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.
Management of Early Breast Cancer (by Dr. Akhil Kapoor)Akhil Kapoor
Comprehensive discussion on Management of Early Breast Cancer along with NCCN guidelines.
Slides prepared by Dr. Akhil Kapoor
(Resident, Department of Radiation Oncology,
Acharya Tulsi Regional Cancer Treatment & Research Institute, Bikaner, Rajasthan, India
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.
Management of Early Breast Cancer (by Dr. Akhil Kapoor)Akhil Kapoor
Comprehensive discussion on Management of Early Breast Cancer along with NCCN guidelines.
Slides prepared by Dr. Akhil Kapoor
(Resident, Department of Radiation Oncology,
Acharya Tulsi Regional Cancer Treatment & Research Institute, Bikaner, Rajasthan, India
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
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.
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
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.
Join Dr. Erica Mayer, medical oncologist at Dana-Farber/Brigham and Women's Cancer Center, to learn about exciting metastatic breast cancer developments from the past year. Dr. Mayer presents an overview on metastatic breast cancer and the subgroups, including Hormone Receptive, HER2+, and Triple Negative, and highlights recent advances for each of these subgroups. She also discusses the importance of clinical trials and what it means to participate in a clinical trial.
For more information on the Breast Cancer Treatment Center at Dana-Farber Cancer Institute, please visit:
http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-Centers-and-Clinical-Services/Breast-Cancer-Treatment-Center.aspx
It contains details about breast carcinoma-pathology,investigations and diagnosis,NACT,surgery and adjuvant therapy. Hope you will find it helpful.....
http://cancer-treatment-madurai.com Breast cancer is a type of cancer that starts in the tissues of the breast. Dr.S.G.Balamurugan is one of the best cancer doctor in India, offers low cost breast cancer diagnosis, breast cancer treatments and breast cancer care at Guru Cancer Hospital, Madurai.
Evaluation and management of Stage III Non-Small Cell Carcinoma Lung including Radiotherapy planning. On a Radiation Oncologist Perspective. MD Radiotherapy discussion - CMC, Vellore
- 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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. INTRODUCTION
Breast cancer, the second-leading cause of cancer
deaths in women, is the disease women fear most.
Breast cancer can also occur in men, but it's far less
common.
Yet there's more reason for optimism than ever
before.
3. Most common Cancer in women in developed countries.
The lifetime risk (upto age 85)
1940 - 5% ---- ----one in 20.
2000- 12.6% -------- one in 8
Incidence worldwide incidence 1.2 million(WHO)
Death – 2nd
leading cause of cancer death. 40,000 in US per
year, worldwide much higher
STATISTICS
4. Hereditary (10% of pts have 1st
deg relatives)
Genetic mutations- BRCA 1, 2
Radiation- esp. during childhood- mantle RT upto 20%
incidence by 50 y.
Benign disease- proliferative, with atypia
Previous h/o breast ca
Diet- obesity; dietary fat, anti-ox.- inconclusive.
Hormonal factors- increased risk with excess exposure to
estrogens; Progesterone containing OCPs
ETIOLOGY
5. RISK FACTOR MODELS
Gail model: ( www.nci.nih.gov )
Uses the following criteria:
-current age
-age at menarche
-age at first child birth
-no. of first degree relatives with breast ca
-no. of previous benign biopsies
-atypical hyperplasia in a prev. biopsy
-race
6. PATHOLOGY
In-situ Carcinomas-
DCIS, LCIS; Paget’s disease of nipple
Invasive Cas-
Invasive Ductal Ca (80%)
Invasive lobular Ca (10%)
Other invasive Cas- Medullary, papillary, tubular,
cribriform, metaplastic, squamous, adenoid cystic,
mucinous, secretory, undifferentiated.
