Breast cancer

BREAST CANCERWorldwide incidence in females*

*Incidence per 100,000 population.

Parkin DM, et al. CA Cancer J Clin. 1999;49:33-64.

67.4

36.0

28.6

71.7

21.2

25.0

31.5

25.5

86.3

Eastern Europe

Japan

Australia/New Zealand

South CentralAsia

Northern Africa

Southern Africa

Central America

Western Europe

NorthAmerica

ARGENTINA

NEOPLASIA DE MAMA 2011

1.1 MILLONES DE CASOS NUEVOS DIAGNOSTICADOS/AÑO 10 % DE TODOS LOS NUEVOS CA EN EL MUNDO 410.000 DEFUNCIONES ANUALES REPRESENTAN EL 1,6 % DE TODAS LAS DEFUNCIONES ANUALES DE

MUJERES. ES UN PROBLEMA DE SALUD URGENTE EN REGIONES DE ALTOS

RECURSOS Y ESTA AUMENTANDO EN LAS REGIONES DE BAJOS RECURSOS HASTA EN UN 5 %. (OMS)

A PESAR DEL AUMENTO DE CASOS DIAGNOSTICADOS, EL NUMERO DE MUERTES ES MENOR GRACIAS A DETECCION TEMPRANA Y MEJORAS EN LOS TRATAMIENTOS.

BREAST CANCER5-year relative survival rates by race

Landis SH, et al. CA Cancer J Clin. 1999;49:8-31.

0 20 40 60 80 100 120

AfricanAmerican

White

All Stages

Localized

Regional

Distant

% Surviving 5 Years

87

98

78

71

89

62

14

23

BREAST CANCERNatural history

Highly variable in different patients

Relatively slow growth rate

Median survival without treatment: 2.8 yrs

Generally present several years by time of diagnosis

Long preclinical period enables early detection

Henderson IC. American Cancer Society Textbook of Clinical Oncology. 1995;198-219.

BREAST CANCERRisk factors

Age Family history of breast cancer Prior personal history of breast cancer Increased estrogen exposure

– Early menarche– Late menopause– Hormone replacement therapy/oral contraceptives

Nulliparity 1st pregnancy after age 30 Diet and lifestyle (obesity, excessive alcohol consumption) Radiation exposure before age 40 Prior benign or premalignant breast changes

– In situ cancer– Atypical hyperplasia– Radial scar

Henderson IC. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;198-219.

Harris J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1557-1616.

Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;231-257.

BREAST CANCERScreening

Breast self-examination Examination Mammography—theby physician only modality shown

to decrease mortality

BREAST CANCERBreast inspection

Skin dimpling

BREAST CANCERBreast palpation

BREAST CANCERRegional node assessment

BREAST CANCERGoals of mammography screening

Earlier diagnosis in asymptomatic individuals Reduction of mortality due to detection at earlier stage

Age Mortality Reduction (%)

40-49 17% 15 years post-screening

50-69 25%-30% 10-12 years post-screening

70+ Insufficient data

PDQ: Screening for breast cancer for health professionals: http://Cancernetnci.nih.gov/. Accessed November 28, 1999.

BREAST CANCERScreening (high-risk)

Annual mammogram, beginning 5 yrs before age of youngest affected relative at time of diagnosis– High familial risk

– BRCA 1/2-positive

Tripathy D, Henderson IC. Current Cancer Therapeutics. 3rd ed. 1999;123-129.

BREAST CANCERScreening mammography

Reduces mortality by 26% in women aged 50-74

Supports view that early diagnosis and treatment can prevent metastasis

ACS recommends– 1st screening mammography by age 40– Mammography every 1 to 2 years between

the ages of 40 and 49– Mammography annually thereafter


Fink DJ, Mettlin CJ. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;128-193.

BREAST CANCERSigns and symptoms at presentation

Mass or painin the axilla

Palpable mass Thickening Pain

Nipple discharge Nipple retraction

Edema or erythemaof the skin

BREAST CANCERAnatomical site

RIGHT

Upper inner

Nipple

Central portion

Lower inner

Upper outer

Axillary tail

Lower outer

SUPERO EXTERNO

BREAST CANCER

BREAST CANCERMammography

BREAST CANCERUltrasonography

BREAST CANCERLiver metastasis

BREAST CANCERMRI scan

CÁNCER DE MAMA

FACTORES A TENER EN CUENTA AL DIAGNOSTICO INICIAL:• EDAD • ESTADO HORMONAL (PRE/POST)• DIAMETRO TUMORAL (T)• ESTADO GANGLIONAR (N)• DETERMINACION DE RECEPTORES HORMONALES• DETERMINACION DE HER 2• GRADO HISTOLOGICO/PERMEACION VASCULAR• PS

BREAST CANCERBiopsy techniques for palpable and mammographically detected masses

Excisional biopsy (usually outpatient)– Tumor size and histologic diagnosis

Core-cutting needle biopsy (in-office)– Histologic diagnosis

Fine-needle aspiration (in-office)– Cytologic diagnosis


BREAST CANCERPathology

Non-invasive carcinoma in situ– Ductal carcinoma in situ (DCIS)– Lobular carcinoma in situ (LCIS)

Invasive carcinoma– Infiltrating ductal or lobular carcinoma– Medullary, mucinous, and tubular carcinomas

Uncommon tumors– Inflammatory carcinoma– Paget’s disease

Dollinger M, et al. Everyone’s Guide to Cancer Therapy. 1997;356-384.

