Diseases of the Breast

Breast Anatomy
GLAND
10 20 Ducts Duct Drains Lobe Lobe Contains 20 40 Lobules Lobule Contains 10 100 Alveoli

Breast Anatomy

Breast Anatomy
A pectoralis major muscle B axillary lymph nodes: levels I C axillary lymph nodes: levels II D axillary lymph nodes: levels III E supraclavicular lymph nodes F internal mammary lymph nodes

Signs and Symptoms

Signs and Symptoms

Peau DOrange

Breast Disease
Nipple Discharge

Benign Malignant

88% 12%

Nipple Discharge

1. 2. 3.

Galactorrhea Intraductal papilloma Duct ectasia

4. Carcinoma

Breast Disease
IMAGING MAMMOGRAPHY ULTRASOUND MRI

ACS Screening Guidelines: Average Risk

Annual mammography age 40 and older
Reduction in mortality by 30-50%

Annual BE age 40 and older

Q 3 years age 20-40

Self breast exam (SBE) yearly after age 20

ACS Screening Guidelines

Annual mammography earlier if mother or sister diagnosed with breast cancer (10 years prior to age of relatives diagnosis) MRI if at high risk for breast cancer

Breast Ultrasound: Indications and Imaging Role

Mammographically detected masses

Palpable masses after mammography

Initial study for palpable masses
Pregnant Lactating Less than age 30

Cystic versus solid Solid masses: benign versus malignant features

Ultrasound Appearance Breast Masses

Simple Cyst

Solid

Complex

Diagnostic Accuracy of Screening Mammography

Sensitivity in women > 50 y.o.

98% fatty breast 84% dense breasts
Specificity

82-98%

LIMITATIONS OF MAMMOGRAPHY
As many as 5 15% of breast cancers are
not detected mammographically A negative mammogram should not deter work-up of a clinically suspicious abnormality

Carcinoma

Microcalcifications

Detection of Malignant Masses

Malignant masses have a more spiculated
appearance

benign malignant

21

Breast Mass Presumed Benign

Needle Aspirations

Non bloody fluid, mass disappears

Bloody fluid, no fluid or incomplete disappearance of mass

Observe X 1 mo

Excisional biopsy

Mass recurrence

No recurrence

Cancer

Benign

Biopsy

Follow

Treatment

Follow

Stereotactic Core Needle Biopsy

Stereotactic Biopsy: Specimen Radiograph

Image Guided Core Needle Biopsy

Percutaneous, minimally invasive procedure Mammography, ultrasound or MRI guided Accurate, fast and well tolerated outpatient procedure Avoids open surgical biopsy for benign lesions

Decreases number of surgeries in patients with

malignant lesions Cost-effective alternative to surgery

Ultrasound Guided Core Needle Biopsy

Image Guided Core Needle Biopsy

Open Surgical Biopsy

Image-Guided Biopsy

Screening Breast MRI

Important new tool for detection of otherwise-occult breast carcinoma High sensitivity

ACS Recommendations for MRI: Moderate Risk

High risk biopsy: ADH, ALH, LCIS Heterogeneously or extremely dense breasts on mammogram Personal history of breast cancer BRCA mutation First-degree relative of BRCA carrier

Clinical Indications for Breast MRI

Patients with newly diagnosed breast cancer
Extent of disease in breast with known cancer
Additional unsuspected disease in approximately 16%

Contralateral breast screening for occult disease

Unsuspected synchronous cancer in approx. 4-5%

Locally advanced breast cancer treated with neoadjuvant chemotherapy

Evaluation of treatment response

Other Clinical Indications for Breast MRI

Axillary metastatic adenopathy, unknown primary
Primary in the breast detected in approximately 60%

Implant evaluation

Non-Cancerous Conditions
Fibrocystic changes: Lumpiness, thickening and swelling, often associated with a womans period Cysts: Fluid-filled lumps can range from very tiny to about the size of an egg

Fibroadenomas: A solid, round, rubbery lump that moves

under skin when touched, occurring most in young women Infections: The breast will likely be red, warm, tender and lumpy

FIBROCYSTIC CHANGES

Manifestations: 1. Unilateral / Bilateral 2. Rubbery in consistency, not encapsulated 3. Size changes / can be tender ---> related to menstrual cycle 4. 15% presents as nipple discharge

