BREAST CANCERBREAST CANCER

DR. GÖKHAN DR. GÖKHAN SÖĞÜTLÜSÖĞÜTLÜ

Breast cancer is either Breast cancer is either noninvasive(in situ) or noninvasive(in situ) or invasive(spreading)invasive(spreading)

Ductal carcinoma in situDuctal carcinoma in situ Lobular carcinoma in situLobular carcinoma in situ

LC in situ is a marker for an LC in situ is a marker for an incresed risk of invasive cancer in incresed risk of invasive cancer in both breasts ( same breast %18 and both breasts ( same breast %18 and other breast %14 after 20 years)other breast %14 after 20 years)

Invasive cancer occurs when cancer Invasive cancer occurs when cancer cells spread beyond the basement cells spread beyond the basement mebrane.mebrane.

Infiltrating ductal caInfiltrating ductal ca

Infiltrating lobular caInfiltrating lobular ca They comprises between 70% and 80% ; They comprises between 70% and 80% ;

10% and 15% of all breast cancers 10% and 15% of all breast cancers respectively.respectively.

The typical carcinoma of the breast (80 The typical carcinoma of the breast (80 to 85 percent) is a scirrhous to 85 percent) is a scirrhous adenocarcinom with prodictive fibrosis adenocarcinom with prodictive fibrosis that orginates in the ductules and that orginates in the ductules and invades the parenchymainvades the parenchyma

RİSK FACTORSRİSK FACTORS AgeAge More than 80 % of breast cancer More than 80 % of breast cancer

cases occur in women over 50 .cases occur in women over 50 . Cancer in women younger than 30 Cancer in women younger than 30

is very rare, accounting for only is very rare, accounting for only 1.5% of all breast cancer cases.1.5% of all breast cancer cases.

AA woman’s chances for breast woman’s chances for breast cancer are cancer are 1/8 in their whole life1/8 in their whole life..

EthnicityEthnicity North America and Northen Europe people high risk North America and Northen Europe people high risk

(industrial countries), Asian and African people low (industrial countries), Asian and African people low risk (non-industrial countries)risk (non-industrial countries)

Genetic factors and family history Genetic factors and family history *20-30% of all women with breast cancer have a *20-30% of all women with breast cancer have a family history family history (familial)(familial)*5-10% of all women with breast cancer have *5-10% of all women with breast cancer have hereditaryhereditary*This often appears in young women under age 50*This often appears in young women under age 50*In such families, some members may also have *In such families, some members may also have developed ovarian cancer as well. developed ovarian cancer as well.

HEREDITARYHEREDITARY

Genes are as follows;Genes are as follows;--BRCA1 or BRCA2BRCA1 or BRCA2 are now believed to be are now believed to be responsible for 30% to 50% of responsible for 30% to 50% of hereditary breast hereditary breast cancercancer, ovarian cancer or both in families with a , ovarian cancer or both in families with a history of these cancers.history of these cancers.- About - About 90% 90% of BRCA1 carriers will develop breast of BRCA1 carriers will develop breast cancer cancer in whole lifetimein whole lifetime..-These mutations can be passed down to the -These mutations can be passed down to the doughter by either mother or the father.doughter by either mother or the father.-These are present in only about 0.1 of the -These are present in only about 0.1 of the population.population.

Other defective genes that Other defective genes that contribute to breast cancer contribute to breast cancer including BRCA3, p53,CDKN2Aincluding BRCA3, p53,CDKN2A

A mutation in a gene located on A mutation in a gene located on chromosome 10 called PTEN gene chromosome 10 called PTEN gene results in a disorder called Cowden results in a disorder called Cowden syndrome, which is associated with a syndrome, which is associated with a higher risk of breast cancer.higher risk of breast cancer.

RİSK FACTORS(con.)RİSK FACTORS(con.)

Over-exposure to estrogenOver-exposure to estrogen

Because growth of breast tissue is Because growth of breast tissue is highly sensitive to estrogens, the highly sensitive to estrogens, the more a women is exposed to more a women is exposed to estrogen over her lifetime,the higher estrogen over her lifetime,the higher the risk for breast cancer.the risk for breast cancer.

For women in whom menopause For women in whom menopause occurs after the age of 45 the risk of occurs after the age of 45 the risk of developing the disease is twice as high developing the disease is twice as high as for those whose menopause started as for those whose menopause started before age 45.before age 45.