BREAST CANCERPathology: Non-invasive DCIS & LCIS

DCIS LCIS

Abnormal mammogram Microscopic characterization on biopsy

Clustered microcalcifications Solid proliferation of small or non-palpable masses cells with uniform round to

oval nuclei

30% risk of invasive cancer 37% chance of subsequent at 10 years at or near invasive cancer original biopsy site

DCIS – ductal carcinoma in situ.LCIS – lobular carcinoma in situ.

Harris J, et al. Cancer: Principles & Practice of Chemotherapy. 5th ed. 1997;1557-1616.

Love S, Barsky SH. Cancer Treatment. 4th ed. 1995;337-340.

BREAST CANCERIncidence of major histologic types

Percent of all invasive carcinomas

Hendersn IC. American Cancer Society Textbook & Clinical Oncology. 1995;198-219.

80%

10%5%

Infiltrating Lobular MedullaryInfiltrating Lobular Medullary

BREAST CANCERInvasive ductal carcinoma

BREAST CANCERSpread to lymph nodes

Supraclavicular

Subclavicular

Distal (upper)axillary

Central (middle)axillary

Proximal (lower)axillary

Mediastinal

Internal mammary

Interpectoral(Rotter’s)

BREAST CANCERSites of distant metastases

Skin

Liver

Bone

Pleura

Lung

Lymph nodes

Brain

BREAST CANCERTNM stage grouping

Stage 0 Tis N0 M0

Stage I T1* N0 M0

Stage IIA T0 N1 M0 T1* N1** M0T2 N0 M0

Stage IIB T2 N1 M0T3 N0 M0

Stage IIIA T0, T1,* T2 N2 M0T3 N1, N2 M0

Stage IIIB T4 Any N M0Any T N3 M0

Stage IV Any T Any N M1

* Note: T1 includes T1 mic.** Note: The prognosis of patients with N1a is similar to that of patients with pN0.

Used with the permission of the American Joint Committee on Cancer (AJCC®), Chicago, Illinois. The original source for this material is the AJCC® Cancer Staging Manual, 5th edition (1997)

published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.

BREAST CANCERTumor definitions TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple with no tumor

T1 Tumor 2 cm or less in greatest dimensionT1mic Microinvasion more than 0.1 cm or less in greatest dimension

T1a Tumor more than 0.1 cm but not more than 0.5 cm in greatest dimensionT1b Tumor more than 0.5 cm but not more than 1 cm in greatest dimensionT1c Tumor more than 1 cm but not more than 2 cm in greatest dimension

T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension T3 Tumor more than 5 cm in greatest dimension T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described

belowT4a Extension to chest wallT4b Edema (including peau d’orange) or ulceration of the skin of the breast

or satellite skin nodules confined to the same breastT4c Both (T4a and T4b)T4d Inflammatory carcinoma

Used with the permission of the American Joint Committee on Cancer (AJCC®), Chicago, Illinois. The original source for this material is the AJCC® Cancer Staging Manual, 5th edition (1997)

published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.

BREAST CANCERStage I

T1a: T 0.5 cm

T1b: 0.5 cm < T 1 cm

T1c: 1 cm < T 2 cm

T1 N0 M0

T 2 cm

T1

N0 = no regional lymph node metastasisM0 = no distant metastasis

BREAST CANCERStage IIA

T2 N0 M0

N1 = metastasis to movable ipsilateral axillary lymph node(s)M0 = no distant metastasis

2 cm < T < 5 cm

No evidenceof tumor

T0

T0 T1

N1 M0}

T2

BREAST CANCERStage IIB

T3 N0 M0

N1 = metastasis to movable ipsilateral axillary lymph node(s) (p) N1a, N1bM0 = no distant metastasis

T > 5 cm

T2 N1 M0

T3

BREAST CANCERStage IIIA

T0T1T2T3

Metastasis to ipsilateral axillary lymph node(s) N1 = movableN2 = fixed to one another or to other structuresM0 = no distant metastasis

T3 N1 M0N2 M0

BREAST CANCERStage IIIB

Any T N3 M0

N3 = metastasis to ipsilateral internal mammary lymph node(s)M0 = no distant metastasis

Tumor of any sizewith direct extensionto chest wall or skin

T4d = inflammatorycarcinoma

T4 any N M0

T4

BREAST CANCERStage IV

M1 = distant metastasis (including metastases to ipsilateral supraclavicular, cervical, or contralateral internal mammary lymph nodes)

