TNBC for Review Board
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Transcript of TNBC for Review Board
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TRIPLE NEGATIVE BREASTTRIPLE NEGATIVE BREAST
CANCERCANCERClinical Features, PatternsClinical Features, Patterns
Of Recurrence, Response toOf Recurrence, Response to
Chemotherapy & Outcomes inChemotherapy & Outcomes inthe Indian Settingthe Indian Setting
DR P SURESHDR P SURESH
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Microarray expression profilingMicroarray expression profiling ----five main groups, two offive main groups, two of
them ER+ (luminal A and B) and three ERthem ER+ (luminal A and B) and three ER-- groupsgroups
[normal breast like, ERBB2 (also known as HER2) and[normal breast like, ERBB2 (also known as HER2) and
basal like]basal like]Breast cancers lacking the expression of ER, PR andBreast cancers lacking the expression of ER, PR and
HER2 receptors are called TripleHER2 receptors are called Triple--Negative BreastNegative Breast
Cancers (TNBC).Cancers (TNBC).
TNBCs comprise approximately 15%TNBCs comprise approximately 15%----20% of breast20% of breast
cancer casescancer cases
Poor prognosis due to aggressive biology and resistancePoor prognosis due to aggressive biology and resistance
to presently available endocrine therapiesto presently available endocrine therapies
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Basal vs triple negativeBasal vs triple negative
BRCA 1BRCA 1
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Younger patients (
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INTRODUCTIONINTRODUCTION
Ten Leading Sites of CancerTen Leading Sites of Cancer -- FemalesFemales (Consolidated Report of(Consolidated Report of
the HBCRs: 2001the HBCRs: 2001--2003)2003)
(Courtesy ICMR cancer registry 2004)(Courtesy ICMR cancer registry 2004)
MUMBAIMUMBAI
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DELHIDELHITen leading sites of cancer (ConsolidatedTen leading sites of cancer (Consolidated
report of PBCRs 2001report of PBCRs 2001------2003)2003)
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ADVANCEMENT IN PAST 20ADVANCEMENT IN PAST 20
YRSY
RSUnderstanding of multistep carcinogenesisUnderstanding of multistep carcinogenesisand the central role of genetic alterations inand the central role of genetic alterations inthe diagnosis, treatment, and prevention ofthe diagnosis, treatment, and prevention of
breast cancer.breast cancer.Advances in DNA microarray technologyAdvances in DNA microarray technology
Estrogen receptor (ER)Estrogen receptor (ER)
Amplification of the HER2 oncogeneAmplification of the HER2 oncogene
Development of gene expression studiesDevelopment of gene expression studiesusing DNA micro arraysusing DNA micro arrays
Luminal and basal breast cancersLuminal and basal breast cancers
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AIMS AND OBJECTIVESAIMS AND OBJECTIVES
Retrospectively analyze the clinicalRetrospectively analyze the clinical
features, response to chemotherapy,features, response to chemotherapy,
patterns of recurrence and outcomes inpatterns of recurrence and outcomes in
Indian settingIndian setting
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MATERIALS AND METHODSMATERIALS AND METHODS
The study will include patients of breast cancerThe study will include patients of breast cancer
diagnosed between Jan 2005to Dec 2008 at Rajivdiagnosed between Jan 2005to Dec 2008 at Rajiv
Gandhi Cancer Institute and Research Centre in DelhiGandhi Cancer Institute and Research Centre in Delhi
Retrospective studyRetrospective study
Triple negative breast cancers will be defined as thoseTriple negative breast cancers will be defined as those
that are estrogen receptor negative, progesteronethat are estrogen receptor negative, progesterone
receptor negative and HER2 neu negativereceptor negative and HER2 neu negative
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STUDYDESIGNSTUDYDESIGN
The study was initially planned for 50 patientsThe study was initially planned for 50 patients
and has now been expanded to include 100and has now been expanded to include 100
patients.patients.
The expected maximum follow up time is 5 yrs.The expected maximum follow up time is 5 yrs.
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INCLUSION CRITERIAINCLUSION CRITERIA
All women with invasive breast cancer treated at RajivAll women with invasive breast cancer treated at Rajiv
Gandhi Cancer Institute and Research Centre, DelhiGandhi Cancer Institute and Research Centre, Delhi
between Jan 2004 to Dec 2009.between Jan 2004 to Dec 2009.
Only those women will be included in the study whoOnly those women will be included in the study who
have been tested for all three markers. ( ER, PR, HER 2have been tested for all three markers. ( ER, PR, HER 2
neu)neu)
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EXCLUSION CRITERIAEXCLUSION CRITERIA
Women with multiple malignancies will be excluded fromWomen with multiple malignancies will be excluded from
the study.the study.
Women with incomplete or ambiguous marker status orWomen with incomplete or ambiguous marker status orincomplete medical records.incomplete medical records.