Artificially surgical menopause Artificially surgical menopause appears to be protective for breast appears to be protective for breast cancer. Protection is lifelong and cancer. Protection is lifelong and removal of endogenous estrogen removal of endogenous estrogen dramatially reduces breast cancer risk.dramatially reduces breast cancer risk.

The earlier the surgical menopause The earlier the surgical menopause (oophorectomy at age thirty five or (oophorectomy at age thirty five or younger), the lower the risk.younger), the lower the risk.

Early menarche also Early menarche also increases increases the the riskrisk

Pregnanncy and abortionPregnanncy and abortion Infertility and nulliparity are Infertility and nulliparity are

associated with a higher probability.associated with a higher probability. With decreasing age at the time of With decreasing age at the time of

first pregnancy,the risk decreases first pregnancy,the risk decreases proportionately.proportionately.

Women impregnated before 18 who Women impregnated before 18 who have a full-term pregnancy have a have a full-term pregnancy have a breast cancer risk 1/3 that for women breast cancer risk 1/3 that for women pregnant after 35.pregnant after 35.

Women,first full-term pregnancy Women,first full-term pregnancy after the age 30, have an even after the age 30, have an even greater risk for breast cancer than greater risk for breast cancer than do nullipars.do nullipars.

Women who have had abortions Women who have had abortions have risk but this is very small.have risk but this is very small.

Oral contraceptionOral contraception New low-dose OCs do not appear to New low-dose OCs do not appear to

pose this risk (more research is pose this risk (more research is needed)needed)

HRT (hormone replacement theraphy)HRT (hormone replacement theraphy) Estrogen use by premenopausal and Estrogen use by premenopausal and

postmenopausal women for HRT may postmenopausal women for HRT may slightly increase the risk of breast slightly increase the risk of breast cancer.cancer.

The risk is said to be accentuated in The risk is said to be accentuated in women with preexisting benign women with preexisting benign disease of the breast.disease of the breast.

Prolonged use increases the riskProlonged use increases the risk Interestingly, some studies suggest Interestingly, some studies suggest

that in women with a history of that in women with a history of breast cancer, HRT does not breast cancer, HRT does not increase risk for recurrenceincrease risk for recurrence

Risk factors (con.)Risk factors (con.)

Physical characteristicsPhysical characteristics Breast cancer risk is directly Breast cancer risk is directly

correlated with relative weight; the correlated with relative weight; the risk for obese women is 1.5 to 2 risk for obese women is 1.5 to 2 times higher than for nonobese times higher than for nonobese women.women.

This relative risk is restricted to This relative risk is restricted to postmenopausal individuals.postmenopausal individuals.

There have been conflicting reports There have been conflicting reports of a link between increased height of a link between increased height and breast cancer risk.and breast cancer risk.

One study found no association.One study found no association. Other studies, however, found that Other studies, however, found that

taller adult height predicted a taller adult height predicted a greater risk, possibly due to the greater risk, possibly due to the higher estrogen levels associated higher estrogen levels associated with greater bone growth.with greater bone growth.

Multipl primary neoplasmsMultipl primary neoplasms Women with a history of primary Women with a history of primary

breast cancer have a risk 3 to 4 breast cancer have a risk 3 to 4 times higher for primary cancer in times higher for primary cancer in the contrlateral breast.the contrlateral breast.

History of previous ovarian and History of previous ovarian and endometrial carcinoma.endometrial carcinoma.

Environmental factorsEnvironmental factors Exposure to estrogen –like industrial Exposure to estrogen –like industrial

chemicals (xenoestrogens). They are chemicals (xenoestrogens). They are found in pesticides and other common found in pesticides and other common industrial products.industrial products.

Radiation exposureRadiation exposure

Children receiving high dose radiation Children receiving high dose radiation theraphy face an increased risk for breast theraphy face an increased risk for breast cancer in adulthood.cancer in adulthood.

Mental healthMental health A 2000 study suggested that women A 2000 study suggested that women

who had a history of major who had a history of major depression were four times as likely depression were four times as likely to develop breast cancer.to develop breast cancer.

Stress was not found as a risk factor. Stress was not found as a risk factor.

Insulin-like growth factorInsulin-like growth factor

Insulin-like growth factor 1 is an Insulin-like growth factor 1 is an important growth hormone during important growth hormone during development in the womb and development in the womb and childhood. High concentrations have childhood. High concentrations have now been linked to cancers, now been linked to cancers, including premenapousal breast including premenapousal breast cancer.cancer.

