Case 58 세 여자 좌측 유방암으로 유방보존술 및 액와림프절절제술 시행함. 수술병리조직소견은 다음과 같음. – 종양크기 : 1.5x1.2cm – 액와림프절 : 0/12 –ER(+), PR(+) –HER-2: +3

유방암치료 병기 – 림프절음성 : – 림프절양성 : 폐경상태 – 폐경전 : – 폐경후 : 호르몬수용체 – 양성 : – 음성 :

유방암치료의 일반지식 병기 – 림프절음성 : 치료하지 않음 – 림프절양성 : 화학요법 폐경상태 – 폐경전 : 항암화학요법 – 폐경후 : 호르몬요법 호르몬수용체 – 양성 : 호르몬요법 – 음성 : 항암화학요법

Adjuvant Therapy - St. Gallen CT = Chemotherapie; Tam = Tamoxifen ER and/or PgR positive Nodal positive CT + Tam Tam ER and PgR negative Chemotherapy Nodal negative Average/High Tam Tam+CT Minimal/Low Tam none

Risk Categories for node (-) breast cancer J Clin Oncol 21:3357, 2003

8th St Gallen breast consensus meeting 2003 J Clin Oncol 21:3357, 2003

St. Gallen March 2003 N negative(average risk), N positive Pre– and Post ER and PR negative Chemotherapy Premenopausal Er and/or PR positive OS* + Tam or Chemo Tam or OS* + Tam +/- Chemo Postmenopausal Er and/or PR positive Tam or Chem Tam OS* OS* = Ovarien Suppression: GnRH (Zoladex), 2 to 5 years. Oophorectomy

Nuclear initiated estrogen signaling

Membrane-initiated steroid signaling (I)

Membrane-initiated steroid signaling (II)

Therapeutic strategy

Aromatase inhibition within the breast tumour cell ANDROGENS OESTROGENS P-450 Aromatase + NADPH-cytochrome P-450 reductase (Testosterone, androstenedione, 16-OH-testosterone) (Oestradiol, oestrone) Aromatase Inhibitors tumourgrowth

Sites of peripheral aromatisation BreasttumourMuscleFatLiver

Femara = Letrozole Non-steroidal Steroidal Arimidex = Anastrozol e CH 3 H3CH3C NCCN N N N H3CH3CCH 3 Chemical Structures of Newer Aromatase Inhibitors NC CN N N N Aromasin = Exemestane O CH 2 O CH 3

AI & tamoxifen response in HER-2 status

AI adjuvant breast cancer trials

Premenopausal ER (+) –Hormonal treatment Ovarian function suppression/ablation –Surgical oophorectomy –Radiation induced ovarian ablation –GnRH analog –Chemotherapy

Premenopausal Ovarian function suppression/ablation –Equivalent to chemothx Tamoxifen –Effective for ER(+) Ovarian function supression + tamoxifen –At least as effective as chemothx –Goserelin (2-3 yrs) + tamoxifne (5 yrs)

Premenopausal Ovarian function suppression + AI : ? Endocrine agent + trastuzumab : ? GnRH analog + tamoxifen –In HER-2 overexpression

Combination chemothx CMF AC Doxorubicin + taxane Capecitabine + docetaxel Gemcitabine + vinorelbine Gemcitabine + paclitaxel Trastuzumab + chemothx

Adjuvant chemotherapy CMF vs AC Taxane Sequential single agents vs simultaneous combination Dose-dense regimen Optimal timing –Postoperative vs preoperative

9 th St. Gallen International Consensus Conference on Primary Therapy of Early Breast 2005 Aromatase inhibitor –Postmenopausal, endocrine responsive –Optimal use ? Taxane –Not conclusive ? Dose dense regimen –Not conclusive ? Trastuzmab –No data are available yet.

Case 58 세 여자 좌측 유방암으로 유방보존술 및 액와림프절절제술 시행함. 수술병리조직소견은 다음과 같음. – 종양크기 : 1.5x1.2cm – 액와림프절 : 0/12 –ER(+), PR(+) –HER-2: +3