1. Update in Treatment of Early Breast Cancer

2. 증례 1 41세 여자. 좌측 유방암 수술(유방보존술). 수술병리조직소견:
infiltrating ductal carcinoma, tumor grade 2
종양크기 1.5 cm
vascular invasion (-)
겨드랑림프절 +2/13
ER(+), PR(+), HER2 (+2, IHC).
이 환자의 향후 치료는?

3. 증례 2 56세 여자 우측 유방암 수술(유방보존술) 병리조직 소견
invasive ductal carcinoma, tumor grade 1
lymphovascular invasion (-)
tumor size: 0.8 cm
LN: 0/12
ER(+), PR(-), HER2(+3, IHC)
이 환자의 향후 치료는?

4. 증례 Factors affecting treatment-decision Risk category ?
Endocrine responsiveness ?
Chemotherapy ?
Trastuzumab treatment ?
Radiation ?

5. Treatment guidelines St Gallen consensus conference of breast cancer
10th conference, 2007
NCCN guideline V

6. 10th St Gallen Consensus

7. NCCN Guideline V2.2007

8. Endocrine Responsiveness
Highly endocrine responsive
Both ER(+) & PR(+)
Incompletely endocrine responsive
Lower expression of ER and/or PR
Endocrine non-responsive
Complete absence of both ER & PR

9. HER2-positivity Strong IHC staining (3+), > 30% of tumor cells
3+: positive
2+: undetermined
0,1+: negative
Gene amplification by FISH
Ratio of HER2 gene copies to chromosome 17 centomers, > 2.2
Trastuzumab(Herceptin®) responsiveness
HERA trial

11. Disease-free survival of HERA trial

12. Risk category
Low risk
Node negative AND all of the following features:
pT ≤ 2cm, AND
Grade 1, AND
Absence of extensive peritumoral vascular invasion, AND
ER and/or PR expressed, AND
HER2 gene neither overexpressed nor amplified, AND
Age ≥ 35 years

13. Risk category Intermediate risk
Node negative AND at least one of the following features:
pT > 2cm, OR
Grade 2-3, OR
Presence of extensive peritumoral vascular invasion, OR
ER and PR absent, OR
HER2 gene overexpressed or amplified, OR
Age < 35 years
Node positive (1-3 involved nodes) AND
ER and/or PR expressed, AND
HER2 gene neither overexpressed nor amplified

14. Risk category High risk Node positive (1-3 involved nodes) AND
ER and PR absent, OR
HER2 gene overexpressed or amplified
Node positive (4 or more involved nodes)

15. Choice of treatment modality
Highly endocrine responsive
Incompletely endocrine responsive
Endocrine non-responsive
HER2 (-)
ET (consider adding CT according to risk) CT
HER2 (+)
ET + Trastuzumab + CT
Trastuzumab
+ CT

16. Endocrine Therapy Postmenopausal Premenopausal Tamoxifen
Aromatase inhibitor
Check ovarian function in young postmenopausal women
Duration: 5-10 years
Premenopausal
Tamoxifen alone
Tamoxifen + ovarian function suppression
GnRH analogue ( or surgical oophorectomy, ovarian radiation)
Duration: 5 years

17. Trastuzumab Action mechanisms Not consider Duration: 1 year
Primary tumor < 1 cm
Axillary LN (-)
Endocrine responsive
Duration: 1 year
Avoid low LVEF (<50%)

18. Four members of the HER family

19. Mechanisms of action of trastuzumab

20. Chemotherapy Endocrine non-responsive Endocrine responsive
Lower expresson of hormone receptor
Involvement of axillary LNs extensively
Higher grade
Larger tumor
Extensive peri-tumoral vascular invasion
Molecular-based technology
OncotypeDXTM, MammaprintTM

21. Gene expression patterns of breast carcinoma
HER2(-)
HER2(+)
ER(+)
Low expression
ER(+)

22. Survival analysis based on different gene expression

23. N Engl J Med 2004;351:

24. Panel of 21 genes: OncotypeDXTM

25. Likelihood of distant recurrence, according to recurrence-score categories

26. Chemotherapy Regimen Anthracycline containing regimen for
Cyclophosphamide, 5-FU, anthracycline
Anthracycline & cyclophosphamide
Anthracycline & cyclophosphamide followed by taxane
Dose-dense therapy
Anthracycline containing regimen for
HER2 positive
Less intensive chemotherapy for
High/incomplete endocrine responsive HER2-negative

27. Summary HER2 status HER2 (-) HER2 (+) Endocrine response high incomp
non
Low risk E
Intermed
Node (-)
CE C
+Tr
Node 1-3 +
> 4 node +
E: endocrine therapy, C: chemotherapy, Tr: trastuzumab, Incomp: incomplete

28. Local & regional treatment
Sentinel node biopsy
Avoid unnecessary axillary surgery
Radiation
>T3, >4 axillary LNs
1-3 axillary LNs ?

29. 증례 1 41세 여자. 좌측 유방암 수술(유방보존술). 수술병리조직소견:
infiltrating ductal carcinoma, tumor grade 2
종양크기 1.5 cm
vascular invasion (-)
겨드랑림프절 +2/13
ER(+), PR(+), HER2 (+, FISH).
이 환자의 향후 치료는?

30. 증례 2 56세 여자 우측 유방암 수술(유방보존술) 병리조직 소견
invasive ductal carcinoma, tumor grade 1
lmphovascular invasion (-)
tumor size: 0.8 cm
LN: 0/12
ER(+), PR(-), HER2(+3)
이 환자의 향후 치료는?