AlcoholAlcohol

Risk is increased 1.5 fold when Risk is increased 1.5 fold when drunk regularly. drunk regularly.

Benign breast diseaseBenign breast disease Hyperplasia without AH 1.5-2 foldHyperplasia without AH 1.5-2 fold AH 4-5 fold AH 4-5 fold

How can the risk of How can the risk of breast cancer be breast cancer be

lowered?lowered? Regular exercise (by modulating Regular exercise (by modulating

estrogen)estrogen) Dietary factorsDietary factors FatsFats

Although some studies have found an Although some studies have found an association between high-fat intake and association between high-fat intake and breast cancer, the most recent data breast cancer, the most recent data suggest that fat from any source plays at suggest that fat from any source plays at most insignificant role in incresing the most insignificant role in incresing the risk for breast cancer. risk for breast cancer.

Vitamins and chemicals in fruits and Vitamins and chemicals in fruits and vegetablesvegetables

Many fresh fruits and vegetables contain Many fresh fruits and vegetables contain chemicals that may be cancer fighter.chemicals that may be cancer fighter.

• Cabbage, broccoli, cauliflower, turnip, Cabbage, broccoli, cauliflower, turnip, kalekale

• Apples, onion, green tea (contains Apples, onion, green tea (contains polyphenols)polyphenols)

• Tomatos(lycopen)Tomatos(lycopen)• Avocado, bananas, fruits, orange juice Avocado, bananas, fruits, orange juice

(folic acid) (folic acid)

IronIron

High iron stores have been High iron stores have been associated with a higher risk for associated with a higher risk for breast cancerbreast cancer

ProteinProtein

Fish may offer some protectionFish may offer some protection

Breast feedingBreast feeding

Evidence on protection from breast Evidence on protection from breast feeding is weakly positive.feeding is weakly positive.

symptomssymptoms

Hard lumpHard lump 50% of such masses are found in the upper 50% of such masses are found in the upper

outer quarter of the breast.outer quarter of the breast. The nipple may be retracted or scalyThe nipple may be retracted or scaly Sometimes, the skin of the breast is Sometimes, the skin of the breast is

dimpled like the dimpled like the skin of an orange.skin of an orange. Skin ulceration may occurSkin ulceration may occur. .

In some cases there is a In some cases there is a bloody or bloody or clear discharge from the nippleclear discharge from the nipple

Axillary massAxillary mass

DiagnosisDiagnosis

Early detection of breast cancer Early detection of breast cancer significantly reduces the risk of deathsignificantly reduces the risk of death

20-49 ages physical examination 20-49 ages physical examination by a health professional every 1 to 2 by a health professional every 1 to 2 years.years.

50 and over should be examined 50 and over should be examined annualy annualy

Women should perform self Women should perform self examination every month. examination every month.

MammogramMammogram

Mammograms are very effective low-Mammograms are very effective low-radiation screeningradiation screening

They are not foolproof, howeverThey are not foolproof, however In general, they still miss up to 25% of In general, they still miss up to 25% of

cancers (which can sometimes be caught cancers (which can sometimes be caught on a physical examination)*****on a physical examination)*****

Screening mammogram every 12 to 33 Screening mammogram every 12 to 33 months significantly reduced mortality, months significantly reduced mortality, at least in women over 55at least in women over 55 (a (a 33% 33% reduction in mortality for woman after reduction in mortality for woman after screening mammogaphyscreening mammogaphy)). .

There are, however, a number of There are, however, a number of issues as to who should screen and issues as to who should screen and when to screen.when to screen.

For women between ages 50 and For women between ages 50 and 69. Evidence suggest that annual 69. Evidence suggest that annual mammograms save lives in this age mammograms save lives in this age group (per 2 years in our country).group (per 2 years in our country).

40-50 should be tested every 1 to 2 40-50 should be tested every 1 to 2 years until age 50.years until age 50.

Overall, diagnostic mammography Overall, diagnostic mammography has a 90% sensitivity, 10% false has a 90% sensitivity, 10% false positive rate and 7% false negative positive rate and 7% false negative rate. rate.

