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.
Chair and Presenter, Prof Eric Van Cutsem, MD, PhD, and Scott Kopetz, MD, PhD, prepared useful Practice Aids pertaining to colorectal cancer for this CME/MOC/NCPD activity titled “Putting a Personalized Colorectal Cancer Treatment Algorithm Into Practice: Navigating Practicalities in the Era of Molecularly Defined Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD information, and to apply for credit, please visit us at https://bit.ly/3aSSAtm. CME/MOC/NCPD credit will be available until November 13, 2022.
Strategies for Managing Recurrent Ovarian Cancerbkling
When ovarian cancer returns, it's not uncommon to experience a range of emotions and feel overwhelmed. But it's important to remember that recurrent ovarian cancer can often be successfully treated. Dr. Shannon N. Westin, gynecologic oncologist and clinical investigator at MD Anderson Cancer Center, goes over the latest treatment options for recurrent disease.
Audio and slides for this presentation are available on YouTube: http://youtu.be/ozNSEND5PbE
Erica Mayer, MD, MPH, of the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, discusses triple-negative breast cancer and what makes it different from other forms of breast cancer. Mayer also talks about treatment options for triple-negative breast cancer and what you need to know about clinical trials for the disease.
Chair and Presenter, Prof Eric Van Cutsem, MD, PhD, and Scott Kopetz, MD, PhD, prepared useful Practice Aids pertaining to colorectal cancer for this CME/MOC/NCPD activity titled “Putting a Personalized Colorectal Cancer Treatment Algorithm Into Practice: Navigating Practicalities in the Era of Molecularly Defined Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD information, and to apply for credit, please visit us at https://bit.ly/3aSSAtm. CME/MOC/NCPD credit will be available until November 13, 2022.
Strategies for Managing Recurrent Ovarian Cancerbkling
When ovarian cancer returns, it's not uncommon to experience a range of emotions and feel overwhelmed. But it's important to remember that recurrent ovarian cancer can often be successfully treated. Dr. Shannon N. Westin, gynecologic oncologist and clinical investigator at MD Anderson Cancer Center, goes over the latest treatment options for recurrent disease.
Audio and slides for this presentation are available on YouTube: http://youtu.be/ozNSEND5PbE
Erica Mayer, MD, MPH, of the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, discusses triple-negative breast cancer and what makes it different from other forms of breast cancer. Mayer also talks about treatment options for triple-negative breast cancer and what you need to know about clinical trials for the disease.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
advancements in the diagnostics help detect states like oligometastasis ,which can lead to selection of patients for local and MDT and prolong the time to adjuvant therapy, at present There is no consensus on the treatment of oligometastatic cancer and clinical trials can help in evidence formation.
Neoadjuvant or adjuvant immunotherapy in melanoma stage iiiSameer Rastogi
The advent of neoadjuvant therapy in malignant melanoma might prove to be practice changing. Though still in research yet OPACIN and Neo OPACIN trials have unraveled the potential of neoadjuvant immunotherapy in malignant melanoma
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Chair and Presenter, Jonathan D. Spicer, MD, PhD, FRCSC, Sara Najmeh, MD, and Paula A. Ugalde Figueroa, MD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Neoadjuvant, Adjuvant, or Both: How to Solve the Puzzle of Perioperative Immunotherapy, Individualize Treatment Plans, and Improve Cure Rates in Resectable NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3K8tKH9. CME/MOC credit will be available until June 5, 2024.
Breast Cancer Treatment: Where we are, Where we're going - April 24th, 2018Summit Health
Summit Medical Group MD Anderson Cancer Center Lecture Series. A lecture and panel discussion format about the latest advances in surgery and innovative therapies for breast cancer presented by Summit Medical Group MD Anderson Cancer Center Specialists Dr. Lisa Mills, Dr. David Schreiber and Dr. Winnie Polen.
Evolution of Hypofractionated Radiotherapy in Breast Cancerkoustavmajumder1986
Hypofractionated radiotherapy in breast cancer is one of the major evolution. It started few decades back. We have to know its history and radiobiological perspective. In this presentation I have tried to cover as much as possible. It would be helpful for all Radiation Oncologist specially the trainees.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
advancements in the diagnostics help detect states like oligometastasis ,which can lead to selection of patients for local and MDT and prolong the time to adjuvant therapy, at present There is no consensus on the treatment of oligometastatic cancer and clinical trials can help in evidence formation.
