This document discusses bone health management in breast cancer patients receiving adjuvant therapies. Key points include:
- Studies have shown that zoledronic acid and denosumab can reduce bone mineral density loss and fracture risk in premenopausal and postmenopausal breast cancer patients receiving adjuvant aromatase inhibitors or tamoxifen.
- The ABCSG-12 trial found that adding zoledronic acid to adjuvant endocrine therapy improved disease-free survival and overall survival in premenopausal breast cancer patients.
- The AZURE trial found no difference in disease-free survival or overall survival between breast cancer patients receiving standard adjuvant therapy with or without zoledronic acid, though pre/perimenopausal patients
Changing Landscape of Treatment for Multiple Myelomaspa718
1) Treatment for multiple myeloma has improved significantly over time, with median overall survival increasing from 30 months in 1971-1996 to 45 months in 1996-2006.
2) Newer proteasome inhibitors like carfilzomib have shown effectiveness in heavily pre-treated multiple myeloma patients, with overall response rates of 15-24% and median durations of response around 7-8 months. Dose escalation studies indicate carfilzomib is generally well-tolerated.
3) Other novel agents in clinical trials for relapsed/refractory multiple myeloma include second-generation proteasome inhibitors (e.g. oprozomib), immunomodulatory drugs (e
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
This document provides an overview of metastatic prostate cancer management by Dr. Mohamed Abdulla of Cairo University. It discusses:
- Basic facts about prostate cancer incidence and mortality worldwide
- Methods of primary hormonal manipulation including surgical or medical castration and LHRH agonists vs antagonists
- Complications of short and long-term androgen deprivation therapy
- The role of cytotoxic chemotherapy and its effect on overall and failure-free survival in metastatic and non-metastatic disease
- Management of oligometastatic disease and strategies to overcome castration-resistant prostate cancer including abiraterone, enzalutamide, docetaxel, cabazitaxel, and
Sequencing therapy for crcp a practical approachMohamed Abdulla
This document discusses sequencing therapy for castration-resistant prostate cancer (CRPC). It provides an overview of prostate cancer as an androgenic disease and summarizes several key clinical trials investigating the efficacy of abiraterone and enzalutamide in both pre-docetaxel and post-docetaxel CRPC patients. It concludes by presenting NCCN guidelines for sequencing CRPC therapies based on disease stage and symptoms.
Urology-Oncology Interface
The Grey Zone in Prostate Cancer Management
1) Prostate cancer is the second most common cancer in men and the second leading cause of cancer death in men. Testosterone and age are closely related to prostate cancer risk.
2) Effective treatments for prostate cancer have included orchiectomy, anti-androgen drugs like DES, and LHRH analogues, with scientists like Drs. Huggins and Schally winning Nobels for their work.
3) Managing testosterone levels is important, with levels of ≤30 ng/dL associated with longer survival versus >30 ng/dL. Maintaining levels <32 ng/dL was linked to longer time
Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of prostate cancer that has spread to other organs and continues to progress despite hormone therapy. Current treatments aim to reduce testosterone levels, disrupt microtubules during cell division, activate the immune system, or use radiopharmaceuticals, but all have limitations like toxicity or development of resistance. Researchers are exploring new targets and combinations of drugs to block cancer progression and prolong survival for men with mCRPC, which remains largely incurable.
The document discusses treatment options for patients with relapsed myeloma. It provides details on current treatment goals, classes of drugs used to treat relapsed myeloma, and clinical trial data on combinations of these drugs. Specifically, it summarizes clinical trial results showing improved progression-free and overall survival for combinations of bortezomib, lenalidomide, and dexamethasone compared to dexamethasone alone in relapsed patients. It also discusses factors to consider when selecting a salvage therapy for relapsed myeloma, including disease characteristics, prior treatments, and toxicity risks.
Changing Landscape of Treatment for Multiple Myelomaspa718
1) Treatment for multiple myeloma has improved significantly over time, with median overall survival increasing from 30 months in 1971-1996 to 45 months in 1996-2006.
2) Newer proteasome inhibitors like carfilzomib have shown effectiveness in heavily pre-treated multiple myeloma patients, with overall response rates of 15-24% and median durations of response around 7-8 months. Dose escalation studies indicate carfilzomib is generally well-tolerated.
3) Other novel agents in clinical trials for relapsed/refractory multiple myeloma include second-generation proteasome inhibitors (e.g. oprozomib), immunomodulatory drugs (e
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
This document provides an overview of metastatic prostate cancer management by Dr. Mohamed Abdulla of Cairo University. It discusses:
- Basic facts about prostate cancer incidence and mortality worldwide
- Methods of primary hormonal manipulation including surgical or medical castration and LHRH agonists vs antagonists
- Complications of short and long-term androgen deprivation therapy
- The role of cytotoxic chemotherapy and its effect on overall and failure-free survival in metastatic and non-metastatic disease
- Management of oligometastatic disease and strategies to overcome castration-resistant prostate cancer including abiraterone, enzalutamide, docetaxel, cabazitaxel, and
Sequencing therapy for crcp a practical approachMohamed Abdulla
This document discusses sequencing therapy for castration-resistant prostate cancer (CRPC). It provides an overview of prostate cancer as an androgenic disease and summarizes several key clinical trials investigating the efficacy of abiraterone and enzalutamide in both pre-docetaxel and post-docetaxel CRPC patients. It concludes by presenting NCCN guidelines for sequencing CRPC therapies based on disease stage and symptoms.
Urology-Oncology Interface
The Grey Zone in Prostate Cancer Management
1) Prostate cancer is the second most common cancer in men and the second leading cause of cancer death in men. Testosterone and age are closely related to prostate cancer risk.
2) Effective treatments for prostate cancer have included orchiectomy, anti-androgen drugs like DES, and LHRH analogues, with scientists like Drs. Huggins and Schally winning Nobels for their work.
3) Managing testosterone levels is important, with levels of ≤30 ng/dL associated with longer survival versus >30 ng/dL. Maintaining levels <32 ng/dL was linked to longer time
Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of prostate cancer that has spread to other organs and continues to progress despite hormone therapy. Current treatments aim to reduce testosterone levels, disrupt microtubules during cell division, activate the immune system, or use radiopharmaceuticals, but all have limitations like toxicity or development of resistance. Researchers are exploring new targets and combinations of drugs to block cancer progression and prolong survival for men with mCRPC, which remains largely incurable.
The document discusses treatment options for patients with relapsed myeloma. It provides details on current treatment goals, classes of drugs used to treat relapsed myeloma, and clinical trial data on combinations of these drugs. Specifically, it summarizes clinical trial results showing improved progression-free and overall survival for combinations of bortezomib, lenalidomide, and dexamethasone compared to dexamethasone alone in relapsed patients. It also discusses factors to consider when selecting a salvage therapy for relapsed myeloma, including disease characteristics, prior treatments, and toxicity risks.
This document summarizes a presentation on tackling prostate cancer and improving treatment outcomes. It discusses that prostate cancer incidence is increasing due to aging and screening. Prostate cancer is the second most common cancer in men and is an androgenic disease related to testosterone and the androgen receptor. The presentation reviews prostate cancer risk stratification and how docetaxel added to androgen deprivation therapy can improve outcomes for metastatic hormone-sensitive prostate cancer based on clinical trial results. It also discusses therapies such as abiraterone that have shown survival benefits for castrate-resistant prostate cancer based on additional clinical trials.
This document summarizes current dilemmas in early management of castration-resistant prostate cancer (CRPC). It discusses definitions of CRPC and its natural history progression. Factors contributing to inevitable disease progression despite androgen deprivation therapy include alternate androgen biosynthesis, androgen receptor abnormalities, proliferation cascades, and changes in histology. Genetic alterations in prostate cancer like BRCA mutations are also reviewed. Recent positive clinical trial results establishing new standards of care for both chemo-naïve and post-docetaxel CRPC are highlighted. Optimal sequencing of available therapies remains an area of ongoing research due to heterogeneity in patient populations and lack of head-to-head trials.
