preoperative hormonal therapy - national cancer institute · preoperative hormonal therapy ian e....
TRANSCRIPT
![Page 1: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/1.jpg)
Preoperative Hormonal TherapyPreoperative Hormonal Therapy
Ian E. SmithIan E. SmithProfessor of Cancer MedicineProfessor of Cancer Medicine
Royal Marsden Hospital, LondonRoyal Marsden Hospital, LondonNCI Conference Washington
27th March 2007
![Page 2: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/2.jpg)
Estrogens Before Surgery for Large Estrogens Before Surgery for Large Breast CancersBreast Cancers
“The cancers in the treated patients were altered by complete or partial softening.
Many of the tumours became mobile, smaller and more difficult or impossible to
palpate….”.
Kennedy et al Cancer Sept 1957Kennedy et al Cancer Sept 1957
![Page 3: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/3.jpg)
How Effective Is Preoperative How Effective Is Preoperative Hormonal Therapy in:Hormonal Therapy in:
1. Achieving Clinical Tumour 1. Achieving Clinical Tumour Regressions?Regressions?
2.2.DownstagingDownstaging to Avoid to Avoid Mastectomy?Mastectomy?
![Page 4: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/4.jpg)
Randomised Preoperative Randomised Preoperative Hormonal Therapy TrialsHormonal Therapy Trials
B-24 Tamoxifen v Letrozole
IMPACT Tamoxifen v Anastrozole v Combination
PROACT Tamoxifen v Anastrozole (+CT)
0223 Anastrozole v Anastrozole + Gefitinib
Tamoxifen v Exemestane
Anastrozole v Exemestane v CT
First 4 double blind, multicentre,postmenopausal, ER and/or PgR+ve
![Page 5: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/5.jpg)
P24: PreoperativeP24: PreoperativeTamoxifenTamoxifen v v LetrozoleLetrozole
• 337 patients Median age 68
• 4 months treatment
• None suitable for conservative surgery
• 14% locally advanced
• Primary endpoint: Clinical Objective Response
Eiermann et al 12:1527 Ann Oncol. 2001
![Page 6: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/6.jpg)
P24: PreoperativeP24: PreoperativeTamoxifenTamoxifen v v LetrozoleLetrozole
LetrozoleTamoxifen
n 170 154
Clinical OR* 36 (4)% 56 (10)% p <0.001
Ultrasound OR* 25% 35% p 0.04
BCS** 35% 45% p 0.02
* Overall Response (CR) **Breast Conserving SurgeryEiermann et al 12:1527 Ann Oncol. 2001
![Page 7: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/7.jpg)
IMPACT: PreoperativeIMPACT: PreoperativeTamoxifenTamoxifen v v AnastrozoleAnastrozole v Combinationv Combination
• 330 patients Median age 73
• Median tumour diameter 3.8 (1-15)cm
• 3 months treatment
• 96 (44%) suitable for conservative surgery
• No locally advanced
• Primary endpoint: Clinical Objective Response
Smith et al JCO 23: 5108 2005
![Page 8: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/8.jpg)
IMPACT: PreoperativeIMPACT: PreoperativeTamoxifenTamoxifen v v AnastrozoleAnastrozole v Combinationv Combination
Tamoxifen Anastrozole Combination
n 108 113 109
Clinical OR* 36% 37% 39% nsd
Ultrasound OR* 20% 24% 28% nsd
BCS** 22% 46% 26% p 0.03
* Overall Response **Breast Conserving SurgerySmith et al JCO 23: 5108 2005
![Page 9: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/9.jpg)
PROACT: PreoperativePROACT: PreoperativeTamoxifenTamoxifen v v Anastrozole Anastrozole
• 451 patients + Chemotherapy
• 330 no CT
• 3 months treatment
• >3cm operable or locally advanced
• Primary endpoint: Clinical Objective Response
Cataliotti et al Cancer 106: 2095; 2006
![Page 10: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/10.jpg)
PROACT: PreoperativePROACT: PreoperativeTamoxifenTamoxifen v v AnastrozoleAnastrozole (Endocrine Therapy only)(Endocrine Therapy only)
Tamoxifen Anastrozole
n 151 163
Clinical OR* 40% 50% nsd
Ultrasound OR* 27% 36% nsd
BCS** 31% 43% p0.04
* Overall Response **Breast Conserving SurgeryCataliotti et al Cancer 2006
![Page 11: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/11.jpg)
Preoperative Exemestane vs Preoperative Exemestane vs TamoxifenTamoxifen151 patients151 patients
<0.050.092<0.05P Value
20.037.340.0Tamoxifen(n=75)
36.860.576.3Exemestane(n=76)
BCSRate (%)
UltrasoundORR (%)
Clinical ORR (%)
Update of Semiglazov et al. J Clin Oncol. 2005;23(16S):11s. Abstract 530.
