. Significantly Higher Survival
Rates with Oncology
Specialists
Type of Surgeon Impacts Type of Hospital Impacts
Survival Rates Survival Rates
1.0 1.0
0.8 0.8
Cumulative Survival
Cumulative Survival
0.6 0.6
TH: Teaching hospital
0.4 0.4
NTH: Nonteaching hospital
0.2 0.2
0.0 0.0
0 200 400 600 800 1000 0 200 400 600 800 1000
Survival in days Survival in days
Paulsen T et al. Int J Gynecol Cancer. 2006:16(suppl 1):11-17.
73. ACOG and SGO Referral Guidelines
Newly Diagnosed Pelvic Mass
Premenopausal Postmenopausal
(<50 years of age) (≥50 years of age)
CA 125 >200 U/ml) CA 125 >35 U/ml
Ascites Ascites
Evidence of abdominal or Nodular or fixed pelvis mass
distant metastasis (by Evidence of abdominal or
exam or imaging study) distant metastasis (by exam or
imaging study)
Family history of breast or
Family history of breast or OC
OC(in a first-degree
(in a first-degree relative)
relative)
ACOG Practice Bulletin No. 83. Obstet Gynecol. 2007;110:201-14.
Im SS, et al. Obstet Gynecol. 2005;105:35-41.
74. Ultrasound Evaluation
of a Pelvic Mass
Sensitivity Specificity PPV NPV
Study
(%) (%) (%) (%)
DePriest et al.
88 40 28 93
(1993)
Pavlik et al. (2009) 73.3 74.4 26.2 95.7
PPV = positive predictive value
DePriest PD, et al. Gynecol Oncol. 1993;51:7-11.
NPV = negative predictive value
NA = not available Pavlik EJ, et al. Cancer. 2009;115:3689-98.
76. RMI
Risk of Malignancy Index
RMI = USG x [M]eno status x serum CA 125 level
USG = 0 for imaging score of 0
= 1 for imaging score of 1
= 3 for imaging score of 2-5
M = 1 if premenopausal
= 3 if postmenopausal
• (1990) 85% sensitivity/97% specificity1
• (2012) 80% sensitivity/92% specificity/PPV 83%2
1. Jacobs I et al. Br J Obstet Gynecol.1990; 97:992-929.
2. Hakansson et al Acta Obstet Gynecol Scand 2012
77. OVA-1™ Multiple Serum Markers
• Approved for presurgical evaluation of women with
ovarian adnexal mass1
• 5 biomarkers2
– 2-microgobulin
– Apolipoprotein A1
– CA125
– Transferrin
– Transthyretin (prealbumin)
• Single numerical score (0-10) that indicates the
likelihood of malignancy1
1. OVA-1 package insert: Executive summary; Vermillion, Inc.2011.
2. OVA-1 test summary; Quest Diagnostics.2011.
78. ROMATM
Risk of Ovarian Malignancy Algorithm
• HE4 and CA125 + menopausal status
• Estimate the risk of malignancy in women
presenting with adnexal mass who will
undergo surgical intervention
• Calculation is performed on internet
Determine if patient should be referred to an
advanced cancer center
79. Pilot Study
Cross-validated Estimates of
Sensitivity Benign vs. Ovarian Cancer:
Average from Sensitivity at
Leave-One-Out Analysis
90% 95% 98%
Marker Combination Specificity Specificity Specificity
CA125 61.2% 43.3% 23.9%
HE4 77.6% 72.9% 64.2%
CA125 + HE4 80.7% 76.4% 71.6%
CA125 + HE4 + SMRP 80.6% 74.7% 71.7%
CA125 + HE4 + CA72-4 82.1% 78.8% 71.5%
Moore RG et al. Gynecol Oncol 2008;108:402-8.
