Breast cancer

Cancer from breast

From

duct and lobule

Invasive ductal carcinoma(IDC) Invasive lobular carcinoma

Others

From stroma: sarcoma(Phyllodes) Squamous cell carcinoma Lymphoma

Normal Breast

A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs

A. Cells lining duct B. Basement membrane C. Open central duct

Invasive ductal carcinoma(IDC)

A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs

A. Cells lining duct B. Cancer cells, breaking through the basement membrane C. Basement membrane

Ductal carcinoma in situ(DCIS)

A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs A. Cells lining duct B. Extra cancer like cells, but aaacontained within duct C. Intact basement membrane D. Open central duct

Invasive lobular carcinoma(ILC)

A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs

A. Cells lining lobule B. Cancer cells, breaking through the basement membrane. C. Basement membrane

Lobular carcinoma in situ(LCIS)

A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs

A. Cells lining lobule B. Cancer cells, but all contained within the lobules C. Basement membrane

DCIS and LCIS

DCIS

Premalignant change Turn out to be cancer in ongoing years

LCIS

Not a premalignent change A sign, which indicate risk of breast ca

Symptoms
In

early breast ca

Easily self palpated Nipple discharge May accompanied with axillary LN

Late

breast ca

Local usually symptomatic Depends on metastatic sites

Diagnosis tool

Breast sonography
Superior in dense breast, young age

Mammography
Superior in loose(fatty) breast, elder

Cytology
Fine-needle aspiration (FNA)

Biopsy
Incision Excision

How to describe a breast ca

TNM

stage morphology

Tumor

Grade VLI PNI

Special

receptor

Hormone receptor: ER and PR Her2/Neu

TNM
T1:

tumor<2cm

T1mic: <0.1cm T1a:0.1-0.5cm, T1b:0.5-1cm T1c:1-2cm

T2:

2-5cm T3: >5cm T4: chest wall, skin invasion, or inflammatory breast cancer

Inflammatory breast cancer

TNM
N

N0: no axilla LAPs N1:1-3 N2:4-9 N3>10

M:

M0 or M1

I IIA IIB

T1N0 T1N1 T2N0

IIIA

IIIB IIIC

T2N1 T3N0 T1N2 T2N2 T3N1 T3N2 T4N0 T4N1 T4N2 N3

Tumor morphology
Grade

Tubule Formation Nuclear Pleomorphism Mitotic Count

Vascular

lymphatic invasion(VLI) Perineural invasion(PNI)

Both indicate aggressive behavior

VLI

A. Veins in breast B. Lymph channels in breast

A. Cells lining duct B. Cancer cells, breaking through the basement membrane. C. Broken basement membrane D. Cancer entering a lymph channel. E. Cancer entering a vein. F. Normal breast tissue.

Receptor status
Hormone

receptor

Estrogen receptor (%) Progesterone receptor (%) >10% predict response to hormone tx
Her2/neu

Associate with invasion, metastasis Predict poor prognosis IHC stain, FISH

The EGFR (erbB) family

Ligands
EGF TGF- Amphiregulin

No specific ligands

Heregulins

NRG2 NRG3 Heregulins

Receptor domain

Extracellular Membrane

Tyrosine kinase domain

Intracellular K K K

erbB1 HER1 EGFR

erbB2 HER2 neu

erbB3 HER3

erbB4 HER4

Current assay of HER2/neu

Immunohistochemistry

0 (negative)

1+ (negative)

2+ (equivocal)

3+ (positive)

Fluorescence in situ hybridization (FISH)

HER2 gene no amplification FISH negative

HER2 gene amplification FISH positive

Treatment
Localized

breast cancer

Surgery is mainstay Halsted, 1882, radical mastectomy

John

Hopkins

Metastatic

breast cancer

Systemic treatment

Radical mastectomy

A. Entire breast and a chest wall muscle is removed.

LNs in the level 1 (B) and level 2 (C ), and even sometimes more distant lymph node groups (D, E and F) were also removed.

Modified radical mastectomy (MRM)

A. Entire breast is removed Classically some lymph nodes in the level 1 (B) and level 2 (C ) were removed, called an axillary lymph node dissection.

