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MANAGEMENT OF ADVANCED BREAST CANCER BY GENY ANN GEORGE 2002 BATCH ADVANCED BREAST CANCER • LOCALLY ADVANCED BREAST CANCER • METASTATIC BREAST DISEASE • RECURRENCE LABC • STAGE II b T3NOMO • STAGE III a T0-2 N2M0, T3N1-2M0 • STAGE III b T4N0-2M0 • STAGE III c anyTN3MO LOCALLY ADVANCED BREAST CANCER • PRESENCE OF TUMOUR >5cm IN SIZE • ASSOCIATED WITH OR WITHOUT SKIN OR CHEST INVOLVMENT • INFLAMMATORY CARCINOMA • WITH FIXED AXILLARY LN/IPSILATERAL INT.MAMMARY LN/SUPRACLAVICULAR LN • IN THE ABSENCE OF ANY EVIDENCE OF DISTANT METASTASIS LABC DIAGNOSIS • HISTORY • PHYSICAL EXAMINATION INVESTIGATIONS • BASELINE MAMMOGRAM 1. MASS LESION 2. ARCHITECTURAL DISTORTION 3. ASYMMETRIC DENSITIES 4. MICROCALCIFICA TIONS • FNAC • TRU-CUT BIOPSY To rule out metastasis • CBC,LFT,CHEST XRAY • USG/CT ABDOMEN • BONE SCAN • CT/MRI BRAIN OTHER INVESTGATIONS • HORMONE RECEPTOR STATUS • HER2/NEU EXPRESSION MANAGEMENT OF LABC • AIM 1. TO ACHIEVE LOCAL CONTROL 2. TO ERADICATE DISSEMINATED METASTASIS TREATMENT OPTIONS • SURGERY • RADIOTHERAPY • SYSTEMIC THERAPY SURGERY • WILLIAM HALSTED DESCRIBED RADICAL MASTECTOMY AT THE END OF 19th CENTURY • MID 20th CENTURY MRM WAS BORN • BCT IS NOW INCREASINGLY BEING PREFERRED RADIOTHERAPY • IT EVOLVED FROM RADICAL-ENBLOCK RADIATION TO RADIATION AS AN IMPORTANT ADJUNCT TO SURGERY SYSTEMIC THERAPY • CHEMOTHERAPY • HORMONE THERAPY • MONOCLONAL ANTIBODY • OVARIAN ABLATION CHEMOTHERAPY • EVOLVED FROM 12 CYCLES CMF REGIME TO 6 CYCLES • POLYCHEMOTHERAPY BETTER THAN MONOTHERAPY • THE USE OF ANTHRACYCLINES TO INTRODUCTION OF TAXANES ROLE OF NEOADJUNCT CHEMOTHERAPY ? NEOADJUVANT CHEMO THERAPY • SYSTEMIC CHEMOTHERAPY GIVEN BEFORE LOCAL THERAPY • SYNONYMSPRIMARY CHEMOTHERAPY INDUCTION CHEMOTHERAPY RATIONALE • TO ACHIEVE EARLY CONTROL OF DISTANT METS • TO DOWN STAGE THE DISEASE • FOR INVIVO ASSESSMENT OF TUMOUR RESPONSIVENESS • TO REDUCE THE TUMOUR BURDEN AT THE PRIMORY SITE DISADVANTAGES • RISK OF DRUG RESISTANCE • SURGERY/ RADIOHERAPY COULD BE DELAYED IN CASE OF NONRESPONDERS • INACCURATE PATHOLOGICAL STAGING EFFECTIVENESS OF NACT • PHYSICAL EXAMINATION • MAMMOGRAM • ULTRASOUND • 10-30% SHOW COMPLETE RESPONSE • 50-60% PATIENTS SHOW PARTIAL RESPONSE CHEMOTHERAPEUTIC AGENTS • ANTHRACYCLINE BASED REGIMEMOST EFFECTIVE • ADDITION OF TAXANES (PACLITAXEL, DOCETAXEL) HAS INCREASED THE EFFICIENCY • CMF IS ALSO BEING USED • EITHER 3-4 CYCLES • CHEMO CAN BE CONTINUED UPTO MAXIMAL RESPONSE ROLE OF NEOADJUVANT HORMONAL THERAPY • FOR HORMONE RECEPTOR POSITIVE DISEASE • IN CASES OF ABSOLUTE /RELATIVE CONTRAINDICATIONS