UltrasonographyUltrasonography New ultrasound techniques can detect New ultrasound techniques can detect

tumors smaller than 1 centimeter.tumors smaller than 1 centimeter. However, ultrasound is a time-However, ultrasound is a time-

consuming procedure, and remains less consuming procedure, and remains less efficient than mammogramefficient than mammogram

Other imaging Other imaging techniquestechniques

ScintomammographyScintomammography Dopler ultrasonographyDopler ultrasonography Breast MRBreast MR

BiopsyBiopsy

A definitive diagnosis of breast cancer A definitive diagnosis of breast cancer can be made only by a biopsy.can be made only by a biopsy.

When a lump can be felt and is When a lump can be felt and is suspicious for cancer on suspicious for cancer on mammography;mammography;

FNABFNAB Excisional biopsyExcisional biopsy İncisional biopsyİncisional biopsy Core biopsyCore biopsy Radioguided biopsy (for occult lumps)Radioguided biopsy (for occult lumps)

A wire localization biopsy may be A wire localization biopsy may be performed if mammography detects performed if mammography detects abnormalities but there is no lump abnormalities but there is no lump (microcalcifications)(microcalcifications)

A new vacuum-assisted device may A new vacuum-assisted device may be useful for some biopsies.be useful for some biopsies.

Prognostic factorsPrognostic factors

A number of factors are used to A number of factors are used to determine outlook;determine outlook; Size and lymh nodes statusSize and lymh nodes status Nuclear gradeNuclear grade AgeAge The location of the tumor and far it has The location of the tumor and far it has

spread (tumors that develop toward the spread (tumors that develop toward the outside of the breast tend to be less outside of the breast tend to be less serious than those that occur more serious than those that occur more toward the middle of the breast).toward the middle of the breast).

Whether the tumor is hormone Whether the tumor is hormone receptor-positive or negativereceptor-positive or negative

• Breast cancer cells may contain Breast cancer cells may contain receptors, or binding sites, for receptors, or binding sites, for hormones like estrogen or hormones like estrogen or progesterone.progesterone.

• Hormone receptor positive cells grow Hormone receptor positive cells grow more slowly than recptor negative cells.more slowly than recptor negative cells.

• Women have a better prognosis if their Women have a better prognosis if their tumors are receptor-positive.tumors are receptor-positive.

The influence of BRCA genesThe influence of BRCA genes• The relevance of the BRCA1 or BRCA2 The relevance of the BRCA1 or BRCA2

mutations to survival is controversialmutations to survival is controversial• Women with these genetic mutations do Women with these genetic mutations do

have a greater risk for a new cancer to have a greater risk for a new cancer to develop.develop.

• Poor differentiation (for BRCA-1)Poor differentiation (for BRCA-1)• Well differentiation (for BRCA-2)Well differentiation (for BRCA-2)• High bilateralismHigh bilateralism• Early onset of ageEarly onset of age

Tumor markersTumor markers• HER-2 is part of the epidermal growth HER-2 is part of the epidermal growth

factor receptor family and is becoming factor receptor family and is becoming an important marker in breast cancer.an important marker in breast cancer.

• The precence of HER-2 may suggest The precence of HER-2 may suggest agresive cancer.agresive cancer.

• Angiogenesis factors (such as vascular Angiogenesis factors (such as vascular endothelial growth factor)endothelial growth factor)

• P53 gene. P53 is a tumor suppessant P53 gene. P53 is a tumor suppessant gene.gene.

• CA 15-3, c-erb-B-2, cathepsin-D, CA 15-3, c-erb-B-2, cathepsin-D, telomerase, b-FGF, Ki-67… are others.telomerase, b-FGF, Ki-67… are others.

Rate of cell division. Mitotic index (MI) Rate of cell division. Mitotic index (MI) is a measurement of the rate at which is a measurement of the rate at which cells divide; the higher the MI, the more cells divide; the higher the MI, the more agresive the cancer.agresive the cancer.