80. ROMA™ vs RMI
Increased Sensitivity with ROMA
Benign (n = 312) vs EOC (n = 123)
All Patients
Sensitivity* (95% CI) Specificity(95% CI)
RMI 83.7% (76.0% - 89.8%) 75%(69.8% - 79.7%)
ROMA™ 94.3% (88.6% - 97.7%) 75%(69.8% - 79.7%)
*Two Sample Test of Equality of Proportions p=0.0129
CI: Confidence Interval
Moore et al, Am J Obstet Gynecol. 2010;203(3):228.e1-6.
82. Summary
The delineation of risk for breast and
ovarian cancer is made primarily by
personal and family history
Offering genetic testing should be only to
those at increased risk – genetic testing is
not yet appropriate for the general
population
Breast cancer is amenable to effective
screening protocols while OEC is amenable
to effective prevention protocols
83. Summary
Genomic factors play an important role in
the risk for development of gynecologic
malignancies except for cervical cancer
Most gynecologic malignancies occur in
women with little or no family history of the
malignancy
Detection of gene(s) that increase the
likelihood of cancer development will likely
improve screening, diagnosis and prognosis
assessment
Editor's Notes
Women at highest risk for being diagnosed with ovarian cancer are women that present with a pelvic mass or ovarian cyst. It is estimated that 1 in 5 women will be diagnosed with an ovarian cyst or adnexal mass sometime in their lifetime; and 5-10% of women will have surgery for an ovarian neoplasm each year in the US.Roughly 13% to 21% of these women will be diagnosed with an invasive epithelial ovarian cancer. ReferenceCurtin JP. Management of the adnexal mass. Gynecol Oncol. 1994;55:S42-S46. NIH Consensus Development Conference Statement. Gynecol Oncol. 1994;55:S4-S14.
ACOG and SGO provide joint guidelines for when to refer a women with a pelvic mass to a gynecological oncologists. ReferenceACOG Practice Bulletin, Clinical management Guidelines for Obstetrician-Gynecologists, Number 83, July 2007. Obstet Gynecol. 2007;110:201-14.Im SS, Gordon AN, Buttin BM, et al. Validation of referral guidelines for women with pelvic masses. Obstet Gynecol. 2005;105:35-41.
In a study, Paulsen demonstrated a significant survival advantage for patients with ovarian cancer that were operated on by gynecologic oncologists, compared with patients operated on by gynecologists or general surgeons. In addition, patients whose surgery was performed at a tertiary care hospital– versus a community hospital–also had a significant survival advantage.ReferencePaulsen T, Kjaerheim K, Kaern J, et al. Improved short-term survival for advanced ovarian, tubal, and peritoneal cancer patients operated at teaching hospitals. Int J Gynecol Cancer. 2006:16(suppl 1):11-17.
ACOG and SGO provide joint guidelines for when to refer a women with a pelvic mass to a gynecological oncologists. ReferenceACOG Practice Bulletin, Clinical management Guidelines for Obstetrician-Gynecologists, Number 83, July 2007. Obstet Gynecol. 2007;110:201-14.Im SS, Gordon AN, Buttin BM, et al. Validation of referral guidelines for women with pelvic masses. Obstet Gynecol. 2005;105:35-41.
ReferenceDePriest PD, Shenson D, Fried A, et al. A morphology index based on sonographic findings in ovarian cancer. Gynecol Oncol. 1993 Oct;51(1):7-11.Pavlik EJ, Saunders BA, Doran S, et al. The Search for Meaning—Symptoms and Transvaginal Sonography Screening for Ovarian Cancer. Cancer. 2009;115:3689–98.
ReferenceCopeland LJ. In Philip J. DiSaia & William T. Creasmann. Clinical Gynecology, 7th edition. Chapter 11 Epithelial Ovarian Cancer. Page 321.