Neoadjuvant or adjuvant immunotherapy in melanoma stage iiiSameer Rastogi
The advent of neoadjuvant therapy in malignant melanoma might prove to be practice changing. Though still in research yet OPACIN and Neo OPACIN trials have unraveled the potential of neoadjuvant immunotherapy in malignant melanoma
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Chair and Presenter, Jonathan D. Spicer, MD, PhD, FRCSC, Sara Najmeh, MD, and Paula A. Ugalde Figueroa, MD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Neoadjuvant, Adjuvant, or Both: How to Solve the Puzzle of Perioperative Immunotherapy, Individualize Treatment Plans, and Improve Cure Rates in Resectable NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3K8tKH9. CME/MOC credit will be available until June 5, 2024.
Breast Cancer Treatment: Where we are, Where we're going - April 24th, 2018Summit Health
Summit Medical Group MD Anderson Cancer Center Lecture Series. A lecture and panel discussion format about the latest advances in surgery and innovative therapies for breast cancer presented by Summit Medical Group MD Anderson Cancer Center Specialists Dr. Lisa Mills, Dr. David Schreiber and Dr. Winnie Polen.
Evolution of Hypofractionated Radiotherapy in Breast Cancerkoustavmajumder1986
Hypofractionated radiotherapy in breast cancer is one of the major evolution. It started few decades back. We have to know its history and radiobiological perspective. In this presentation I have tried to cover as much as possible. It would be helpful for all Radiation Oncologist specially the trainees.
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
What’s New with PARP Inhibitors and Ovarian Cancer?bkling
PARP inhibitors have revolutionized ovarian cancer treatment, but recent updates to the FDA-approved indications have caused confusion and raised questions for patients. So what do these changes mean? Dr. Thomas Herzog, Deputy Director of the University of Cincinnati Cancer Center, discusses the current landscape of PARP inhibitors for ovarian cancer and what it means for you.
Globally, breast cancer is the most diagnosed cancer and the leading cause of cancer death among females.
representing 23% of the total cancer cases and 14% of the cancer deaths.
Breast cancer is now also the leading cause of death among women from all cancers in developing countries .
Additionally, breast cancer mortality rates in African women are higher in comparison to women living in Western countries .
A Trilogy of GI Updates
Right vs Left Sidedness in Colon Cancer
KRAS ,NRAS,BRAF and the All RAS Phenotype
MSI-MMR- What’s it All About?
Malcolm Brigden MD FRCP
Associate Clinical Professor of Medical oncology
University of Calgary
Topics to be covered in this presentation:
KRAS ,NRAS,BRAF and the All RAS Phenotype.
Right vs Left Sidedness in Colon Cancer- a newer concept.
MSI-MMR-and the Lynch Syndrome- What’s it All About?
Based on RAS/BRAF, sidedness and MSI/MMR-what might be. Current optimum treatment recommendations?
Conclusions.
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
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
2. Clasificacion Genomica
Diferentes Tipos de TNBC
Importancia de la Clasificacion
Caracteristicas Clinicas del TNBC
Opciones de Tratamiento
Opciones a Futuro
7. . Adapted from Hanahan and Weinberg. Cell. 2000;100:57.
Evading
apoptosis
Self-sufficiency in
growth signals
Tissue invasion
and metastasis
Limitless replicative
potential
Sustained
angiogenesis
Insensitivity to
antigrowth signals
Cancer
cells
Fundamental Hallmarks of Cancer
13. Clasificación molecular del
Cancer de Mama
6 biomarcadores:
1. RE
2. RP
3. HER2
4. EGFR
5. CK5/6
6. Ki67
SJ Schnitt et al - 2010
St. Gallen 2011:
