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Vivianne Tjan-Heijnen, MJ Pepels, M de Boer, GF Borm, JA van Dijck, CH van Deurzen, EM Adang, MB
Menke-Pluymers, PJ van Diest and P Bult
On behalf of the Dutch Breast Cancer Trialists’ Group (BOOG)
Funded by The Netherlands organization for health research and development (ZonMw)
Impact of omission of completion ALND or axRT in breast cancer patients with pN1mi or pN0(i+) in SN: results from the Dutch MIRROR study
Micrometastases and Isolated tumor cells:
Relevant and Robust Or Rubbish?
A cohort study from the Netherlands
in 2680 early stage breast cancer patients who had undergone a SN
procedurein 1997 – 2005
The MIRROR study
Background MIRROR study• SN procedure has led to an increased
detection of isolated tumor cells, pN0(i+),
and micrometastases, pN1mi
• Previous studies - before the SN era -
showed conflicting results on the prognostic
impact of small nodal metastases
MIRROR conclusions, SABCS ‘08• In patients not receiving AST, pN0(i+) and
pN1mi were prognostic factors for DFS – pN0(i+): HR 1.50 (95%CI 1.15-1.95)
– pN1mi: HR 1.52 (95%CI 1.11-2.09)
• Our data show that both patients with pN0(i+) and pN1mi benefit from AST– pN0(i+): HR 0.67 (95%CI 0.46-0.96)
– pN1mi: HR 0.50 (95%CI 0.35-0.72)
De Boer et al. SABCS dec 2008; oral #23
• Nearly 50% of 795 patients with pN0(i+)(sn) and approximately 15% of 1028 patients with pN1mi(sn) had not received further axillary treatment
• In 8% of patients with pN0(i+)(sn) or pN1mi(sn) axillary treatment consisted of axRT only
• Data on safety and efficacy of such strategies regarding axillary recurrence (AR) are, however, lacking
Background 2nd MIRROR analyses
• Patients selected from the Netherlands Cancer Registry
– invasive breast cancer diagnosed 1997 - 2005
– SN procedure
– final N-status: pN0, pN0(i+) or pN1mi
– favorable characteristics (Dutch guidelines 2002)
• tumor size ≤ 1 cm irrespective of grade OR
tumor size 1-3 cm and grades I-II
Patients and methods
•no pathology review•macrometastases
•unfavorable tumor characteristics •other reasons
n = 3205selected from Netherlands
Cancer Registry
n = 2680inclusion after central
pathology review
Accrual
SN onlyN= 1218
cALNDN= 1314
axRTN= 148
•no pathology review•macrometastases
•unfavorable tumor characteristics •other reasons
n = 3205selected from Netherlands
Cancer Registry
n = 2680inclusion after central
pathology review
Accrual
SN onlyN= 1218
cALNDN= 1314
axRTN= 148
•no pathology review•macrometastases
•unfavorable tumor characteristics •other reasons
n = 3205selected from Netherlands
Cancer Registry
n = 2680inclusion after central
pathology review
Accrual
SN onlyN= 1218
cALNDN= 1314
axRTN= 148
Present analysis: categorized by SN-status
SN onlyn= 1218
cALND n= 1314
axRTn= 148
P-valueSN only
vs cALND / RT
SN status
pN0 60% 9% 3%
pN0(i+) 28% 30% 36% <0.0001
pN1mi 12% 61% 61%
Baseline characteristics
SN onlyn= 1218
cALND n= 1314
axRTn= 148
P-valueSN only
vs cALND / RT
Tumor size
≤ 1 cm 36% 25% 24%
<0.00011.1-2.0
cm54% 58% 64%
2.1-3.0 cm
10% 18% 13%
Baseline characteristics
SN onlyn= 1218
cALND n= 1314
axRTn= 148
P-valueSN only
vs cALND / RT
Adjuvant systemic therapy
No 87% 45% 39%<0.0001
Yes 13% 55% 61%
Baseline characteristics
SN onlyn= 1218
cALND n= 1314
axRTn= 148
P-valueSN only
vs cALND / RT
RT breastNo 29% 35% 5%
0.09Yes 71% 65% 95%
Baseline characteristics
Axillary recurrence rate in all included patients
5-yrs AR 1.7%
Objectives
1. To determine the impact of omission of axillary therapy on 5-yrs AR rate by SN status
2. To determine the efficacy of axRT vs cALND
3. To determine other factors predictive for AR
Objectives
1. To determine the impact of omission of axillary therapy on 5-yrs AR rate by SN status
Variable N5-yrsAR
HR 95 % CI
pN0(sn) * cALND 125 1.6% 1.00
pN0(sn) * SN only 732 2.3% 1.08 0.23-4.98
HR, corrected for age, tumor size, differentiation grade, hormone receptor status, adjuvant systemic therapy, radiotherapy to the breast
MV analysis: axillary recurrence (AR)
Variable N5-yrsAR
HR 95 % CI
pN0(i+)(sn) * cALND/axRT
450 0.9% 1.00
pN0(i+)(sn) * SN only 345 2.0% 2.39 0.67-8.48
HR, corrected for age, tumor size, differentiation grade, hormone receptor status, adjuvant systemic therapy, radiotherapy to the breast
MV analysis: axillary recurrence (AR)
Variable N5-yrsAR
HR 95 % CI
pN1mi(sn) * cALND / axRT
887 1.0% 1.00
pN1mi(sn) * SN only 141 5.0% 4.391.46-13.24
HR, corrected for age, tumor size, differentiation grade, hormone receptor status, adjuvant systemic therapy, radiotherapy to the breast
