1. Adjuvant therapy of breast cancer
종양혈액내과
백선경

2. Two types of cancer treatment
Systemic treatment
Chemotherapy (Hormonal therapy, Molecular targeted therapy)
Biologic therapy (immunotherapy)
Local treatment
Surgery
Radiation therapy
Ablative approaches – radiofrequency/crysurgical therapy

3. Today’s talk Introduction Adjuvant therapy Summary
Adjuvant Chemotherapy & targeted agents
Adjuvant Hormone therapy
Summary

4. Breast cancer

5. Age-specific incidence

6. The goal of cancer treatment
Adjuvant therapy : Eradicate micrometastases to reduced the incidence of both local and systemic recurrence and to improve the overall survival VS Amelioration of symptoms, preservation of quality of life, extend life Palliative chemotherapy.

7. Selection of adjuvant chemotherapy -stratified by risk group
Axillary lymph node status
HER2
Tumor size
ER and PR receptor
Histologic grade
Young age < 35

8. Intrinsic subtypes of breast cancer
Luminal epithelial
Her2 overexpression
Basal epithelial
Basal epithelial
Charles et al. Nature 2000

9. Mammary development meets cancer genomics
Prat et al. Nature 2009

10. Molecular class and clinicopathological features of breast cancer
10%<
>30%
Christos et al. NEJM 2009

11. Genomic Assays in Patients with Breast Cancer
Mamma print
Oncotype DX
PAM50 (prosigna)
Endopredict
Type of assay
70-gene assay
21-gene recurrence score
50-gene
11 gene
Type of tissue sampe
Fresh or frozen
Formalin-fixed paraffin-embedded
Formalin-fixed, paraffin-embedded
Tenicique
DNA microarray
Q-RT-PCR
PCR
Availability
Europe, US

12. Adjuvant therapy according to subtype
Luminal A
Endocrine therapy: TOC
Adjuvant Chemotherapy : high tumor load (≥ 4 involved LNs, stage T3)
Luminal B
Adjuvant chemotherapy is usually indicated
Endocrine therapy
HER2-positive
Adjuvant chemotherapy with trastuzumab for 1 year
adjuvant anti-HER2 targeted therapy is indicated for T1b
double antibody blockade with trastuzumab/pertuzumab
Triple-negative
anthracycline/taxane-based regimens : TOC
Use of a platinum-based regimen as an adjuvant treatmen

14. Cytotoxic treatment per cycle
Scheduled number of cycles and cytotoxic treatment per cycle
CMF
6 cycles of C100 x14 M40x2 F500x2, 4 weekly
4AC
4 cycles of A60 C600, 3 weekly
4EC
4 cycles of E90 C600, 3 weekly
CAF
6 cycles of C100 x14 A30x2 F500x2, 4 weekly
CEF
6 cycles of C75 x14 E60x2 F500x2, 4 weekly

15. Meta-analysis by Early Breast Cancer Trialists’ Collaborative Group
EBCTCG Lancet 2012

16. Paclitaxel After Doxorubicin Plus Cyclophosphamide: NSABP B-28
Adjuvant for LN+ breast cancer
N=3060
Randomize 1:1
AC#4  paclitaxel#4
Eleftherios P et al. JCO 2005

17. Meta-analysis by Early Breast Cancer Trialists’ Collaborative Group
EBCTCG Lancet 2012

18. Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer
Paclitaxel 3week x 4cycle : 175mg
LN+ or T2 BC
(n=4950)
Docetaxel 3week x 4cycle : 100 mg
Randomize 1:1:1:1
AC#4
Paclitaxel weekly x 12cycle: 80 mg
Docetaxel weekly x 12cycle: 35 mg
Joseph NEJM 2008

19. Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer
Joseph NEJM 2008

20. Concurrent Taxen with AC
Adjuvant for high risk LN- breast cancer
N=1060
FAC #6
Randomize 1:1
TAC #6
Miguel et al. NEJM 2010

21. Non-anthracycline adjuvant regimen
1Tumor size< 7cm
N=1016
AC #4
Randomize 1:1
TC #4
Stephen et al. JCO 2009

22. Weekly paclitaxel for 12 weeks
Her2+
1cm  Tumor size <7cm
LN-
Weekly paclitaxel for 12 weeks
Sara et al. NEJM 2015

23. dose-intensity
Drug delivery over time Adjusted dose/time on therapy ex) giving drug “X” at dose “Y” once every 3 weeks  Y/3 per week increasing dose size reducing the overall treatment duration
Clifford Breast J 2014