Fibrosystic Changes
TREATMENT

Avoid Caffeine Avoid Nicotine Vitamin E

Fibroadenoma
Age 20 49 yrs Firm, Painless

Bilateral 15 25%
DX: FNA TX: Observe, Excise

Phyllodes Tumor

Age: 30 55 yrs Slow Growing Bulk of tumor is connective tissue Similar to fibroadenoma but with higher mitoses 10% Sarcoma DX: FNA TX: Excision
Cystosarcoma Phyllodes

Intraductal Papilloma

Age: 45 50 yrs

Proliferation of the ductal

epithelium Bloody Discharge

Unilateral, small
TX: Excision

Ductal Ectasia
Age: Perimenopausal
Bilateral

Sticky, Thick, Green Discharge

DX: Exam

TX: ABX, Excision

Breast Cancer
One out of every seven women will be diagnosed with breast cancer Breast cancer is second only to lung cancer as a cause of cancer deaths in American women

41

Established Risk factors For Breast Cancer in Females:

Risk factor
Age Socioeconomic status
Place of residence
Race > 45 years < 40 years Nulliparity

High risk
old high
urban
white black yes

Low risk
young low
rural
black white

Relative risk
>4.0 2.0 4.0
1.1 1.9
1.1 1.9 1.1 1.9 1.1 1.9

Age of first full-term pregnancy

Age at menopause Age at menarche

> 30 y/o
late early

< 20 y/o
early late

2.0 4.0
1.1 1.9 1.1 - 1.9

Weight, postmenopausal women Hx of benign or cancer in one breast

heavy yes

thin

1.1 1.9 2.0 4.0

Hx of breast Ca 1st degree relative

Mother or sister w/ hx. Of breast CA Hx. Of primary ovarian or endometrial CA Mammographic parenchymal patterns Radiation to chest

yes
yes yes Dysplastic parenchyma yes Normal parenchyma

2.0 4.0
> 4.0 1.1 9.0 2.0 4.0 2.0 4.0

Breast Cancer Location

Presentation of Breast Cancer (744 Patients)

45
Illustration Mary K. Bryson

Histological Classification of Breast Cancer

Cancers of the Mammary Gland can be Classified:
1. 2. 3. 4. Histogenesis duct, lobule (acini) Histologic Characteristic adenocarcinoma, epidermoid CA, etc. Gross Characteristic Scirrhous, colloid, medullary, papillary, tubular Invasive Criteria Infiltrating, in-situ

Non-infiltrating (In-situ) Carcinoma of duct and lobules:

Increase in diagnosis likely due to mammography DCIS : LCIS (3:1)

1.

LOBULAR CARCINOMA in SITU:

Considered as a risk factor Observed only in females, premenopousal No involvement of the basement membrane Tx: 1. Close observation 2. Hormonal treatment (Tamoxifen/aromatase inhibitor) for 5 years 3. Surgery (bilateral mastectomy) w/ immediate reconstruction

Histological Classification of Breast Cancer

Non-infiltrating (In-situ) Carcinoma of duct and lobules:
2.

Ductal Carcinoma In Situ:

Absence of invasion of surrounding stroma, hence confined w/in the basement membrane Types:

1.
2. 3. 4. 5.

PAPILLARY
MICRO-PAPILLARY SOLID CRIBRIFORM COMEDOCARCINOMA Hyperplasia is more extreme choking the entire duct w/ masses of cells developing central necrosis of cells Most aggressive treated as an early cancer

Treatment:

Ductal Carcinoma in situ (DCIS)

48

Histological Classification of Breast Cancer

Non-infiltrating (In-situ) Carcinoma of duct and lobules:

LCIS
Age Incidence Clinical Signs Mammographic signs Incidence of Synchronous Invasive CA Multicentricity Bilaterality Subsequent carcinomas: Incidence Laterality Interval to diagnosis Histology
5% 60 90% 50 70% 25 35% Bilateral 15 20 yrs ductal 44 - 47 2 - 5% None

DCIS
54 58 5 - 10% Mass, Pain, Nipple discharge Microcalcification 2 46% 40 80% 10 20% 25 70% Ipsilateral 5 10 yrs ductal

Invasive Ductal Carcinoma (IDC 80% of breast cancer)

50

Invasive Lobular Carcinoma

Infiltrating Carcinomas of the Breast

1. Pagets disease of the nipple (1%):

Primary carcinoma of mammary duct that invaded the skin

Chronic eczematoid lesion of the nipple

Tenderness, itching, burning and intermittent bleeding Palpable mass in the sub-areolar area PAGET cells: Large cell w/ clear cytoplasm and bi-nucleated 100% 5yr survival

Histological Classification of Breast Cancer

2.