MV analysis: axillary recurrence (AR)
Conclusions• For low-risk patients with pN0(sn), we confirm the
safety of no further axillary treatment
• For low-risk patients with pN0(i+)(sn), omission of axillary treatment resulted in an increased hazard ratio (HR 2.39) for AR, though statistically not significant
• For patients with pN1mi(sn), omission of axillary treatment resulted in a significantly increased AR rate (5% at 5 yr, HR 4.39)
Objectives
1. To determine the impact of omission of axillary therapy on 5-yrs AR rate by SN status
2. To determine the efficacy of axRT vs cALND
Variable N5-years
AR
pN0(i+)(sn) * cALND 396 1.0%
pN0(i+)(sn) * axRT 54 0%
pN0(i+)(sn) * SN 345 2.0%
pN1mi(sn) * cALND 793 1.1%
pN1mi(sn) * axRT 94 0%
pN1mi(sn) * SN 141 5.0%
Efficacy of axRT
Conclusion
• An AR rate of 0% at 5-years in patients treated with axRT is provocative, challenging the current recommendation of cALND
• However, more data on axRT are needed for a meaningful statistical analysis and before firm conclusions can be drawn (e.g. AMAROS study)
Axillary recurrence rate in pN1mi(sn)
SN only: HR 4.39 (95% CI 1.46 –13.24)
Objectives
1. To determine the impact of omission of axillary therapy on 5-yrs AR rate by SN status
2. To determine the efficacy of axRT vs cALND
3. To determine other factors predictive for AR
Variable HR 95 % CI P-value
Tumor size 8.62 1.38 – 53.84 0.021
MV analysis: 5-yrs AR rate pN1mi(sn)
Variable HR 95 % CI P-value
Tumor size 8.62 1.38 – 53.84 0.021
Histological grade III 25.05 1.26 – 497.18 0.035
MV analysis: 5-yrs AR rate pN1mi(sn)
Variable HR 95 % CI P-value
Tumor size 8.62 1.38 – 53.84 0.021
Histological grade III 25.05 1.26 – 497.18 0.035
Negative ER / PgR status
4.96 1.48 – 16.62 0.010
MV analysis: 5-yrs AR rate pN1mi(sn)
Variable HR 95 % CI P-value
Tumor size 8.62 1.38 – 53.84 0.021
Histological grade III 25.05 1.26 – 497.18 0.035
Negative ER / PgR status
4.96 1.48 – 16.62 0.010
No systemic therapy 1.36 0.47 – 3.99 0.572
MV analysis: 5-yrs AR rate pN1mi(sn)
Variable HR 95 % CI P-value
Tumor size 8.62 1.38 – 53.84 0.021
Histological grade III 25.05 1.26 – 497.18 0.035
Negative ER / PgR status
4.96 1.48 – 16.62 0.010
No systemic therapy 1.36 0.47 – 3.99 0.572
No breast radiotherapy
1.01 0.36 – 2.88 0.979
MV analysis: 5-yrs AR rate pN1mi(sn)
Conclusion
• Tumor size, grade, and hormone receptor status were predictive for AR in patients with pN1mi(sn)
• Omission of adjuvant systemic therapy resulted in an increased hazard ratio for AR, though statistically not significant
• Radiotherapy on the breast had no impact on AR rate
Take Home Message• For patients with pN0(sn), omission of axillary
therapy is safe and standard policy
• For patients with pN0(i+)(sn), omission of axillary therapy may only be safe in the presence of otherwise favorable tumor characteristics
• We recommend completion axillary treatment in patients with pN1mi(sn) to reduce the AR rate
Take Home Message
• More data are needed on the efficacy of axRT, though results are provocative
• Unfavorable tumor size, grade, and hormone receptor status should be taken into account when considering ‘SN only’ in patients with pN0(i+)(sn) or pN1mi(sn)
Project Leader:Vivianne Tjan-Heijnen, Maastricht University Medical
Centre
Study Coordinators:Maaike de Boer, Maastricht University Medical CentreManon Pepels, Maastricht University Medical Centre
Steering Committee:Peter Bult, Radboud University Nijmegen Medical
CentrePaul van Diest, University Medical Centre UtrechtJos van Dijck, Comprehensive Cancer Centre East,
NijmegenEddy Adang, Radboud University Nijmegen Medical
CentreHans Nortier, Leiden University Medical CentreEmiel Rutgers, National Cancer Institute / A. van
Leeuwenhoek Hospital, AmsterdamCaroline Seynaeve, University Medical Centre
RotterdamMarian Menke-Pluymers, University Medical Centre
Rotterdam
Central Pathology Review:Peter Bult, Radboud University Nijmegen Medical
CentreCarolien van Deurzen, University Medical Centre
UtrechtPaul van Diest, University Medical Centre Utrecht
Statistical Analysis:George Borm, Radboud University
Nijmegen Medical CentreWim Lemmens, Radboud University
Nijmegen Medical Centre
Participating Centres:All Dutch Pathology Laboratories (n
= 60)All Dutch Hospitals (n = 113)All Dutch Comprehensive Cancer
Centres (n = 8)
Data Management:Comprehensive Cancer Centre EastJolanda van Beek - Schoester
Supported by:Dutch Breast Cancer Trialists’ Group
(BOOG)
Funded by:The Netherlands organization for
health research and development (ZonMw)
Steering group - acknowledgements