7. “Intrinsic” breast cancer subtypes
Basal-like ER- PR- HER2- ck5/6+ and /or HER1+
Luminal A ER+ and/or PR+ HER2-
Luminal B ER+ and/or PR+ HER2+
HER2+ / ER – ER- PR- HER2+
“Unclassified” Negative for all five markers
9. Direct invasion- into chest muscles, wall, skin/nipple-
areola.
Lymphatic- Locoregional - axilla, supraclavicular,
infraclavicular and Internal mammary
Blood- Bones, lungs, liver, brain– Distant metastasis-
stage IV
MODES OF SPREAD
10. Local- Lump, discharge, skin/nipple changes,
axillary, arm swelling, ulcer ,Pain, tenderness-
Inflammatory Ca
Distant- back ache, cough, breathlessness, headache,
vomiting, anorexia, etc.
O/E – lump-hard, irregular , nipple retraction, peau de
orange/puckering.
Nipple discharge, axillary nodes
CLINICAL SYMPTOMS-
11. History and physical Examination.
Mammography.
FNAC/biopsy of the lump/gland- histology and
receptor status studies
Her 2 /neu, prognostic indicator studies
Evaluation- CBC, RFT, LFT, ALP, S. Ca++, Cardiac
evaluation,
Metastatic work up- CXR, USG A+P, Bone scan, ?
PET. CT thorax, brain- only if symptoms suggestive.
DIAGNOSIS
12. American Joint Committee on Cancer
Staging System for Breast Cancer
(p)T (Primary Tumor)
Tis Carcinoma in situ (lobular or ductal)
T1 Tumor ≤2 cm
T1a Tumor ≥0.1 cm, ≤0.5 cm
T1b Tumor >0.5 cm, ≤1 cm
T1c Tumor >1 cm, ≤2 cm
T2 Tumor >2 cm, ≤5 cm
T3 Tumor >5 cm
T4 Tumor any size with extension to the chest wall or skin
T4a Tumor extending to the chest wall (excluding the pectoralis)
T4b Tumor extending to the skin with ulceration, edema,nodules
T4c Both T4a and T4b
T4d Inflammatory carcinoma
13. N0 No regional node involvement, no special studies
N0 (i-) No regional node involvement, negative IHC
N0 (i+) Node(s) with isolated tumor cells spanning <0.2 mm
N0 (mol-) Negative node(s) histologically, negative PCR
N0 (mol+) Negative node(s) histologically, positive PCR
N1 Metastasis to 1-3 axillary nodes and/or int.
mammary positive by biopsy
N1(mic) Micrometastasis (>0.2 mm, none >2.0 mm)
N1a Metastasis to 1-3 axillary nodes
N1b Metastasis in int. mammary by sentinel biopsy
N1c Metastasis to 1-3 axillary nodes and int. mammary
by biopsy
(P)N (NODES)
14. N2 Metastasis to 4-9 axillary nodes or int. mammary
clinically positive, without axillary metastasis
N2a Metastasis to 4-9 axillary nodes, at least 1 >2.0 mm
N2b Int. mammary clinically apparent, negative axillary nodes
N3 Metastasis to ≥10 axillary nodes or combination of
axillary and int. mammary metastasis
N3a ≥10 axillary nodes (>2.0 mm), or infraclavicular nodes
N3b Positive int. mammary clinically with ≥1 axillary nodes or
>3 positive axillary nodes with int. mammary positive
by biopsy
N3c Metastasis to ipsilateral supraclavicular nodes
22. Locally Advanced and Metastatic Breast Cancer
Overview:
Principles of neoadjuvant chemotherapy for locally
advanced and inflammatory breast cancer
Systemic therapy of metastatic breast cancer
Chemotherapy
Hormonal agents
Biologic agents
Bisphosphonates
Rationale for selection of treatment in metastatic
disease
chemotherapy vs. hormonal agents
Ideal first line agents?
23. Locally Advanced Breast Cancer
Definition: breast cancer, without distant metastatic
spread, which is unresectable due to
Satellite skin nodules
Extensive regional lymph node involvement
Fixation to skin or chest wall
Inflammatory breast cancer
24.