Scirrhous carcinoma: (sclerosing CA):

78% (most common) Increased Desmoplastic response to invading CA cells Originate in the mammary duct Desmoplastic ---> shortened Coopers ligament ---> dimpling over the tumor

3.

Medullary carcinoma:
2-15% Soft, bulky and large tumors w/ necrotic areas 5 year survival = 85 90% Good prognosis

Histological Classification of Breast Cancer

4.

Mucinous (Colloid) carcinoma:

2% Soft, bulky w/ ill defined borders Cancer cells floats in large mucinous lakes

5.

Tubular carcinoma
Well differentiated Ducts lined by a single layer of well differentiated cancer cells

Absence of well defined basement membrane

Common in premenopausal pts usually detected w/ mammography

Histological Classification of Breast Cancer

6. Papillary carcinoma:
2 %; present in 7th decade Has the lowest frequency of axillary nodal involvement; has the

best 5 and 10 yrs survival rates

Even if w/ axillary metastases, it is still indolent and a more slowly progressive disease than the common adenocarcinoma

7. Adenoid cystic carcinoma:

Rare axillary involvement

Histological Classification of Breast Cancer

8. Carcinoma of Lobular origin:
10% of breast CA Arises from the terminal ducts and acini High propensity for bilaterality (35-60%), multicentricity (88%) and multifocality

9. Squamous Carcinoma:
Metaplasia w/in the lactiferous duct system Metastasize thru the lymphatics

Histological Classification of Breast Cancer

10. Sarcoma of the Breast: (Fibrosarcoma,

liposarcoma, leiomyosarcoma)
Large, painless breast mass w/ rapid growth Histologically: Spindle cell neoplasm, margin either pushes or infiltrates adjacent structures Treatment: --> total mastectomy

Histological Classification of Breast Cancer

11. Lymphoma of the Breast:
Similar to other malignant lymphoma Mastectomy w/ axillary LN sampling Tx: radiotherapy / chemotherapy

12. Inflammatory Carcinoma of the Breast

1.5 3% Clinically: erythema, Peau-d orange, w/ or w/o a mass. Skin is warm sometimes scaly and indurated (cellulitis), nipple retraction. Diagnosis: skin biopsy Histologically: ---> no predominant histological type
Subdermal lymphatic and vascular channels are permeated w/ highly undifferentiated tumor

Rapid growth and majority has (+) cervical LN and distant metastasis

TNM Staging System for Breast Carcinoma

Primary Tumor (T)
TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis CA in situ (LCIS / DCIS/Pagets) T1 2 cm or less T1a <0.5 cm T1b - > 0.5 cm to 1 cm T1c 1 cm to 2 cm T2 2 to 5 cm T3 - > 5 cm T4 any size w/ direct extension to chest wall or skin T4a extension to chest wall T4b edema / ulceration of the skin / satellite nodule T4c both T4a and T4b T4d Inflammatory carcinoma

TNM Staging System for Breast Carcinoma

Regional Lymph Nodes (N):
NX Not assessed/unknown N0 No regional LN metastasis N1 movable ipsilateral axillary LN N2 LN fixed to one another, matted N3 internal mammary, infraclavicular or supraclavicular LNs
pNX not assessed pNO no regional LN mets pN1 movable ipsilateral axillary LN, 1-3 LNs pN2 4-9 LNs, Axillary LN fixed with each other pN3 > 10 nodes, internal mammary, infraclavicular or supraclavicular LNs MX not assessed M0 no mets M1 distant mets (lung, brain, bone) including metastasis to ipsilateral supraclavicular LN

Pathological Classification LN (pN):

Distant Metastasis (M):

TNM Staging System for Breast Carcinoma

Stage Grouping:
Stage 0 Stage I Stage IIA Tis T1 T0 T1 T2 T2 T3 T0 T2 T3 T4 Any T Any T N0 N0 N1 N1 N0 N1 N0 N2 N1-2 Any N N3 Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

