Carcinoma Carcinoma BreastBreast

Epidemiology, diagnosis Epidemiology, diagnosis and managementand management

OverviewOverview

StatisticsStatistics Most common Ca in women in developed Most common Ca in women in developed

countries. The lifetime risk (upto age 85) countries. The lifetime risk (upto age 85)

19401940 - - 5%5% - one in - one in 20;20;

2000- 2000- 12.6%12.6% - one in - one in 88.. Incidence India- Incidence India- 80,00080,000 per year, per year,

worldwide incidence worldwide incidence 1.2 million1.2 million(WHO) (WHO) Death – 2Death – 2ndnd leading cause of cancer death. leading cause of cancer death.

40,00040,000 in US per year, worldwide much in US per year, worldwide much higherhigher

Age specific incidence- steep Age specific incidence- steep increase after 35 yrs, max at 75-80 increase after 35 yrs, max at 75-80 yrs.yrs.

High incidence among Caucasians; High incidence among Caucasians; less common among Asiansless common among Asians

Increasing frequency; steep increase Increasing frequency; steep increase in 80s with mammo; marginal fall in 80s with mammo; marginal fall over the last few years.over the last few years.

EtiologyEtiology Hereditary (10% of pts have 1Hereditary (10% of pts have 1stst deg deg

relatives)relatives) Genetic mutations- BRCA 1, 2Genetic mutations- BRCA 1, 2 Radiation- Radiation- esp. during childhood- mantle esp. during childhood- mantle

RT upto 20% incidence by 50 y.RT upto 20% incidence by 50 y. Benign disease- Benign disease- proliferative, with atypiaproliferative, with atypia Previous h/o Previous h/o breast cabreast ca Diet- Diet- obesity; dietary fat, anti-ox.- obesity; dietary fat, anti-ox.-

inconclusive.inconclusive. Hormonal factors- Hormonal factors- increased risk with increased risk with

excess exposure to estrogens; Progesterone excess exposure to estrogens; Progesterone containing OCPscontaining OCPs

Risk factorsRisk factors High risk-High risk- Age, previous history of breast Age, previous history of breast

Ca, family history, atypical Ca, family history, atypical hyperplasia, Nulliparous women, hyperplasia, Nulliparous women, radiationradiation

Low risk-Low risk-Menstrual history, estrogens, DM, Menstrual history, estrogens, DM, alcohol. alcohol.

Early pregnancy, Asian race, early Early pregnancy, Asian race, early menopause menopause reduce the risk. reduce the risk.

Risk factor modelsRisk factor models

Gail model:Gail model: ( www.nci.nih.gov )( www.nci.nih.gov )Uses the following criteria:Uses the following criteria:

-current age-current age-age at menarche-age at menarche-age at first child birth-age at first child birth-no. of first degree relatives with -no. of first degree relatives with

breast cabreast ca-no. of previous benign biopsies-no. of previous benign biopsies-atypical hyperplasia in a prev. biopsy-atypical hyperplasia in a prev. biopsy-race-race

PathologyPathology In-situ Carcinomas-In-situ Carcinomas-

DCIS, LCIS; Paget’s disease of DCIS, LCIS; Paget’s disease of nipplenipple

Invasive Cas-Invasive Cas-Invasive Ductal Ca (80%)Invasive Ductal Ca (80%)Invasive lobular Ca (10%)Invasive lobular Ca (10%)

Other invasive Cas- Medullary, Other invasive Cas- Medullary, papillary, tubular, cribriform, papillary, tubular, cribriform, metaplastic, squamous, adenoid metaplastic, squamous, adenoid cystic, mucinous, secretory, cystic, mucinous, secretory, undifferentiated.undifferentiated.