25.
26. Locally Advanced Breast Cancer
Combined modality treatment is the standard
of care for locally advanced breast cancer.
Neoadjuvant chemotherapy
Goals are to improve resectability of the tumour
and to increase rates of breast conserving
treatment and establish tumor sensitivity
Locoregional therapy
Surgery, or radiotherapy, or both.
27. Locally Advanced Breast Cancer
Response rates to neoadjuvant chemotherapy:
Major responders: 47-100%
Clinical complete responders: 8-63%
Pathologic complete responders: 3-30%
A major response to chemotherapy is associated
with improved disease-free and overall survival.
28. Locally Advanced Breast Cancer
Survival is related to axillary lymph node
status after neoadjuvant chemotherapy.
Positive nodes 5-year overall survival
0 75%
1-4 40-50%
5-10 30%
>10 20%
29. Locally Advanced Breast Cancer
Survival is related to response of primary tumour to neoadjuvant
chemotherapy.
Author Median
follow-up,
years
Survival,
patients with
complete
response
Survival,
patients with
partial
response
Method of
response
assessment
Eltahir,
1998
5 74%
overall
survival
36%
overall
survival
Clinical
response
Kuerer,
1999
5 89%
overall
survival
64%
overall
survival
Pathologic
response
Bonnadonn
a,1998
8 86%
disease-free
survival
56%
disease-free
survival
Clinical
response
30. Locally Advanced Breast
Cancer
Duration of neoadjuvant chemotherapy
Optimal duration of treatment is not known.
Rule of thumb: “treat until maximal response.”
May require from 2-8 treatments, depending on
rapidity of response.
Patients should be assessed by multidisciplinary
team after every 2 cycles of chemotherapy to
determine optimal timing of surgery.
31. DEFINITIONS FOR RESPONSE EVALUATION OF
PRIMARY SYSTEMIC THERAPY
CLINICAL DEFINITION
Complete: no palpable mass detectable (cCR)
Partial: reduction of tumour area to < 50% (cPR)
IMAGING DEFINITION
No tumour visible by mammogram and/or ultrasound and/or MRI
PATHOLOGICAL DEFINITION
Only focal invasive tumour residuals in the removed breast tissue
Only in situ tumour residuals in the removed breast tissue (pCR inv)
No invasive or in situ tumour cells (pCR)
No malignant tumour cells in breast and lymph nodes (pCR breast
and nodes).
32. Locally Advanced Breast Cancer
Ideal neoadjuvant chemotherapy regimen has not
been identified.
Anthracycline based (epirubicin or adriamycin)
chemotherapy is often used at start (AC, CAF, FEC).
Taxanes (taxol, taxotere) are also extremely effective
and have been shown to increase the rate of
pathologic complete responses.
33. Locally Advanced Breast Cancer
Impact of Taxanes in NeoadjuvantChemotherapy.
