� 葉葉葉葉*賢賢賢賢, 58y/o, female

� Time of admission:97/05/26

� Source of admission: OPD

� Occpation: housewife

� Residence: Kaoshoung

Basic Data

Chief complaint

� an ill-defined mass in right upper quadrant breast

Present illness

� 96-01She first found right breast mass with mild yellow nipple discharge

� 96-07She didn’t go to see the doctor until last July because of increasing nipple discharge

� The patient visited LMD � excision was done, pathology report

revealed benign

Present illness

� A new palpable solid mass was noted in the right breast since last winter

� 長庚 Hospital (97-年初)� Mammogram

� suspected malignancy breast tumor

� 97-05-22 she visited Dr.吳’s OPD for second opinion

� nipple discharge(+),

skin eczema change(-)

tenderness(-), local heat(-)

Skin dimping (-), Nipple retraction (-)

Peau d'orange (-)

Present illness

� Dr.吳's OPD (97-05-22):

� PE:

� R't side breast mass with tenderness

� ill-defined, hard

� in upper outer quadrant

(9 o'clock, 2cm from areola)

� measured about 3cm x 2.5cm

Present illness

� Dr.吳's OPD (97-05-22):

� core needle biopsy :

� (97-05-24) Pathological proved of

infiltrating ductal carcinoma

at Rt breast

� Breast MRI with contrast

Personal History

� contraceptives use : (-)

� Late parity : (-)

� Menopause : 55 y/o

� Drug allergy：denied

� Food allergy：denied

� Smoking：denied

� Alcohol：denied

� Usual medication: nil

� Betel nut chewing：denied

� Social activity：active

� Life style：normal

Family History

� Breast ca(-), colon ca(-), ovarian ca(-)

� Lung cancer(+): her father

past History

� Medical history：Nil

� Surgical history：Nil

PE

� 90 Kg, 162 cm� Vital Signs：stable� clear consciousness, oriented, well-looking� HEENT: grossly normal, pink conjunctiva,

anicteric sclera� Chest: symmetrical expansion,

clear breathing sound� Heart: regular heart beat,

without murmur

PE

� Breast:

� Palpable Mass(+): 3*2.5*2 cm, hard, irregular surface, at right breast, (4cm from areola)

� nipple discharge(+), bloody discharge(-)

� Nipple retraction (-)

� tenderness(-)

� local heat(-)

� skin erythema(-),skin edema(-), nipple eczema(-), Skin dimping (-), Peau d'orange (-)

� Axillary LN (+/-)

PE

� Abdomen:

� soft and flat, OP scar(-)

� bowel sound：normoactive(+)

� RUQ pain(-), Murphy sign(-)

� palpable mass(-), tenderness(-)

� rebounding pain(-), shifting dullness(-)

� Back: knocking tenderness (-)

� Extremities: pitting edema(-)

取樣日期取樣日期取樣日期取樣日期 970527 970619

取樣時間 0955 1338

HBsAg results(0.0-2.0 S/N)

0.5 COI [0.0-1.0]

HBsAg (血液) Negative

Anti-HCV results[0-1.0 S/CO]

0.28 S/CO [0.00-1.00]

Anti-HCV (血液) Negative

CEA (血液) [<4.6 ng/ml] 1.24 ng/ml [<3.40]

CA125 (血液) [<35 U/ml]

8.34 U/ml [<35.00]

取樣日期取樣日期取樣日期取樣日期 970526

取樣時間 1109

Glucose(血液)1 [70-110 mg/dl]

106 mg/dl [55-110]

BUN (血液) [7-18 mg/dl] 15.3 mg/dl [6.0-20.0]

Creatinine(血)[0.5-1.3 mg/dl]

0.4 mg/dl [0.5-1.2]

GOT(血液) [0-40 IU/L] 21 IU/L [<37]

GPT (血液) [0-40 IU/L] 20 IU/L [<41]

Bilirubin T(血)[0.2-1.2 mg/dl]

Na (血液)[135-148 mEq/L]

139 mEq/L [136-145]

K (血液)[3.5-5.3 mEq/L] 3.6 mEq/L [3.5-5.1]

