This document discusses various treatments for breast carcinoma including chemotherapy, hormonal therapy, and targeted therapy. It provides details on:
- The indications for chemotherapy including tumor size, node involvement, and molecular factors.
- How prognostic factors like tumor grade and molecular markers help determine treatment.
- Studies that helped establish chemotherapy regimens and combinations like adding taxanes or using dose-dense schedules.
- The use of neoadjuvant chemotherapy and outcomes seen with complete responses.
- Hormonal therapies for hormone receptor positive cancers including tamoxifen, aromatase inhibitors, and ovarian ablation.
- Targeted therapies for HER2 positive cancers including trastuzumab and newer agents.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
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
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.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
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
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.
Dr. Patty Tenofsky of Via Christi Clinic spoke at the Via Christi Women's Connection luncheon about breast cancer statistics, screening for breast cancer, treatment options, radiation therapy and chemotherapy.
Other Mechanisms of Molecular Pathogenesis of CancerReshma Ann Mathew
Other Mechanisms of Molecular Pathogenesis of Cancer - Evasion of Apoptosis, Defects in DNA repair, Limitless Replicative Potential, MicroRNAs in cancer,
Chemotherapy is a widely used treatment for cancer. More specifically, this therapy is administered to destruct cancer cells. However, it may also include some antibiotics along with other medications for treating severe infection or illness.
El 3 de noviembre de 2015, la Fundación Ramón Areces organizó en su sede en Madrid (C/ Vitruvio, 5) una jornada sobre ‘El cáncer como consecuencia del envejecimiento: posibles soluciones’. Coordinado por la investigadora María Vallet Regí, del Departamento de Química Inorgánica y Bioinorgánica de la Universidad Complutense de Madrid, contó con la presencia, entre otros científicos, de Mariano Barbacid, Lodovico Balducci y Theresa Guise.
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.
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
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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
4. Indication
• Generally recommended for >1 cm tumors
• Node positive disease.
• Consider for all triple negative tumors,
• Given high rates of recurrence and lack of options
for targeted or endocrine therapies.
• Risk Stratification for Adjuvant Therapy based on
• Oncotype DX and
• MammaPrint
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5. Various Prognostic Factors
1. Anatomic:
1. Size of tumor
2. Lymph node (LN) involvement
1. The most powerful prognostic factor
2. Histologic:
1. Tumor grade
2. LV Invasion,poorly differentiated
3. Markers of increased proliferation:mitotic index,high
Ki67,elevated S-phase fraction
4.
3. Molecular factors:
1. ER/PR status
2. HER2/neu over expression
3. 21-gene or 70-gene recurrence score
6/23/2016 5dr rahul ts
6. Oncotype Dx: The 21-Gene Assay
• RT-PCR was used to quantify gene expression
• from fixed, parafin-embedded tumor tissue
• Designed to quantify the risk of distant recurrence in patients with
newly diagnosed,eariy stage,LN(-), ER(+) tumors receiving
tamoxifen.
• recurrent score calculated from 0-100
• NSABP trial B-14 ,patients classified according to the recurrent
scores(RS) based on 10 year distant disease free survival into
• high risk(RS 31&above),
• intermediate risk(RS 18 and <31) and
• low risk(RS <18)
• From these studies, 16 genes (+5 reference genes) were selected
that correlated with proliferation and endocrine response
6/23/2016 6dr rahul ts
7. Levels of Gene Expression Determine
Recurrence Score
21-gene assay = 16 outcome-related genes + 5 reference genes
Higher expression levels of
“favorable” genes = ↓ RS
Higher expression levels of
“unfavorable” genes = ↑ RS
A risk score is calculated from 0 -100
Cutoff points chosen based on
Results of NSABP trial B-20
Sparano, J & Paik, S. JCO, 2008.6/23/2016 7dr rahul ts
8. •NCCN guidelines include Oncotype DX® testing in the
treatment-decision pathway for node-negative and
micrometastatic disease
•Adapted from NCCN Practice Guidelines in Oncology – v.1.2010.