TAX-301 trial
162 patients, randomly assigned to pre-operative
CAVP X 8 cycles vs CAVP x 4 then Taxotere X4
5 year overall survival:
CAVP X 8: 78%
CAVP X 4 + Taxotere X 4: 97%
36. 4 cycles of Taxotere
4 cycles of CVAP
No Response
Response
RandomiseAll Patients
4 cycles of CVAP
First Phase
Tax301 Study
Conducted by the Aberdeen Breast Group
Second phase
4 cycles of Taxotere
FinalAssessment/Surgery
37. Aberdeen Tax 301
Objective clinical response rates
1st phase: 4 cycles CVAP
Response % of patients
Complete 15
Partial 52
Stasis 33
Progression 1
ORR - 67%
N=162 patients; 4 cycles of CVAP given to all patients
40. Aberdeen Tax301Aberdeen Tax301
Type of surgeryType of surgery undertaken
Breast conservation surgery
Taxotere 67%
CVAP 48%
Conservation Mastectomy
0
20
40
60
80
100
Taxotere
CVAP
Type of surgery
%ofpatients
(p<0.01)
43. NSABP B-27
Operable Breast CancerOperable Breast Cancer
RandomizationRandomization
AC x 4AC x 4
Tam X 5 YrsTam X 5 Yrs
AC x 4AC x 4
Tam X 5 YrsTam X 5 Yrs
AC x 4AC x 4
Tam X 5 YrsTam X 5 Yrs
SurgerySurgery Taxotere x 4Taxotere x 4 SurgerySurgery
SurgerySurgery Taxotere x 4Taxotere x 4
( 2411 pts )
45. NSABP B-27
Pathological Response (pCR) in Breast
p < 0.001
AC Taxotere
N=786
AC
N=1567
3.9%
9.8%
7.2%
18.9%
20
10
0
30 No Tumour
Non-Invasive
26.1%
13.7%
46. NSABP B-27:
Proportion of Patients with negative axillary lymph
nodes
58.2
p < 0.001p < 0.001
ACAC
N=1534N=1534
AC TaxotereAC Taxotere
N=752N=752
8080
6060
4040
2020
00
%%
50.8
47. NSABP B-27: Breast Conservation: Breast Conservation
p = 0.70
61 63
8080
6060
4040
2020
00
%%
ACAC
(N=1492)(N=1492)
AC TaxotereAC Taxotere
N=718N=718
48. LOCALLY ADVANCED BREAST
CANCER
Role of Herceptin (trastuzumab):
Initial reports are encouraging, but use of herceptin cannot be
recommended outside of a clinical trial.
Role of High-dose chemotherapy with stem cell
support:
No improvement in DFS or OS, with significant increase in
toxicity and worsening of quality of life, therefore not
recommended.
49. LOCALLY ADVANCED BREAST
CANCER
Hormonal Management
Acceptable in Estrogen Receptor and/or
Progesterone Receptor positive cancers.
Best used in patients where chemotherapy is
relatively contraindicated
Elderly
Poor performance status
Comorbid illness
Patient reluctance to accept chemotherapy
50. LOCALLY ADVANCED BREAST
CANCER
Hormonal Management, continued:
Rate of pathologic complete response is greatly
diminished.
Rate of breast-conserving treatment is greatly
diminished.
Response to treatment is much slower, e.g. 3-9
months.
54. Multidisciplinary Cancer Breast Management
Trials of Neoadjuvant Trastuzumab:
Summary of Efficacy
•Preoperative clinical responses observed
– Overall response rate, 70% to 90%
– Clinical complete response, 15% to 30%
– Pathologic complete response, approximately 18%
•Responses higher for patients with 3+ expression of
HER2
55. The relative efficacy of neoadjuvant endocrine
therapy versus chemotherapy in postmenopausal
women with ER positive breast cancer
Methods: 121 postmenopausal women with ER(+) and/or
PgR(+) breast cancer T2N1–2, T3N0–1, T4N0M0
assigned to NAT with either CT Dox 60 mg/m2 + Pac 200
mg/m2, every 3 weeks, 4 cycles, n=62 patients (pts), or HT
with aromatase inhibitors, anastrazole 1 mg, n = 30 pts, 3
months).
In CT arm the most frequent grade III/IV toxicity was alopecia ( 79.3 % ), neutropenia ( 43.1 %),
cardiotoxicity (6.8 %), diarrhea (1.7%). HT was well tolerated. The most commonly adverse events
were hot flushes (23.3%), vaginal discharge (6.6%), musculosskeletal disorders (1.7%).
Note this does not give the pathologic CR rate.
59. Letrozole Is More Effective Neoadjuvant Endocrine
Therapy Than Tamoxifen for ErbB-1– and/or
ErbB-2–Positive, Estrogen Receptor–Positive
Primary Breast Cancer: Evidence From a Phase III
60. LOCALLY ADVANCED BREAST CANCER
Summary:
Standard of care is multimodality treatment.