DCISDCIS

Without e/o invasionWithout e/o invasion Progresses to invasive if untreatedProgresses to invasive if untreated Usual diagnosis by mammo (asymptomatic)Usual diagnosis by mammo (asymptomatic) Histologically- Comedo vs Non- Comedo Histologically- Comedo vs Non- Comedo

(papillary, cribriform, micropapillary, solid)(papillary, cribriform, micropapillary, solid) Treatment= excision with negative Treatment= excision with negative

margins, then RT; Tamoxifenmargins, then RT; Tamoxifen Prognosis- 95 + % cure ratesPrognosis- 95 + % cure rates

Paget’s diseasePaget’s disease

LCISLCIS

Commonly B/L, multifocalCommonly B/L, multifocal Diagnosis by biopsy; incidentalDiagnosis by biopsy; incidental Increased risk of malignancy- Increased risk of malignancy-

1%/year, reaching 17-20%1%/year, reaching 17-20%life long risklife long risk

No treatment requiredNo treatment required-follow up with CBE, annual -follow up with CBE, annual mammo; mammo;

tamoxifen/raloxifene decrease risk of Ca. tamoxifen/raloxifene decrease risk of Ca.

Other pathologic Other pathologic characteristicscharacteristics

Grade ( modified SBR)Grade ( modified SBR) Estrogen, Progesterone Estrogen, Progesterone

receptorreceptor Her2/neu expressionHer2/neu expression Other markers- Other markers-

S- phase S- phase Ki-67 Ki-67 DNA ploidyDNA ploidy

Her 2 amplification by FISH

Estrogen receptor +vity by IHC

Spread of breast cancerSpread of breast cancer

Modes of SpreadModes of Spread

Direct invasion- Direct invasion- into chest into chest muscles, wall, skin/nipple-areola.muscles, wall, skin/nipple-areola.

Lymphatic- Lymphatic- Locoregional - axilla, Locoregional - axilla, supraclavicular, infraclavicular and supraclavicular, infraclavicular and Internal mammaryInternal mammary

Blood- Blood- Bones, lungs, liver, brain– Bones, lungs, liver, brain– Distant metastasis- stage IVDistant metastasis- stage IV

Clinical symptoms-Clinical symptoms-

LLocal- ocal- Lump, discharge, skin/nipple changes, Lump, discharge, skin/nipple changes, axillary, arm swelling, ulceraxillary, arm swelling, ulcerPain, tenderness- Inflammatory CaPain, tenderness- Inflammatory Ca

Distant- Distant- back ache, cough, breathlessness, back ache, cough, breathlessness, headache, vomiting, anorexia, etc.headache, vomiting, anorexia, etc.

O/E – O/E – lump-hard, irregular , nipple retraction, peau lump-hard, irregular , nipple retraction, peau de orange/puckering.de orange/puckering.Nipple discharge, axillary nodesNipple discharge, axillary nodes

DiagnosisDiagnosis

FNAC/biopsy of the lump/gland- FNAC/biopsy of the lump/gland- histology and receptor status studieshistology and receptor status studies

Her 2 /neu, DNA ploidy, S phase # Her 2 /neu, DNA ploidy, S phase # - - prognostic indicator studiesprognostic indicator studies

Evaluation- Evaluation- CBC, RFT, LFT, ALP, S. CBC, RFT, LFT, ALP, S. Ca++, Cardiac evaluation, Ca++, Cardiac evaluation, mammographymammography

Metastatic work up- Metastatic work up- CXR, USG CXR, USG A+P, Bone scan, ? PET. CT thorax, A+P, Bone scan, ? PET. CT thorax, brain- only if symptoms suggestivebrain- only if symptoms suggestive. .

Breast cancer screeningBreast cancer screening

Women who undergo breast cancer Women who undergo breast cancer screening mammograms have screening mammograms have demonstrated significantly demonstrated significantly reduced reduced deathsdeaths from the disease due to from the disease due to early detection and treatment. early detection and treatment.

SCREENING METHODSSCREENING METHODS

Breast self examinationBreast self examination ( (BSEBSE))

Clinical breast examinationClinical breast examination- by physicians- by physicians

MammogramsMammograms

Ductal LavageDuctal Lavage – investigational – investigational

Others– Breast Scintigraphy, USG, or MRIOthers– Breast Scintigraphy, USG, or MRI

  

MammographyMammography

An X-ray photograph of the breast An X-ray photograph of the breast The technique has been in use for about The technique has been in use for about

thirty yearsthirty years Safe and highly accurateSafe and highly accurate Low kV (25-30 kV), high mA (25-100)Low kV (25-30 kV), high mA (25-100) Combined with sonographyCombined with sonography

Probably the most important tool Probably the most important tool doctors havedoctors have

To diagnose To diagnose To evaluateTo evaluate To follow women who've had To follow women who've had

breast cancer. breast cancer.