FOR CHEMOTHERAPY SURGERY • MODIFIED RADICAL MASTECTOMY • BREAST CONSERVATIVE SURGERY 1.WIDE LOCAL EXCISION 2.LUMPECTOMY • AXILLA HAS TO BE TREATED SEPARATELY IN ALL CASES OF LABC • EITHER BY AXILLARY DISSECTION OR AXILLARY RADIATION • AXILLARY DISSECTION UPTO LEVEL II BCT IN LABC • PATIENT PREFERENCE IS IMPORTANT • RESIDUAL TUMOUR <5cm • NO SKIN OEDEMA • ABSENCE OF MICROCALCIFICATI ON & MULTICENTRICITY ADJUVANT CHEMOTHRAPY • ANTHRACYCLINE BASED REGIMES FOUND TO BE MORE EFFECTIVE (4-6 CYCLES OF AC/CAF) • BETTER RESPONSE IN c-erb B2+VE CASES • ADDITION OF TAXANES IMPROVE RESPONSE • CMF REGIME IS ALSO BEING USED DOSES • CYCLOPHOSPHAMI DE- 100mg/m2 • ADRIAMYCIN30mg/m2 • 5FU- 600mg/m2 • 3 WEEKLY* 6 CYCLES RADIOTHERAPY • TECHNIQUES 1. WHOLE EN BLOC RADIATION 2. LOCO REGIONAL RADIATION WHOLE EN BLOC TECHNIQUE • RADIATION IS DELIVERED BY 2 TANGENTIAL FIELDS ENCOMPASSING THE WHOLE BREAST • THE MEDIAL BORDER IS 2cm ON THE OPPOSITE SIDE • UPPER MARGIN SUPRASTERNAL NOTCH • LOWER MARGIN 2cm BELOW THE OPPOSITE BREAST LOWER LIMIT • THE LATERAL BORDER IS MIDAXILLARY LINE • TREATMENT PLANNING IS DONE WITH THE HELP OF CT RT FIELDS LOCO REGIONAL RADIATION • SET OF SEPARATE FIELDS 1. BREAST OR CHEST WALLS 2. IPSIATERAL AXILLA/ SUPRA/ INFRA CLAVICULAR FIELD 3. INT.MAMMARY NODES INDICATION FOR AXILLARY RADIATION 1. 4 OR MORE AXILLARY LYMPH NODES 2. EXTRANODAL DISEASE 3. INADEQUATE AXILLARY CLEARANCE/RESIDUAL DISEASE 4. UNKOWN AXILLARY STATUS HORMONAL THERAPY • TAMOXIFEN • AROMATASE INHIBITOR • LHRH AGONISTS TAMOXIFEN • STILL CONSIDERED AS THE FIRST LINE HORMONAL THERAPY • REDUCES ANNUAL RECURRENCE RATE • REDUCES THE INCIDENCE OF CONTRALATERAL BREAST CANCER MOA • SERM • AGONIST – ANTAGONIST ACTION • BINDS TO ER & TERMINATES THE CASCADE LEADING TO THE TRANSCRIPTION OF GENES INDICATIONS • ALL WOMEN WITH INVASIVE CA BREAST • TUMOUR > 1cm & ER +VE • TUMOUR < 1cm & ER –VE , TAMOXIFEN MAY BE GIVEN AS THE BENEFITS OUTWEIGH RISK DOSAGE • 20mg/day FOR 5 YEARS DISADVANTAGES • ENDOMETRIAL CA • DVT & PULMONARY EMBOLISM • DEPRESSION, DERMATITIS • CATARACT • VAGINAL DISCHARGES • HOT FLUSHES • NAUSEA, ANOREXIA NEWER ANTI ESTROGENS • RALOXIFENE • TORMIFENE • DROLOXIFENE • IDOXIFENE • PURE ANTIESTROGENFULVESTRANT AROMATASE INHIBITORS 1. AMINOGLUTETHEMIDENON SELECTIVE USED IN PRE MENOPAUSAL WOMEN RESULTS IN MEDICAL ADRENALECTOMY SELECTIVE AROMATASE INHIBITORS • BLOCK THE PERIPHERAL CONVERSION OF ANDROSTENEDION E TO ESTRONE • EG. ANASTRAZOLE, LETRAZOLE • FORMESTANE, EXAMESTANE LHRH AGONISTS • SUPER AGONISTCAUSE EARLY MASSIVE RELEASE OF PITUITARY GONADOTROPIN > PARALYSIS OF PITUITARY & RESISTANCE TO LHRH • EG.GOSERLINE CONTND…. • LEADS TO SUPPRESSION OF OVARIAN HORMONE FUNCTIONS • CONSIDERED AS AN ALTERNATIVE TO SURGICAL OOPHORECTOMY IN PREMENOPAUSAL WOMEN TRANSTUZUMAB (HERCEPTIN) • MONOCLONAL ANTIBODY RAISED AGAINST erb B2 OR HER2 SURFACE RECEPTORS • DECREASES LOCAL RECURRENCE & INCREASES D/S FREE INTERVAL INFLAMMATORY CARCINOMA BREAST • DIFFUSE BRAWNY INDURATION , ERYTHEMA, EDEMA &PEAU D’ ORANGE OF THE SKIN OF BREAST. • PALPABLE MASS ABSENT TREATMENT • NEOADJUVANT CHEMOTHERAPY > SURGERY > RADIOTHERAPY • CLINICAL RESPONSE TO NACT VERY HIGH • SURVIVAL RATE POOR.MEDIAN SURVIVAL 3-4YRS LOCOREGIONAL RECURRENCE • IN CASE THE PATIENT WAS TREATED WITH BCT, MRM+/AXILLARY CLEARANCE IS GIVEN • IF MRM,RADIOTHERA PY CAN BE GIVEN • AXILLA- BIOPSY EXICISION/RT METASTATIC BREAST DISEASE STAGE IV-anyT, anyN, M1 SITES OF SPREAD • BONE > LUNG > LIVER > CNS • OTHER SITES SPINAL CORD, OVARIES, EYES GENERAL WORK UP • ROUTINE INVESTIGATIONS • LFT • CXR • USG/CT/MRI • BONE SCAN • SERUM ALP • SERUM CALCIUM • TUMOUR MARKERS • CEA – RAISED IN 40-50% PATIENTS NONSPECIFIC • CA 15-3 MORE SPECIFIC FOR METS GOAL OF THERAPY • PALLIATIVE • TO IMPROVE QUALITY OF LIFE • TO PROLONG SURVIVAL BONE METASTASIS • SPINE > RIBS > PELVIS > SKULL > LONG BONES • PRESENT WITH PAIN PARALYSIS, FRACTURE. • TREATMENTBISPHOSPHONATES, EXTERNAL BEAM IRRADIATION INTERNAL FIXATION • LUNG & LIVER BIOPSY NECESSARY TREATMENT SYMPTOMATIC • CNS • TREATMENT – CRANIAL IRRADIATION HORMONAL/ CHEMOTHERAPY? HORMONAL THERAPY – INDICATIONS • PRE/POST MENOPAUSAL WHO ARE RECEPTOR +VE • PATIENTS WITH ONLY SKELETAL /SOFT TISSUE METASTASIS • LONG D/S FREE INTERVAL • PROLONGED INDOLENT COURSE WHEN ER/PR +VE – HORMONAL THERAPY • 1st LINE TAMOXIFEN • 2ND LINE AROMATASE INHIBITORS • 3RD LINE FULVESTRANT CHEMOTHERAPY • RECEPTOR NEGATIVE • VISERAL METASTASIS • RAPIDLY GROWING TUMOUR IN YOUNG WOMEN • FAILURE OF HORMONAL TREATMENT • 1ST LINE CAF/CMF • 2ND LINE TAXANES • 3RD LINE 5FU, VINCA ALKALOIDS, GEMCITABINE NEWER TRIALS • INHIBITORS OF SIGNAL TRANSDUCTION PATHWAY • INHIBITORS OF ANGIOGENESIS • IMMUNE MODULATORS SUMMARY • LABC- STAGE IIB- IIIC • TREATMENT- NACT > LOCAL TREATMENT >SYSTEMIC THERAPY > RADIOTHERAPY • LOCALLY ADVANCED INOPERABLE TUMOURS – SYSTEMIC THERAPY (TOILET MASTECTOMY/RADIOTHERAPY TO CONTROL A FUNGATING TUMOUR) • INFLAMMATORY CARCINOMA – TREATMANT OPTIONS SAME • METS –STAGE IV • TREATMENT –PALLIATIVE HORMONAL/CYTOTOXIC THERAPY • LOCAL TREATMENT –RADIOTHERAPY FOR PAINFUL BONY DEPOSITS & LOCOREGIONAL CONTROL, INTERNAL FIXATION FOR PATHOLOGICAL #, SPINAL CORD DECOMPRESSION THANK YOU