![Page 12: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/12.jpg)
ACOSOG Z1031: Randomized Neoadjuvant AI Protocol
Exemestane
ER+ PMWStage II and IIITarget: 375 pts
Letrozole
4 months
Postsurgery management atinvestigator’s
discretion
Anastrozole
ACOSOG = American College of Surgeons Oncology Group.
SURGERY
RANDOMIZE
![Page 13: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/13.jpg)
Is Preoperative Endocrine Therapy As Is Preoperative Endocrine Therapy As Effective As Chemotherapy?Effective As Chemotherapy?
![Page 14: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/14.jpg)
Randomise
Exemestane AnastrozoleOR 80% 91% 38% BCS 33% 38% 21%
117 older patients ER+ve
Semiglazov SABCC. 2004
Adria/ Taxol
Preoperative Preoperative ExemestaneExemestane v v AnastrozoleAnastrozole v CTv CT
![Page 15: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/15.jpg)
37
61
Res
pons
e %
2 consecutive trials run by same investigatorswith similar entry criteria
56
What Is the Optimal Duration of Preoperative Endocrine Therapy?AI Response Rates %
223P24 IMPACT3mo 4mo4mo
Letrozole Anastrozole
![Page 16: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/16.jpg)
Tamoxifen Alone v Surgery + Tamoxifen:‘Golden Oldies’
• CRC UK trial tamoxifen alone v surgery and tamoxifen
• 451 women 70 years or over• significantly higher loco-regional relapse rate with
tamoxifen alone [23% v 8%] • Overall and breast cancer mortality worse (HR 1.68)
although curves did not diverge for 3 years
Bates et al Br J Surg 78:591-594, 1991Fennessy et al Br J Surg 91:699 2004
![Page 17: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/17.jpg)
% C
hang
e in
Cli
n V
olum
e
1 2 -2 4 months9 -1 2 months6 months3 months
1 0 0
8 0
6 0
4 0
2 0
0
M ean , M edian an d 95% CI of M ean
63 patients on 63 patients on LetrozoleLetrozole > 3 months> 3 monthsChanges in Clinical Volume over TimeChanges in Clinical Volume over Time
Dixon et al Edinburgh Breast Unit
![Page 18: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/18.jpg)
63 patients on 63 patients on LetrozoleLetrozole > 3 months> 3 months :
Time to Treatment FailurePr
obab
ility
of D
isea
se C
ontr
ol
Dixon et al Edinburgh Breast UnitYears
![Page 19: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/19.jpg)
Duration of Duration of NeoadjuvantNeoadjuvant AI Therapy:AI Therapy:ConclusionsConclusions
• Continuing Response for up to 2 years in some patients
• Longer duration may increase breast conservation
• Optimum duration not yet clear
• In general, not a long term substitute for surgery
![Page 20: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/20.jpg)
Which Patients Are Most Likely to Which Patients Are Most Likely to Respond to Preoperative Respond to Preoperative
Endocrine Therapy?Endocrine Therapy?
![Page 21: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/21.jpg)
Neoadjuvant Letrozole vs Tamoxifen (P024): Response by ER Expression
% of cases in each category
0
10
20
30
40
50
60
70
0 2 3 4 5 6 7 8ER Allred score
% R
espo
n
Logistic regression analysis of linear model
7.0 1.5 1.5 3.0 2.2 7.0 21.4 56.5
*
*
*
Tamoxifen(n=142) (P=0.0061)
Letrozole(n=136)(P=0.001)
*Only 18 patients had ER scores of 3-5.Ellis et al. J Clin Oncol. 2001;19:3808. .
