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Early Cancer Breast     Treatment           By  Prof U.K.Shrivastava          Head    Faculty of Surgery          AIMST   ...
Early Cancer BreastInvasive cancer,contained in breast and mayor may not have spread to draining lymph nodeof breast or ar...
RISK FactorsGender- woman greatest risk factorAge- Generally 50 years and above .Ethnicity- African American higher %Genet...
Risk FactorsPrevious exposures to chest wall radiationsFamily history of ca breast , mother , sisterPersonal H/O ca breast...
Pre Operative EvaluationsGold standard – surgeons clinical exam and                  history, Risk factorsMust assess the ...
Pre Operative EvaluationsDigital mammography –differs from analogmammography. here images are digitized &stored in compute...
Pre Op Evaluations  MRI--- very usefulInterpretation based on uptake and washout of contrast media from breast tissueSmoot...
MRIMRI -- very useful as screening tool in high       risk patients, especially for BRCAI II       Helpful in deciding the...
PET-CT 90% sensitivity for diagnosing Recurrence Confirms distant metastasis Evaluates the response of Neoadjuvant  chemot...
Molecular markers of Breast      cancer -HormonalMajority of cancer are Hormonal dependent70to80%of invasive ca and all in...
Anti estrogen Selective Estrogen Receptor modulator***Stilbesterol-like agents----Raloxifen ( Evista) dose 60mg for 5 year...
Aromatase InhibitorsThese are helpful in blocking synthesisof estrogens from Androgens viaAromatase Enzymes in post men. f...
Non Hormonal Targets         cellular Markers***Growth FactorsEpidermal growth factor imp. Role in   epithelial cell growt...
Herceptin              TrastuzumabHER2/new gene protein, member tyrosinekinase receptor, amplified one third of patient.It...
Cell Cycle And Apoptosis                   P 53 GeneDNA damage and hypoxia are stimuliboth activate the p53 tumor suppress...
Vascular Endothelial Growth              FactorVEGF enhances angiogenesis, tumor growth Tumor expressingVEGF have higher m...
Hereditary Breast Cancer               BRCA I BRCA IIDiscovered 1994,gene protein ,breast tissueHelps in repairing damaged...
Types of Breast CarcinomaI Non Invasive– DCIS and LCIS2 Invasive----- Invasive intra ductal cancer                Invasive...
Treatment Early Breast CancerNon Invasive Breast Cancer Incidence gone up due to better screening Local disease, highly cu...
Non Invasive cancer Breast-         TreatmentDCIS lymph node involvement 1% o 3%Positivity means undiagnosed invasive caif...
Treatment of Invasive         BreastCancerLess controversialTreatment of choice BCS, Lumpectomy                     with R...
Surgical TechniqueLumpectomy,Quadrnectomy Seg MastectomyIncision– curvilinear, close to tumor, 2 to 3mmMargin microscopica...
MastectomyIndicated for different sets of women— 1st Those who are not fit for BCS 2nd Those who do not wish to have BCS 3...
MastectomySentinel lymph adenectomy must be doneSSM, NSM,ASM done for reconstructionRecurrence 3 to 10% in these groupIn p...
Prophylactic MastectomyIt is advised to women having high riskMostly those who are carriers of BRCA Iand BRCA II mutationa...
Breast Reconstructive surgery            Goal• To diminish chest wall deformity• Improve the psycho social well being• Bet...
Immediate Reconstruction  Types of Reconstruction—   A Implant – Saline or Silicon gel   B Autologous tissues - TRAM Flap ...
Breast reconstruction• Immediate—  Disadvantage- Delay in adjuvant therapy  partial loss of mastectomy skin flap  for resi...
Treatment of Axillary NodesLymph node metastases- prognostic factorSLNB preferred method Axillary stagingT1-3Those with ne...
Axillary DissectionsAvoid skeletonizing the axillary vein.Preserve long thoracic and throracodorsal nervePreserve inter co...