1. Tumor 0.6-1.0 cm,
2. Moderately or poorly
differentiated,
3. Intermediate or high
grade, or
4. Vascular invasion
5. Tumor > 1 cm with
favorable or
unfavorable
pathologic features
•Consider
Oncotype
DX
•Hormone receptor-positive, HER2-negative disease
•pT1, pT2, or pT3 and pN1mi
•No test
•RS < 18
•RS 18-30
•RS ≥ 31
•Adjuvant endocrine therapy
•± adjuvant chemotherapy
•Adjuvant endocrine therapy
•endocrine therapy
•± adjuvant chemotherapy
•Adjuvant endocrine
therapy
•+ adjuvant chemotherapy
6/23/2016 8dr rahul ts
9. Mammaprint
• DNA microassay
• consisting of 70 genes regulating
• cell cycle, invasion, metastasis, and angiogenesis.
• Requires fresh tumor tissue
• Gene expression signature that was strongly prognostic for
development of distant metastasis in lymph node negative patients
was identified
• Both ER –negative and ER-positive patients were included
6/23/2016 9dr rahul ts
10. Evolution
• Improvements in disease-free survival (DFS) with
single-agent chemotherapy after radical
mastectomy in the 1970s.
• Polychemotherapy was first evaluated by
Bonadonna
– randomized women with node-positive breast cancer
to 12 monthly cycles of cyclophosphamide,
methotrexate, and 5-fluorouracil (CMF) chemotherapy
– or no further therapy after radical mastectomy
6/23/2016 10dr rahul ts
11. • NSABP B-20 (Fisher et al. 2004):
• 2,306 patients status post sur gery with
pathologically LN−, ER+ breast ca randomized to
• tamoxifen alone vs. tamoxifen + MF chemotherapy
vs. tamoxifen + CMF chemotherapy.
• The addition of chemotherapy to tamoxifen
improved 12-year DFS (HR = 0.52) and OS (HR =
0.78, p = 0.068).
6/23/2016 11dr rahul ts
12. • NSABP-B28 (Mamounas et al. 2005):
• 3,060 LN+ patients randomized to
• AC × 4 ± Paclitaxel.
• Addition of taxane improved 5-year DFS
(72→76%) and LRR, despite delay of RT (9.7 vs.
3.7%).
6/23/2016 12dr rahul ts
13. CALGB 9344 (Sartor et al.2005;Henderson et al. 2003)
• Randomization : Standard dose AC vs. dose escalation
of doxorubicin ± sequential addition of paclitaxel.
• The sequential Continued addition of adjuvant paclitaxel to AC for
LN+ patients
• improves DFS and OS vs. adjuvant AC alone, and further improves
5-year LRC in patients treated with BCS+RT despite delaying RT
delivery.
• No DFS or OS improvement with dose escalation of
doxorubicin.
6/23/2016 13dr rahul ts
14. CALGB 9741 (Citron et al. 2003).
Four arm randomized trial:
• sequential vs. concurrent addition of paclitaxel (T)
to AC chemotherapy, every 3 weeks vs. every 2
week (dose dense) dosing.
• Increased 4-year DFS with dose-dense chemo (82
vs. 75%),
• No difference between sequential or concurrent
delivery.
6/23/2016 14dr rahul ts
15. USOT (Jones et al. 2009):
1,016 Stage I–III patients randomized to AC × 4 vs.
TCx4.
With a median of 7-year follow-up,
TC improved DFS (81 vs. 75%) and OS (87% TC v
82).
TC improved outcomes regardless of age, hormone
receptor, or HER2 expression status.
6/23/2016 15dr rahul ts
18. Principles of Adjuvant Therapy
1. Decrease the risk of recurrence and death from
breast cancer with local therapy alone
2. Endocrine therapy benefits only those with
hormone receptor positive disease
3. Chemotherapy benefits everyone
4. To eradicate “micrometastasis”
5. Combination chemotherapy is more effective than
monotherapy
6/23/2016 18dr rahul ts
19. 6. Adjuvant chemotherapy reduces LR after lumpectomy +
RT
7. Anthracycline (doxorubicin)-based regiments (± taxanes
for high-risk disease) have been associated with superior
outcomes(USOT 9735, Jones et al. 2009).