This document discusses the case of a 48-year-old female diagnosed with grade III invasive ductal carcinoma of the right breast in 2014. She received breast-conserving surgery along with sentinel lymph node biopsy, which showed triple positive disease. She was treated with FEC chemotherapy but received no further adjuvant treatment. In 2018, she presented with local recurrence and underwent a right modified radical mastectomy. The document discusses treatment options and ongoing clinical trials for triple positive breast cancer. Panelists debate preferences for first-line and second-line treatment of metastatic triple positive disease.
This document summarizes the risk of thrombosis/deep vein thrombosis (DVT) associated with multiple myeloma and its treatments. It finds that the risk of DVT is increased by certain drugs like thalidomide, lenalidomide, and dexamethasone, especially when combined with chemotherapy. Studies show aspirin, low molecular weight heparin, and warfarin can effectively prevent DVT when used as prophylaxis, with aspirin and heparin posing a lower bleeding risk than warfarin. A phase III trial compared aspirin, low dose warfarin, and low molecular weight heparin for DVT prevention in newly diagnosed multiple myeloma patients on thalidomide-containing regimens
Everything you need to know about moa of bone targeted agents amgen 2017Mohamed Abdulla
This document summarizes key information about giant cell tumor of bone (GCTB) and a phase II study of the RANK ligand inhibitor denosumab for treatment of GCTB. The study showed that nearly all GCTB patients treated with denosumab had stable disease or an objective response, with few experiencing disease progression. Histological analysis found that denosumab significantly reduced or eliminated RANK-positive tumor giant cells in GCTB tissue specimens. These results suggest that denosumab is an effective treatment that stabilizes disease in the majority of GCTB patients.
1) The document discusses endocrine therapy options for ER+ HER2- metastatic breast cancer (MBC), including first-line aromatase inhibitors versus tamoxifen, comparisons between different aromatase inhibitors, and the role of fulvestrant.
2) The FIRST trial found that fulvestrant 500 mg had significantly longer time to progression compared to anastrozole as first-line therapy for postmenopausal women.
3) For premenopausal women, combinations of luteinizing hormone-releasing hormone agonists with tamoxifen or aromatase inhibitors showed benefits, with no differences between the arms.
Lapatinib is an oral tyrosine kinase inhibitor that is effective for HER2-positive breast cancer patients, including those with brain metastases. A phase II trial found that lapatinib led to partial responses in 6% of patients with HER2-positive breast cancer and brain metastases who progressed on prior trastuzumab therapy. Volumetric reductions of at least 20% in brain lesions on MRI were associated with improved progression-free survival. The most common adverse events were diarrhea and rash, which were primarily grades 1-2 in severity. Lapatinib is an important treatment option for HER2-positive breast cancer patients with brain metastases.
1. The management of prostate cancer has undergone a paradigm shift with upfront intensified treatment of metastatic hormone-sensitive prostate cancer and the introduction of new treatment options for metastatic castrate-resistant prostate cancer.
2. Final analyses of trials such as LATITUDE and ARCHES showed a survival benefit of adding abiraterone or enzalutamide to androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.
3. Trials such as PROSPER and SPARTAN demonstrated a delay in disease progression with the use of enzalutamide or apalutamide for non-metastatic castrate-resistant prostate cancer.
4. Questions remain about optimal treatment sequencing
This document provides an overview of breast cancer therapy. It discusses trends in breast cancer incidence in the United States, declining mortality rates, and treatment approaches for early stage disease including local and systemic therapies guided by risk assessment. Key aspects of risk assessment using tools like Oncotype DX are outlined. The roles of endocrine therapy and chemotherapy in adjuvant treatment are summarized, including evolving regimens and trial results demonstrating improved outcomes. Potential toxicities of different systemic therapies are also highlighted.
1) Anti-angiogenic therapy targets tumor angiogenesis and has become an established treatment for metastatic colorectal cancer (mCRC).
2) Bevacizumab, a monoclonal antibody targeting VEGF, has shown efficacy in multiple phase III trials in combination with chemotherapy as first-line and maintenance therapy for mCRC.
3) Additional anti-angiogenic agents approved for mCRC include aflibercept, ramucirumab, and regorafinib, which have demonstrated benefits in later lines of therapy.
Ohio State's ASH Review 2017 - Update in MyelomaOSUCCC - James
Don M. Benson Jr., MD, PhD, FACP
Associate Professor of Medicine
Head of Translational Research
Division of Hematology
The Ohio State University Comprehensive Cancer Center -
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
Pruebas genómicas de recurrencia en cáncer de mama - OncotypeDx y su entornoMauricio Lema
Presentación para el simposio satélite de Amarey en el marco del congreso de los 85 años del Instituto Nacional de Cancerología, Hotel Hyatt, 29.08.2019, Bogotá
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
The document discusses the long-term side effects of androgen deprivation therapy (ADT) for prostate cancer, including increased risks of osteoporosis, cardiovascular events, sarcopenic obesity, and bone loss. It provides evidence that ADT increases standard cardiovascular risk factors and cardiovascular events. While the effect on cardiovascular mortality is disputed, age and pre-existing conditions are the main risk factors. Exercise and drugs like SERMs may help mitigate side effects, but do not reduce cardiovascular events. Careful management of known risk factors is important when treating with ADT.
This document presents the rankings of the top 10 women drivers, listing the positions from 10th to 1st. However, it does not provide the names of any of the drivers, only their positions. The top ranked driver earns the gold medal as the champion of champions.
This document provides information on honeymoon options in Cancun, Mexico. It describes three resort options: the Sun Palace, a couples-only all-inclusive resort located close to the airport with 252 rooms and beautiful beaches; the Excellence Playa Mujeres, an adult-only luxury resort about 30 minutes from Cancun with numerous dining options and pools; and Secrets The Vine, an adult-only resort located on the beach with three infinity pools and a spa. Each resort offers oceanview rooms and an all-inclusive experience with meals, drinks and activities.
This document summarizes a presentation on tackling prostate cancer and improving treatment outcomes. It discusses that prostate cancer incidence is increasing due to aging and screening. Prostate cancer is the second most common cancer in men and is an androgenic disease related to testosterone and the androgen receptor. The presentation reviews prostate cancer risk stratification and how docetaxel added to androgen deprivation therapy can improve outcomes for metastatic hormone-sensitive prostate cancer based on clinical trial results. It also discusses therapies such as abiraterone that have shown survival benefits for castrate-resistant prostate cancer based on additional clinical trials.
This document summarizes current dilemmas in early management of castration-resistant prostate cancer (CRPC). It discusses definitions of CRPC and its natural history progression. Factors contributing to inevitable disease progression despite androgen deprivation therapy include alternate androgen biosynthesis, androgen receptor abnormalities, proliferation cascades, and changes in histology. Genetic alterations in prostate cancer like BRCA mutations are also reviewed. Recent positive clinical trial results establishing new standards of care for both chemo-naïve and post-docetaxel CRPC are highlighted. Optimal sequencing of available therapies remains an area of ongoing research due to heterogeneity in patient populations and lack of head-to-head trials.
This document discusses the case of a 48-year-old female diagnosed with grade III invasive ductal carcinoma of the right breast in 2014. She received breast-conserving surgery along with sentinel lymph node biopsy, which showed triple positive disease. She was treated with FEC chemotherapy but received no further adjuvant treatment. In 2018, she presented with local recurrence and underwent a right modified radical mastectomy. The document discusses treatment options and ongoing clinical trials for triple positive breast cancer. Panelists debate preferences for first-line and second-line treatment of metastatic triple positive disease.