![Page 22: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/22.jpg)
IMPACT (Anastrozole, Tamoxifen and Combination)Clinical Response Rate by ER Quartiles
Overall correlation p=0.02
Smith I.E. et al. J Clin Oncol; 23:5108-5116 2005
![Page 23: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/23.jpg)
IMPACT (Anastrozole, Tamoxifen and Combination)Clinical Response Rate by ER Quartiles
Overall correlation p=0.02
Smith I.E. et al. J Clin Oncol; 23:5108-5116 2005
![Page 24: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/24.jpg)
Clinical Response (%) in HER2+ TumoursClinical Response (%) in HER2+ TumoursR
espo
nse
rate
(%)
21%
88%
0
20
40
60
80
100
L T
Res
pons
e ra
te (%
)
22%
58%
0
20
40
60
80
100
A TLetrozole:P024
227 ptsIMPACT239 pts
pp=0.0004=0.0004
7/12 2/915/17 4/19
Ellis et al. J C.O. 2001;19:3808. .
pp=0.09 =0.09
Smith et al JCO 23: 5108 2005
![Page 25: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/25.jpg)
LetrozoleLetrozole v v tamoxifentamoxifen by HER2 statusby HER2 statusDFS DFS (BIG 1(BIG 1--98 Central Analysis)98 Central Analysis)
0.71 All patients (n=4399)
0.72 ER+ / HER2- (n=3971)
0.68 ER+ / HER2+ (n=234)
0.5 0.75 1.0 1.25 1.5
Favors L Favors T
Hazard Ratio (L:T) Viale et al SABCC.2005
![Page 26: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/26.jpg)
Anastrozole vsAnastrozole vs tamoxifentamoxifen by HER2 status: DFS by HER2 status: DFS ((TransATACTransATAC central analysis)central analysis)
Patients Events HR
HER2-
HER2+
Combined
2.01.00.5
1526 0.66149
0.9245190
200 0.721786
HR (A:T) and 95% CI
Anastrozole (A)better
Tamoxifen (T) better
Dowsett et al SABCC.2006
![Page 27: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/27.jpg)
Can Can NeoadjuvantNeoadjuvant Endocrine Therapy Endocrine Therapy Provide Short Term Surrogate Endpoints Provide Short Term Surrogate Endpoints
for Long Term Outcome? for Long Term Outcome?
![Page 28: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/28.jpg)
Can Neoadjuvant Endocrine Therapy Provide Short Term Surrogate Endpoints
for Long Term Outcome?
• Clinical Objective Response?
Neoadjuvant AdjuvantP24 Letrozole v Tam BIG 1-98 YesIMPACT A v T v C ATAC NoPROACT A v Tam ATAC NoHER2+ve P24/ IMPACT ATAC/B 1-98 No
![Page 29: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/29.jpg)
Can Neoadjuvant Endocrine Therapy Provide Short Term Surrogate Endpoints
for Long Term Outcome?
• Path Complete Remission?pCR
IMPACT A v T v C 0.5%223 A v A +G 0%P24 L v T 1.5%
![Page 30: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/30.jpg)
Can Neoadjuvant Endocrine Therapy Provide Short Term Surrogate Endpoints
for Long Term Outcome?
• Molecular Endpoints?