1. RE
2. RP
3. HER2
4. Ki67
14. Why is subtype important?
• Different outcomes
• Prognostic significance
• Selection of therapeutic
options
• Response to treatment
22. Triple
Negative
Basal
~75% of TNBC have
Basal gene expression
1. Pal & Mortimer. Maturitas 2009;
2. Gluz et al. Ann Oncol 2009;
3. Anders & Carey. Oncology 2008.
4. Young et al. BMC Cancer 2009
5. Schneider, B. P. et al. Clin Cancer Res 2008;14:8010-8018
Triple-Negative vs. Basal-Like: Definitions
ER- / PR- / HER2-
~15% of all breast carcinomas
Poorly differentiated
Express CK 5/6, 17, EGFR (+)
• BRCA1-2 mutated tumors
•~5% of Breast Cancer
• 50% BRCA-1 carriers are basal-like
• Basal but not
triple negative
• Definition by
gene
expression
• Includes most
BRCA1 mutated
tumors
• 15-40% are
ER+, PR+ or
HER2+
• Triple negative
but not basal
• Definition by IHC
• Includes other
histologies
(medullar,
adenoid cystic)
• 10-30% can also
include “claudin-
low,” a subtype
notable for high
expression of
stem cell
markers
• 90% of TNBC do
not have BRCA
mutations
BRCA 1-2
25. Prat A, Perou CM, 2009
En resumen….
(con respecto a la clasificación)
26. New Developments in Metastatic Breast Cancer
What Is a Triple-Negative Breast Cancer
(TNBC)?
“Triple negative”: ER negative, PgR negative, HER2
negative
– Depending on thresholds used to define ER and PgR
positivity and methods for HER2 testing
TNBC accounts for 10% to 17% of all breast carcinomas
Significantly more aggressive than other molecular
subtype tumors
Majority grade 3 tumors
Most frequently high grade invasive ductal carcinomas of
no special type
Reis-Filho JS, et al. Histopathology. 2008;52:108-118.
29. New Developments in Metastatic Breast Cancer
Characteristics and Features of TNBC
Phenotype
Weak relationship between tumor size and nodal status
Rapid rise in risk of recurrence following diagnosis
Peak risk of recurrence at 1-3 yrs
Distant recurrence rarely preceded by local recurrence
Local recurrence not predictive of distant recurrence
Increased mortality rate first 5 yrs
Majority of deaths occurs within first 5 yrs
Rapid progression from distant recurrence to death
Dent R, et al. Clin Cancer Res. 2007;13:4429-4434.
30. New Developments in Metastatic Breast Cancer
Clinical Characteristic of Metastatic TNBC
No consistent association
with nodal status or stage
Relapse pattern
– Higher risk
– Early timing
– Sites differ from luminal:
– CNS 46% of time n Bone, % Soft Tissue, % Viscera, %
TNBC 79 13 13 74
ER+ 123 39 7 54
HER2+ 78 7 12 81
Liedtke C, et al. J Clin Oncol. 2008;26:1275-1281. Lin NU, et al. Cancer. 2008;113:2638-2645.
0.35
0.30
0.25
0.15
0.10
0.05
0
HR
0.20
0 1 2 3 4 5 6 7 8 9 10
Yrs After First Surgery
Other (290 of 1421)
Triple negative (61 of 180)
33. Opciones de manejo
Ca de mama RE/P (+) Ca de mama HER2 (3+)
Cirugía
Neoadyuvancia
/adyuvancia
(antraciclinas – taxanos)
Radioterapia +/-
Terapia endócrina
(5 años)
Recaída: hormonoterapia
2da y 3era linea
Cirugía
Neo Ady (antraciclinas –
taxanos
Trastuzuma/Pertuzumab)
Radioterapia +/-
Recaída: ( Kadcyla,
capecitabina, lapatinib,
gemcitabina,vinorelbine,
eribulina, ixabepilona, etc)
34. Myths about triple negative breast
cancer
• There are no effective treatments.
• Patients are doomed to relapse.
• Women with triple negative cancers are
doomed to die of their disease.
• You have to have a mastectomy for triple
negative breast cancer.
35. Opciones de manejo
Ca de mama Triple (-)
• Cirugía
• Neoadyuvancia /adyuvancia
(antraciclinas – taxanos)
• Radioterapia +/-
• Recaída
( capecitabina, platinos,
• gemcitabina, inhib. de PARP
• Bevacizumab, PIK3, PDL1.