This document summarizes the risk of thrombosis/deep vein thrombosis (DVT) associated with multiple myeloma and its treatments. It finds that the risk of DVT is increased by certain drugs like thalidomide, lenalidomide, and dexamethasone, especially when combined with chemotherapy. Studies show aspirin, low molecular weight heparin, and warfarin can effectively prevent DVT when used as prophylaxis, with aspirin and heparin posing a lower bleeding risk than warfarin. A phase III trial compared aspirin, low dose warfarin, and low molecular weight heparin for DVT prevention in newly diagnosed multiple myeloma patients on thalidomide-containing regimens
Everything you need to know about moa of bone targeted agents amgen 2017Mohamed Abdulla
This document summarizes key information about giant cell tumor of bone (GCTB) and a phase II study of the RANK ligand inhibitor denosumab for treatment of GCTB. The study showed that nearly all GCTB patients treated with denosumab had stable disease or an objective response, with few experiencing disease progression. Histological analysis found that denosumab significantly reduced or eliminated RANK-positive tumor giant cells in GCTB tissue specimens. These results suggest that denosumab is an effective treatment that stabilizes disease in the majority of GCTB patients.
1) The document discusses endocrine therapy options for ER+ HER2- metastatic breast cancer (MBC), including first-line aromatase inhibitors versus tamoxifen, comparisons between different aromatase inhibitors, and the role of fulvestrant.
2) The FIRST trial found that fulvestrant 500 mg had significantly longer time to progression compared to anastrozole as first-line therapy for postmenopausal women.
3) For premenopausal women, combinations of luteinizing hormone-releasing hormone agonists with tamoxifen or aromatase inhibitors showed benefits, with no differences between the arms.
Lapatinib is an oral tyrosine kinase inhibitor that is effective for HER2-positive breast cancer patients, including those with brain metastases. A phase II trial found that lapatinib led to partial responses in 6% of patients with HER2-positive breast cancer and brain metastases who progressed on prior trastuzumab therapy. Volumetric reductions of at least 20% in brain lesions on MRI were associated with improved progression-free survival. The most common adverse events were diarrhea and rash, which were primarily grades 1-2 in severity. Lapatinib is an important treatment option for HER2-positive breast cancer patients with brain metastases.
1. The management of prostate cancer has undergone a paradigm shift with upfront intensified treatment of metastatic hormone-sensitive prostate cancer and the introduction of new treatment options for metastatic castrate-resistant prostate cancer.
2. Final analyses of trials such as LATITUDE and ARCHES showed a survival benefit of adding abiraterone or enzalutamide to androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.
3. Trials such as PROSPER and SPARTAN demonstrated a delay in disease progression with the use of enzalutamide or apalutamide for non-metastatic castrate-resistant prostate cancer.
4. Questions remain about optimal treatment sequencing
This document provides an overview of breast cancer therapy. It discusses trends in breast cancer incidence in the United States, declining mortality rates, and treatment approaches for early stage disease including local and systemic therapies guided by risk assessment. Key aspects of risk assessment using tools like Oncotype DX are outlined. The roles of endocrine therapy and chemotherapy in adjuvant treatment are summarized, including evolving regimens and trial results demonstrating improved outcomes. Potential toxicities of different systemic therapies are also highlighted.
1) Anti-angiogenic therapy targets tumor angiogenesis and has become an established treatment for metastatic colorectal cancer (mCRC).
2) Bevacizumab, a monoclonal antibody targeting VEGF, has shown efficacy in multiple phase III trials in combination with chemotherapy as first-line and maintenance therapy for mCRC.
3) Additional anti-angiogenic agents approved for mCRC include aflibercept, ramucirumab, and regorafinib, which have demonstrated benefits in later lines of therapy.
Ohio State's ASH Review 2017 - Update in MyelomaOSUCCC - James
Don M. Benson Jr., MD, PhD, FACP
Associate Professor of Medicine
Head of Translational Research
Division of Hematology
The Ohio State University Comprehensive Cancer Center -
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
The document discusses renal cancer (kidney cancer) and advances in its treatment. It describes several targeted drugs that have improved outcomes for metastatic renal cell carcinoma (mRCC) compared to previous immunotherapy options. Drugs include tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib and axitinib as well as the mTOR inhibitor temsirolimus. Clinical trials have established these as standard first and second line options depending on a patient's risk level and prior treatment history. Ongoing research focuses on optimizing treatment sequencing and identifying biomarkers to guide more personalized therapy selection.
Pruebas genómicas de recurrencia en cáncer de mama - OncotypeDx y su entornoMauricio Lema
Presentación para el simposio satélite de Amarey en el marco del congreso de los 85 años del Instituto Nacional de Cancerología, Hotel Hyatt, 29.08.2019, Bogotá
Recent advances in targeted therapy for metastatic lung cancerAlok Gupta
This document discusses recent advances in targeted therapy for metastatic lung cancer. It summarizes key findings from several clinical trials evaluating third-generation EGFR TKIs like osimertinib for patients with EGFR mutation-positive NSCLC. The document highlights that osimertinib provides significantly longer progression-free survival compared to earlier generation EGFR TKIs, with a median PFS of 18.9 months versus 10.2 months. Osimertinib also demonstrated a higher objective response rate and longer duration of response. Benefits were consistent across patient subgroups.
The document discusses the long-term side effects of androgen deprivation therapy (ADT) for prostate cancer, including increased risks of osteoporosis, cardiovascular events, sarcopenic obesity, and bone loss. It provides evidence that ADT increases standard cardiovascular risk factors and cardiovascular events. While the effect on cardiovascular mortality is disputed, age and pre-existing conditions are the main risk factors. Exercise and drugs like SERMs may help mitigate side effects, but do not reduce cardiovascular events. Careful management of known risk factors is important when treating with ADT.
This document presents the rankings of the top 10 women drivers, listing the positions from 10th to 1st. However, it does not provide the names of any of the drivers, only their positions. The top ranked driver earns the gold medal as the champion of champions.
This document provides information on honeymoon options in Cancun, Mexico. It describes three resort options: the Sun Palace, a couples-only all-inclusive resort located close to the airport with 252 rooms and beautiful beaches; the Excellence Playa Mujeres, an adult-only luxury resort about 30 minutes from Cancun with numerous dining options and pools; and Secrets The Vine, an adult-only resort located on the beach with three infinity pools and a spa. Each resort offers oceanview rooms and an all-inclusive experience with meals, drinks and activities.
The document discusses various body modification traditions among different African tribes. It describes how face and body painting is used in tribes such as the Efik, Xhosa, Pondo, Karo, Woodabe, and Maasai for purposes such as expressing identity, beauty, rituals, and cultural celebrations. Different tribes use paints made from materials like white clay, charcoal, and red ochre to create distinctive patterns on the face and body for these purposes. Body painting traditions carry important symbolic meanings and cultural significance among African tribes.
The document discusses various traditional body modification practices among different African tribes and cultures, including face and body painting. It provides examples of several tribes in Africa and the symbolic meanings and purposes of their traditional face and body painting practices, such as using paint to signify love, purity, clan identity, and important life events or ceremonies. It also briefly mentions other body modification practices outside of Africa, such as neck rings, foot binding, and corsetry.
Tattooing and piercing have been practiced for centuries and have become more mainstream. Tattooing involves inserting ink under the skin to change pigment using an electric tattoo machine. Piercing is puncturing or cutting parts of the body for religious, self-expression, or cultural reasons. Other body modifications include scarification, branding, tongue splitting, subdermal and transdermal implants, and ocular implants. Views on body modification vary from acceptance to controversy depending on cultural norms and extremes.