Cl (血液)[98-108 meq/L] 104 mEq/L [98-107]

取樣日期取樣日期取樣日期取樣日期 970526 970526

取樣時間 1109 1109

確認日期 970526 970526

確認時間 1156 1144

WBC [4.0-11.0 x10.e3/uL]

11.49 10^3/uL [4.00-11.00]

RBC [4.2-6.1 x10.e6/uL]

4.49 10^6/uL [4.20-6.10]

HGB [12-18 g/dL] 13.0 g/dL [12.0-

18.0]

HCT [37-52 %] 37.3 % [37.0-52.0]

MCV [80-99 fL] 83.1 fL [80.0-99.0]

MCH [26-34 pg] 29.0 pg [26.0-

34.0]

MCHC [31-37 g/dL]

34.9 g/dL [33.0-37.0]

RDW [11.5-14.5 %]

13.1 % [11.5-14.5]

PLT [130-400 x10.e3/uL]

274 x10^3 /uL [130-400]

MPV [7.2-11.1 fL] 10.00 fL [7.20-

11.10]

RDW-SD 39.3 fL

PDW 11.4 fL

%NEUT [40-74 %] 69.2 % [40.0-74.0]

%LYM [19-48 %] 25.9 % [19.0-48.0]

%MONO [2.0-10.0 %]

3.2 % [2.0-10.0]

%EOS [0-7 %] 1.4 % [0.0-7.0]

%BASO [0-1.5 %] 0.3 % [0.0-1.5]

Blood grouping (血液)

O

Rh type (血液) Positive

Bleeding time(血)

Mammography in 長庚 Hospital

R’t side breast outer quadrant ill-defined hyperdensity lesion about 3cmx2cm

Mammography in 長庚 Hospital

Breast Imaging Reporting And Data System (BIRADS): category V

97-05-22 Breast MRI(R’t breast)

Early phase subtraction

remarkable ill-defined heterogenous mass with high and iso-hyperintense mass(3.45x2.45x1.51cm) noted at lateral (9 'o'clock from nipple) of Rt breast

� There are two individual hyperintense spots noted inside the lesion, at Rt lateral aspect

Late phase subtraction

� Rapid of initial rise and wash out of delayed phases

� Highly suspect malignancy

� Non specific LN with preserved of hilar fat

97-05-26 Breast echo

97-05-26 Breast echo

(9,4), irregular heterogenous hypoechoic mass 32.0mmx19.0mmx32.3mm (BIRADS V)

Operation note

� OP date : 97-5-27

� OP method :

� R’t side Modified radical Mastectomy

� OP finding :

� Ill-defined hard mass

� LN(+)

� Clinical: T2N0M0 (IIA)

� Surgical: T2N1M0 (IIB)

Pathology 97-06-02

� Pathologic Staging (pTNM)

� Primary Tumor (pT): pT2: Tumor more than 2.0 cm but not more than 5.0 cm in greatest dimension

� Regional Lymph Nodes (pN): pN0: No regional lymph node metastasis histologically) (Specify: Number examined: 18 ; Number involved: 0 )

� Distant Metastasis (pM): pMX: Cannot be assessed

� Stage Groupings Stage IIA : p T2 pN0 MX

� Estrogen receptor (+)

� Progesterone receptor (+)

� HER-2/neu (-)

Clinical course

� 97-年初 長庚長庚長庚長庚HospitalMammography revealed malignancy

� 97-05-22 OPDcore needle biopsy, breast MRI

� 97-05-24 Pathological proved of invasive ductal carcinoma at Rt breast

� 97-05-26 admission, sono, CXR

� 97-05-27 operation (R’t side Modified radical Mastectomy)

� 97-06-02 Pathological proved of No regional lymph nodemetastasis

Differential & Diagnosis

� Fibrocystic change

� Fibroadenoma

� Phyllodes tumor(=Cystosarcoma phyllodes)

� Intraductal papilloma

Fibrocystic change

� Etiology

� more than 50 percent of women of reproductive age have fibrocystic changes

� imbalance between estrogen and progesterone

� Symptoms

� painful breast tissue before menses

� report improvement during menstruation

� Clinical

� fibrotic tissue may be palpated and is generally found in the upper outer quadrants of the breast