Chemotherapy: should contain anthracyclines and/or taxanes
and should begin before surgery.
Locoregional therapy: should be performed when a maximal
tumour response has been obtained.
Post-operative chemotherapy: should be performed if less
than 8 cycles were given pre-operatively, until a total of 8
cycles of chemotherapy have been given.
Hormonal management: is a slower option, and is restricted
to ER and/or PR positive tumours.
61. METASTATIC BREAST CANCER
Goals of treatment of metastatic breast cancer:
Cure: not a realistic goal
Few patients have complete responses, and disease free
intervals are short.
Prolongation of survival:
5-10% of patients will survive 5 years or more.
2-5% of patients are long-term survivors (>10 years).
Improvement of Quality of Life:
Most patients experience fewer disease symptoms, with
manageable treatment side effects.
63. METASTATIC BREAST CANCER
Different options can be combined.
Herceptin and chemotherapy.
Hormonal agents and bisphosphonates.
Herceptin, chemotherapy and bisphosphonates.
64. METASTATIC BREAST CANCER
How is initial therapy selected?
Patient factors: age, comorbid conditions,
willingness to accept side effects.
Tumour factors: ER, PR, her-2/neu status.
Course of illness: extent and location of metastases,
disease-free interval, pace of spread of metastases.
Treatment factors: adjuvant chemotherapy, adjuvant
hormonal agents, adjuvant radiotherapy.
65. METASTATIC BREAST CANCER
The use of hormonal agents is favoured if:
Tumour is ER and/or PR positive.
Disease-free interval is long.
Few sites of metastases.
Metastases do not involve visceral organs.
Pace of disease progression is slow.
Patient has responded to previous hormonal agents.
66. METASTATIC BREAST CANCER
Use of hormonal agents, continued
Hormonal agents require 8-12 weeks to determine
their efficacy, thus they are not recommended for
patients with extensive visceral metastases.
Initial response to hormonal agents is 50-60% in
ER/PR positive patients.
67. METASTATIC BREAST
CANCER
The use of chemotherapy is favoured if:
Tumour is negative for ER and PR.
Disease-free interval is short.
Extensive metastases are present, especially visceral
disease (liver, lung).
Disease is progressing rapidly.
Patient has not responded to previous hormonal
agents.
Initial response to chemotherapy is 50-75%.
No clear advantage of combination regimens over
use of sequential single agents.
68. METASTATIC BREAST CANCER
Hormonal agents:
Tamoxifen:
Mixed estrogen receptor agonist-antagonist.
Can be used in premenopausal and postmenopausal
women.
Response rates are 50-60%.
Duration of response may be years.
Toxicities: hot flashes, increased risks of DVT/
pulmonary embolism, endometrial cancer
May be associated with tumour reluctance in up to
13% of patients.
69. METASTATIC BREAST CANCER
Hormonal agents, continued:
Aromatase inhibitors:
Anastrozole (Arimidex), non-steroidal
Letrozole (Femara), non-steroidal
Exemestane (Aromasin), steroidal
Method of action: block conversion of adrenal androgens
to estrogen in adipose tissue and in the breast.
Use is restricted to postmenopausal women.
Side effects: hot flashes, myalgias/arthralgias, increased
risk of osteoporosis, altered lipid profiles.
70. METASTATIC BREAST CANCER
Hormonal agents, continued:
Aromatase inhibitors:
Anastrozole and Letrozole:
are non-steroidal aromatase inhibitors.
are both superior to Megace in tamoxifen refractory
patients.
Have similar efficacy to tamoxifen, with fewer
side effects.
71. METASTATIC BREAST CANCER
Hormonal agents, continued:
Aromatase inhibitors:
Exemestane:
is a steroidal aromatase inhibitor.
is superior to Megace, and at least as effective as
Tamoxifen.
can be effective in patients who have failed non-
steroidal aromatase inhibitors.
