sentinel lymph node dissection (slnd) for breast cancer

1

ACOSOG Z0011: A Randomized Trial of Axillary

Node Dissection in Women with Clinical T1-2 N0 M0 Breast

Cancer who have a Positive Sentinel Node

Giuliano AE, McCall L, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt K,

Morrow M, Ballman KV

2

• SLND has replaced axillary lymph node dissection (ALND) for histopathologically node-negative women

• Numerous studies have demonstrated its staging efficacy and safety

• ALND remains the gold standard for node-positive women

• ALND more morbidity than SLND

Sentinel Lymph Node Dissection (SLND) for Breast Cancer

3

Contemporary Breast Cancer• Tumors are smaller than in past

• Fewer node-positive patients

• Sentinel node (SN) often only node involved (40-70%)

• BCT common – tangential field irradiation treats much of axilla

• Adjuvant systemic therapy usually given for node-positive women

4

Modern Randomized Trials of Axillary Treatment with BCT

Martelli G, Ann Surg 2005, 242:1; Louis-Sylvestre C, JCO 2004, 22:97; Veronesi U, Ann Oncol 2005, 16:383.

ALND vs. Ax RT

Author

Median F/U

N

Axillary Recurrence

Ax RT vs. ObsALND vs. Obs

Louis-SylvestreVeronesiMartelli

5

219

0 vs 1.8%

5.3

435

0.5% vs 1.5%

15

658

1% vs 3%

No significant differences in survival

5

Hypothesis:

SLND alone achieves

similar locoregional control

and survival as

Level I and II ALND for H&E

SN node-positive women.

6

ACOSOG Z0011

A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive SN

165 Investigators / 177 Institutions

50 investigators with 5 or more patients

Target accrual 1900 patients (non-inferiority)

Closed early

7

Inclusion/Exclusion Criteria

Eligibility• Clinical T1 T2 N0 breast

cancer• H&E-detected

metastases in SN (AJCC 5th edition)

• Lumpectomy with whole breast irradiation

• Adjuvant systemic therapy by choice

Ineligibility• Third field (nodal

irradiation) or APBI• Metastases in SN

detected by IHC• Matted nodes• 3 or more involved

SN

8

Z0011 Study Design Schema

9

Study Population Schema 5/99–12/04

10

All analyses performed on both intent-to-treat and

actual treatment received.No meaningful differences

in findings. Intent-to-treat analysis

reported.

11

Patient and Tumor Characteristics

Age (median range)

Clinical Stage T1T2

ER(+)(-)

LVI YesNo

56 (24-92)

67.9%32.1%

83.0%17.0%

67.7%32.3%

40.6%59.4%

ALND (420 pts)

54 (25-90)

29.4%

17.0%

64.8%

70.6%

83.0%

69.9.%

35.2%

SLND(436 pts)

30.1%

PR(+)(-)

12

Patient and Tumor Characteristics

Modified Bloom-Richardson22.0%

48.9%

1.7 (0.4-7.0)

46.8%

25.6%

1.6 (0.0-5.0)Clinical Tumor Size (median cm.)

29.1% 27.5%

I

II

III

ALND (420 pts)

SLND(436 pts)

SLNDSLNDALNDALND

Adjuvant Systemic Therapy

Chemotherapy 57.9% 58.0%

Hormonal therapy 46.4% 46.6%

Either/Both 96.0% 97.0%

P = N.S.

14

Median Number of Lymph Nodes Removed

15

Size of SN Metastasis

16

Number of Positive Lymph Nodes

17

106 (27.4%) patients treated with ALND

had additional positive nodes removed

beyond SN.

18

Locoregional Recurrences

SLND(436 pts)

ALND (420 pts)

2 (0.5%) 4 (0.9%)Regional (Axilla, Supraclavicular)

15 (3.6%) 8 (1.8%)Local (Breast)

17 (4.1%) 12 (2.8%)Total Locoregional

Recurrence

Median follow-up = 6.3 years

Regional recurrence seen in only 0.7% of the entire population

P = 0.11

19

It is highly improbable that the 0.9% regional or 2.8% locoregional recurrence with SLND would significantly impact

survival.

20

Locoregional Recurrence-Free Survival

21

Associations of Prognostic Variables with Locoregional Recurrence

ER status

PR status

Tumor Size

Histologic Type

0.0002

NS

NS

NS

0.0012

NS

0.0002

0.0421

NS

LVI present vs. absent

SN Metastasis Size

# Positive Total LN

Modified Bloom-Richardson

Treatment Arm

Adjuvant Systemic Therapy

Age (< 50, > 50)

0.0207

NS

NS

NS

NS

NS

NS

NS

0.0258

0.0260

NS

NS

NS

Univariable AnalysisP value

Multivariable AnalysisP value

22

ER/PR Status and 5-Year Locoregional Recurrence-Free Survival

23

Disease-Free Survival

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Time (Years)

% R

ecu

rren

ce-F

ree

and

Aliv

e

ALND

No ALND

P-value = 0.14

24

Associations of Prognostic Variables with Disease-Free Survival

PR status

Tumor Size

Histologic Type

0.031

0.002

0.016Adjuvant Systemic Therapy

NSTreatment Arm NS

0.005# Positive Total LN NS

ER status 0.0003 0.007

NS

Age (< 50, > 50) NS NS

0.006

NS

NS NS

LVI present vs. absent NS NS

Modified Bloom Richardson

Univariable AnalysisP value

Multivariable AnalysisP value

NSNS

NSSN Metastasis Size NS

25

ER/PR Status and 5-Year Disease-Free Survival

260

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8

Time (Years)

% A

live

ALND

No ALND

P-value = 0.25

Overall Survival

27

Associations of Prognostic Variables with Overall Survival

PR status

Tumor Size

Histologic Type

NS

0.042

0.020

Univariable AnalysisP value

Multivariable AnalysisP value

Adjuvant Systemic Therapy

NSTreatment Arm NS

0.044# Positive Total LN NS

ER status 0.012 0.013

NS

Age (< 50, > 50) 0.002 0.006

0.025

NS

NS NS

LVI present vs. absent NS NS

Modified Bloom Richardson NS NS

NSSN Metastasis Size NS

28

ER/PR Status and 5-Year Overall Survival

29

Summary

• Locoregional recurrence in only 2.8% of SLND and 4.1% of ALND patients.

• Only age (< 50) and higher Bloom-Richardson score were associated with locoregional recurrence by multivariable analysis.

• Neither number of positive SN, size of SN metastasis, nor number of lymph nodes removed was associated with locoregional recurrence.

Locoregional Recurrence-Free Survival

30

Summary

• No significant difference in DFS between patients treated with SLND (83.9%) or ALND (82.2%)

• No significant difference in OS between patients treated with SLND (92.5%) or ALND (91.8%)

• Only older age, ER-, and lack of adjuvant systemic therapy - not operation - were associated with worse OS by multivariable analysis.

Disease-Free and Overall Survival

31

Conclusion

In this prospective randomized study SLNDalone provided excellentlocoregional control andsurvival comparable to

completion ALND.

32

This study does not support the routine use of ALND in early

nodal metastaticbreast cancer. The role of this operation should be

reconsidered.

33

Acknowledgments

The authors thank our

courageous patients as well as

the ACOSOG staff and

investigators for their

contributions to this study.