� cysts are more frequent in women in their 30s and 40s

� A nonbloody, green or brown nipple discharge may be present

Fibroadenoma(juvenile fibroadenomas)

� Etiology

� most common breast lesion in adolescents ( 20-25 y/o)

� Symptoms

� typically asymptomatic

� may cause discomfort for a few days before the onset of menses

� Clinical

� PE: rubbery, well circumscribed, and mobile

� average size is 2 to 3 cm (range 1 to 10 cm)

� most frequently found in the upper, outer quadrants

� recurrent or multiple in 10 to 25 percent of cases

� Ultrasonographic : reveals a solid avascular mass that is well circumscribed.

� Mammography is not indicated : because the large amount of glandular tissue present in adolescents

Fibroadenoma(juvenile fibroadenomas)

� All presumed fibroadenomas <5 cm can be safely observed with serial examinations.

� Most fibroadenomas decrease in size and some completely disappear with time

� Giant fibroadenoma

� Giant fibroadenomas grow rapidly to greater than 5 cm

� may compress or replace normal breast tissue

� Giant fibroadenomas should be excised because they cannot be easily distinguished from phyllodes tumors by physical examination, ultrasonography, or mammography

Phyllodes tumor

� Etiology

� rare primary tumor that typically occurs in older women(42 to 45)

� girls as young as 10 years of age

� Symptoms

� with a large breast mass that is usually painless

� skin may be shiny and stretched from rapid growth

� A bloody discharge may be present

� Clinical

� Ultrasonographic findings : suggest phyllodes tumors that include lobulations, a heterogeneous echo pattern, and an absence of microcalcifications

Phyllodes tumor

� most are benign(80~90%), but still have chance to be malignancy

� recommended treatment is excision

� criteria used for classification of benign versus malignant tumors

� The degree of stromal cellular atypia

� Mitotic activity (mitotic figure > 3/10 HPF )

� Infiltrative as compared to circumscribed tumor margins

� Presence or absence of stromal overgrowth (ie, presence of pure stroma devoid of epithelium)

Intraductal papilloma� Etiology

� rare benign breast tumor (1.2%)

� arising from proliferation of mammary duct epithelium

� typically presents in women between 20~40 y/o

� Symptoms

� clinical presentation : bloody nipple discharge, breast enlargement.

� bilateral in approximately one-fourth of patients

� Clinical

� PE: well-circumscribed nodules may be palpated under the areola or in the ducts at the periphery of the breast

� Cytology of the nipple discharge : demonstrates ductal cells, which differentiates it from fibrocystic disease

� Excision may be indicated to confirm the diagnosis and is curative

Final diagnosis

� PE

� Mammography

� core needle biopsy

� MR Image

� Sono

� Invasive ductal carcinoma

Discussion

Clinical

� Malignant masses

� Hard

� Painless : Malignant masses are painful in only 10-15% of patients.

� Irregular

� Possibly fixed to the skin or chest wall

� Skin dimpling

� Nipple retraction

� Bloody discharge

Risk factor

� Factors with relative risk greater than 4 � Advanced age

� Being born in North America or northern Europe

� High premenopausal blood insulinlike growth factor (IGF)–1 level

� High postmenopausal blood estrogen level

� History of mother and a sister with breast cancer

� Factors associated with a relative risk of 2-4 � High socioeconomic status

� Age at first full-term pregnancy older than 30 years

� History of cancer in one breast

� Any first-degree relative with a history of breast cancer

� History of a benign proliferative lesion, dysplastic mammographic changes, and a high dose of ionizing radiation to the chest

Risk factor

� Factors associated with a relative risk of 1.1-1.9 � Nulliparity

� Early menarche (age <11 y)

� Late menopause (age >55 y)