8. Dose-dense regimens may have increased efficacy in
highrisk patients.
Principles of Adjuvant Therapy
6/23/2016 19dr rahul ts
36. Neoadjuvant chemotherapy is considered standard of
care in high-risk populations such as
• young patients and/or
• advanced-stage disease,
• Stage IIb–III breast
• Inflammatory ca
• T4, N3, bulky or matted N2
Principles of Neoadjuvant
chemotherapy
6/23/2016 36dr rahul ts
37. Principles of Neoadjuvant
chemotherapy
Typically, similar indications as adjuvant chemotherapy
Advantages of neoadjuvant chemotherapy:
• assessment ofdisease response,
• increased rate of BCT
• Neoadjuvant chemotherapy converts 20–30% of patients
initially ineligible for BCT to eligible
• Complete clinical (cCR) and pathological response rates
• 20–40% achieve cCR , 10–20% achieve pCR
• Alow time for genetic testing
– Diminished response noted in ER+, low grade, or invasivelobular cancers
6/23/2016 37dr rahul ts
40. Metastatic breast cancer
• Except in rare cases stage IV cancer is
considered incurable
• Focus of treatment should be on palliation of
disease related symptoms
6/23/2016 40dr rahul ts
46. Pregnant and Recently Postpartum
• 1/3000 pregancies or 1-4% of BrCa in women under 50
• Greatest risk from chemo in 1st trimester
• In 2nd/3rd trimester still carries risk of IUGR, etc
Mostly AC or FAC, little data for taxanes
Don’t use Mtx
Generally, don’t recommend delaying chemo
Stensheim et al, JCO, 20096/23/2016 46dr rahul ts
49. Rationale for endocrine therapy of breast
cancer
Risk factors for Br Ca include prolonged estrogen
exposure states such as
early menarche,
late menopause,
nulliparity and
estrogen replacement therapy.
6/23/2016 49dr rahul ts
50. ESTROGEN RECEPTOR
Protein molecule- mainly in nucleus
small amount in cytoplasm and plasma memb
2 isoforms – ERά and ER β
ER ά - predominates in uterus, breast, pituitary, bone,
CNS,CVS
ER β - predominates in prostate, ovary,
6/23/2016 50dr rahul ts
51. Mech. of carcinogenesis
• ER is overexpressed in as many as 70% of breast
cancers .
• Estrogen exerts its actions by both
• Genomic - through nuclear receptors
• Nongenomic - cytoplsmic receptors.
6/23/2016 51dr rahul ts
52. NSABP B-14 (Fisher et al. 2004):
• 2,644 patients status-post surgery for breast ca
(pathologically LN−, ER+) randomized to
• tamoxifen × 5 years vs. placebo.
• Adjuvant tamoxifen improved 15-year DFS (HR
= 0.58) and OS (HR = 0.80).
6/23/2016 52dr rahul ts
53. ATAC Trial (2002; Lancet 2005): Arimidex, Tamoxifen, Alone or in Combination
• 9,366 postmenopausal patients (both ER +/-)
status-post definitive therapy for earlystage breast
ca randomized to anastrozole, tamoxifen, or both
given concurrently.
• Anastrozole alone improved 3-year DFS compared
with tamoxifen (89 vs. 87%) or both (87%).
• Benefit observed only in ER+ patients.
• Anastrozole better tolerated with respect to side-
effects.
6/23/2016 53dr rahul ts
54. Goss (Goss et al. 2003):
• 5,187 postmenopausal patients (98% ER+)
status-post definitive therapy and adjuvant
tamoxifen × 5 years for early-stage breast ca
randomized to letrozole (2.5 mg) or placebo
daily × 5 years.
• Addition of letrozole improved 4-year DFS
(87→93%).