![Page 31: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/31.jpg)
IMPACT: Ki67 % Change (95% CI)from Baseline* During Treatment
Weeks0
2 12
A T C-10
-20
-30
-40
Ki6
7
-50
-60
-70
-80A v T p=0.004-90 A v T p<0.001
AnastrozoleTamoxifenCombination
-100
* Via transformation of geometric mean proportion of baseline
Dowsett and Smith Clin Cancer Res 2005; 11: 951s-958s
![Page 32: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/32.jpg)
IMPACT Ki67 (%): individual patient plots —anastrozole
Prol
ifera
tion
Ki6
7 (%
)Pr
olife
ratio
n K
i67
(%)
Time (weeks)Time (weeks)0
50
40
30
20
10
0122
Poor Ki67 respondersGood Ki67 respondersShort Ki67 responders
![Page 33: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/33.jpg)
223 Anastrozole ± GefitinibNeoadjuvant Trial Design
206 pts Randomise
Anastrozole AnastrozoleGefitinibMolecular Response- 2wks
-Ki67-mRNA
Clinical Response- 4months
4mo
4mo
Surgery Surgery
![Page 34: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/34.jpg)
Mean change in Ki67: baseline to 16 wksAnastrozole
V. Placebo
16 weeks
A + G(n=59)
A alone(n=50)
-77.4% -83.6%
AnastrozoleGefitinib
Change in Ki67 levels (%)
0
-20
-40
-60
-80
p=0.26-100
Dowsett, Smith et al ASCO 2006
![Page 35: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/35.jpg)
Objective tumour response rates
Initially sensitive and less sensitive (Ki67)
46% 66% 38% 48%
Anastrozole + gefitinibAnastrozole alone
p=0.500b
Initially less sensitive(Ki67)
p=0.083a
Initially sensitive(Ki67)Patients (%) 100
8025/38
6012/2518/39
8/2140
20
0Objective response rate (CR + PR)
aTreatment difference: -19.6 (-41.4, 2.1); bTreatment difference: -9.9 (-38.5, 18.6)
![Page 36: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/36.jpg)
Can Short Term Molecular Endpoints With Neoadjuvant Endocrine Therapy Predict for Long
Term Outcome In the Individual Patient?
![Page 37: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/37.jpg)
Relapse Free Survival by Baseline LnKi67
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8
Years since randomisation
Rel
apse
Fre
e Su
rviv
<=2.252.25-2.993+
<=2.25 N = 51 O = 5 E = 8.42.25-2.99 N = 55 O = 8 E = 9.93+ N = 52 O = 13 E = 7.7 Chis = 4.68 df = 1 p = 0.03
IMPACT RFS by Baseline Ln Ki67
![Page 38: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/38.jpg)
Relapse Free Survival by 2 week LnKi67
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8
Years since Randomisation
Rel
apse
Fre
e Su
rviv
al %
<=0.80.81-1.992+
<=0.8 N = 45 O = 3 E = 7.90.81-1.99 N = 60 O = 9 E = 10.62+ N = 54 O = 14 E = 7.4 χ2 = 8.65 df = 1 p = 0.003
IMPACT 2005
IMPACT RFS by 2 week Ln Ki67
Professor Dowsett to Discuss
![Page 39: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/39.jpg)
UK POETIC Trial PPrereooperative perative EEndocrine ndocrine TTherapy herapy
IIndividualising ndividualising CCareare
Standard Adjuvant TherapyS•Postmenopausal.
•HR+veR
2 wks Standard Adjuvant TherapyS
Ki67molecular
DFSEndpoints
![Page 40: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/40.jpg)
Preoperative EndocrineTherapy:Conclusions (1)
• Aromatase inhibitors are more effective than tamoxifen
• Around 50% objective responses
• Breast conservation in >40% initially requiring mastectomy
![Page 41: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/41.jpg)
Preoperative EndocrineTherapy:Conclusions (2)
• Optimum duration uncertain but at least 4 months
• Well worth thinking about instead of chemotherapy in older patients with strongly ER/PgR+ cancers
• How to select?
![Page 42: Preoperative Hormonal Therapy - National Cancer Institute · Preoperative Hormonal Therapy Ian E. Smith Professor of Cancer Medicine Royal Marsden Hospital, London NCI Conference](https://reader031.vdocuments.net/reader031/viewer/2022020305/5c69631b09d3f263648d1404/html5/thumbnails/42.jpg)
Preoperative Hormonal TherapyConclusions (3)
• Clinical response is not a reliable surrogate for long term outcome
• PathCRs are too rare to be a useful surrogate
• Molecular markers (including after short term therapy) are more likely to be useful as short term predictors of outcome