� Postmenopausal obesity

� High-fat diet/saturated fat–rich diet

� Residence in urban areas and northern United States

� White race - Older than 45 years

� Black race - Younger than 45 years

� History of endometrial or ovarian cancer

� Identified factors with a protective role against breast cancer

� Age at first period older than 15 years

� Breastfeeding for longer than 1 year

� Monounsaturated fat–rich diet

� Physical activity

� Premenopausal obesity

� breast cancer

Image study

� Ultrasonography� Mammography

� Screening mammography� Diagnostic mammography

� Computed tomography (CT scan)� Magnetic resonance imaging (MRI)� Positron emission tomography (PET scan)

� Others

Breast Imaging Reporting and Data System (BIRADS): Final Assessment Category

Category Definition

0 Incomplete assessment; need additional imaging evaluation

I Negative; routine mammography in 1 year recommended

II Benign finding; routine mammography in 1 year

recommended

III Probably benign finding; short-term follow up suggested

IV Suspicious abnormality; biopsy should be considered

V Highly suggestive of malignancy; appropriate action should

be taken

Diagnostic Procedures

� Fine-needle aspiration cytology

� Core needle biopsy

� Mammotome biopsy

� Open biopsy

� Excisional biopsy

� Incisional biopsy

� Wire/needle localization biopsy

Histologic Findings

� Ductal � Intraductal (in situ)

� Invasive with predominant intraductal component: Infiltrating or invasive ductal cancer is the most common breast cancer histologic type, comprising 70-80% of all cases

� Invasive, not otherwise specified

� Scirrhous

� Tubular

� Medullary with lymphocytic infiltrate

� Mucinous (colloid)

� Papillary

� Inflammatory

� Comedo

� Other

Histologic Findings

� Lobular � In situ

� Invasive with predominant in situ component

� Invasive

� Nipple � Paget disease, not otherwise specified

� Paget disease with intraductal carcinoma

� Paget disease with invasive ductal carcinoma

� Undifferentiated carcinoma

� Rare tumor subtypes� Cystosarcoma phyllodes

� Angiosarcoma

� Primary lymphoma

Staging of Breast CancerTNM definitions

� Primary tumor

� TX - Cannot be assessed

� T0 - No evidence of primary tumor

� Tis - Carcinoma in situ, intraductal carcinoma, LCIS, or Paget disease of the nipple with no associated tumor (Note: Paget disease associated with a tumor is classified according to the size of the tumor.)

� T1 - Tumor 2 cm or smaller in greatest dimension

� T1mic - Microinvasion 0.1 cm or less in greatest dimension

� T1a - Tumor larger than 0.1 cm but not larger than 0.5 cm in greatest dimension

� T1b - Tumor larger than 0.5 cm but not larger than 1 cm in greatest dimension

� T1c - Tumor larger than 1 cm but not larger than 2 cm in greatest dimension

� T2 - Tumor larger than 2 cm but not larger than 5 cm in greatest dimension

� T3 - Tumor larger than 5 cm in greatest dimension

� T4 - Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below (Note: Chest wall includes ribs, intercostal muscles, and serratus anterior muscle, but not pectoral muscle.)

� T4a - Extension to chest wall

� T4b - Edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast

� T4c - Both of the above (T4a and T4b)

� T4d - Inflammatory carcinoma (Note: Inflammatory carcinoma is a clinicopathologic entity characterized by diffuse brawny induration of the skin of the breast with an erysipeloid edge, usually without an underlying palpable mass. Radiologically, a detectable mass and characteristic thickening of the skin may be present over the breast. This clinical presentation is due to tumor embolization of dermal lymphatics with engorgement of superficial capillaries.)

� Regional lymph nodes

� NX - Cannot be assessed (eg, previously removed)

� N0 - No regional lymph node metastasis

� N1 - Metastasis to movable ipsilateral axillary lymph node(s)

� N2 - Metastasis to ipsilateral axillary lymph node(s) fixed to each other or to other structures

� N3 - Metastasis to ipsilateral internal mammary lymph node(s)

� Pathologic classification

� pNX - Regional lymph nodes cannot be assessed (eg, not removed for pathologic study or removed previously)

� pN0 - No regional lymph node metastasis

� pN1 - Metastasis to movable ipsilateral axillary lymph node(s)

� pN1a - Only micrometastasis (none >0.2 cm)

