Halstead

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+ ? ?


about 6570% of patients with operable breast cancer and clinically negative axillary lymph nodes will have negative axillary nodes on histologic examination about 50% of patients with positive SLN will have no additional non-sentinel axillary nodal metastases
Voogd AC, Coebergh JW, Repelaer van Driel OJ et al, The risk of nodal metastases in breast cancer patients with clinically negative lymph nodes: a population-based analysis. Breast Cancer Res Treat 2000; 62: 639. Van Zee KJ, Manasseh DM, Bevilacqua JL, et al: A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol 10:1140-1151, 2003

 ?
American College of Surgeons Oncology Group (ACOSOG) Z0011
phase III trial, in which patients with nodal metastases identied by SLNB were randomly assigned to no additional axillary surgery or to completion ALND to assess differences in axillary recurrence and survival 1998-2005 had reached only 36% of the goal, and the axillary recurrences were lower than expected. The trial was closed in 2004 (they had scared!!)

Dutch MIRROR study (1998-2005)

is the largest cohort study on pN1mi and pN0(i+) in the SN era with long-term follow-up, central pathology review (6th AJCC-classification), and separate analyses on the use of adjuvant systemic therapy (AST).

conflicts???

The American Society of Clinical Oncology (ASCO) 45th Annual Meeting (june 2009):

American College of Surgeons Oncology Group (ACOSOG) Z0011

Node Positive (n = 97,314)

SLNB for Stages I-III Breast Cancer (N = 403,167)

Node Negative (n = 305,853)

Macroscopic Nodal Disease (n = 87,055)

Microscopic Nodal Disease (n = 10,259)

SLNB Alone (n = 16,543)

SLNB + cALND (n = 70,512)

SLNB Alone (n = 3,674)

SLNB + cALND (n = 6,585)

American College of Surgeons Oncology Group (ACOSOG) Z0011

Of the 97,314 patients who underwent SLNB and had nodal involvement, 20.8% of patients underwent SLNB alone, 79.2% underwent SLNB with a completion ALND.

Median follow-up was 63 months for patients diagnosed in 1998 to 2000.

American College of Surgeons Oncology Group (ACOSOG) Z0011

From1998 to 2005, the proportion of patients who underwent SLNB alone for macroscopic disease declined : 24.2% to 16.7%; P .001; however, the proportion of patients who underwent SLNB alone for microscopic metastases increased 24.7% to 45.3%; P .001

American College of Surgeons Oncology Group (ACOSOG) Z0011 Patient Characteristics: SLNB Alone v SLNB With Completion ALND
All (n = 97,314) Tumor size, cm Pathologic T classication 1 2 3 Grade Low/indeterminate High Unknown Adjuvant chemotherapy received 2.0 (1.5-3.0 1.8) SLNB Alone (n = 20,217) 2.1 (1.3-2.5) SLNB With Completion ALND (n = 77,097) 1.8 (1.5-3.0)
 .001

50,599 (52.0%) 40,643 (41.8%) 6,072 (6.2%)

12,724 (62.9%) 6,960 (34.4%) 533 (2.6%)

37,875 (49.1%) 33,683 (43.7%) 5,539 (7.2%)

52,807 (54.3%) 36,829 (37.8%) 7,678 (7.9%) 66,111 (67.9%)

11,888 (58.8%) 6,579 (32.5%) 1.750 (8.7%) 12,392 (61.3%)

40,919 (53.1%) 30,250 (39.2%) 5,928 (7.7%) 53,719 (69.7%)

 .001

Adjuvant radiation therapy received After breast conservation surgery 39,434 (72.1%) After mastectomy 13,570 (31.8%) Hormonal therapy received 38,456 (39.5%)

11,874 (72.1%) 795 (21.2%) 8,260 (40.9%)

27,560 (72.1%) 12,775 (32.8%) 30,196 (39.2%)


American College of Surgeons Oncology Group (ACOSOG) Z0011
In 1998 to 2000, the median number of nodes examined was similar for the SLNB-alone group (n=11; interquartile range, 4 to 16) and for SLNB with completion ALND group (n=14; interquartile range, 10 to 19). In 2004 to 2005, the median numbers of nodes examined in the SLNB-alone (n=3 interquartile range, 2 to 5) And for SLNB with completion ALND group (n=13 interquartile range, 9 to 18)

American College of Surgeons Oncology Group (ACOSOG) Z0011

There was not a signicant difference in outcomes between SLNB alone (5 or fewer nodes) versus SLNB with cALND(9 or more nodes) in patients with macroscopic nodal metastases SLNB cALND v 1.2%; P
.40 axillary recurrence 1.0 relative survival 98.5% v 98.2%; P
.72 observed survival 82.1% v 81.8%; P
.55

American College of Surgeons Oncology Group (ACOSOG) Z0011

There was a nonsignicant trend toward worse outcomes with SLNB alone (5 or fewer nodes) versus SLNB with cALND (9 or more nodes) for macroscopic disease as follows: axillary recurrence (hazard ratio, 0.58; 95% CI, 0.32 to 1.06) overall survival (hazard ratio, 0.89; 95% CI, 0.76 to 1.04)

American College of Surgeons Oncology Group (ACOSOG) Z0011

In patients with microscopic nodal metastases, we found that there were no signicant differences in axillary recurrence or survival for SLNB alone versus SLNB with completion ALND.