Chapter 7 Reproduction and Sexuality in ART profmedina
This chapter discusses the depiction of reproduction and sexuality in art throughout history. It begins by examining primordial couples and Adam and Eve in creation myths. It then explores the symbolism and iconography used in depictions of marriage, temptation, and the fall from grace in works like Jan van Eyck's Arnolfini Marriage. The chapter also analyzes the use of the human body, especially female nudes, to represent fertility, sexuality, and the male gaze. It concludes by comparing the portrayal of male and female nudity in art and considering these issues from a feminist perspective.
Presentation is highlighting the integration of different modalities in the management of locally advanced and metastatic prostate cancer pointing to the proven values of adding chemotherapy. A special note has been made to oligometastatic disease.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
- Bone metastases affect up to 70% of breast cancer patients and are a major source of morbidity. They develop through a 'vicious cycle' where tumor cells stimulate bone resorption.
- Bisphosphonates like zoledronic acid and denosumab inhibit bone resorption by targeting RANK ligand, breaking this cycle. They significantly reduce skeletal complications in metastatic breast cancer.
- A large trial found denosumab reduced the risk of first skeletal-related event compared to zoledronic acid and time to first on-study bone metastasis. It provides an effective alternative to bisphosphonates for preventing bone complications.
This document summarizes prognostic factors and treatment approaches for follicular lymphoma. Some key points:
- Prognostic factors include age, histologic grade, FLIPI score, gene expression profiling, and metabolic tumor volume on PET scans.
- First-line treatment for symptomatic advanced disease is usually rituximab plus chemotherapy such as bendamustine, followed by rituximab maintenance for 2 years.
- The PRIMA trial showed improved progression-free survival with 2 years of rituximab maintenance compared to observation alone in patients achieving response to first-line treatment.
- The GALLIUM trial found improved progression-free survival for first-line treatment of follicular
This document provides an overview of the management of gliomas. It discusses the general management and specific management of low grade and high grade gliomas.
For low grade gliomas, the main treatment options are observation, surgery, radiation, and chemotherapy. Surgery aims for maximal safe resection followed by radiation therapy. Chemotherapy with PCV may provide a survival benefit for high risk patients based on one trial, but requires further study.
For high grade gliomas, prognostic factors like age, performance status, extent of resection, and molecular markers are discussed. Treatment involves maximal safe surgery followed by concurrent chemoradiation and adjuvant chemotherapy with temozolomide, which has become the standard of care based on clinical trials
This document provides a summary of neuroendocrine tumors (NETs):
- NETs arise from neuroendocrine cells throughout the body and can be functional or nonfunctional. Gastroenteropancreatic NETs are the most prevalent.
- NET incidence has increased 5-fold over the past 30 years. They are often advanced at diagnosis due to nonspecific symptoms and long diagnostic delays.
- Treatment options include surgery, chemotherapy, targeted therapies like somatostatin analogues, interferon, and newer agents inhibiting angiogenesis and mTOR pathways. Clinical trials are evaluating these targeted agents.
- The PI3K/Akt/mTOR pathway is frequently deregulated in cancers including NETs and represents a
This document discusses treatment options for a 55-year-old postmenopausal woman with newly diagnosed, hormone receptor-positive, HER2-negative metastatic breast cancer. Based on evidence from clinical trials, fulvestrant alone or in combination with a CDK 4/6 inhibitor plus an aromatase inhibitor are both recommended first-line treatment options. Fulvestrant has shown superior progression-free survival compared to anastrozole alone in the first-line setting. Adding a CDK 4/6 inhibitor to endocrine therapy further improves progression-free survival and response rates and is now considered a standard first-line treatment option for this patient population.
Renal Cell Carcinoma A New Standard Of Carefondas vakalis
This document summarizes the current standard of care for renal cell carcinoma (RCC), focusing on targeted therapies such as anti-angiogenesis agents. It reviews the biology and risk factors for RCC, the clinical efficacy and safety profiles of drugs like sorafenib and sunitinib, and phase III trial results demonstrating improved progression-free and overall survival compared to interferon-alpha. It concludes that anti-angiogenic therapies such as sorafenib, sunitinib, and temsirolimus have become the new standard first-line treatment for metastatic RCC based on superior clinical outcomes over existing immunotherapy options.
1. Androgen deprivation therapy (ADT) for prostate cancer is associated with rapid bone loss and increased fracture risk. Several treatments have been shown to prevent bone loss and reduce fractures in men receiving ADT, including zoledronic acid, denosumab, and bisphosphonates.
2. Bone markers like N-telopeptide and bone-specific alkaline phosphatase can help predict risks of skeletal-related events and survival in men with bone metastases from prostate cancer. High bone marker levels are associated with worse outcomes.
3. Having multiple bone metastases is also associated with shorter time to first skeletal-related event and reduced survival compared to having fewer bone lesions. Normalizing elevated bone marker levels in response
Estado actual de terapia sistémica en cáncer renal metastásicoMauricio Lema
This document discusses the current management of metastatic renal cell carcinoma (mRCC). It provides an overview of targeted therapies for mRCC including tyrosine kinase inhibitors (TKIs) such as sunitinib, pazopanib, and cabozantinib that target the VEGF pathway. Clinical trial results are presented comparing TKIs in first-line mRCC. Active surveillance is also discussed as a treatment option for select asymptomatic or minimally symptomatic mRCC patients. Toxicities of TKIs like fatigue, diarrhea and hand-foot syndrome are reviewed along with their negative impact on quality of life.
Breast cancer oncotype-dx.. by dr.Kamel Farag, MDKamelFarag4
This document discusses factors oncologists consider when determining if a patient with hormone receptor-positive breast cancer can skip chemotherapy.
It begins by explaining the three main breast cancer subtypes and that chemotherapy is usually only necessary for triple-negative and HER2-positive cancers. For hormone receptor-positive cancers, chemotherapy may have a lesser role since patients benefit greatly from anti-estrogen medications.
It then discusses tools oncologists use to assess risk, such as genomic tests like Oncotype DX that provide recurrence scores, and clinicopathologic factors like tumor grade and size. Large clinical trials like TAILORx and RxPONDER helped establish cut-offs for recurrence scores below which chemotherapy provided little additional benefit
Breast cancer is the most common cancer in women worldwide, with an estimated 1.6 million new cases and over 500,000 deaths per year. A key document summarizes evidence from several studies showing that the addition of ovarian suppression/ablation through drugs like Zoladex to standard therapies improves outcomes for premenopausal breast cancer patients. Specifically, it improves disease-free survival when added to chemotherapy for young premenopausal patients. It also improves disease-free and overall survival when given for 2 years after chemotherapy compared to chemotherapy alone in high-risk premenopausal breast cancer patients.
Colon cancer is the second and third most common cancer in males and females. Screening programs have led to a reduction in late-stage diagnoses and mortality. Precise identification of prognostic patient groups allows for more targeted adjuvant therapy, improving disease-free and overall survival. Molecular markers of tumor aggressiveness aid in selecting optimal treatment approaches, increasing response rates, progression-free, and overall survival. A multidisciplinary team approach is essential for managing metastatic colon cancer with the goal of surgical cure in organ-limited disease.
This document discusses the management of triple negative breast cancer (TNBC). It begins with an overview of the three main subtypes of breast cancer and their associated treatments. It then focuses on the characteristics and treatment challenges of TNBC, including its aggressiveness, younger patient population, and lack of targeted therapies. Current treatment options for metastatic TNBC are discussed, including various chemotherapy regimens. The document also touches on neoadjuvant and adjuvant systemic therapy approaches as well as ongoing research into better understanding the biology of TNBC to revolutionize outcomes.