• Terapia endócrina NO
• Terapia dirigida NO
42. Basal-like BC Responds to Conventional Chemotherapy
T-FAC
(N=82)*
AC-T
(n=107)*
Luminal A/B 7% 7%
Normal-like 0 NA
HER2+/ER- 45% 36%
Basal-like/triple negative 45% 26%
Rouzier, et al. Clin Cancer Res, 2005
Carey LA, et al. Clin Cancer Res 2007
• Basal-like / triple negative breast cancer responds
to primary chemotherapy.
Explanation of higher response but worse outcome?
Pathologic Complete Response:
45. The Role of Carboplatin in TNBC (Neo)
Trial N
Standard
Chemotherapy
Chemo +
Carboplatin
P-value
CALGB 40603 443 41% 54% 0.003
I-SPY 2 NA 26% 52%
90% prob. for
superiority
GeparSixto
(TNBC pts)
315 38% 59% <0.05
Sikov W, et al. SABCS 2013.
Rugo H, et al. SABCS 2013.
Von Minckwitz G, et al, The Lancet Oncology 15:747, 2014.
55. Study Schema
Carboplatin
AUC5
q3wks x 4
Paclitaxel
80 mg/m2 qwk x 12
CP-CEF
P-CEF
HER2 (-) BC
Stage II/IIIA
18-70 years
PS 0/1
Good Organ
function
Written IC
SURGERY
CEF
500/100/500 mg/m2
q3wks x 4
R
CEF
500/100/500 mg/m2
q3wks x 4
Paclitaxel
80 mg/m2 qwk x 12
Enrolled 181 pts
N= 75 for TNBC
56% Node positive
57. PARP Inhibitors in Development
• Olaparib (Astra Zeneca) PO
• Veliparib (ABT888 - Abbvie) PO
• BMN-673 (Biomarin) PO
• Niraparib (MK-4827) PO
• CEP 9722 (Cephalon) PO
• GPI 21016 (MGI Pharma) PO
• Iniparib (BSI 201 – Sanofi-Aventis) IV
• Rucaparib aka AGO 14699 (Pfizer) IV
• INO 1001 (Inotek – Genentech/Roche) IV
• Others?
58. Opciones de manejo:
Inhibidores del PARP
PARP 1:
Prot. nuclear que va al sitio donde se halla
el DNA dañado y cataliza la transferencia
de ADP-ribosas del NAD+ para modular
la reparación del DNA.
Paciente con BRCA mutado:
No tienen mecanismo de reparación del DNA
por este medio.
60. Mechanisms of Synthetic
Lethality-PARP-1
60
Image from: Iglehart JD, Silver DP. Synthetic Lethality-A new direction in cancer-drug
development. NEJM 2009; 361 (2) ; 189-191. 2009 Massachusetts Medical Society.
All rights reserved. Permission requested.
61. Rugo H, et al. SABCS 2013
I-Spy 2 Trial
Neoadjuvant Veliparib/Carboplatin followed by wPac/AC
62. Parp Inhibitors
One trial in metastatic
TNBC patients.
Gemcitabine/carboplatin
Improvement in tumor
response and survival
with Parp inhibitors
63. Opciones de manejo:
Inhibidores de PARP
DNA
DNA
dañado
REPARACIÓN
BRCA
Reposición
de
nucleótidos
EVENTO MUTADO
PARP
Inhibidor
del
PARP
64. Paclitaxel +
Trastuzumab* +
New Agent A
Paclitaxel +
New Agent C
Patient
is on
Study
Paclitaxel+
Trastuzumab
Paclitaxel +
Trastuzumab* +
New Agent B
Paclitaxel
Paclitaxel +
New Agent E
AC
ACHER 2
(+)
HER 2
(–)
Randomize
Randomize
Surgery
Surgery
Learn and adapt
from each patient as
we go along
Paclitaxel +
New Agent F
Paclitaxel +
Trastuzumab* +
New Agent C
Paclitaxel +
New Agent D
Paclitaxel +
New Agent GH
Paclitaxel +
Trastuzumab* +
New Agent F
MRI
Residual
Disease
(Pathology)
Key
64
I-SPY 2 TRIAL:
Learn, Drop, Graduate, and Replace Agents Over Time
65. Veliparib/Carboplatin GRADUATES
in the Triple Negative Signature
SIGNATURE
Estimated pCR Rate
(95% probability interval)
Probability
Veliparib +
Carbo is
Superior to
Control
Predictive
Probability of
Success in
Phase 3
Veliparib/
Carbo
Concurrent
Control
All HER2- 33%
(22-43%)
22%
(10-35%)
92% 55%
HR+/HER2- 14%
(4-27%)
19%
(6-35%)
28% 9%
HR-/HER2- 52%
(35-69%)
26%
(11-40%)
99% 90%
Rugo et. al. SABCS 2013
66. EGFR inhibitors
Two trials in metastatic
breast cancer
Irinotecan/carboplatin +
cetuximab