Identifies breast cancers too small to palpate Identifies breast cancers too small to palpate on physical examination- 0.5 cm on physical examination- 0.5 cm (classified as T 1 lesion, with high curability)(classified as T 1 lesion, with high curability)

Different types of calcifications within the Different types of calcifications within the breast tissue are visualized, which may be breast tissue are visualized, which may be or may not be cancerous.or may not be cancerous.

Reported as a BI-RADS category ( 1 to 5; 5= Reported as a BI-RADS category ( 1 to 5; 5= highly suspicious; 0- incomplete, 6- proven highly suspicious; 0- incomplete, 6- proven Ca).Ca).

  

All women 50+ (?40+) should get the benefit All women 50+ (?40+) should get the benefit of annual mammograms and CBEs. of annual mammograms and CBEs. Sonography might be added.Sonography might be added.

With serial mammograms it is possible to With serial mammograms it is possible to detect earliest lesionsdetect earliest lesions

Mammograms can save lives as most of the Mammograms can save lives as most of the early breast cancers are curableearly breast cancers are curable

StagingStaging

TNMTNM – clinical & pathological – clinical & pathological

T stageT stage--T1- < 2 cms in sizeT1- < 2 cms in sizeT2- 2-5 cmsT2- 2-5 cmsT3- >5 cmsT3- >5 cmsT4- with chest wall (4a), skin (4b), T4- with chest wall (4a), skin (4b), both (4c), or inflammatory ca (4d)both (4c), or inflammatory ca (4d)

N stage N stage (clinical)(clinical)

N1- ipsilateral movable axillary nodesN1- ipsilateral movable axillary nodesN2- ipsilateral matted/fixed nodes; N2- ipsilateral matted/fixed nodes; clinically apparent ipsilateral IMNs in clinically apparent ipsilateral IMNs in absence of axillary nodesabsence of axillary nodesN3- ipsilateral infraclavicular, clinically N3- ipsilateral infraclavicular, clinically apparent ipsilateral IMNs in presence of apparent ipsilateral IMNs in presence of axillary nodes, ipsilateral axillary nodes, ipsilateral supraclavicular nodessupraclavicular nodes

Stage groupingStage grouping

II T1N0M0T1N0M0 IIAIIA T2N0M0, T1N1M0T2N0M0, T1N1M0 IIBIIB T3N0M0, T2N1M0T3N0M0, T2N1M0 IIIAIIIA T3N1-2M0, T2N2M0T3N1-2M0, T2N2M0 IIIBIIIB T4N0-2M0T4N0-2M0 IIICIIIC anyTN3M0anyTN3M0 IVIV anyTanyNM1anyTanyNM1

TreatmentTreatment

Depends on:Depends on:Stage Stage Hormone receptor status Hormone receptor status Her2/neu receptor status Her2/neu receptor status AgeAge

Early stage (EBC)Early stage (EBC)

Locally advanced (LABC)Locally advanced (LABC)

Metastatic diseaseMetastatic disease

Treatment modalities- SxTreatment modalities- Sx BCS vs MRMBCS vs MRM Contraindications to BCS- Contraindications to BCS-

1. multifocal disease 1. multifocal disease 2. extensive microcalcifications 2. extensive microcalcifications 3. unable to get negative margins 3. unable to get negative margins 4. prior RT 4. prior RT 5. Pt preference5. Pt preference

Relative-Relative- CVDs, large tumors, large CVDs, large tumors, large breasts, pregnancy, breasts, pregnancy,

Role of Sentinel l. n. biopsy- Role of Sentinel l. n. biopsy-

Treatment modalities- Treatment modalities- ChemoRxChemoRx

Required for most patients.Required for most patients. Curative: Neoadjuvant or adjuvant;Curative: Neoadjuvant or adjuvant;

Combination chemo- Anthracycline Combination chemo- Anthracycline based; Paclitaxel added for high risk based; Paclitaxel added for high risk cases; 6-8 cycles (4 months)cases; 6-8 cycles (4 months)

Palliative: single or combination Palliative: single or combination chemochemo

Treatment modalities- Treatment modalities- RTRT

DefinitiveDefinitive: usually adjuvant;: usually adjuvant; Must after BCS, in mastectomy patients with Must after BCS, in mastectomy patients with

high risk of Local recurrence (large tumors, high risk of Local recurrence (large tumors, >4 axillary l.n. +, positive margins, etc)>4 axillary l.n. +, positive margins, etc)

45-50 Gy to whole breast/chest wall; followed 45-50 Gy to whole breast/chest wall; followed by boost to the tumor bed (in BCS) to 10-16 Gyby boost to the tumor bed (in BCS) to 10-16 Gy

+/- RT to axillary, Supraclavicular l.n.+/- RT to axillary, Supraclavicular l.n.