The document discusses treatment options for patients with relapsed myeloma. It provides details on current treatment goals, classes of drugs used to treat relapsed myeloma, and clinical trial data on combinations of drugs like bortezomib, lenalidomide, and dexamethasone. It also presents a case study of a 65-year old male patient who achieved a complete response after stem cell transplant but relapsed 15 months later, and discusses factors to consider in selecting a re-treatment plan for this patient.
1) Endocrine therapy resistance in estrogen receptor positive breast cancer can occur through various mechanisms including loss of ER expression, crosstalk between ER and growth factor receptor pathways, and activation of the mTOR pathway.
2) Clinical trials have shown that combining endocrine therapies like aromatase inhibitors with targeted therapies against HER2 or mTOR can help overcome resistance, improving outcomes.
3) Further research is still needed to better understand resistance mechanisms and identify biomarkers to predict which combinations may help individual patients.
This document discusses testosterone inactivating pharmaceuticals (TIP), also known as androgen deprivation therapy (ADT), for treating prostate cancer. It provides details on 6 types of anti-testosterone therapies with varying levels of potency. TIP is used as preliminary treatment before radiation to reduce prostate size, as ancillary treatment with radiation or surgery to improve cure rates, and as standalone therapy for intermediate-risk, high-risk, or advanced disease. TIP is also used after PSA relapse or for second-line treatment after other therapies stop working. Side effects of TIP include bone loss, metabolic effects, sexual dysfunction, and increased risk of fractures. Strategies are discussed to prevent bone complications like osteopor
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
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Este documento discute el abordaje del paciente con densidad mineral ósea disminuida. Presenta factores de riesgo para osteoporosis, medicamentos asociados con disminución de la densidad ósea, y principales tratamientos farmacológicos para la osteoporosis en Panamá. El objetivo del tratamiento no es mejorar la cantidad de hueso sino prevenir fracturas por fragilidad a lo largo de la vida del paciente.
Este documento trata sobre la fisiología y regulación del hueso. Explica las funciones y composición de los osteocitos, osteoblastos y osteoclastos, así como los procesos de modelado y remodelado óseo. Describe los mecanismos de regulación de estas células óseas y los factores que influyen en la salud ósea.
Este documento discute el tratamiento con bifosfonatos para la osteoporosis. Comienza describiendo cuándo iniciar el tratamiento farmacológico y las opciones disponibles como alendronato, risedronato e ibandronato. Luego explica el mecanismo de acción de los bifosfonatos al inhibir la enzima FPP sintetasa en los osteoclastos. Finalmente, resume los estudios clínicos que muestran que el alendronato y el risedronato reducen significativamente el riesgo de fracturas vertebrales y de c
Este documento discute la importancia de la vitamina D para los huesos y músculos. La deficiencia de vitamina D es un problema de salud pública, con hasta el 100% de adultos mayores en los Estados Unidos, Canadá y Europa teniendo niveles deficientes. La deficiencia de vitamina D causa alteraciones en el metabolismo óseo y muscular. Se recomienda suplementar con 800 UI de vitamina D diariamente para prevenir deficiencia y caídas en personas mayores.
Este documento discute los marcadores de formación y remodelado óseo. Proporciona información sobre varios marcadores como la fosfatasa alcalina ósea, la osteocalcina, los propéptidos del colágeno tipo I y la fosfatasa ácida resistente al tartrato. También analiza los efectos de diferentes medicamentos antirresortivos en estos marcadores y la necesidad de estándares internacionales para el uso de marcadores en la predicción de fracturas y el monitoreo del tratamiento de la osteoporosis.
El documento presenta varios casos clínicos de pacientes femeninas de entre 59 y 84 años que se sometieron a evaluaciones de densidad mineral ósea y fracturas vertebrales. También incluye el caso de un hombre de 54 años con adenoma de paratiroides. Se plantean preguntas sobre el diagnóstico y tratamiento más adecuado para algunos de los pacientes.
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The document summarizes the WHO Classification of Postmenopausal Osteoporosis published in 1994. It establishes diagnostic criteria for normal bone mass, osteopenia, and osteoporosis based on T-scores measured by DXA of the spine, hip, or forearm in postmenopausal Caucasian females. Osteoporosis is defined as a T-score of -2.5 or lower. The classification system is intended to assess disease prevalence in populations and does not necessarily imply prior bone loss in individuals with low bone mass.
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Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
2. CA DE MAMA TEMPRANO: PREVENCIÓN DE FX
AUMENTO DE LA SLE CON TERAPIAS
ADYUVANTES ÓSEAS
ENFERMEDAD METASTASICA
3. Predictors of Fracture Risk
• BMD (DXA), femoral neck T-score
– Serial monitoring should be done on the same
equipment with the same reference standards at the
same site
• Age
• Drugs
• History/presence of vertebral fracture
– Best predictor of a subsequent fracture is an existing
one
• Risk of falls
• Vitamin D levels
4. Tasa de Pérdida Ósea
1. Kanis JA. Osteoporosis. 1997:22-55. 2. Eastell R, et al. J Bone Miner Res. 2006;21:1215-1223.
3. Maillefert JF, et al. J Urol. 1999;161:1219-1222. 4. Gnant M, et al. Lancet Oncol. 2008;9:840-849.
5. Shapiro CL, et al. J Clin Oncol. 2001;19:3306-3311.
BoneLossat1Yr(%)
Naturally Occurring Bone Loss CTIBL
0
2
4
6
8
10
Normal
Men[1]
Postmenopausal
Women[1]
Al Therapy in
Postmenopausal
Women[2]
ADT[3]
Al Therapy
+ GnRH
Agonist in
Premenopausal
Women[4]
Premature
Menopause
Secondary to
Chemotherapy[5]
0.5
1.0
2.6
4.6
7.0
7.7
5. Tamoxifen
LetrozoleAnastrozole
Fractures(%)
11.0
7.7
5.7
4.0
7.0
5.0
P < .0001
P < .001
0
2
4
6
8
10
12
14
P = .003
Exemestane
ATAC[1]
(68 mos)
IES[2]
(58 mos)
BIG 1-98[3]
(26 mos)
Riesgo de fx elevado de los IA esteroidales y
noesteroidales vs Tamoxifeno
1. Howell A, et al. Lancet. 2005;365:60-62. 2. Coleman RE, et al. Lancet Oncol. 2007;8:119-127.
3. Thürlimann B, et al. N Engl J Med. 2005;353:2747-2757.
6. Oral Bisphosphonate Impact on BMD
in Patients With Breast Cancer
• Clodronate in breast cancer patients with chemotherapy-induced
premature ovarian failure
Saarto T, et al. J Clin Oncol. 1997;15:1341-1347.
• Risedronate reduces bone loss in women with chemotherapy-
induced ovarian failure
Delmas PD, et al. J Clin Oncol. 1997;15:955-962.
• Alendronate in GnRH agonist-induced premature menopause
(patients without cancer)
Ripps BA, et al. J Reprod Med. 2003;48:761-766.
• Monthly ibandronate and anastrozole-induced bone loss
Lester JE, et al. Clin Cancer Res. 2008;14:6336-6342.
• SABRE trial: study of anastrozole with risedronate
Van Poznak C, et al. J Clin Oncol. 2010;28:967-975.
7. Management of Bone Health Using
BMD
T-Score: NCCN Task Force Report
• T-score: > -1 (normal)
• T-score: -1.0 to -1.5
• T-score: -1.5 to -2.0
• T-score < -2.0 or
FRAX 10-yr fracture risk:
> 20% major fracture
> 3% for hip fracture
• Repeat DXA every 2 yrs*
• Repeat DXA every 2 yrs*
• Consider checking 25(OH) level
• Repeat DXA every 2 yrs*
• Consider checking 25(OH) level
• Consider pharmacologic
therapy
• Repeat DXA every 2 yrs*
• Consider checking 25(OH) level
• Strongly consider
pharmacologic therapy
Gralow JR, et al. J Natl Compr Canc Netw. 2009;7:S1-S32.