Let’s examine how ROMA performs compared with risk assessment tools currently used in clinical practice.An algorithm that is used either formally or informally by clinicians to assess risk in a patient with a pelvic mass is the Risk of Malignancy Index or RMI developed by Ian Jacobs.The RMI employs an imaging score along with CA125 values and menopausal status to calculate a risk for malignancy. This is an algorithm that employs clinical findings on imaging and uses quantitative data to derive a patient’s risk for malignancy.ROMA was comparied to the RMI, which uses clinicopathologic variables to demonstrate that the performance of ROMA as a stand-alone test is superior to a currently used clinical algorithm.
OVA-1 is a risk-stratification tool intended for the presurgical evaluation of women with ovarian adnexal mass.1{PI, Exec Summary, p.1, para 2}OVA-1 utilizes the results of five biomarkers-- 2-microgobulin, apolipoprotein A1, CA125, transferrin, and transthyretin (prealbumin) to generate a numerical score between 0 and 10 that reflects the likelihood of ovarian malignancy.2{OVA1 test Summary, p.2, Method} The derived single score that separates low probability from high probability of malignancy is slightly different in premenopausal and postmenopausal women.1{PI, Exec Summary, p.2, last para}Low probability of malignancy in premenopausal women: < 5.0Low probability of malignancy in postmenopausal women: < 4.4References1. OVA-1 package insert: executive summary; Vermillion, Inc. (Accessed February 8, 2011, at http://www.ova-1.com/physicians/package-insert.)2. OVA-1 Test summary; Quest Diagnostics. (Accessed February 8, 2011, at http://www.questdiagnostics.com/hcp/intguide/jsp/showintguidepage.jsp?fn=HematOnc/Ovary/TS_OVA1.htm.)
The Risk of Ovarian Malignancy Algorithm, or ROMA, represents a risk assessment tool for ovarian cancer that combines HE4 and CA125 estimates, in conjunction with menopausal status. ROMA is intended to aid in estimating the risk of malignancy in premenopausal and postmenopausal women presenting with an adnexal mass who will undergo surgical intervention. ROMA findings must be interpreted in combination with independent clinical assessments.This tool will provide more useful information to physicians to ensure that patients are treated by the right physician in the right facility, and to better plan for and implement the most appropriate treatment and postoperative care.ReferenceROMA package insert {p.1, para 1}
We were able to calculate an RMI for 80% of the study patients. We compared these results to the ROMA for those individual patients. We found at a specificity of 75%, the RMI had a sensitivity of 85%, compared to the ROMA, which achieved a sensitivity of 94%. ReferenceMoore RG, Jabre-Raughley M, Brown AK, et al. Comparison of a novel multiple marker assay vs the Risk of Malignacy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol. 2010;203(3):228.e1-6.
OVA-1 was evaluated in a multicenter, prospective, double-blind clinical study in a total of 516 women, 54.5% of whom were postmenopausal.1 {PI Exec Summary, p 2, para 1} For subjects evaluated by a nongynecological oncologist, the sensitivity for ovarian malignancy increased from 72% to 92% with the dual use of a presurgical assessment and OVA-1 versus a single presurgical assessment alone. Specificity for ovarian malignancy declined however from 83% with the single presurgical assessment to 42% with the dual assessment that included OVA-1.1{PI Exec Summary, p.3, Table 2, para 3}With the use of the dual assessment, positive predictive value also declined; however, negative predictive value increased from 89.1% 93.2%.For nongynecological oncologists and oncological oncologists, the dual assessment using OVA-1 and a presurgical assessment, detected 82.5% of the cases missed by the clinical assessment alone.1 {PI ExecSummary, p.3, para 3}ROMA—combination of pre and post menopausal women.Cost of OVA-1: $650.00 retail; $516.25 Medicare (As per Vermillion’s Director of Marketing, Scott Henderson, May 18, 2011)ReferenceOVA-1 package insert: executive summary; Vermillion, Inc. (Accessed February 8, 2011, at http://www.ova-1.com/physicians/package-insert.)Moore RM, et al. Obstet Gynecol. 2001, In press.ROMA CSR, page 60Vermillion, Inc Press Release? Cost of test