72. METASTATIC BREAST
CANCER
Hormonal agents, continued:
Megace (megestrol acetate)
Is a progestin
Before aromatase inhibitors, was considered
second-line therapy, after tamoxifen.
May still have activity in some patients who have
failed tamoxifen and/or aromatase inhibitors.
Side effects: increased appetite, weight gain,
increased risk of DVT/pulmonary embolism.
73. Sequencing of Hormonal agents in metastatic
breast cancer:
Postmenopausal patients:
Anastrozole or Letrozole as first line
Exemestane as second line
Tamoxifen and Megace remain options for third line
OR for patients who do not tolerate aromatase
inhibitors.
Premenopausal patients:
Tamoxifen as first line
Megace OR aromatase inhibitor with ovarian
ablation as second line.
METASTATIC BREAST
CANCER
74. Chemotherapy:
Numerous agents have activity in metastatic
breast cancer:
Anthracyclines
Taxanes
Fluoropyrimidines
Vinca alkaloids
Other drugs: cyclophosphamide, methotrexate,
gemcitabine
METASTATIC BREAST
CANCER
75. Anthracyclines
doxorubicin (Adriamycin),epirubicin, mitoxantrone
liposomal-PEGylated doxorubicin (Doxil-Caelyx)
Are among the most active agents in breast cancer
(response rate at least 50%)
METASTATIC BREAST
CANCER
76. Taxanes
Paclitaxel (Taxol)
Docetaxel (Taxotere)
Nanoparticle albumin-bound paclitaxel (Abraxane)
Are the single most active drugs in breast cancer
and the most active in adriamycin-refractory
patients. (RR = 60%)
Common toxicities include peripheral neuropathy,
myalgias, arthralgias and alopecia.
METASTATIC BREAST
CANCER
77. Paclitaxel (taxol)
can induce anaphylactoid reactions, requiring
premedication with steroids and antihistamines.
Efficacy and toxicity profile can be improved by
weekly administration (as opposed to q3weeks).
Docetaxel (taxotere)
Can induce responses in 25% of patients who are
resistant to paclitaxel.
Cumulative toxicities include fluid retention,
sclerosis of tear ducts, loss of fingernails/toenails.
METASTATIC BREAST
CANCER
78. Nanoparticle albumin-bound paclitaxel
(Abraxane)
Novel formulation, does not require Cremophor.
No risk of anaphylactoid reaction, thus no need for
steroids.
Better tissue penetration.
Less toxic and more effective than paclitaxel.
Approved in the USA, not yet approved in Canada.
METASTATIC BREAST
CANCER
79. Fluoropyrimidines:
5-fluorouracil:
is commonly used in combinations, such as CMF,
CAF, FEC.
Has activity as a single agent, esp. in prolonged
infusions, but these regimens are not convenient.
Toxicities: mucositis (stomatitis, enteritis, colitis),
hand-foot syndrome, some myelosuppression
METASTATIC BREAST
CANCER
80. Fluoropyrimidines, cont’d
Capecitabine (Xeloda)
Oral 5-FU derivative, given BID X14 days
q21days.
Prodrug is activated to 5-FU in tumour cells,
mimics a prolonged 5-FU infusion.
Has activity even in patients who are refractory to
anthracyclines and taxanes!! (RR=25%)
Dose limiting toxicity is usually hand-foot
syndrome.
NOT HEPATICALLY METABOLIZED, thus ideal
agent in patients with severe liver dysfunction!
METASTATIC BREAST
CANCER
81. Vinca alkaloids:
Vinorelbine (Navelbine)
Semi-synthetic vinca alkaloid, related to VCR/VBL
Less neurotoxicity, due to diminished binding to
axonal microtubules.
Active even in heavily pretreated patients (response
rates = 25-50%).
Excellent toxicity profile: no nausea, no alopecia,
no mucositis
Well tolerated by elderly, frail patients
METASTATIC BREAST
CANCER
83. Biologic agents
Herceptin (trastuzumab)
Humanized mouse monoclonal antibody directed
against the her-2/neu protein.