SLNBCurrently standard of care is completeAxillary dissection for all NI(mi)and NI cases        ADJUVANT THERAPIES----    ...
Accelerated Partial Breast          IrradiationIt shortens the treatment time 4 to 5 daysIt is interstitial brachytherapy,...
Post Mastectomy RadiationPMRT---required-   a Pts with 4to5 positive axillary nodes   b Pts with T3 Larger tumors size   c...
PMRTFollowing groups benefit with PMRT 1 age and positive axillary nodes 2 Lympho vascular& perineural invasion 3 High Tum...
Systemic TherapyAdjuvant Chemotherapy-    Suitable to all invasive Cancer Breast    Best combined chemo than single agent ...
Hormonal TherapyTamoxifen and Aromatase Inhibitor    * Given to all Receptor positive case    * Regardless to pts Age, Lym...
Hormone Therapy* Tamoxifen is good as adjuvant therapy  In cases having BRCAI& BRCAII genes * For better result Anastrazol...
Endocrine Therapy Regimens    Invasive cancer BreastPremenopausal- Tamoxifen - 10mg b.d. or 20mg o.d 5 yr Goserelin LHRH--...
HER 2 Disease TreatmentHER positive cases -- aggressive., Locallyadvanced and resistant to Hormonal therapyPresent in 20to...
Targeted TherapyAnother drug Lapatinib given orallyWorks against epidermal growth factor andHERII over expression gene tog...
VaccineIdeal to have vaccine—   should be inexpensiv   easy to administer   well tolerated,- target only disease entity   ...
THANK YOU•
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Early breast cancer by Dr. U.K.Shrivastava (MS,FAIS,DHA), Prof. & Head of Surgery, AIMST University, Malaysia

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Early breast cancer by Dr. U.K.Shrivastava (MS,FAIS,DHA), Prof. & Head of Surgery, AIMST University, Malaysia

  1. 1. Early Cancer Breast Treatment By Prof U.K.Shrivastava Head Faculty of Surgery AIMST Malaysia
  2. 2. Early Cancer BreastInvasive cancer,contained in breast and mayor may not have spread to draining lymph nodeof breast or armpit. Some cancer cells mighthave gone out of breast,or armpit ,but can notbe detected. They are– stage o, I and II casesat times stage IIIa cases with little tethering
  3. 3. RISK FactorsGender- woman greatest risk factorAge- Generally 50 years and above .Ethnicity- African American higher %Genetic evaluation- BRCA I BRCA II ,P53Dense breast tissues, more glandular,tissueLCIS and DCISEarly menarche and late menopauseUse of oral contra septics and HRT
  4. 4. Risk FactorsPrevious exposures to chest wall radiationsFamily history of ca breast , mother , sisterPersonal H/O ca breast to one breastBBD- ductal hyperplasia,sclerosing adenosis complex fibroadenoma,pappilomatosis
  5. 5. Pre Operative EvaluationsGold standard – surgeons clinical exam and history, Risk factorsMust assess the extent of disease, local, regional and distant sitesMammography—types – Screening DiagnosticFor evaluations- add. Views, compressionMagnifications,coputerised enhancement
  6. 6. Pre Operative EvaluationsDigital mammography –differs from analogmammography. here images are digitized &stored in computerized formatIt can be magnified, contrast can decreasedor increased to see the pathologyULTRASOUND– Not a very good modalitywell indicated for pregnant ,juvenile andadolescent,and with breast infections No ionizing radiations- advantage
  7. 7. Pre Op Evaluations MRI--- very usefulInterpretation based on uptake and washout of contrast media from breast tissueSmooth, round, oval – mostly benign Irregular ,speculated –malignant MRI detect lesion up to 5mm of size Mammography only detect 10mm of size It detects,nipple and chest wall invasion