*In selected cases, longer or shorter intervals may be considered. If a major change in patient risk
factors or a major intervention occurs, then repeating DXA at 1 yr is reasonable.
8. Key endpoints:
Primary: BMD at 12 mos
Secondary: BMD at 36 and 60 mos, disease recurrence, fractures, safety
Letrozole +
immediate Zoledronic Acid
4 mg every 6 mos
Breast cancer
stage I to IIIa
(N = 1065)
Postmenopausal or
amenorrheic due to
cancer treatment
ER+
and/or PgR+
T-score ≥ -2.0
Letrozole +
Treatment duration: 5 yrs
R
Delayed Zoledronic Acid
If 1 of the following occurs:
BMD T-score < -2
Clinical fracture
Asymptomatic fracture at
36 mos
Coleman R, et al. Ann Oncol. 2012. Oct 9.
ZO-FAST: A Phase III Study of the Use of
Zoledronic Acid With Adjuvant Letrozole
9. Coleman R, et al. Ann Oncol. 2012. Oct 9. [Epub ahead of print]
ZO-FAST (Primary Endpoint): Median
Change in LS BMD With Zoledronic Acid
Immediate zoledronic acid
Delayed zoledronic acid
P < .0001 for each
ChangeinLS(LS-L4)BMD(%)
12 Mos 24 Mos 36 Mos 48 Mos 60 Mos-6
-4
-2
0
2
4
6
+4.3
-5.4
Δ 5.9 Δ 8.2 Δ 8.8 Δ 9.2 Δ 10.0
10. Modalidades de tratamiento
Bifosfonatos orales
• Buena adherencia a sus
meds
• Rechazan meds IV
• No quieren o pueden ir a
la clínica
• Menos costosos
• Menos efectos 2os
• < riesgo de osteonecrosis
o de fx subtrocantéricas
Bifosfonatos IV
• Mayor adherencia en
pacientes con
intolerancia GI (RGE) u
otros síntomas.
11. ABCSG-12: Phase III Study of Adjuvant
Endocrine Therapy ± Zoledronic Acid
• Key endpoints
– Primary: DFS at 5 yrs
– Secondary: recurrence-free survival, OS, BMD, safety
TAM 20 mg/day
ANA 1 mg/day
Treatment 3 yrs
(median follow-up: 48 mos)
TAM + ZA 4 mg q6m
ANA + ZA 4 mg q6m
R
Long-term
monitoring
for 5 yrs for
recurrence
and survival
(DFS, OS)
3-yr
BMD
5-yr
BMD
Premenopausal patients with
stage I/II breast cancer
(goserelin 3.6 mg/28 days)
stratified by:
ER+ and/or PgR+
Age
Stage
Grade
Lymph nodes
(N = 1803)
Gnant M, et al. N Engl J Med. 2009;360:679-691.
12. Gnant M, et al. Lancet Oncol. 2008;9:840-849.
ABCSG-12 Bone Substudy: Change in
BMD at Yrs 3 and 5
10
5
0
-5
-10
-15
PercentChangeinLS
BMD(g/cm2
)FromBaseline
Mos
Mos
No Zoledronic Acid
Tamoxifen Anastrozole
36 60
-9.0
P < .0001
-4.5
NS
-13.6
P < .0001
-7.8
P = .003
36 60
36 60 36 60
Zoledronic Acid
Tamoxifen Anastrozole
+1.0
NS
+5.2
P = .04
-0.1
NS
+3.1
NS
13. *
*
*
Ellis GK, et al. J Clin Oncol. 2008;26:4875-4882.
Denosumab in Patients With Breast
Cancer Receiving Adjuvant AIsPercentChangeinBMDFrom
BaselineatLS
8
7
6
5
4
3
2
1
0
-1
-2
-3
1 3 6 12 24
Mos
5.5% difference
at 12 mos
7.6% difference
at 24 mos
*P < .0001 vs placebo
Placebo (n = 122)
Denosumab 60 mg q6m (n = 123) *
*
Toxicity: no significant difference in AEs between denosumab and placebo arm
14. Checklist for Bone Health in Patients With
Breast Cancer
Item Description
Determine
osteoporosis risk
factors
•T-score < -1.5?
•Older than 65 yrs?
•Low BMI (< 20)?
Other factors
•Family history of hip fracture?
•Personal history of fragility after 50 yrs of age?
•Oral corticosteroid use of > 6 mos?
•Smoking (current or past history)?
•10-yr probability for hip fracture (by FRAX)?
Cancer treatment–
related factors
•AIs?
•Ovarian ablation?
Assays
•DXA to assess BMD (every 2 yrs)
•25(OH)D level
•Serum calcium level
Treat the following
with bone-directed
therapy
•Hip or vertebral fracture
•T-score < -2.0
•10-yr probability for hip fracture ≥ 3%
•10-yr probability of a major osteoporotic event ≥ 20%
Hadji P, et al. Ann Oncol. 2011;22:2546-2555. National Osteoporosis Foundation.
15. T-score < -2.0Any 2 of the following risk factors
T-score < -1.5
Aged younger than 65 yrs
Low BMI (< 20)
Family history of hip fracture
Personal history of fragility fracture after
50 yrs of age
Oral corticosteroid use of > 6 mos
Smoking (current or history of)
T-score > -2.0, no risk
factors
Monitor risk status and
BMD q12m*
Monitor BMD on case by case
basis for IV bisphosphonates;
q12-24m for oral
bisphosphonates
Exercise
Calcium and vitamin D
supplements
*If ≥ 10% decrease in BMD (≥ 4% to 5% if osteopenic at baseline),
investigate secondary causes and begin antiresorptive treatment. Use lowest T-score from 3 sites.
Exercise
Treatment including
bisphosphonates,
denosumab,
Calcium, and vitamin D
supplements
Guidance for Women With Breast
Cancer Initiating AI Therapy: European
Guidelines
Hadji P, et al. Ann Oncol. 2011;22:2546-2555.
17. DFS
ABCSG-12 (84 Mos): Efficacy
100
80
60
40
20
0
DFS(%)
0 12 24 36 48 60 72 84 96 108
Mos Since Randomization
Patients at Risk, n
No ZA
ZA
903
900
858
862
833
841
807
822
758
788
653
674
521
544
405
419
191
208
Events,
n
Univariate Multiple Cox
Regression
HR
(95% CI)
P
Value
HR
(95% CI)
P
Value
vs no
ZA
vs no
ZA
(Log-
rank)
No
ZA
132/903
0.72
(0.56-0.94)
.014 0.71
(0.55-0.92)
.01198/900ZA
OS
100
80
60
40
20
0
DFS(%)
0 12 24 36 48 60 72 84 96 108
Mos Since Randomization
Patients at Risk, n
No ZA
ZA
903
900
864
868
856
858
839
849
811
818
706
708
576
587
456
454
215
232
Events,
n
Univariate Multiple Cox
Regression
HR
(95% CI)
P
Value
HR
(95% CI)
P
Value
vs no
ZA
vs no
ZA
(Log-
rank)
No
ZA
49/903
0.63
(0.40-0.99)
.049 0.61
(0.39-0.96)
.03333/900ZA
Gnant M, et al. SABCS 2011. Abstract S1-2.