American College of Surgeons Oncology Group (ACOSOG) Z0011

Thus, completion ALND does not appear to benet patients with microscopic nodal disease

American College of Surgeons Oncology Group (ACOSOG) Z0011

Also was found that patients were more likely to undergo SLNB alone if they were older, had smaller primary tumors, or were treated at non-NCI (National Cancer Institute) -designated cancer centers. Race/ethnicity was only associated with lymph node evaluation for macroscopic disease

Potential limitations of this study

First, retrospective evaluation of treatment can be confounded by indication, as patients are not randomly assigned to treatment groups (patients who were selected or elected to undergo SLNB alone would have fewer axillary recurrences and better survival, as they were more likely to have tumors more favorable to response).

Potential limitations of this study

Second, analyses are limited by the data collected by cancer registries. The NCDB does not contain data regarding the method of pathologic evaluation of lymph node specimens, whether additional lymph nodes were positive in completion ALND specimens, or whether the axilla was specically included in the radiation eld.

Potential limitations of this study

Third, the proportion of patients with axillary recurrences in this study is low relative to older reports, although this may reect the effect of adjuvant therapy. Recurrences and the dates of recurrence are difcult to capture and may be underreported to cancer registries. Longer surveillance may reveal a subtle increase in axillary recurrences, but most axillary recurrences occur within 24 to 36 months of surgery, and the median follow-up of this study was 63 months.

Potential limitations of this study

Finally, we performed a subgroup analysis by using lymph node count constraints of ve or fewer lymph nodes for SLNB alone and nine or more lymph nodes for ALND alone. This may introduce an immeasurable bias

American College of Surgeons Oncology Group (ACOSOG) Z0011

In conclusion: This study offers evidence that axillary recurrence and survival are comparable for SLNB alone versus SLNB with completion ALND for microscopic nodal disease and, in selected patients, for macroscopic nodal metastases

The Dutch MIRROR study

The largest cohort study on pN1mi and pN0(i+) in the SN era with long-term follow-up, central pathology review (6th AJCC-classification), and separate analyses on the use of adjuvant systemic therapy (AST).

The Dutch MIRROR study

Patients operated for breast cancer in all Dutch hospitals in the years 1998-2005, having favorable primary tumor characteristics, and having undergone an SN biopsy without macrometastases as final N-stage were included. Median follow-up was 4.7 years.

The Dutch MIRROR study Results

n
pN0(i-)(sn) cALND pN0(i-)(sn) SN

5-year AR(%) 1.9 2.2 1.1 1.7 1.2 6.2

HR AR (95%CI)* 1.00 1.07 (0.23 - 4.94) 1.00 2.14 (0.57 - 7.96) 1.00 4.45 (1.46 - 13.54)

113 722 459 340 828 130

pN0(i+)(sn) cALND or ax RT pN0(i+)(sn) SN pN1mi(sn) cALND or ax RT pN1mi(sn) SN

all

2.592

* Corrected for AST, age, (log) tumor size, grade, hormone receptor status.

The Dutch MIRROR study Conclusions

Omission of cALND or ax RT in patients with pN1mi(sn) resulted in a significantly higher 5-year AR rate, even after correction for AST, and other patient and tumor characteristics. This indicates that patients with pN1mi(sn) should undergo cALND or ax RT to prevent AR.

they worked with different definitions of the small amounts of disease that can be found by SLNB.

 In the Dutch study, the investigation separated microscopic disease into 2 groups: the smaller isolated tumor cells (<0.2 mm) and the larger micrometastases (0.2 to 2.0 mm). The American study did not separate the 2 classifications because, before 2002, both categories were "lumped together," and thus were analyzed as "microscopic" disease, said Dr. Tjan-Heijnen, explaining that the American study's outcome findings date from before 2002.

:
"We have relied upon that operation too much, and this paper points out that we may not need to do it in terms of a survival difference or a regional recurrence difference. This is an operation associated with significant morbidity," Dr. Winchester said in a statement. For instance, the risk for edema is 30% to 40% with completion ALND, and 2% to 5% with SLNB, he said.

:
An American breast cancer expert attending the meeting felt swayed by the Dutch findings. "We might have to be more aggressive with micrometastases they should not be ignored," Julie Gralow, MD