1. Breast cancer

2. Cancer from breast From duct and lobule Others
Invasive ductal carcinoma(IDC)
Invasive lobular carcinoma
Others
From stroma: sarcoma(Phyllodes)
Squamous cell carcinoma
Lymphoma

3. 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

4. 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

5. 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

6. 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

7. 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

8. DCIS and LCIS DCIS LCIS Premalignant change
Turn out to be cancer in ongoing years
LCIS
Not a premalignent change
A sign, which indicate risk of breast ca

9. Symptoms In early breast ca Late breast ca Easily self palpated
Nipple discharge
May accompanied with axillary LN
Late breast ca
Local usually symptomatic
Depends on metastatic sites

10. Diagnosis tool Breast sonography Mammography Cytology Biopsy
Superior in dense breast, young age
Mammography
Superior in loose(fatty) breast, elder
Cytology
Fine-needle aspiration (FNA)
Biopsy
Incision
Excision

11. How to describe a breast ca
TNM stage
Tumor morphology
Grade
VLI
PNI
Special receptor
Hormone receptor: ER and PR
Her2/Neu

12. TNM T1: tumor<2cm T2: 2-5cm T3: >5cm
T1mic: <0.1cm
T1a: cm, T1b:0.5-1cm
T1c:1-2cm
T2: 2-5cm
T3: >5cm
T4: chest wall, skin invasion, or inflammatory breast cancer

13. Inflammatory breast cancer

14. TNM N
N0: no axilla LAPs
N1:1-3
N2:4-9
N3>10
M: M0 or M1

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

16. Tumor morphology Grade Vascular lymphatic invasion(VLI)
Tubule Formation
Nuclear Pleomorphism
Mitotic Count
Vascular lymphatic invasion(VLI)
Perineural invasion(PNI)
Both indicate aggressive behavior

17. 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.

18. Receptor status Hormone receptor Her2/neu Estrogen receptor (%)
Progesterone receptor (%)
>10% predict response to hormone tx
Her2/neu
Associate with invasion, metastasis…
Predict poor prognosis
IHC stain, FISH

19. The EGFR (erbB) family Ligands Receptor domain Extracellular Membrane
NRG2
NRG3
Heregulins
EGF
TGF-
Amphiregulin
No specific ligands
Ligands
Heregulins
Receptor domain
Extracellular
Membrane
The epidermal growth factor receptor (EGFR) belongs to a family of four closely related cell surface receptors: EGFR (HER1 or erbB1), erbB2 (HER2/neu), erbB3 (HER3), and erbB4 (HER4).1
These receptors are transmembrane glycoproteins comprising an extracellular ligand-binding domain and an intracellular domain with tyrosine kinase activity.1
Several ligands bind to the EGFR, including EGF and TGF-α. There are no defined ligands for erbB2; erbB3 and erbB4 bind heregulins and neuregulins.1
Dimerization of erbB receptors may occur as follows:
EGFR homodimerization
EGFR heterodimerization with erbB2 or erbB3 receptors
erbB4 heterodimerization with erbB2.1
Dimer formation will dictate the resultant signaling cascade.1
Reference
Wells A. Int J Biochem Cell Biol 1999; 31:
Intracellular
Tyrosine kinase
domain K K K
erbB1 HER1
EGFR
erbB2
HER2 neu
erbB3
HER3
erbB4
HER4

20. 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

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

22. 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.

23. 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

24. Breast conserving surgery
Also called lumpectomy
RT should be followed

25. Surgical evolution Radical mastectomy
Modified radical mastectomy: 1970s
Lumpectomy + RT, 1970s
NSABP B-06, NEJM 1985
Lumpectomy vs. MRM
Milan Cancer Institute, NEJM 1977
Lumpectomy vs. RM

26. 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

28. Adjuvant systemic treatment
Hypothesis:
Eradicate micrometastasis
From effective tx for overt(macro) metastasis
Chemotherapy
Hormone therapy

29. Adjuvant chemotherapy
CMF, first generation, 1970s
Cyclophosphamide
Methotrexate
5-FU
Benefit in
Distant recurrence
Survival

30. 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

31. 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

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

33. 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

34. 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

35. 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?

36. 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

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

38. Chemotherapy In general, chemotherapy Hormone therapy
Single agent: RR: 20-30%
Combination: doublet: 40-60% triplet: 70-80%
Hormone therapy
Tamoxifen: RR 15-20%
Aromatase inhibitor: RR 30-35%

39. Chemotherapeutic agents
Single agents:
Doxorubicin/Epirubucin
Cyclophosphamide
MTX
5-FU
Taxane(Paclitaxel, Docetaxel)
Navelbine
Gemcitabine
BCNU

40. Chemotherapy regimens
Combination:
Navelbine-HDFL
Paclitaxel-Cisplatin
Doxorubicin-Cyclophosphamide
Gemcitabine-Paclitaxel
Combination C/T provide better RR, but overall survival not different

41. 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

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

43. 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

44. Example - 4 55 y/o woman, ER/PR +/+ Dyspnea progressively
Lung mets bilaterally
Systemic chemotherapy, combination

45. 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