PalliativePalliative: for specific symptoms- bone mets, : for specific symptoms- bone mets, brain mets, etc.brain mets, etc.

Treatment modalities- Treatment modalities- HTHT

Only in Hormone Receptor +ve Only in Hormone Receptor +ve casescases

SERMS- Tamoxifen, RaloxifeneSERMS- Tamoxifen, Raloxifene Aromatase inhibitors- Letrozole, Aromatase inhibitors- Letrozole,

anastrazole, exemestaneanastrazole, exemestane GnRH analogues- leuprolide, GnRH analogues- leuprolide,

goserelingoserelin

Treatment modalities- Treatment modalities- MAbMAb

Trastuzumab- monoclonal Trastuzumab- monoclonal antibody against Her2/neu antibody against Her2/neu receptor; used in receptor; used in Her2/neu positive cases onlyHer2/neu positive cases only

Lapatinib (T K I)Lapatinib (T K I)

Early breast cancer Early breast cancer (EBC)(EBC)

Breast conservation(lumpectomy/wide Breast conservation(lumpectomy/wide excision) with axillary clearance or excision) with axillary clearance or MRMMRM

Followed by adjuvant RT + Followed by adjuvant RT + Chemotherapy +/- Hormonal therapyChemotherapy +/- Hormonal therapy

Locally advanced breast Locally advanced breast cancer (LABC)cancer (LABC)

Large tumors, Difficult to get Large tumors, Difficult to get clearance,clearance,

Patient wishes to conserve the Patient wishes to conserve the breastbreast

Neo adjuvant/upfront chemotherapy Neo adjuvant/upfront chemotherapy followed by reassessment and followed by reassessment and surgery + Adjuvant RT + surgery + Adjuvant RT + Chemotherapy +/- HormonesChemotherapy +/- Hormones

Metastatic Ca breast at Metastatic Ca breast at presentationpresentation

Palliative treatmentPalliative treatment

1. Chemotherapy- 1. Chemotherapy- single or combination single or combination chemochemo

2. Surgery – 2. Surgery – Toilet mastectomy only if Toilet mastectomy only if fungating/ulcerative/painful lumpfungating/ulcerative/painful lump

3. Radiation- 3. Radiation- In Bone and brain metastasis- In Bone and brain metastasis- for symptomatic relief of pain/ raised ICPfor symptomatic relief of pain/ raised ICP

4. Hormonal- 4. Hormonal- for HR +ve cases, with for HR +ve cases, with oligometastases with no requisite for oligometastases with no requisite for immediate responseimmediate response

5. Supportive treatment5. Supportive treatment

Commonly used chemo drugs Commonly used chemo drugs

AdriamycinAdriamycin

CyclophosphamideCyclophosphamide

PaclitaxelPaclitaxel

DocetaxolDocetaxol

CapecitabineCapecitabine

5 Fluro uracil5 Fluro uracil

MethotrexateMethotrexate

Prognosis-Prognosis-

1. Stage - 1. Stage - nodal status, number of nodesnodal status, number of nodes

2. ER/PR receptor status 2. ER/PR receptor status

3. Her 2/neu receptor status 3. Her 2/neu receptor status

4. other histological features: 4. other histological features: Grade, Grade, size, presence of LVSI, S phase, DNA size, presence of LVSI, S phase, DNA ploidyploidy

5.5. Site of mets- Site of mets- Bone vs other sites, size Bone vs other sites, size of mets, etc.of mets, etc.

SurvivalSurvival

I stage – 85-90%I stage – 85-90%

II stage - 65-70 %II stage - 65-70 %

III stage - 35 %III stage - 35 %

IV stage- 10 %IV stage- 10 %

THANK YOUTHANK YOU