Cetuximab alone or with
carboplatin
67. EGFR Inhibition for TNBC
• TNBC is strongly associated with EGFR expression
• EGFR inhibitors combined with platinum
• Current data are conflicting
TBCRC 001
(n=102)
O’Shaugnessy et al
(n=78)
Cetuximab
Carboplatin +
Cetuximab
Irinotecan +
Carboplatin
Irinotecan +
Carboplatin
+ Cetuximab
ORR,% 6 18 49 30
Clinical benefit, % 10 27 NR NR
PFS, mo 2 5.1 4.7
Efficacy data from phase II trials
NR=not reported; PFS=progression-free survival; RR=response rate;
TBCRC=Translational Breast Cancer Research Consortium
Carey et al. ASCO 2008; abstr 1009;
O’Shaughnessy et al. SABCS 2007; abstr 308.
68. TNBC recent perspectives
Looking for a target...
• Other Chemotherapy?
• Androgen Receptor
• PI3K pathway alterations
• EGFR inhibitors
• Anti-angiogenics
• Src inhibitors
• C-Kit alteration
• Clinical Trail
• Likely will need combos
69. Opciones de manejo:
Otras “potenciales” opciones
1. Anti – EGFR:
cetuximab
2. Inhibidores de Tirosin-
kinasa:
sunitinib
3. Anti – mTOR:
everolimus
4. Antiandrógenos:
bicalutamida
Santana-Davila R, Pérez EA - 2010
71. SWOG Proposed Study
R
TNBC
Post NAC
PT1C or N+
N=400
Placebo x 1 year
MK3475 x 1 year
Anti-PD1 antibody
Primary
endpoint:
DFS
A randomized, phase III trial to evaluate the efficacy and safety of MK-
3475 as adjuvant therapy for triple receptor-negative breast cancer
with >1 cm residual invasive cancer or any positive lymph nodes
(>pN1mic) after neoadjuvant chemotherapy
74. TNBC: Conclusions
• TNBC is a recognized distinct subtype of BC
– ER, PR, HER2-negative by IHC
• Surrogate of basal-like BC
– More aggressive biology (morphology, clinical, molecular)
• TNBC responds to a variety of CT agents although no
specific standard regimen or agent can be singled out
• TNBC has no identified specific therapeutic target
• Represents an heterogeneous group of tumors probably
with different response patterns to different treatments
– Introduction of novel agents (PARPi, others) ?
– Biomarkers: RAD-51, Neuropilin ?
75. En conclusión…
• Presente como cáncer de intervalo
• Poca asociación entre tamaño de tumor
y estado axilar.
• Metástasis tempranas y agresivas.
• Recurrencia pico entre 1º y 3º años
del diagnóstico.
• La recurrencia local no predice recaída
a distancia.
76. En conclusión…
• Más prevalente en jóvenes.
• Fuerte asociación con obesidad.
• Alta prevalencia de mets cerebrales.
• La mayoría de las muertes son a 5 años.
• Altamente quimiosensible.
• Todos los tratamientos en estudios.
77. Triple Negative Breast Cancer
• Represents a subtype of breast cancer with
unique molecular and clinical characteristics .
• Characterized by more aggressive
clinicopathologic features including younger age,
higher mean tumor size, and higher-grade
tumors .
• More likely to occur among premenopausal
women of African-American descent .
• Association with BRCA1 mutation status.
• More likely to develop a recurrence during the
first 3 years following therapy
• More aggressive visceral and soft-tissue relapse
and less common bone recurrence.
• High response to systemic chemotherapy.
103
78. Future Directions
• Increase participation in clinical trials.
• Design and implement cancer prevention trials
applicable to at risk populations.
• Increase understanding of risk factors and
biology underlying triple-negative breast cancer.
• Improving treatment strategies.
• Continuous review of current methods.
104