  8. 8. MRIMRI -- very useful as screening tool in high risk patients, especially for BRCAI II Helpful in deciding the BCS surgery But it is 15 times costly than MammoPositron Emission Tomography ---PET It detects the patients base line glucose level after injecting theFDG Increase uptake worst prognosis
  9. 9. PET-CT 90% sensitivity for diagnosing Recurrence Confirms distant metastasis Evaluates the response of Neoadjuvant chemotherapy** Biopsy– Most important FNAC-office procedure, least invasive Excellent cytologist, if more tissue Do Core biopsy U/S stereotactic Bx
  10. 10. Molecular markers of Breast cancer -HormonalMajority of cancer are Hormonal dependent70to80%of invasive ca and all intra ductal caEstrogen effects mediated by ER α ERβAntiestrogen Tamoxifen blocks the receptorReduces the risk contra lateral/metastaticLeads to38% reduction in ca breastDoses 20mg daily for 5 yearsGood for DCIS Chemoprevention high riskpt
  11. 11. Anti estrogen Selective Estrogen Receptor modulator***Stilbesterol-like agents----Raloxifen ( Evista) dose 60mg for 5 yearsKnown as SER Modulators***Steroid Analogue of Estrogens--------These compound are pure anti estrogensDrug is FulvestrantBenefits- No hot flush no thrombo embolism and low risk for uterine cancer
  12. 12. Aromatase InhibitorsThese are helpful in blocking synthesisof estrogens from Androgens viaAromatase Enzymes in post men. femaleDrugs-- Anastrazole,Exemestane and LetrazoleBenefits –Prolong DFS, OS &Reduction in contralateral ca,Metastasis
  13. 13. Non Hormonal Targets cellular Markers***Growth FactorsEpidermal growth factor imp. Role in epithelial cell growth(EGF) HER/erbB family includes HER1HER2Both are related with ca breast pathogenesisEpithelial hyperplasia & neo angiogenesis Monoclonal antibody- Zd1839and HerceptinVery effective for this aggressive ca breast
  14. 14. Herceptin TrastuzumabHER2/new gene protein, member tyrosinekinase receptor, amplified one third of patient.Its presence shortens DFS and overall SHER2/new over expression should be testedTrastuzumab humanized monoclonal anti body First FDA approved biological agent ca-breast It is Not, cytotoxic, targeted therapy, Variety of chemo. can be combined , good result with Taxane and doxirubicin
  15. 15. Cell Cycle And Apoptosis P 53 GeneDNA damage and hypoxia are stimuliboth activate the p53 tumor suppressor geneNegative correlation betweenp53 positivity andage,ER and PRstatus,Positive with Tumor grade Activation leads to growth arrest, apoptosisloss of p53 function with mutation –cancer this gene get mutated with carriers of BRCA I ,IIAggressive tumor early mets poor survival,
  16. 16. Vascular Endothelial Growth FactorVEGF enhances angiogenesis, tumor growth Tumor expressingVEGF have higher micro vessel density and often associated ,p 53 expression. Targeted therapy required in future to act . to stop angiogenesis lead to tumor cell death, without causing harm to normal cells AVASTIN--CA COLON
  17. 17. Hereditary Breast Cancer BRCA I BRCA IIDiscovered 1994,gene protein ,breast tissueHelps in repairing damaged DNA ,If mutated, damaged DNA not repairedUncontrolled growth occurs leading cancerOverExpression life time risk ca breast 70%High risk patient DNA testing is MUSTPatients with mutated genes poorer prognosis
  18. 18. Types of Breast CarcinomaI Non Invasive– DCIS and LCIS2 Invasive----- Invasive intra ductal cancer Invasive lobular carcinoma Pagets disease of nipple3 Inflammatory Breast Carcinoma4 Locally advance Breast carcinoma5 Secondary( metastatic )Breast carcinoma
  19. 19. Treatment Early Breast CancerNon Invasive Breast Cancer Incidence gone up due to better screening Local disease, highly curable BCS is ideal, than historically Mastectomy Lumpectomy along with Radiation BCS to be based on several factors Size of breast,multicintric,tumor grade, nipple areola status, genetic testing,inability to receive radiation,pregnancy