StagingStaging Histopatologic types are as follows:Histopatologic types are as follows:

CarcinomaCarcinomaDuctalDuctal• İntraductal (in situ)İntraductal (in situ)• InvasiveInvasive

• ScirrhousScirrhous (adenoca. with productive fibrosis) (adenoca. with productive fibrosis)• MedullaryMedullary• Mucinous (colloid)Mucinous (colloid)• TubulerTubuler• PapillaryPapillary• InflammatoryInflammatory

LobularLobular• In situIn situ• InvasiveInvasive

NippleNipple• Paget’s diseasePaget’s disease

SarcomaSarcoma

Relaviley rare carcinomas Relaviley rare carcinomas

Infiltrating ductal Infiltrating ductal carcinoma with prodictive carcinoma with prodictive

fibrosis (scirrhous)fibrosis (scirrhous) The 80 percent frequency of The 80 percent frequency of

adenocarcinoma of the breast (ductal adenocarcinoma of the breast (ductal carcinoma)carcinoma)

The tumor characteristically possesses a The tumor characteristically possesses a poorly defined border, firm, immobile.poorly defined border, firm, immobile.

It’s cut surfaces show a central stellate It’s cut surfaces show a central stellate configuration with white or yellow streaks configuration with white or yellow streaks extending into surrounding breast tissues. extending into surrounding breast tissues.

Medullary carcinomaMedullary carcinoma 44%% Orginates in large ductusOrginates in large ductus Grossly, the tumor is characterised by its Grossly, the tumor is characterised by its

soft, hemorrhagic bulky presentationsoft, hemorrhagic bulky presentation Commonly, the lesion is positioned deep Commonly, the lesion is positioned deep

within the breast and mobile.within the breast and mobile. Diagnosis of this lesion connotes a better Diagnosis of this lesion connotes a better

5-year survival than pure invasive ductal 5-year survival than pure invasive ductal or lobular carcinomaor lobular carcinoma

Mucinous (colloid) carc.Mucinous (colloid) carc.

This adenocarcinoma of ductal origin This adenocarcinoma of ductal origin constitutes approximately 2constitutes approximately 2% % of all of all breast cancers and typically presents breast cancers and typically presents as a bulky, mucinous (colloid) tumor as a bulky, mucinous (colloid) tumor that is largely confined to the elderly that is largely confined to the elderly population.population.

5- year surv5- year surviival better than ductal and val better than ductal and lobular carcinomas (5-year survival lobular carcinomas (5-year survival rates is reported as about 73%)rates is reported as about 73%)

Tubuler carcinomaTubuler carcinoma

This lesion is a well-differantiated This lesion is a well-differantiated variant of breast carcinoma with an variant of breast carcinoma with an incidence of approximately 2 incidence of approximately 2 percent.percent.

Most commonly, is diagnosed in the Most commonly, is diagnosed in the perimenapousal or early menopausal perimenapousal or early menopausal population.population.

Long term survival is perfectLong term survival is perfect

Papillary carcinomaPapillary carcinoma Papillary cacinoma accounts for less Papillary cacinoma accounts for less

than 2 percent of all breast carcinomas than 2 percent of all breast carcinomas and generally presents in the 7. decade.and generally presents in the 7. decade.

Typically, papillary cancer is small and Typically, papillary cancer is small and rarely attains sizes greater than 2 to 3 rarely attains sizes greater than 2 to 3 cm in diameter.cm in diameter.

Papillary carcinoma is more indolent, Papillary carcinoma is more indolent, slowly progressive disease than the slowly progressive disease than the common adenocarcinomacommon adenocarcinoma

Best 5 and 10 year survival ratesBest 5 and 10 year survival rates

Lobular carcinomaLobular carcinoma These carcinomas originate in terminal ductules These carcinomas originate in terminal ductules

of the lobule and posses characteristic features of the lobule and posses characteristic features that distinguish them from lesions of the larger, that distinguish them from lesions of the larger, lactiferous ducts.lactiferous ducts.

The noninvasive form is lobular carcinoma in situ The noninvasive form is lobular carcinoma in situ (LCIS).(LCIS).

Constitutes approximately 10 percent of breast Constitutes approximately 10 percent of breast cancerscancers

At presentation, ILC varies from clinically At presentation, ILC varies from clinically unapparent cancers to those that replace entire unapparent cancers to those that replace entire breast with a poorly defined mass breast with a poorly defined mass

These lesions have a high propensity for These lesions have a high propensity for bilaterality, multicentrity and multifocality.bilaterality, multicentrity and multifocality.