6/23/2016 54dr rahul ts
55. BIG 1-98249
• 8028 patients on RCT with 4 groups
– Tamoxifen (Tam) x 5 yr;
– Letrozole (Let) x 5 yr;
– Tam x 2 yr → Let x 3 yr
– Let x 2yr → Tam x 3 yr
• 51 months follow up the use of upfront letrozole for
5 years resulted in a significant reduction in the risk
of an event (HR.82; P = .007) compared with
upfront tamoxifen for 5 years
6/23/2016 55dr rahul ts
56. Types of endocrine therapy
ovarian suppression /ablation
surgical oopherectomy
radiation ,,
medical ,, ,,
anti estrogen drugs.
SERM, SERD, AI
6/23/2016 56dr rahul ts
59. Mechanism of Action
ANDROSTENEDIONE ESTRONE
AROMATIZATION ESTRIOL
TESTOSTERONE ESTRADIOL
Aromaters inhibitors
Type 1 - steroidal and irreversible
e.g.. EXEMESTANE
Type 2 - nonsteroidal and reversible
e.g.. LETROZOLE ANASTROZOLE
In peripheral tissues
6/23/2016 59dr rahul ts
60. NCCN guidelines.
All pts. c. invasive Br. Cancer, who are ER or PR +ve
should be considered for adj. hormonal therapy,
regardless of
Age
LN status
Her 2 status
Adj.chemo given or not
6/23/2016 60dr rahul ts
61. Radiation oopherectomy
• Radiation used for ablation of ovarian function.
• Given in pts. c. medical c/i for tamoxifen,
• Can be considered in young highrisk pt. completd
5 yrs of tamo. or who progressed while on
tamoxifen.
• Now, medical oopherectomy is preferred.
6/23/2016 61dr rahul ts
62. Radiation oopherectomy
Target vol. is true pelvis.
Sup.brdr. ----- inferior brdr. of S1 jt.L5/S1
Infr. brdr ----- lower brdr. of obturator fora.
Lateral .. ---- bony pelvic sidewall
AP – PA portals.
usually 12 x 12 cm field
Dose. 15 Gy in 5 # given
6/23/2016 62dr rahul ts
63. Duration ?
Scottish Adjuvant Tamoxifen Trial
• patients who were disease free at 5 years were
randomly assigned either to stop taking tamoxifen
or to continue taking it indefinitely until relapse or
death.
• With a median follow-up of 15 years,
• No additional benefit was observed in taking
tamoxifen beyond 5 years.
6/23/2016 63dr rahul ts
64. • Despite the preponderance of evidence suggesting
that extension of tamoxifen therapy beyond 5 years
is not beneficial, two large ongoing trials,
• ATLAS (Adjuvant Tamoxifen-Longer Against
Shorter) and
• aTTom (Adjuvant Tamoxifen Treatment-Offer
More) may offer new insight into the optimal
duration of tamoxifen therapy.
6/23/2016 64dr rahul ts
67. • HER-2 is overexpressed or gene amplified in
20% to 25% of breast cancers.
• The anti-HER-2 monoclonal antibody
trastuzumab targets HER-2-positive tumors,
– inhibits proliferation, and
– induces cell death
6/23/2016 67dr rahul ts
69. NSABP B-31 & NCCTG N9831 (Romond et al. 2005):
• 3,351 patients with resected LN+ or high-risk LN−,
HER2+ breast cancer randomized to
• ACT chemo (doxorubicin, cyclophosphamide, and
paclitaxel) vs. chemo + trastuzumab (ACT-H).
• Trastuzumab increased 3-year DFS (75→87%) and
OS (92→94%), but was associated with increased
risk of heart failure or cardiac death (3–4%).
6/23/2016 69dr rahul ts
70. HERA BIG 01-01 (Piccart-Gebhart et al. 2005):
• 5,090 patients status postsurgery ± RT and
neoadjuvant or adjuvant chemo ± HT (if ER/PR+)
with HER2 overexpression randomized to
• Observation , 1-year trastuzumab (q3 week), or 2-
year trastuzumab.
• On interim analysis, trastuzumab × 1 year
improved 2-year DFS (77→86%), but no difference
in OS (95–96%).