  20. 20. Non Invasive cancer Breast- TreatmentDCIS lymph node involvement 1% o 3%Positivity means undiagnosed invasive caif so – go for sentinel lymph node biopsyIndications Extensive disease, high grade doubt of invasion, plan for Mastectomy , pts choiceAdjuvant therapy--- hormonal Tamoxifen It is individualized
  21. 21. Treatment of Invasive BreastCancerLess controversialTreatment of choice BCS, Lumpectomy with Radiation Axillary sampling, in all cases Sentinel L.NBiopsy Those meet requirement of Mastectomy offer them Reconstruction By Implant or by Autologous tissues TRAM ,Lattismus dorsi
  22. 22. Surgical TechniqueLumpectomy,Quadrnectomy Seg MastectomyIncision– curvilinear, close to tumor, 2 to 3mmMargin microscopically free,Handle thespecimen carefully, Take additional tissue from margins, Meticulous hemo stasis, No drain, Apply micro clips for radiologist, Do not reapproximate breast tissue for dead space Do two layer skin closure
  23. 23. MastectomyIndicated for different sets of women— 1st Those who are not fit for BCS 2nd Those who do not wish to have BCS 3rd Those identified a high risk genetically 4th Those who do not wish RadiotherapySurgery-Simple mastectomy,ssm, nsm asm CARE-preserve viability skin flap, thickness of flap considered carefully
  24. 24. MastectomySentinel lymph adenectomy must be doneSSM, NSM,ASM done for reconstructionRecurrence 3 to 10% in these groupIn properly selected patients NSSM andSSM results are equivocal in prognosis Lot of studies on NAC preservation as they contain duct tissues –RecurrencesOne should choose the case very carefully
  25. 25. Prophylactic MastectomyIt is advised to women having high riskMostly those who are carriers of BRCA Iand BRCA II mutational genesLife time risk general population 12.7%compared to36%to %85with BRCA I and IIPersonal history of having cancer in oneBreast 18% to 36% in contra lateral breastSurgical principle be same as wth ca breast
  26. 26. Breast Reconstructive surgery Goal• To diminish chest wall deformity• Improve the psycho social well being• Better body image, self esteem and satisfaction ** Timing of reconstruction** Immediate – Done along Mastectomy Delayed----- After wound healed and adjuvant therapy given
  27. 27. Immediate Reconstruction Types of Reconstruction— A Implant – Saline or Silicon gel B Autologous tissues - TRAM Flap or Lattismus dorsi muscle flapsome prefer natural looking feeling breast where as others don’t want body morbidity Those not willing Reconstruction ---- Breast Prosthesis-simple,&comfortable
  28. 28. Breast reconstruction• Immediate— Disadvantage- Delay in adjuvant therapy partial loss of mastectomy skin flap for residual disease, and close surgical margin may need radiation, can’t be done Advanced disease stage iii and above (ir needs radiotherapy post op) Delayed - After mastectomy&adju. therapy
  29. 29. Treatment of Axillary NodesLymph node metastases- prognostic factorSLNB preferred method Axillary stagingT1-3Those with negative reports spared from axillary dissectionsSLNB – injection of vital blue 5ccof isosulfan intra tumoral or periareolar later, blue tinged lymph nodes removed and tested if node positive do the axillary dissection Debate for level I II III removal mostly I II
  30. 30. Axillary DissectionsAvoid skeletonizing the axillary vein.Preserve long thoracic and throracodorsal nervePreserve inter costal nerve if feasibleDrain is used from a separate stab incisionSLNB positive up to .2mm –No up to 2mmNImLarger than 2mm NI statusNo - Does not need axillary dissection, But Nim& NI disease should go for axillary dissection