Has activity against breast cancers that strongly
overexpress her-2/neu (score= 3+/3).
Has activity as a single agent, even in heavily pre-
treated patients.
METASTATIC BREAST
CANCER
84. Herceptin, cont’d
Can be safely administered with taxanes and
vinorelbine, with increased response rates (compared
to chemotherapy alone).
Cannot be given with adriamycin; response rates
increase BUT rate of cardiomyopathy rises to 27%!!!
Patients on herceptin who have received anthracyclines
in the past need monitoring for cardiac toxicity.
METASTATIC BREAST
CANCER
85. Bisphosphonates:
Pamidronate (Aredia)
Zolendronate (Zometa)
Given monthly to patients with bone metastases.
Leads to decreased risk of skeletal complications
(pain, fractures, need for radiotherapy)
Few toxicities: fever and chills post-infusion,
muscle spasms (transient hypocalcemia)
Rare cumulative toxicity: osteonecrosis of the
mandible (!)
METASTATIC BREAST
CANCER
86. A rational approach to selecting therapy for patients with
metastatic breast cancer:
For patients with bone metastases:
monthly administration of Pamidronate or
Zolendronate (regardless of ER/PR/her-2 status)
For patients with ER and/or PR positive breast
cancer, with low burden of metastases and slow
pace of disease:
start with hormonal agents.
If patient was on a hormonal agent at time of relapse,
try to select a non cross-resistant agent.
METASTATIC BREAST
CANCER
87. A rational approach to selecting therapy for patients
with metastatic breast cancer:
For patients with ER-negative/PR-negative disease
OR for patients with high tumour burden OR with
rapid disease progression:
Start with chemotherapy
In anthracycline-naïve patients, use anthracyclines.
In patients who had adjuvant anthracyclines, use
taxanes.
METASTATIC BREAST
CANCER
88. A rational approach to selecting therapy for patients
with metastatic breast cancer:
For patients with ER-negative/PR-negative disease OR
for patients with high tumour burden OR with rapid
disease progression:
2nd
, 3rd
, 4th
lines of treatment depend on patient’s
previous side effects and current symptoms.
e.g. navelbine contraindicated in patient with
abnormal liver function tests; capecitabine would be
a safer choice.
METASTATIC BREAST CANCER
89. A rational approach to selecting therapy for
patients with metastatic breast cancer:
For patients with her-2/neu 3+ disease:
Herceptin should be given with taxane or
vinorelbine chemotherapy.
Herceptin can be given as a single agent even in
heavily pre-treated patients.
Herceptin as a single agent can be given as
“maintenance” therapy after “inducing” a major
reduction in tumour burden with herceptin-chemo
combination.