24. Dose-dense chemotherapy versus conventional chemotherapy

25. Dose-dense chemotherapy versus conventional chemotherapy
Igor et al. The Breast 2011

26. Mechanisms of action of trastuzumab

27. Adjuvant herceptin

28. Adjuvant herceptin Perez et al. JCO 2011 P<0.001, 0.52 (0.45-0.60)

29. Cardiotoxicity of trastzumab

30. Case 1 C.C. for adjuvant chemotherapy P.I. 54/F
우측 유방 종괴로 BCS 시행하여 breast cancer stage IIB (T2N1M0, ER-PR-Her2+)로 수술 후 보조 항암요법 위해 내원함
PMHx : DM/HTN/Hepatitis/TBc (-/+/-/-)
Personal Hx : Smoking (-), Alcohol (-)

31. Pathologic report I
Breast and axillary lymph nodes, right, lumpectomy: Invasive ductal carcinoma 1) Size of tumor: 3.0x2.0x1.8 cm (pT2) 2) Histologic grade: 3 / 3 (tubule formation: 3 / 3, nuclear pleomorphism: 3 / 3, mitotic count: 3 / 3, 12 / 10 HPFs) 3) Ductal carcinoma in situ: present, extratumoral (nuclear grade: 3 / 3, necrosis: absent, architectural pattern: cribriform, papillary extensive intraductal component: absent) 4) Skin: no tumor 5) Surgical margins: no tumor a) superior margin: 4 cm b) inferior margin: 3 cm c) medial margin: 3 cm d) lateral margin: 3 cm e) deep margin: 0.7 cm 6) Lymph node involvement: a) metastasis in 2 out of 10 axillary lymph nodes ( 2/10, pN1c ) (sentinel: 1/1, axillary: 1/9) b) perinodal extension: absent c) size of metastatic carcinoma: 15 mm 7) Vascular invasion: absent 8) Lymphatic invasion: present Immunohistochemical finding: ER negative PR negative Her-2 positive, score 3 CK5 negative

32. Next treatment? Adjuvant chemotherapy Adjuvant radiotherapy
Adjuvant hormone therapy
Adjuvant targeted therapy

33. 폐경: 영구적인 월경 중단 이전에 양측 난소 절제술을 시행한 경우 나이  60세
나이< 60세, 항암화학요법, tamoxifen, toremifene, 난소 억제제를 투여하지 않은 상태에서 12개월 이상 무월경이고 혈중 FSH 와 estradiol 농도가 폐경후 여성의 수치에 합당한 경우
나이< 60세, tamoxifen, toremifene 을 투여받고 있는는 경우 혈중 FSH 와 estradiol 농도가 폐경 후 여성의 수치에 합당한 경우
- LH-RH agonist/antagonist를 투여받는 여성은 무월경이어도 폐경상태로 정의할 수 없다.

34. 𝚾

35. Summary of AI adjuvant trial
Anastozole
Letrozole
Exemestane
Initial adjuvant therapy
Efficacy (vs tamoxifen) 𝜰 𝚾
Tolerability
Risk/benefit profile
Switching from TMX
Extended adjuvant setting
Efficacy (vs placebo) ?

36. Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer
Olivia NEJM 2014

37. Disease-free survival
Olivia NEJM 2014

38. the comparison of DFS according to treatment
Olivia NEJM 2014

39. Comparisons of Tamoxifen plus Ovarian Suppression (OS) with Tamoxifen Alone
Prudence NEJM 2015

40. Extended hormone therapy
Paul JCO 2007

41. Toxicities

42. Extended Adjuvant Tamoxifen

43. Summary
Breast cancer is systemic disease. Adjuvant therapy is considered according to subtype Nonanthracycline regimens in the adjuvant treatment of breast cancer. Adjuvant herceptin is a critical role on Her2+ breast cancer and is considered earlier Adjuvant endocrine therapy with exemestane plus ovarian suppression improved outcomes of premenopausal women with HR+ breast cancer Extended adjuvant endocrine therapy is still controversial

44. THANK YOU FOR YOUR ATTENTION