????? ?????????????

1

• ?"? ????? ???????
• ??????????

2
???????????? ???? ????? ??????? ?????? ?????
????? ??????, ??????? ?? ?????? ?????? ?????????
????? ????? ?????? ???????? ?????.
3

• ?????????? ???????? ?????????????
• ?????????? ?? ??? ???????.
• ????? ????????????? ?????? ??????
  ???????? ?????? ????? ????? ?????
• ?????? ??????? ??????
• ????? ?? ???? ???? ?? ?????

4
Adjuvant Zomera
5
Adjuvant Zomera
6
(No Transcript)
7
(No Transcript)
8
(No Transcript)
9
(No Transcript)
10
Zomera For Adjuvant Treatment
11
(No Transcript)
12
Recommendations for Women With Breast Cancer
Initiating AI Therapy
T-score lt 2.0

• Any 2 of the following risk factors
• T-score lt 1.5
• Age gt 65 years
• Low BMI (lt 20 kg/m2)
• Family history of hip fracture
• Personal history of fragility fracture after age
  50
• Oral corticosteroid use of gt 6 months
• Smoking (current or history of)

T-score 2.0, No risk factors
Zoledronic acid (4 mg / 6 months)calcium and
vitamin D supplements
Calcium and vitamin D supplements
Monitor risk status and BMD every 1 to 2 years
Monitor BMD every 2 years

• Data for oral bisphosphonates are emerging
• Evidence from 4 clinical trials indicate that
  zoledronic acid prevents AI-associated bone loss

5 drop in BMD should trigger zoledronic acid
treatment (4 mg / 6 months). Use lowest T-score
from 3 sites. Hadji P, et al. Presented at SABCS
2007. Abstract 504.
13
All Aromatase Inhibitors Increase Fracture Risk
Exemestane
Letrozole
Placebo
Tamoxifen
Anastrozole
P lt .0001
11
P .003
7.7
P lt .001
7.0
P .25
Fractures,
5.7
5.3
5.0
4.6
4.0
ATAC2 (68 months)
IES3 (58 months)
BIG 1-984 (26 months)
MA.175 (30 months)
1. Adapted from Hadji P, et al. US Oncological
Disease 2007. 2007118-21 2. Howell A, et al.
Lancet. 200536560-62 3. Coleman RE, et al.
Lancet Oncol. 20078119-127 4. Thurlimann B,
et al. N Engl J Med. 20053532747-2757 5. Goss
PE, et al. J Natl Cancer Inst. 2005971262-1271.
14
Z-FAST,1 ZO-FAST2, and E-ZO-FAST3 Study Design
R A N DO M I Z E D

• Eligibility
• ER/PR BC
• PMW withT-score 2
• Stratification
• Adjuvant CT(yes or no)
• T score (gt 1 or between 1 and 2 )

LET (2.5 mg/day) UPFRONT ZOL 4 mg q 6 mo
LET (2.5 mg/day) DELAYED ZOL 4 mg q 6 mo
0
5 yearsFinal analysis
3 years
1 year
Accrual completed Z-FAST N
602 ZO-FAST N 1,066
E-ZO-FAST N 527 Total N 2,195
ER Estrogen receptor PR Progesterone
receptor BC Breast cancer PMW
Postmenopausal women CT Chemotherapy LET
LetrozoleZOL Zoledronic acid.Initiation of
zoledronic acid determined by postbaseline BMD
T-score lt 2.0, any clinical fracture, or any
asymptomatic fracture at 36 months. 1. Brufsky ,
et al. Presented at 30th Annual SABCS December
13-16, 2007 San Antonio, Texas. Abstract 272.
DeBoer R, et al. Presented at 30th Annual SABCS
December 13-16, 2007 San Antonio, Texas.
Abstract 501 3. Llombart A, et al. Presented
at 14th ECCO Conference September 23-27, 2007
Barcelona, Spain. Abstract 2044.
15
Conclusions

• Upfront Zoledronic acid (4 mg IV q6mo) prevents
  bone loss in women with early stage BC receiving
  adjuvant letrozole
• Zoledronic acid has potential to have an impact
  on clinical outcomes other than bone health

16
Local and Distant recurrences
Upfront group Delayed group P value
12 months 1(0.3) 6(2) 0.056
24 months 7(2.3) 12 (4) 0.207
36 months 9(3) 16 (5.3) 0.127
The Zometa-Femara Adjuvant Synergy Trial (Z-FAST)
17
?????? ???? ????? ??????