Any T any N M1

BREAST CANCER5-year survival as function of the number of positive axillary lymph nodes

0%

20%

40%

60%

80%

5-Y

ear

Su

rviv

al

0 1 2 3 4 5 6-10 11-15 16-20 >20

Number of Positive Nodes


CÁNCER DE MAMAMOMENTOS PARA TRATAMIENTO

DIAGNOSTICO:

INICIAL METASTASICO

PROGRESION RECAIDO

RECURRENTE

TRATAMIENTO: “MEDICINA BASADA EN LA EVIDENCIA”

CÁNCER DE MAMA

FACTORES A TENER EN CUENTA AL DIAGNOSTICO INICIAL:• EDAD • ESTADO HORMONAL (PRE/POST)• DIAMETRO TUMORAL (T)• ESTADO GANGLIONAR (N)• DETERMINACION DE RECEPTORES HORMONALES• DETERMINACION DE HER 2• GRADO HISTOLOGICO/PERMEACION VASCULAR• PS

NEOPLASIA DE MAMA 2011

NORMAS DE LA OMS1)DETECCION TEMPRANA Y ACCESO A LA ATENCION2)DIAGNOSTICO Y PATOLOGIA3)TRATAMIENTO Y ASIGNACION DE RECURSOS4)SISTEMAS DE ATENCION DE SALUD Y POLITICAPUBLICA.

PILARES DEL TRATAMIENTOCIRUGIA

RADIOTERAPIA QUIMOTERAPIA

MEDICINA PALIATIVA INVESTIGACION CLINICA!!

HORMONOTERAPIA

MODULADORES SELECTIVOS DE RECEPTOR DE ESTROGENO:

TAMOXIFENOTAROMIFENO

ABLACION OVARICA:ANALOGOS LHR GOSERELIN/LEUPROLIDEOOFORECTOMIA

PROGESTAGENOS:ACETATO DE MEGESTROLACETATO DE MEDROXIPROGESTERONA

HORMONOTERAPIA

INHIBIDORES DE AROMATASAS:

ANASTRAZOL

LETROZOL

EXAMESTANE

ANTIESTROGENOS PUROS (ER DOWN REGULATORS):

FULVESTRANT

ONCOLOGYCancer biologyTumor growth and detection

1012

109

time

Diagnosticthreshold

(1cm)

Undetectablecancer

Detectablecancer

Limit ofclinical

detection

Hostdeath

Nu

mb

er o

fca

nce

r ce

lls

Antibiotics

Antimetabolites

S(2-6h)

G2

(2-32h)

M(0.5-2h)

Alkylating agents

G1

(2-h)

G0

Vinca alkaloids

Mitotic inhibitors

Taxoids

ONCOLOGYPrinciples of chemotherapy

Cell cycle level

Action sites of cytotoxic agents

DNA synthesisAntimetabolites

DNA

DNA transcription DNA duplication

Mitosis

Alkylating agents

Spindle poisons

Intercalating agentsCellular level

ONCOLOGYPrinciples of chemotherapyAction sites of cytotoxic agents

QUIMIOTERAPIA

ANTRACICLINAS:

DOXORRUBICINA

EPIRRUBICINA

MITOXANTROMA

DOXORRUBICINA LIPOSOMAL

AGENTES ALQUILANTES:

CICLOFOSFAMIDA

QUIMIOTERAPIA

ALCALOIDES DE LA VINKA:

VINORELBINE (EV/VIA ORAL)

TAXANOS:

PACLITAXEL

DOCETAXEL

EPOTILONAS:

IXABEPILONA

QUIMIOTERAPIA

OTROS:

5 FLUORURACILO

CAPECITABINE

METOTREXATO

GEMCITABINE

INCREASED EFFICACY

Different mechanisms of action Compatible side effects

Different mechanisms of resistance

ACTIVITY SAFETY

ONCOLOGYPrinciples of chemotherapyAim of combination therapy

Mucositis

Nausea/vomiting

Diarrhea

Cystitis

Sterility

Myalgia

Neuropathy

Alopecia

Pulmonary fibrosis

Cardiotoxicity

Local reaction

Renal failure

Myelosuppression

Phlebitis

ONCOLOGYPrinciples of chemotherapySide effects of chemotherapy

TOXICIDAD:

* NEUTROPENIA (PANCITOPENIA)* NEUTROPENIA FEBRIL* ALOPECIA* NAUSEAS Y VOMITOS* REACCIONES HIPERSENSIBILIDAD* NEUROTOXICIDAD* NEFROTOXICIDAD* CARDIOTOXICIDAD* PIEL Y FANERAS* NEUMONITIS INTERSTICIAL* DIARREA* RETENCION DE LIQUIDO* ASTENIA / ANOREXIA

COMPLICACIONES DE LA RADIOTERAPIA I

COMPLICACIONES DE LA RADIOTERAPIA II

RESOLUCION

THE END MUCHAS GRACIAS.

Health & Medicine

Breast cancer