METASTATIC BREAST
CANCER
92. Lapatinib
Oral dual tyrosine kinase inhibitor
of HER2 and EGFR
FDA approved in combination with
capecitabine for trastuzumab-
resistant disease
May have CNS penetration
Well tolerated; common toxicities
include rash and diarrhea
93. Pertuzumab with trastuzumab
HER2 receptor
Trastuzumab
Pertuzumab
Dimerisation domain
of HER2
• Inhibitor of HER dimerization: binds HER2 and prevents formation of homo- or heterodimers
• Suppresses activation of several intracellular signaling cascades driving cancer cell growth
• Synergistic with trastuzumab
• Approved for first-line treatment of metastatic Her2+ breast cancer in combination with trastuzumab
and taxane chemotherapy
94. CLEOPATRA: phase 3 study of
pertuzumab in untreated metastatic disease
1:1
HER2-positive
MBC
Docetaxel + trastuzumab
+ placebo
Docetaxel + trastuzumab
+ pertuzumab
N=808
Pertuzumab prolongs time until progression by
six months (from 12.5 to 18.5 months)
95. Trastuzumab Emtansine (T-DM1)
T-DM1 is an antibody
drug-conjugate
Trastuzumab linked to a
potent chemotherapy
(DM1)
Average of 3.5 DM1 per
antibody
96. T-DM1 selectively delivers DM1
to HER2+ cells
Receptor-T-DM1 complex is
internalized into HER2-
positive cancer cell
Potent antimicrotubule
agent is released once
inside the HER2-
positive
tumor cell
T-DM1 binds to the HER2
protein on cancer cells
HER2
97. EMILIA: randomized trial comparing T-
DM1 to capecitabine and lapatinib in
previously treated patients
1:1HER2+ MBC (N=980)
•Prior taxane and
trastuzumab
PD
T-DM1
3.6 mg/kg q3w IV
Capecitabine
1000 mg/m2
orally bid, days 1–14, q3w
+
Lapatinib
1250 mg/day orally qd
PD
T-DM1 prolongs time until progression by three
months (from 6.4 to 9.6 months)
R
E
S
U
L
T
E
98. Th3RESA: randomized trial comparing T-DM1
to physician’s choice
Study treatment
continues until disease
progression or
unmanageable toxicity
HER2 positive
Metastatic breast
cancer
Prior trastuzumab,
lapatinib and
chemotherapy
T-DM1 q3w
Treatment of
physician’s choice
N = 795
2:1 randomization
2
1
T-DM1 prolongs time until progression by three months
(from 3.3 to 6.2 months)
99. T-DM1 is well-tolerated
Common side effects:
Decreased platelet count
Elevated liver tests
Does not cause typical chemotherapy side effects
No hair loss
Significant nausea or diarrhea are not common
Does not cause immune suppression or significant
neuropathy
102. New drug approval: everolimus
Approved by the FDA in 2012 for patients with metastatic, hormone-receptor positive,
HER2-negative breast cancer
*Median time from study entry until worsening of cancer
103. What’s next for everolimus?
Multiple studies underway
In HER2+ cancers
In triple negative cancers
Studying this drug in combination with other
therapies
105. Other agents of interest in ER+ disease
Endoxifen
CDK 4/6 inhibitors
PI3Kinase inhibitors
Anti-IGF-1R Ab
SRC/Abl tyrosine kinase inhibitors
Combination therapy with targeted agents that may
overcome endocrine resistance
107. There are many chemotherapies that are
active against metastatic disease
Mitotic inhibitors
vinorelbine
paclitaxel
docetaxel
Antifolates
methotrexate
Topoisomerase inhibitors
doxorubicin
108. Platinums
Sledge reported 47% response rate in first line metastatic
disease
Abandoned for many years because of concerns about
toxicity—largely replaced by taxanes
Recent interest in patients with triple negative breast cancer
DNA crosslinking mechanism of action
New data from a series of neoadjuvant studies supports activity in
TNBC
110. PARP inhibitors
PARP1 is a protein that is important for repairing
single-strand DNA breaks
PARP inhibitors prevent DNA repair, leading to cell
death
Fast-dividing tumors and tumors containing BRCA
mutations, which also impair DNA repair, may be most
sensitive to PARP inhibitors
Ongoing trials are investigating the efficacy of PARP
inhibitors in breast cancer, particularly triple negative
breast cancer and BRCA-associated breast cancer
111. Inhibit binding to receptor (AR)
T
AR
T
Cell nucleus AR
Cell cytoplasm
Inhibit nuclear translocation of AR
Inhibit AR-mediated DNA binding
Targeting the androgen receptor in
triple negative breast cancer
112. Other agents of interest in triple
negative disease
PI3Kinase inhibitors
SRC/Abl tyrosine kinase inhibitors
HSP90 inhibitors
More to come…
Editor's Notes
by selectively delivering drugs to overexpressed antigens on tumor cells than could be achieved by administration of either antibody or chemotherapy as free agents
No crossover allowed for control arm to T-DM1 after PD (OS)