18. ZA treatment duration: 5 yrs
AZURE: Study Design
Accrual September 2003 - February 2006
Country Centers,
n
Patients, n
United
Kingdom
123 2710
Ireland 10 247
Australia 28 226
Spain 8 107
Portugal 1 32
Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
Standard therapy
Standard therapy +
ZA 4 mg
Mos 6 30 60
3360 patients
with stage II/III
breast cancer
R
6 doses
q3-4w
8 doses
q3m
5 doses
q6m
Primary endpoint: DFS, with recurrence
defined as date first suspected
19. AZURE: DFS and IDFS
Patients at Risk, n
1681 1591 1465 1354 1241 580 83
1678 1583 1445 1344 1252 561 71
DFS
0
ZA
Control
0
Patients at Risk, n
1681 1578 1443 1337 1222 570 82
1678 1574 1426 1316 1221 544 68
IDFS
0
ZA
Control
DFS IDFS
1 2 3 4 5 6 7
20
40
60
80
Yrs
Control (n = 1678)
Adjusted HR: 0.98 (95% CI: 0.85-1.13;
P = .79)
Surviving(%)
0
0
ZA (n = 1681)
0
100100
0
0 1 2 3 4 5 6 7
20
40
60
80
Yrs
Surviving(%)
0
0
100
0
0
Control (n = 1678)
Adjusted HR: 0.98 (95% CI: 0.85-1.12;
P = .73)
ZA (n = 1681)
Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
20. AZURE: IDFS and OS by
Menopausal Status
0
Mos Since Randomization
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAliveand
invasiveDiseaseFree
IDFS: Pre, Peri, and Unknown Menopausal Status
Adjusted HR: 1.15
(95% CI: 0.97-1.36; P = .11)
288 vs 256 events
Patients at Risk, n
ZA:
No ZA:
1162 1088 996 919 829 393 57 0
1156 1092 995 920 853 388 47 0
0
Mos Since Randomization
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAlive
OS: Pre, Peri, and Unknown Menopausal Status
Adjusted HR: 0.97
(95% CI: 0.78-1.21; P = .81)
161 vs 165 events
Patients at Risk, n
ZA:
No ZA:
1162 1131 1078 1020 955 466 71 0
1156 1123 1076 1032 963 446 60 0
0
Mos Since Randomization
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAliveand
invasiveDiseaseFree
IDFS: > 5 Yrs Postmenopausal
Adjusted HR: 0.75
(95% CI: 0.59-0.96; P = .02)
116 vs 147 events
Patients at Risk, n
ZA:
No ZA:
519 490 447 418 393 177 25 0
522 482 431 396 368 156 21 0
0
Mos Since Randomization
1.0
6 12 18 24 30 36 42 48 54 60 66 72 78 84
0.8
0.6
0.4
0.2
0
ProportionAlive
OS: > 5 Yrs Postmenopausal
Adjusted HR: 0.74
(95% CI: 0.55-0.98; P = .04)
82 vs 111 events
Patients at Risk, n
ZA:
No ZA:
519 502 482 448 422 190 29 0
522 509 475 441 401 177 26 0
Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
21. Typical OR
Menopausal Group
Description
Total: -1% ± 7%
Z = .13; P = .9
χ2
1 (heterogeneity) = 7.91; P = .005
Odds Reduction (± SD)
n = 1041
263 events
n = 2318
544 events
HR: 0.75
(95% CI: 0.59-0.96)
HR: 1.15
(95% CI: 0.97-1.36)
Pre + < 5 yrs post
+ unknown status
> 5 yrs postmenopausal
High estrogen
environment
Low estrogen
environment
1.0 1.2 1.4 1.6 1.8 2.00.2 0.4 0.6 0.8
AZURE: Treatment Effect on IDFS
by Menopausal Status
Coleman RE, et al. N Engl J Med. 2011;365:1396-1405.
22. Niveles de Vit D 25 OHD > 30 ng/ml (suficientes)
predicen beneficio del Ac Zoledrónico en las
tasas de recidiva a distancia en pacientes
posmenopausicas
23. Marshall H, et al. ASCO 2012. Abstract 502.
Adjuvant Zoledronic Acid in Early Breast
Cancer: Expert Perspectives
• No benefit in overall unselected population
• Significant benefit in postmenopausal women seen in
multiple studies
– Effect of menopause on DFS driven by influences on
nonbone recurrence
• Potential for harm in pre- and perimenopausal women
• These subset analyses do not justify the routine use of
adjuvant zoledronic acid in postmenopausal women
24. Letrozole +
ZA 4 mg q6m
Letrozole + Delayed*
ZA 4 mg q6m
*If 1 of the following occurs:
BMD T-score < -2 SD
Clinical fracture
Asymptomatic fracture at 36 mos
Stage I-IIIa breast cancer
Postmenopausal or
amenorrheic due to
cancer treatment
ER+ and/or PgR+
T-score ≥ -2 SD
N = 1060
Treatment duration: 5 yrs
De Boer R, et al. SABCS 2011. Abstract S1-3.
ZO-FAST: 5-yr Final Analysis
25. *Censored patients at initiation of D-ZA (n = 144).
Time on Study (mos)
532
533
518
511
500
491
488
475
475
463
376
368
IM-ZA
D-ZA
Patients at Risk, n
Time on Study (mos)
532
533
518
459
500
402
488
376
475
350
376
267
IM-ZA
D-ZA
Patients at Risk, n
ITT Population
100
90
80
70
60
50
40
30
20
10
0
DFS(%)
0 6 12 18 24 30 36 42 48 54 60 66
HR: 0.66; log-rank P value = .0375
IM-ZA 4 mg (42 events)
D-ZA 4 mg (62 events)
Censored Analysis*
100
90
80
70
60
50
40
30
20
10
0DFS(%)
0 6 12 18 24 30 36 42 48 54 60 66
HR: 0.62; log-rank P value = .024
IM-ZA 4 mg (42 events)
D-ZA 4 mg (53 events)
De Boer R, et al. SABCS 2011. Abstract S1-3.
27% of patients (n = 144) in the delayed arm initiated ZA on-study
DFS HR: 0.46; P = .033
ZO-FAST: Final 5-yr DFS
26. HR
ZO-FAST[1]
104 events
ABCSG-12[3]
230 events
0.2 0.4 0.6 0.8 1 1.2 1.4
N = 1803
1. De Boer R, et al. SABCS 2011. Abstract S1-3. 2. Coleman RE, et al. N Engl J Med. 2011;365:1396-
1405. 3. Gnant M, et al. SABCS 2011. Abstract S1-2.
N = 1065
n = 1041
AZURE - > 5 yrs postmenopausal[2]
263 events
P Value
.02
.0375
.011
0.75
0.66
0.71
ZA Studies: DFS Comparison
27. NSABP B-34: Phase III Study of
Adjuvant Clodronate in Breast Cancer
• Primary endpoint: DFS
• Secondary endpoints: incidence of metastases, OS,
SREs, adverse events, and prognostic serum markers
Clodronate
1600 mg qd
Placebo
3323 patients with
stage I-II breast cancer
receiving adjuvant
standard therapy
Treatment duration: 3 yrs
R
Median follow-up: 8.4 yrs
Two thirds aged > 50 yrs; 25% N positive
28. NSABP B-34: DFS
Paterson A, et al. SABCS 2011. Abstract S2-3.
DiseaseFree(%)
100
80
60
40
20
0
0 2 4 6 8
Yrs After Randomization
Treatment
Placebo
Clodronate
N
1656
1655
Events, n
312
286
HR: 0.91; P = .27
29. NSABP B-34: Analysis of
Specified Endpoints and Safety
• Adverse events comparable in clodronate and placebo arms
– 1 case of ONJ observed in clodronate arm vs no cases in placebo
arm
Endpoint Events, n HR (95% CI) P Value
Clodronate
(n = 1662)
Placebo
(n = 1661)
DFS 286 312 0.913 (0.778-1.072) .266
OS 140 167 0.842 (0.672-1.054) .131
RFI 148 177 0.834 (0.671-1.038) .101
BMFI 61 80 0.765 (0.548-1.068) .114
NBMFI 78 105 0.743 (0.554-0.996) .046
Paterson A, et al. SABCS 2011. Abstract S2-3.