  31. 31. SLNBCurrently standard of care is completeAxillary dissection for all NI(mi)and NI cases ADJUVANT THERAPIES---- ** Whole Breast Radiotherapy----- Women opting for BCS, have to go for whole breast radiotherapy, after lumpectomy with negative margins , failing recurrence high**Accelerated Partial Breast Irradiation(APBI)
  32. 32. Accelerated Partial Breast IrradiationIt shortens the treatment time 4 to 5 daysIt is interstitial brachytherapy,by Seeds or Needle ,Balloon catheter based,and intra- operative radiotherapy,these method targetthe lumpectomy cavity, plus1to2 cm margin Benefit – Less irradiation to surrounding breast tissue and normal tissue 45 to 60 Gy in4 to 6 days, very effective
  33. 33. Post Mastectomy RadiationPMRT---required- a Pts with 4to5 positive axillary nodes b Pts with T3 Larger tumors size c Pts with Stage III cancersRadiation field includes- Chest wall, and supra clavicular nodes Avoid radiations to axilla,Int mammaryRecurrence rate goes down
  34. 34. PMRTFollowing groups benefit with PMRT 1 age and positive axillary nodes 2 Lympho vascular& perineural invasion 3 High Tumor grade 4 Extra capsular extension of lymph node metastasis 5 Hormone receptor status 6 Gene expression profile,& Margin status 7 After Neoadjuvant chemo,T4 bulky T&LN
  35. 35. Systemic TherapyAdjuvant Chemotherapy- Suitable to all invasive Cancer Breast Best combined chemo than single agent CMF 1970, CAF 1980,TAC 1990 8, 6 & 4 cycles Rpt on 21to 28 days gapIf Metastatic--- Gemcitabine with Paclitaxel Capecitabine with DocetaxelDose Density Chemo 2 wks gap, growth Horm
  36. 36. Hormonal TherapyTamoxifen and Aromatase Inhibitor * Given to all Receptor positive case * Regardless to pts Age, Lymph node Status, HER II and menopausal status * It falls in Three Category- a Blockade of estrogen activity b Surgical or medical ovarian ablation, c Aromatase enzyme inhibition,Letrazole ** Tamoxifen used as Chemoprevention**
  37. 37. Hormone Therapy* Tamoxifen is good as adjuvant therapy In cases having BRCAI& BRCAII genes * For better result Anastrazole, Letrazole aromatase inhibitors can beused in post- menopausal period * Given for period of 5 years * Risk- uterine cancer,thrombo embolism *Better-DFS,and OS ,prevents opposite ca
  38. 38. Endocrine Therapy Regimens Invasive cancer BreastPremenopausal- Tamoxifen - 10mg b.d. or 20mg o.d 5 yr Goserelin LHRH-- Reversible ovarian suppressiopn 3.6mg s.c.every 28days 2yrPostmenopausal-- Tamoxifen 10mg bd or 20mg od 5 yr anastrazole 1mg daily 5 years
  39. 39. HER 2 Disease TreatmentHER positive cases -- aggressive., Locallyadvanced and resistant to Hormonal therapyPresent in 20to 30% of all cancer Breast pts.This targeted therapy , Decrease recurrenceand improved over all survivalTrastuzumb(Herceptin,Genentech)is a humanized monoclonal antibody stops tumor growth, Works better with Taxane and Anthracycles
  40. 40. Targeted TherapyAnother drug Lapatinib given orallyWorks against epidermal growth factor andHERII over expression gene together Resistant to Herceptin give– Lapatinib ** Antiangiogenic Agents**VEFG plays important role in angiogenesisOver expression of gene flares tumor growthAssocited with higher hormone receptor genesTr by monoclonal antibody Avastin Bvacizumab
  41. 41. VaccineIdeal to have vaccine— should be inexpensiv easy to administer well tolerated,- target only disease entity Not to the host Major advances in understanding of the tumor, biology are being done but nothing has so far ,to prevent Cancer breast
  42. 42. THANK YOU•

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