Download management of advanced breast cancer

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