30. NSABP B-34 Subset Analysis: DMFI,
RFI, BMFI, and NBMFI in Patients ≥ 50
Yrs
Endpoint for Patients 50
Yrs of Age or Older
HR P Value
DMFI 0.62 .003
RFI 0.76 .05
BMFI 0.61 .024
NBMFI 0.63 .015
Paterson A, et al. SABCS 2011. Abstract S2-3.
DMFI: distant metastasis-free interval
RFI: relapse-free interval
BMFI: bone-metastasis-free interval
NBMFI: non-bone metastasis-free interval
31. GAIN Trial: Study Design
Möbus V, et al. SABCS 2011. Abstract S2-
4.
Arm A1: Arm B1:
Epirubicin
150 mg/m2
q2w
Ibandronate
50 mg PO QD 2 yrs
Paclitaxel
225 mg/m2
q2w
Cyclophosphamide
2000 mg/m2
q2w
Arm B2:
Observation
Arm A2:
Paclitaxel
67.5 mg/m2
qw
Capecitabine
2000 mg/m2
Days 1-14 q3w
Epirubicin
112.5 mg/m2
Cyclophosphamide
600 mg/m2
q2w
Pegfilgrastim
Ciprofloxacin
Darbepoetin alfa or Epoetin beta
Ciprofloxacin
Pegfilgrastim
Darbepoetin alfa or Epoetin beta
32. GAIN: DFS and OS (ITT)
1.0
0.8
0.6
0.4
0.2
0
SurvivalProbability(%)
DFS (Mos)
0 12 24 36 48 60
1
2
1996
998
1814
871
1590
727
1057
483
555
264
210
105
3-Yr DFS
Ibandronate: 87.6%
Observation: 87.2%
Cox Regression
HR: 0.945 (95% CI: 0.768-1.16; P = .
59)
Ibandronate Observation
Product-Limit Survival Estimates
With Number of Patients at Risk
+ Censored
1.0
0.8
0.6
0.4
0.2
0.0
OS (Mos)
0 12 24 36 48 60
1
2
1996
998
1836
886
1653
756
1121
506
586
277
219
112
3-Yr OS
Ibandronate: 94.7%
Observation: 94.1%
Cox Regression
HR: 1.04 (95% CI: 0.763-1.42; P = .80)
Product-Limit Survival Estimates
With Number of Patients at Risk
+ Censored
Möbus V, et al. SABCS 2011. Abstract S2-
4.
33. GAIN: Subgroup Analyses
DFS for Ibandronate in Subgroups
HR
0.5 1.0 1.5
Better With Ibandronate Worse With Ibandronate
pN1
pN2
pN3
ER and/or PgR positive
ER and PgR negative
Pre- and perimenopausal
Postmenopausal
< 60 yrs
≥ 60 yrs
HR: 1.04 (95% CI: 0.652-1.65; P = .877)
HR: 0.875 (95% CI: 0.599-1.28; P = .490)
HR: 0.951 (95% CI: 0.710-1.27; P = .734)
HR: 0.952 (95% CI: 0.736-1.23; P = .706)
HR: 0.856 (95% CI: 0.604-1.21; P = .383)
HR: 1.02 (95% CI: 0.756-1.37; P = .912)
HR: 0.897 (95% CI: 0.671-1.20; P = .462)
HR: 1.02 (95% CI: 0.807-1.30; P = .842)
HR: 0.746 (95% CI: 0.490-1.14; P = .172)
Möbus V, et al. SABCS 2011. Abstract S2-
4.
34. Variable Efficacy in
an Unselected Population
*Analysis relates to bone metastasis-free survival.
1. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 2. Gnant M, et al. SABCS 2011. Abstract S1-2.
3. De Boer R, et al. SABCS 2011. Abstract S1-3. 4. Paterson A, et al. SABCS 2011. Abstract S2-3.
5. Powles T, et al. Breast Cancer Res. 2006;8:R13. 6. Mobus V, et al. SABCS 2011. Abstract S2-4.
35. Consistent Efficacy in
“Postmenopausal” Women
*Includes patients > 40 yrs on goserelin; no significant effect for patients < 40 yrs.
†
Analysis relates to OS.
‡
≥ 60 yrs at study entry.
1. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 2. Gnant M, et al. SABCS 2011. Abstract S1-2.
3. De Boer R, et al. SABCS 2011. Abstract S1-3. 4. Paterson A, et al. SABCS 2011. Abstract S2-3.
5. Powles T, et al. Breast Cancer Res. 2006;8:R13. 6. Mobus V, et al. SABCS 2011. Abstract S2-4.
36. Conclusions
• Targeting the host environment may complement activity
of direct anticancer treatments
• Adjuvant benefit from bone-targeted treatment appears to
be dependent on a low reproductive hormone environment
– Biologic mechanisms need further evaluation
• Inhibiting the vicious cycle may not always be beneficial
• Adjuvant ZA should be considered in women with a low
estrogen environment
– Prevent bone loss and fragility fracture
– Potentially improve disease outcomes
37. Shepherd LE, et al. ASCO 2012. Abstract 501. Used with permission.
Exemestane vs Anastrozole in Early Breast
Cancer (MA.27): EFS Analysis
• EFS significantly improved with vs without osteoporosis therapy
(HR: 0.70; P < .00001)
Patient-
Reported
Outcome,
n (%)
Osteoporosis
Yes
(n =
1294)
No
(n =
6282)
Osteoporosis
therapy
(n = 2711)
1101
(85)
1610
(25.6)
No
osteoporosis
therapy
(n = 4865)
193
(15)
4672
(74.4)
100
80
0
PatientsWithoutEvent(%)
0 1 2 3 4 5 0
Yrs
P = .0003
Osteoporosis/no osteoporosis therapy
Osteoporosis/osteoporosis therapy
No osteoporosis/no osteoporosis therapy
No osteoporosis/osteoporosis therapy
38. FDA-Approved Antiosteoclast Agents for
Reduction of SREs in MBC
• Both ASCO and NCCN recommend all 3 agents
• No agent recommended over another
Agent Drug Class
Recommended Dose and
Schedule
Zoledronic
acid
Bisphosphonate 4 mg IV q3-4w
Pamidronate Bisphosphonate 90 mg IV q3-4w
Denosumab RANKL-targeted MAb 120 mg SQ q4w
1. Van Poznak CH, et al. J Clin Oncol. 2011;29:1221-1227. 2. National Comprehensive Cancer Network.
Clinical practice guidelines in oncology: breast cancer. v.1.2012.
39. Denosumab vs Zoledronic Acid: Time to
First On-Study SRE
Zoledronic acid 1020 829 676 584 498 427 296 191 94 29
Denosumab 1026 839 697 602 514 437 306 189 99 26
Patients at Risk, n
KM Estimate of
Median Mos
Denosumab
Zoledronic acid
Not reached
26.4
HR: 0.82 (95% CI: 0.71-0.95; P < .001
noninferiority; P = .01 superiority*)
Mos
0
1.00
ProportionofSubjects
WithoutSRE
0 3 6 9 12 15 18 21 24 27 30
0.25
0.50
0.75
Stopeck AT, et al. J Clin Oncol. 2010;28:5132-5139.
40. 40
20
0
Mo 12 Mo 18 At Time of Analysis
Denosumab (n = 1026)Zoledronic acid (n = 1020)
PercentofSubjects
WithSREs(95%CI)
4.5%
relative reduction
11.4%
relative reduction
15.4%
relative reduction
10
30
28.8%32.5% 32.9%38.9%25.4%26.6%
Stopeck A, et al. SABCS 2010. Abstract P6-14-01.
Denosumab vs Zoledronic Acid: Proportion
Experiencing ≥ 1 SRE