� pN1b - Metastasis to lymph node(s), any larger than 0.2 cm

� pN1bi - Metastasis in 1-3 lymph nodes, any larger than 0.2 cm and all smaller than 2 cm in greatest dimension

� pN1bii - Metastasis to 4 or more lymph nodes, any larger than 0.2 cm and all smaller than 2 cm in greatest dimension

� pN1biii - Extension of tumor beyond the capsule of a lymph node metastasis, smaller than 2 cm in greatest dimension

� pN1biv - Metastasis to a lymph node 2 cm or larger in greatest dimension

� pN2 - Metastasis to ipsilateral axillary lymph node(s) fixed to each other or to other structures

� pN3 - Metastasis to ipsilateral internal mammary lymph node(s)

� Distant metastasis

� MX - Cannot be assessed

� M0 - No distant metastasis

� M1 - Distant metastasis present (includes metastasis to ipsilateral supraclavicular lymph nodes)

Stage 0 Tis N0 M0

Stage I T1* N0 M0

Stage IIA T0 N1 M0

T1* N1 M0

T2 N0 M0

Stage IIB T2 N1 M0

T3 N0 M0

Stage IIIA T0 N2 M0

T1* N2 M0

T2 N2 M0

T3 N1 M0

T3 N2 M0

Stage IIIB T4 N0 M0

T4 N1 M0

T4 N2 M0

Stage IIIC Any T N3 M0

Stage IV Any T Any N M1

Treatment

� Surgical Treatment for Breast Cancer

� Radical Mastectomy

� Modern Mastectomy

� Wide Local Excision and Primary Radiation Therapy (Conservative Breast Surgery)

� Sentinel Lymph Node Biopsy

� Total or simple mastectomy� Skin-sparing mastectomy

� Modified radical mastectomy

� Breast-conserving treatment (BCT)� Wide local excision

� Postsurgical radiation therapy

� Axillary nodes dissection

� Radiotherapy

� Adjuvant chemotherapy

� Adjuvant hormonal therapy

� Hormonal therapy

� Postmastectomy radiotherapy

Prognosis� The prognosis depending on the number of axillary

lymph nodes involved in patients who received adjuvant chemotherapy is as follows:

� With 0 positive nodes � Recurrence rate at 5 years - Approximately 20%

� Survival rate at 10 years - 65-80%

� With 1-3 positive nodes � Recurrence rate at 5 years - 30-40%

� Survival rate at 10 years - 35-65%

� With 4 positive nodes � Recurrence rate at 5 years - Approximately 44%

� Survival rate at 10 years - Not available

� With more than 4 positive nodes � Recurrence rate at 5 years - 54-82%

� Survival rate at 10 years - 13-24%

Prognosis

� tumor size is highly correlated with lymph node involvement and clinical outcome� Tumor smaller than 0.5 cm - Approximately 20%

� Tumor 0.5-0.9 cm - Approximately 20%

� Tumor 1-1.9 cm - 33%

� Tumor 2-2.9 cm - 45%

� Tumor 3-3.9 cm - 52%

� Tumor 4-4.9 cm - 60%

� Tumor larger than 5 cm - 70%

Prognosis� The 5-year survival rate based on tumor size and axillary

lymph node status is as follows

� Tumor smaller than 2 cm � Negative nodes - 96%

� One to 3 positive nodes - 87%

� Four or more positive nodes - 66%

� Tumor 2-5 cm � Negative nodes - 89%

� One to 3 positive nodes - 79%

� Four or more positive nodes - 58%

� Tumor larger than 5 cm � Negative nodes - 82%

� One to 3 positive nodes - 73%

� Four or more positive nodes - 45%

Prognosis� Cancers overexpressing HER2/neu are frequently poorly

differentiated and lymph node–positive

� HER2/neu overexpression correlates with more aggressive behavior and shortened disease-free survivaland overall survival rates

� EGF receptor familyOverexpression of the EGF receptor family is inversely correlated with ER positivity and is usually associated with a poor prognosis

� S-phaseA high S-phase indicates a rapid proliferation rate and is associated with a worse prognosis.

� DNA ploidy diploid tumors are usually associated with a good prognosis