Paget’s disease of the Paget’s disease of the nipplenipple

Approximately 2%Approximately 2% It is almost always associated with It is almost always associated with

an underlaying an underlaying extensive extensive intraductalintraductal (DCIS)(DCIS) or invasive carcinoma or invasive carcinoma

It presents as an encrusted, scaly, It presents as an encrusted, scaly, hyperemic, and enlarged tumor that hyperemic, and enlarged tumor that occupies the surface of the nipple-occupies the surface of the nipple-areola complexareola complex

Symptoms include tenderness, itching, Symptoms include tenderness, itching, burning, and intermittent hemorrhage.burning, and intermittent hemorrhage.

Intraductal adenocarcinomas often Intraductal adenocarcinomas often involve the epidermis of the nipple and involve the epidermis of the nipple and areola by intraepithelial dissemination.areola by intraepithelial dissemination.

Physical findings in the nipple-areola Physical findings in the nipple-areola complex precede the identification of a complex precede the identification of a palpabl mass in the subareolar area.palpabl mass in the subareolar area.

In general, better prognosis than the In general, better prognosis than the majority of lesions, because the nipp-majority of lesions, because the nipp-areol cahareol cahaanges promote early nges promote early consulatationconsulatation

Differantiation from pagetoid Differantiation from pagetoid intraepithelial melanoma is based on intraepithelial melanoma is based on S-100 antigen immunostaining in S-100 antigen immunostaining in melanoma and CEA immunostaining melanoma and CEA immunostaining in Paget’s disease.in Paget’s disease.

Surgical theraphy may involve Surgical theraphy may involve lumpectomy or MRM. lumpectomy or MRM.

SarcomasSarcomas

Rarely tumoursRarely tumours These tumors include fibromatosis, These tumors include fibromatosis,

fibrosarcoma, liposarcoma, fibrosarcoma, liposarcoma, leimyosarcoma, angiosarcoma…leimyosarcoma, angiosarcoma…

Inflammatory carcinomaInflammatory carcinoma 1.5 to 3%1.5 to 3% Clincal features of erythema, peau d’orange, and Clincal features of erythema, peau d’orange, and

skin ridging skin ridging (at least 50% of whole brast) (at least 50% of whole brast) with or with or without the presence of a palpabl mass are without the presence of a palpabl mass are evident.evident.

Typically the skin over the lesion is warm, Typically the skin over the lesion is warm, diffusely scaly, and indurated with ridgingdiffusely scaly, and indurated with ridging

It may present with the charecteristics of a It may present with the charecteristics of a cellulits.cellulits.

The tumor mass may be diffuse or nondefinableThe tumor mass may be diffuse or nondefinable Diagnosis is established by biosy of skin, Diagnosis is established by biosy of skin,

subcutaneous tissue, and parenchymasubcutaneous tissue, and parenchyma This disease progresses rapidly and prognosis is This disease progresses rapidly and prognosis is

poor.poor.

TNMTNM Tx Tx No evidence of primary tumor No evidence of primary tumor Tis Tis Carcinoma in situCarcinoma in situ T1 T1 Tumor 2cm or <Tumor 2cm or < T2T2 2 to 5 cm2 to 5 cm T3T3 T> 5cmT> 5cm T4aT4a extension to chest wallextension to chest wall T4b T4b edema (including peau d’orangeedema (including peau d’orange)),,

ulceration ulceration of skin,of skin, satellite satellite nodulesnodules

T4cT4c T4a + T4bT4a + T4b T4dT4d Inflammatory carcinomaInflammatory carcinoma

Peau d’orange:Peau d’orange: With progressive diffuse skin infiltration With progressive diffuse skin infiltration

in the subdermal in the subdermal lymphatic lymphatic plexusplexus.. TThere here is extensive edema of the skin, reffered to is extensive edema of the skin, reffered to as peau d’orange as peau d’orange

Skin retraction:Skin retraction: CCharacteristic involvement of Cooper’s haracteristic involvement of Cooper’s

ligamentsligaments

Regional lymh nodesRegional lymh nodes

N0N0 no regional lymh node met.no regional lymh node met. N1N1 Movable ipsilateral axillary l.nod.Movable ipsilateral axillary l.nod. N2N2 Fixed ipsilateral axillary lymph n.Fixed ipsilateral axillary lymph n. or or

İnternal mammary lymh nodesİnternal mammary lymh nodes N3N3 --İpsilateral supraclavicular l.n.İpsilateral supraclavicular l.n.

--Fixed ipsilateral axillary lymph n.Fixed ipsilateral axillary lymph n. and and İnternal mammary lymh nodesİnternal mammary lymh nodes

--İpsilateral İpsilateral infrainfraclavicular l.n.clavicular l.n.