• 65-75 ????? ???? ???????? ?????? ???? ??????
  ??????.
• 65-75 ?????? ???? ??? ?????? ???? ??????
  ??????.
• 30-40 ????? ???? ?????? ?????? ???? ??????
  ??????.
• 95-100 ????? ??????? ????? ?????? ???? ??????
  ??????.

18
??????? ??????? ?????? ??????? ????.

1. ????? ??????.
2. ????? ???????? ?????? ????? ?????? ?????.
3. ????? ??? ?????? ??? ????? ????? ??????.
4. ???? ???? ????? ??? ??????????.

19
????? ??????? ??????? ?????? ??????? ????

• ????? ???"? ?????? ???????? ?????? ????? ????
  ?????? ?????.
• ????? ??? ???? ??????? ?????? ??????? ??????
  ??????? ???? ?????? ??? ????? ?? ????? ???????
  ??????.
• CT ???? ?????? ??????? ???? ??? ???? ??? ???,
  ????? ?? ????? ???? ?????? ????? ??????.
• MRI ??? ???? ??????? ???? ??? ?????? ????? ????
  ?????? ?????? , ??? ??? ?????? ?????? ???"?.

20
Bisphosphonates in patients with Breast cancer
Bone metastases

• Delay in the onset of skeletal events
• Reduction in bone pain
• Decrease need for radiation therapy
• Reduction in skeletal morbidity rate
• No effect on overall survival

21
?????? ?? ?????

• ???? ?? ?????
• ????
• ??????
• ???????????
• ?????? ?????
• ?????? ??

22

• ????? ?????? ??????? ??????
• ???? ??? ?????? ???????
• ??????- ??? ??? ????? ?????? ?? 4?"? ?????? ??
  100 ??"? ?????? ?????? 0.9 ???? ?? ???? ?- 15
  ????.
• ?????? ?????? ???? ??? ?????? ?? ????? ??????.
• ????? ???? ?????? ??????? ?????.
• ?????, ????? ??? ?????? ?? ????? ????? ???????/?
  ????/? ?? ?? ?????? ?????? ??? ???????, ????
  ????? ?? ?? ?????? ????? ??????.

23
???? ?????????

• ??????? ???? ????? ????????? ??????? ????? ?-60
  ?"? ???? ????? ????? ????? ????? ?????? ?????
  ??????? ???? ?????.

24
?????? ???? ?? ?? ?????? ?????

• ???
• ???? ?????
• ??? ???????? ???
• ????? ??????

25
?????? ????? ?????? ?????? ?????????????

• ?????? ????? ??????
• ????? ??? ?- 24-38 ???? ???????.
• ????? ???? ??????? ???????
• ?????????? (????? ???? ????? ???)
• ???????????? (????? ??? ??????? ???)

26
?????? ?????- ????

• ???? ??????
• ????? ???????????
• ????? ?????? ????? ??????
• ????? ????? ??????? ???????
• ?????? ?????????????????(??????, ???????, ????
  ???)
• ?????????? (????? ??? ???????? ???)

27
?????? ????? - ????

• ?????? ????? ??????
• ?????? ??? ?? ?????
• ?????????? ?????????? (???????? ??????, ??????
  ??, ??????? ??.?.?.)
• ?????? ?????? ?????
• ???? ???????
• ??????????????
• ????????? ??????.

28
? ? ? ? ? ??????? ??????? ?????

• ???? ?????? ????? ?????
• ????? ???? ?????? ??????? ??? ??????? ????? ????
  ?????.

29
?????? ????? ?????? ???????

• ?????????????, ?????????????? ??? ????? ?? ???
  ????.
• ??????
• ???? ???? ???? ?????? ?????.
• ??????? ?????????? ??????????????.
• ??????? ?????? ?????? ??? ??? ????? ?????????.

30

• ???? ???