6/23/2016 70dr rahul ts
71. Pertuzumab - perjeta
• inhibition of heterodimerization of HER2
with other HER family members, including
EGFR, HER3, and HER4
• Pertuzumab binds to a different HER2 epitope
than trastuzumab
6/23/2016 71dr rahul ts
72. • The dosage of pertuzumab used in the pivotal phase III
CLEOPATRA (Clinical Evaluation of Pertuzumab and
Trastuzumab) trial was as follows: IV 840 mg loading
dose followed by IV 420 mg every three weeks
• MARIANNE (advanced breast cancer),
• NEOSPHERE (early breast cancer),
• TRYPHAENA (HER2-positive stage II/III breast cancer) and
• APHINITY (HER2-positive nonmetastatic breast cancer)
– On going trials
6/23/2016 dr rahul ts 72
73. • Ado-trastuzumab emtansine
– an antibody-drug conjugate consisting of
the monoclonal antibody trastuzumab (Herceptin)
linked to the cytotoxic agent emtansine (DM1)
– EMILIA clinical trial
» for treatment of HER2-positive mBC , treated previously
with trastuzumab and a taxane (paclitaxel or docetaxel),
and who have already been treated for mBC or developed
tumor recurrence within six months of adjuvant therapy
6/23/2016 dr rahul ts 73
74. EMILIA study,
• 991 people with unresectable, locally advanced or
metastatic HER2-positive breast cancer who had
previously been treated with trastuzumab and taxane
chemotherapy
• a phase III clinical trial that compared
• trastuzumab emtansine Vs capecitabine (Xeloda)
plus lapatinib (Tykerb).
• This trial showed improved progression-free survival in
patients treated with trastuzumab emtansine (median
9.6 vs. 6.4 months), along with improved overall
survival (median 30.9 vs. 25.1 months)
6/23/2016 dr rahul ts 74
75. Lapatinib
• Inhibits the tyrosine kinase activity associated with
two oncogenes,
– EGFR (epidermal growth factor receptor) and
– HER2/neu (Human EGFR type 2)
• ER+/EGFR+/HER2+ breast cancer patients and in
patients who have HER2-positive advanced breast
cancer that has progressed after previous treatment
with other chemotherapeutic agents, such
as anthracycline, taxane-derived drugs, or trastuzumab
6/23/2016 dr rahul ts 75
76. Adjuvant Lapatinib and/or Trastuzumab Treatment
Optimisation (ALTTO) trial
• an international research study that will randomize
more than 8000 patients
– to receive trastuzumab alone for 52 weeks,
– lapatinib alone for 52 weeks,
– trastuzumab for 12 weeks, followed by a 6-week
break, followed by lapatinib for 34 weeks, or
– lapatinib in combination with trastuzumab for 52
weeks
6/23/2016 76dr rahul ts
77. Olaparib (AZD2281)
• an oral PARP inhibitor 600mg o.d
• in the treatment of patients with metastatic
previously treated breast
• The use of inhibitors of poly (ADP-ribose)
polymerase in triple negative metastatic breast
cancer has been reported in a randomized phase II
trial of gemcitabine/carboplatin with or without
PARP inhibition
6/23/2016 77dr rahul ts
Main point: The National Comprehensive Cancer Network (NCCN) Practice Guidelines in Oncology for breast cancer suggests the use of Oncotype DX® in patients with hormone receptor-positive, HER2-negative, node-negative or micrometastasis-involved disease.
The option of using a gene-based assay of tumor tissue, namely the Oncotype DX assay, to help guide chemotherapy treatment decisions is now included within the systemic adjuvant treatment decision pathway for patients with node-negative or pN1mi (micrometastasis: 0.2-2.0 mm), hormone receptor-positive, HER2-negative tumors that are 0.6-1.0 cm and moderately/poorly differentiated or with unfavorable features or tumors that are > 1 cm.
Category 2B: The recommendation is based on lower level evidence, and there is nonuniform NCCN consensus (but no major disagreement).
http://www.nccn.org/professionals/physician_gls/categories_of_consensus.asp
National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed [Apr 27, 2009].