MRM = simple mastectomy + ALND

Breast conserving surgery

Also called lumpectomy RT should be followed

Surgical evolution
Radical

mastectomy

1885 ~ 1960s
Modified

radical mastectomy: 1970s + RT, 1970s

Lumpectomy

NSABP B-06, NEJM 1985

Lumpectomy vs. MRM Lumpectomy vs. RM

Milan Cancer Institute, NEJM 1977

Impact of surgical evolution

Local

control: no survival benefit

Local control: RM>MRM>BCT+RT>BCT Survival no different

Why?

distant metastasis is the main cause

Distant

micrometastasis

Not from local residual dz Does exist at diagnosis

Adjuvant

systemic treatment

Adjuvant systemic treatment

Hypothesis:

Eradicate micrometastasis From effective tx for overt(macro) metastasis

Chemotherapy Hormone

therapy

Adjuvant chemotherapy
CMF,

first generation, 1970s

Cyclophosphamide Methotrexate 5-FU

Benefit in
Distant

recurrence Survival

Adjuvant chemotherapy
CAF

or CEF, 2nd generation, 1980s

Cyclophophamide Adramycin(or Epirubicin) 5-FU

More toxic than CMF CAF better than CMF in high-risk group
Axilla

LN+ LN-, but tumor large or other risk factor

Adjuvant chemotherapy
Incorporate

Taxane TAC, 3rd generation, mid-1990s

Taxotere Adriamycin Cyclophosphamide More toxic than CAF Better than CAF in high-risk group
Need

more time to observe

Adjuvant Herceptin
Effective

in Her2+ pts

ICH3+ FISH+
Herceptin

+ adjuvant chemotherapy

Optimal role to be defined

Concurrent

or sequential? Maintenance ? Duration ?

Adjuvant hormone therapy

In

premenopausal woman

Oophorectomy could control metastatic disease

Tamoxifen

Selective estrogen receptor antagonist Effective in pre- and post-menopausal Effective in adjuvant setting

Adjuvant hormone therapy

Aromatase

inhibitor

Effective in post-menopausal state Aromatase, in fat tissue,

Convert

androgen to estrogen Main estrogen source in post-menopausal

Exemestane : Aromasin Letrozole: Femara Anastrozole: Arimidex

More

effective than Tamoxifen

Adjuvant ovarian suppression

Effective

in pre-menopausal state

Type

Surgical ablation RT ablation GnRH analogue: Goserelin, Leupride

Exact

role to be defined

Combination with chemotherapy? Combination with AI or TAM?

Treatment of metastatic dz
Usual sites: bone, lung, liver, brain Incurable

Goal: live with dz for longest time

Systemic treatment is mainstay

Chemotherapy Hormone therapy

Palliative local therapy

Radiotherapy Palliative surgery

Treatment strategy
Principle:

Save your bullet Right time, right treatment

Why?

Treatment effectiveness only in limited duration To avoid unnecessary toxicity Ultimately incurable

Chemotherapy
In

general, chemotherapy

Single agent: RR: 20-30% Combination: doublet: 40-60% triplet: 70-80%

Hormone

therapy

Tamoxifen: RR 15-20% Aromatase inhibitor: RR 30-35%

Chemotherapeutic agents
Single

agents:

Doxorubicin/Epirubucin Cyclophosphamide MTX 5-FU Taxane(Paclitaxel, Docetaxel) Navelbine Gemcitabine BCNU

Chemotherapy regimens
Combination:

Navelbine-HDFL Paclitaxel-Cisplatin Doxorubicin-Cyclophosphamide Gemcitabine-Paclitaxel

Combination

C/T provide better RR, but overall survival not different

Example - 1
55y/o woman, ER/PR +/+, Dz recurred 5yrs after surgery Only neck and mediastinum LNs Slowly progressed clinically(!)

Hormone therapy May do RT for symptomatic site

Example - 2
45 y/o woman, ER/PR -/ Dz recurred 3 yrs after operation Only right supraclavicle LNs Slowly progressed
RT alone Observation

Example - 3
50 y/o woman, ER/PR +/+ Back, shoulder, hips pain, 3m, progress Massive bone mets over spine, pelvis, shoulder, and ribs

Systemic chemotherapy, combination

RT for symptomatic sites

Bisphosphonate: Aredia or Zometa

Example - 4
55 y/o woman, ER/PR +/+ Dyspnea progressively Lung mets bilaterally

Systemic chemotherapy, combination

Treatment principle
For

visceral organ crisis

Combination chemotherapy Failure is not allowed (high RR necessary)

For

isolated LN or bone mets

Hormone tx (more chance to try) RT alone in hormone unresponder