Breast cancer

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Breast cancer
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Cancer from breast

• From duct and lobule
• Invasive ductal carcinoma(IDC)
• Invasive lobular carcinoma
• Others
• From stroma sarcoma(Phyllodes)
• Squamous cell carcinoma
• Lymphoma

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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

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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

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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

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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

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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

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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

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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

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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

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How to describe a breast ca

• TNM stage
• Tumor morphology
• Grade
• VLI
• PNI
• Special receptor
• Hormone receptor ER and PR
• Her2/Neu

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TNM

• T1 tumorlt2cm
• T1mic lt0.1cm
• T1a0.1-0.5cm, T1b0.5-1cm
• T1c1-2cm
• T2 2-5cm
• T3 gt5cm
• T4 chest wall, skin invasion, or inflammatory
  breast cancer

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Inflammatory breast cancer
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TNM

• N
• N0 no axilla LAPs
• N11-3
• N24-9
• N3gt10
• M M0 or M1

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I T1N0
IIA T1N1 T2N0
IIB T2N1 T3N0
IIIA T1N2 T2N2 T3N1 T3N2
IIIB T4N0 T4N1 T4N2
IIIC N3
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Tumor morphology

• Grade
• Tubule Formation
• Nuclear Pleomorphism
• Mitotic Count
• Vascular lymphatic invasion(VLI)
• Perineural invasion(PNI)
• Both indicate aggressive behavior

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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.

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Receptor status

• Hormone receptor
• Estrogen receptor ()
• Progesterone receptor ()
• gt10 predict response to hormone tx
• Her2/neu
• Associate with invasion, metastasis
• Predict poor prognosis
• IHC stain, FISH

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The EGFR (erbB) family
NRG2 NRG3 Heregulins
EGF TGF-? Amphiregulin
No specific ligands
Ligands
Heregulins
Receptor domain
Extracellular
Membrane
Intracellular
Tyrosine kinase domain
K
K
K
erbB2 HER2neu
erbB4 HER4
erbB3 HER3
erbB1HER1 EGFR
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Current assay of HER2/neu

• Immunohistochemistry

• Fluorescence in situ hybridization (FISH)

HER2 gene no amplification FISH negative
HER2 gene amplification FISH positive
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Treatment

• Localized breast cancer
• Surgery is mainstay
• Halsted, 1882, radical mastectomy
• John Hopkins
• Metastatic breast cancer
• Systemic treatment

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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.

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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
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Breast conserving surgery

• Also called lumpectomy
• RT should be followed

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Surgical evolution

• Radical mastectomy
• 1885 1960s
• Modified radical mastectomy 1970s
• Lumpectomy RT, 1970s
• NSABP B-06, NEJM 1985
• Lumpectomy vs. MRM
• Milan Cancer Institute, NEJM 1977
• Lumpectomy vs. RM

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Impact of surgical evolution

• Local control no survival benefit
• Local control RMgtMRMgtBCTRTgtBCT
• Survival no different
• Why? distant metastasis is the main cause
• Distant micrometastasis
• Not from local residual dz
• Does exist at diagnosis
• Adjuvant systemic treatment

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Adjuvant systemic treatment

• Hypothesis
• Eradicate micrometastasis
• From effective tx for overt(macro) metastasis
• Chemotherapy
• Hormone therapy

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Adjuvant chemotherapy

• CMF, first generation, 1970s
• Cyclophosphamide
• Methotrexate
• 5-FU
• Benefit in
• Distant recurrence
• Survival

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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

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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

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Adjuvant Herceptin

• Effective in Her2 pts
• ICH3
• FISH
• Herceptin adjuvant chemotherapy
• Optimal role to be defined
• Concurrent or sequential?
• Maintenance ? Duration ?

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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

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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

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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?

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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

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Treatment strategy

• Principle
• Save your bullet
• Right time, right treatment
• Why?
• Treatment effectiveness only in limited duration
• To avoid unnecessary toxicity
• Ultimately incurable

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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

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Chemotherapeutic agents

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

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Chemotherapy regimens

• Combination
• Navelbine-HDFL
• Paclitaxel-Cisplatin
• Doxorubicin-Cyclophosphamide
• Gemcitabine-Paclitaxel
• Combination C/T provide better RR, but overall
  survival not different

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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
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Example - 2

• 45 y/o woman, ER/PR -/-
• Dz recurred 3 yrs after operation
• Only right supraclavicle LNs
• Slowly progressed

RT alone Observation
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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
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Example - 4

• 55 y/o woman, ER/PR /
• Dyspnea progressively
• Lung mets bilaterally

Systemic chemotherapy, combination
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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

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