Distant recurrences during a 90 day post surgery periodDistant recurrences during a 90 day post surgery period
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Patient information that will be collected andPatient information that will be collected and
analysedanalysed
Age,Age,
Clinical stage at presentation,Clinical stage at presentation,
Pathological stage,Pathological stage,Types of metastasis at presentation,Types of metastasis at presentation,
Results of breast conservation vs radical surgery,Results of breast conservation vs radical surgery,
Adjuvant chemotherapies used and the incidence ofAdjuvant chemotherapies used and the incidence ofrelapse,relapse,
Neoadjuvant chemotherapies in cases of locallyNeoadjuvant chemotherapies in cases of locallyadvanced breast cancers and the pathological CR rates,advanced breast cancers and the pathological CR rates,
Average time to relapseAverage time to relapse
Overall survival ratesOverall survival rates
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IMMUNOHISTOCHEMISTRYIMMUNOHISTOCHEMISTRY
For each patient in the database, antibody staining of a set ofFor each patient in the database, antibody staining of a set of
paraffin embedded slides for ER / PR has been done using theparaffin embedded slides for ER / PR has been done using the
BioGenex kit.BioGenex kit.
The over expression of HER2 status was evaluated using theThe over expression of HER2 status was evaluated using theHercep Test kit from Dako, Denmark.Hercep Test kit from Dako, Denmark.
HER 2 positivity will be taken as strong complete membraneHER 2 positivity will be taken as strong complete membrane
staining in at least 10% of tumor cells.staining in at least 10% of tumor cells.
A HER 2 report of 3+ by IHC will be considered as positive.A HER 2 report of 3+ by IHC will be considered as positive.HER 2 report of 2+ usually confirmed by FISHHER 2 report of 2+ usually confirmed by FISH
All others will be considered as HER 2 negative.All others will be considered as HER 2 negative.
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FOLLOW UPFOLLOW UP
Maintained by reviewing OPD and admission records ofMaintained by reviewing OPD and admission records of
the patientsthe patients
LocoLoco--regional relapses and the subsequent surgeryregional relapses and the subsequent surgery
during the 90 day post surgery period will be consideredduring the 90 day post surgery period will be considered
to be part of the primary management: distantto be part of the primary management: distant
recurrences during this time will disqualify the patientrecurrences during this time will disqualify the patient
from the studyfrom the studyRelapses after 90 days will be considered as events.Relapses after 90 days will be considered as events.
For deceased patients dates and causes of death will beFor deceased patients dates and causes of death will be
obtained from the medical recordsobtained from the medical records
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OUTCOMESOUTCOMES
Overall survival is defined as from the time of diagnosis toOverall survival is defined as from the time of diagnosis to
last follow up or time of death.last follow up or time of death.
Breast specific survival will be determined from the time ofBreast specific survival will be determined from the time of
diagnosis until death from breast cancer. (Patients dyingdiagnosis until death from breast cancer. (Patients dying
from other causes will be censored at the time of death.)from other causes will be censored at the time of death.)
Relapse free survival will be defined as from the time ofRelapse free survival will be defined as from the time of
diagnosis to development of first evidence of clinical ordiagnosis to development of first evidence of clinical orradiological metastatic disease.radiological metastatic disease.
Local recurrence free survival is defined as from the time ofLocal recurrence free survival is defined as from the time of
diagnosis to development of local recurrencediagnosis to development of local recurrence..
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CLINICALCLINICAL
STAGESTAGEFrequencyFrequency PercentPercent
II 99 15.8%15.8%
IIAIIA 1818 31.6%31.6%
IIBIIB 1414 24.6%24.6%
IIIAIIIA 44 7.0%7.0%
IIIBIIIB 88 14.0%14.0%
IIICIIIC 11 1.8%1.8%
IVIV 33 5.3%5.3%
TotalTotal 5757 100.0%100.0%
ADJ CHEMOADJ CHEMO FrequencyFrequency PercentPercent
CMFCMF 11 1.9%1.9%
DACDAC 1818 34.0%34.0%
DEDE 44 7.5%7.5%
DECDEC 33 5.7%5.7%
FEC100FEC100 55 9.4%9.4%
FEC75FEC75 11 1.9%1.9%
GEM CISGEM CIS 11 1.9%1.9%
PACLIPACLI 11 1.9%1.9%
PACS01PACS01 1919 35.8%35.8%
TotalTotal 5353 100.0%100.0%
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PATH CRPATH CR FrequencyFrequency
NONO 1111
YESYES 22
TotalTotal 1313
NACTNACTFrequencFrequenc
yyPercentPercent
DAC*DAC*
3344 7.0%7.0%
DE*3DE*3 77 12.3%12.3%
FECFEC 22 3.5%3.5%
TotalTotal 1313 22.822.8
SURGESURGE
RYRY
FrequencFrequenc
yy
PercenPercen
tt
BCSBCS 1111 20.4%20.4%
MRMMRM 4343 79.6%79.6%
TotalTotal 5454 100.0%100.0%
TYPE OF METSTYPE OF METS
ATAT
DIAGNOSISDIAGNOSIS
FrequencFrequenc
yy
PercenPercen
tt
BONEBONE 11 1.7%1.7%
BONE +BONE +
VISCERALVISCERAL22 3.4%3.4%
NO METSNO METS 5555 94.8%94.8%
TotalTotal 5858 100.0%100.0%
TYPE OF RELAPSETYPE OF RELAPSE FrequencyFrequency PercentPercent
BONEANDBONEANDVISCERALVISCERAL
22 3.8%3.8%
LOCALLOCAL ONLYONLY 11 1.9%1.9%
LOCAL AND BONELOCAL AND BONE 11 1.9%1.9%
LOCAL ANDLOCAL AND
VISCERALVISCERAL11 1.9%1.9%
NO RELAPSE AS YETNO RELAPSE AS YET 4646 86.8%86.8%
VISCERAL ONLYVISCERAL ONLYMETSMETS
22 3.8%3.8%