Pathologic Pathologic classification (pN)classification (pN)

pNX: Regional lymph nodes cannot be assessed (e.g., not removed for pathologic study or pNX: Regional lymph nodes cannot be assessed (e.g., not removed for pathologic study or previously removed) previously removed)

pN0: No regional lymph node metastasis histologically, and no additional examination for pN0: No regional lymph node metastasis histologically, and no additional examination for isolated tumor cells (ITC) isolated tumor cells (ITC)   [Note: ITCs are defined as single tumor cells or small cell clusters not larger than 0.2 mm, [Note: ITCs are defined as single tumor cells or small cell clusters not larger than 0.2 mm, usually detected only by immunohistochemical (IHC) or molecular methods but that may be usually detected only by immunohistochemical (IHC) or molecular methods but that may be verified on hematoloxylin & eosin (H&E) stains. ITCs do not usually show evidence of verified on hematoloxylin & eosin (H&E) stains. ITCs do not usually show evidence of malignant activity, e.g., proliferation or stromal reaction.]malignant activity, e.g., proliferation or stromal reaction.]

pN0(I-): No regional lymph node metastasis histologically, negative IHCpN0(I-): No regional lymph node metastasis histologically, negative IHC

pN0(I+): No regional lymph node metastasis histologically, positive IHC, and no IHC cluster pN0(I+): No regional lymph node metastasis histologically, positive IHC, and no IHC cluster larger than 0.2 mmlarger than 0.2 mm

pN0(mol-): No regional lymph node metastasis histologically, and negative molecular pN0(mol-): No regional lymph node metastasis histologically, and negative molecular findings (RT-PCR)*findings (RT-PCR)*

pN0(mol+): No regionally lymph node metastasis histologically, and positive molecular pN0(mol+): No regionally lymph node metastasis histologically, and positive molecular findings (RT-PCR)* findings (RT-PCR)*

* [Note: RT-PCR: reverse transcriptase-polymerase chain reaction.]* [Note: RT-PCR: reverse transcriptase-polymerase chain reaction.]

pN1: Metastasis in 1-3 axillary lymph nodes, and/or in internal mammary pN1: Metastasis in 1-3 axillary lymph nodes, and/or in internal mammary nodes with microscopic disease detected by SLN dissection but not nodes with microscopic disease detected by SLN dissection but not clinically apparent**clinically apparent**

pN1mi: Micrometastasis (larger than 0.2 mm but not larger than 2.0 mm)pN1mi: Micrometastasis (larger than 0.2 mm but not larger than 2.0 mm)

pN1a: Metastasis in one to three axillary lymph nodes pN1a: Metastasis in one to three axillary lymph nodes

pN1b: Metastasis in internal mammary nodes with microscopic disease detected pN1b: Metastasis in internal mammary nodes with microscopic disease detected by SLN dissection but not clinically apparent** by SLN dissection but not clinically apparent**

pN1c: Metastasis in one to three axillary lymph nodes and in internal mammary pN1c: Metastasis in one to three axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by SLN dissection but not lymph nodes with microscopic disease detected by SLN dissection but not clinically apparent.** (If associated with more than three positive axillary lymph clinically apparent.** (If associated with more than three positive axillary lymph nodes, the internal mammary nodes are classified as pN3b to reflect increased nodes, the internal mammary nodes are classified as pN3b to reflect increased tumor burden.)tumor burden.)

pN2: Metastasis in 4-9 axillary lymph nodes, or pN2: Metastasis in 4-9 axillary lymph nodes, or in clinically apparent ** internal mammary lymph in clinically apparent ** internal mammary lymph nodes in the nodes in the absenceabsence of axillary lymph node of axillary lymph node metastasis to ipsilateral axillary lymph node(s) metastasis to ipsilateral axillary lymph node(s) fixed to each other or to other structures fixed to each other or to other structures

pN2a: Metastasis in four to nine axillary lymph nodes pN2a: Metastasis in four to nine axillary lymph nodes (at least one tumor deposit larger than 2.0 mm)(at least one tumor deposit larger than 2.0 mm)

pN2b: Metastasis in clinically apparent* internal pN2b: Metastasis in clinically apparent* internal mammary lymph nodes in the mammary lymph nodes in the absenceabsence of axillary lymph of axillary lymph node metastasisnode metastasis