Stage IIB

Stage IIIA

Stage IIIB Stage IIIC Stage IV

Five-Year Breast Cancer Suvival Rates According to the Size of the Tumor and Axillary Node Involvement
5 Year Survival, % 0 Positive Tumor Size, cm Nodes < 0.5 0.5-0.9 1.0-1.9 2.0-2.9 3.0-3.9 4.0-4.9 5.0 99.2 98.3 95.8 92.3 86.2 84.6 82.2 Nodes 95.3 94.0 86.6 83.4 79.0 69.8 73.0 Nodes 59.0 54.2 67.2 63.4 56.9 52.6 45.4 1-3 Positive 4 or More Positive

Relationship Between Morphologic Types of Invasive Breast Cancer, Lymph Node Involvement, and Patient Survival

Type
Ductal Lobular Medullary Comedo Colloid Papillary

Frequency % w/ nodal involvement

78 9 4 5 3 1 60 60 44 32 32 17

% Survival 5 yr 10 yr 54
50 63 73 73 83

38
32 50 58 59 56

Survival Rates for Patients w/ Breast Cancer Relative to Clinical Stage

Clinical staging (American Joint Committee)
STAGE I Tumor < 2cm in diameter negative nodes Crude 5-yr survival (%) Range Survival (%)

85

82 - 94

STAGE II Tumors > 5 cm in diameter Nodes, if palpable, not fixed STAGE III Tumor > 5cm in diameter Tumor any size w/ invasion of skin attached to chest wall Nodes in supraclavicular area STAGE IV With distant metastases

66

47 74

41

7 80

10

Breast Cancer
TREATMENT
Surgery Radiation Chemotherapy Hormones

Treatment:
Criteria of Inoperability / Incurability
a) extensive edema of the skin over the breast

b) satellite nodule in the skin over the breast

c) inflammatory carcinoma of the breast d) parasternal tumor nodule e) supraclavicular metastasis f) edema of the arm g) distant metastasis h) Any 2 or more of the following : i. ulceration of skin ii. Edema of skin iii. Solid fixation of tumor to the chest wall iv. Axillary LN 2 cm or more v. Fixation of axillary LN to skin and/or deep structures

Surgical Management of Breast Cancer

Radical Mastectomy

Modified Mastectomy

Partial Mastectomy

Surgical Management
Subcutaneous Mastectomy:
Nipple is retained for T1s

Partial Mastectomy and Radiation:

Lumpectomy, segmental resection Histologically free margin of breast CA (1cm) Advent of radiotherapy with skin sparing effect To determine adjuvant chemotherapy adequate sampling of axillary LN (level I), If LN (+) ----> adjuvant chemotherapy

Indications for Conservative Surgery:

1. 2. Small breast CA < 4cm Clinically (-) axillary LN

Radiotherapy:
Local control Pre-operative / post-operative radiation

Chemotherapy:
CMF, CAF, CA, AV, doxorubicin

Hormonal Therapy:
Receptor Assay (ER/PR)

Breast Cancer
ADJUVANT THERAPY

Premenopausal Chemo Postmenopausal Hormones

Breast Cancer
CHEMOTHERAPY Regimens
CMF CAF AC

6 12 Cycles

Breast Cancer
RADIOTHERAPY

All Breast Conserving Surgical Therapies High Risk Patients

Breast Cancer
HORMONE THERAPY

Tamoxifen x 5 years

Tamoxifen

Carcinoma in Situ:
1. DCIS:
a. b. Breast conserving surgery + radiation therapy w/ or w/o tamoxifen Total mastectomy w/ or w/o tamoxifen

2.

Lobular Carcinoma in Situ:

a.
b. c.

Observation after diagnostic biopsy

Tamoxifen to decrease the incidence of subsequent breast cancer Bilateral prophylactic total mastectomy, w/o axillary dissection

Inflammatory Breast Carcinoma:

3 5% 5 year survival Primary therapy is chemotherapy and radiotherapy and if possible surgery CAF regression extended mastectomy irradiation of axilla and skin flap (30% - 5 yr survival)

Breast Cancer and Pregnancy/Lactation:

The risk of aggressive and distant metastasis is profound due to high level of estrogen and progesterone secreted from the placenta and corpus luteum Treat patient as if she is not pregnant Treatment:
MRM / Segmental resection + radiation (after delivery) (+) axillary nodes ---> chemotherapy is delayed to the 2nd trimester (single agent) 11 12% teratogenicity in 1st trimester.

Breast Cancer in Men:

Age: 60-70y/o s/sx: breast mass, nipple retraction and/or discharge, ulceration and pain. Commonly ER positive and well differentiated Prognosis is similar