pN3: Metastasis in 10 or more axillary lymph nodes, or in pN3: Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in clinically apparent* ipsilateral infraclavicular lymph nodes, or in clinically apparent* ipsilateral internal mammary lymph node(s) in the internal mammary lymph node(s) in the presencepresence of 1 or more positive of 1 or more positive axillary lymph node(s); or, in more than three axillary lymph nodes axillary lymph node(s); or, in more than three axillary lymph nodes with clinically negative microscopic metastasis in internal mammary with clinically negative microscopic metastasis in internal mammary lymph nodes; or, in ipsilateral supraclavicular lymph nodes lymph nodes; or, in ipsilateral supraclavicular lymph nodes

pN3a: Metastasis in 10 or more axillary lymph nodes (at least 1 tumor pN3a: Metastasis in 10 or more axillary lymph nodes (at least 1 tumor deposit larger than 2.0 mm); or, metastasis to the infraclavicular lymph deposit larger than 2.0 mm); or, metastasis to the infraclavicular lymph nodesnodes

pN3b: Metastasis in clinically apparent* ipsilateral internal mammary pN3b: Metastasis in clinically apparent* ipsilateral internal mammary lymph nodes in the lymph nodes in the presencepresence of one or more positive axillary lymph of one or more positive axillary lymph node(s); or, in more than three axillary lymph nodes and in internal node(s); or, in more than three axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent**lymph node dissection but not clinically apparent**

pN3c: Metastasis in ipsilateral supraclavicular lymph nodespN3c: Metastasis in ipsilateral supraclavicular lymph nodes

Distant metastasisDistant metastasis

M0M0 M1M1

TreatmentTreatment

Surgery, radiation or drug theraphy.Surgery, radiation or drug theraphy. Breast cancer treatment are defined Breast cancer treatment are defined

as local or systemicas local or systemic Local: Surgery and radiation.Local: Surgery and radiation.

• Surgery is usually the standart initial Surgery is usually the standart initial treatmenttreatment

Systemic: Drug treatmentSystemic: Drug treatment

Stage 0Stage 0

Also called noninvasive carcinoma or Also called noninvasive carcinoma or carcinoma in situ.carcinoma in situ. Lobular carcinoma in situLobular carcinoma in situ• Careful monitoring with or without Careful monitoring with or without

preventive use of tamoxifenpreventive use of tamoxifen• In selected cases, consideration of In selected cases, consideration of

removal of both breastsremoval of both breasts

Ductal carcinoma in situDuctal carcinoma in situ• Mastectomy (previously was the commonly Mastectomy (previously was the commonly

recommended treatment)recommended treatment)• Breast-sparing surgery followed by Breast-sparing surgery followed by

radiotheraphy is reasonable treatment for radiotheraphy is reasonable treatment for many womenmany women

• Use of tamoxifen or other SERMs after Use of tamoxifen or other SERMs after surgery and radiation to prevent recurrence surgery and radiation to prevent recurrence in selected patientsin selected patients

Stage I and IIStage I and II

Breast sparing surgery Breast sparing surgery (lumpectomy, quadranectomy…) (lumpectomy, quadranectomy…) followed by external beam radiation followed by external beam radiation theraphytheraphy

Modified radical mastectomyModified radical mastectomy Adjuvant theraphyAdjuvant theraphy

Combination chemotheraphyCombination chemotheraphy Hormonal theraphyHormonal theraphy

StageIIIStageIII

Mastectomy usually with Mastectomy usually with radiotheraphy and systemic radiotheraphy and systemic treatment (combination treatment (combination chemotheraphy, hormonal theraphy chemotheraphy, hormonal theraphy or both)or both)

Neoadjuvat chemotheraphy followed Neoadjuvat chemotheraphy followed by surgery + adjuvant by surgery + adjuvant chemotheraphy is recommended.chemotheraphy is recommended.

Five-year survival rates for individuals Five-year survival rates for individuals with breast cancer who receive with breast cancer who receive appropriate treatment are approximately: appropriate treatment are approximately:

100% for stage 0 100% for stage 0 100% for stage I 100% for stage I 92% for stage IIA92% for stage IIA 81% for stage IIB 81% for stage IIB 67% for stage IIIA67% for stage IIIA 54% for stage IIIB 54% for stage IIIB 20% for stage IV20% for stage IV