from ASCO ?practice changing studies regarding sentinel lymph node biopsy vs

[Lani]

axillary clearance and need for immunohistochemistry of nodes biopsied

Sentinel Node Biopsy Studies Provide Practice-changing Results for Breast Cancer

New data indicate that axillary lymph node dissection is not necessary for women with clinically node-negative breast cancer who undergo sentinel node biopsy. In addition, immunohistochemistry (IHC) provides no additional benefit for patients with clinically node-negative disease and histologically negative nodes.

The American College of Surgeons Oncology Group (ACOSOG) study Z0010, which explored the clinical significance of sentinel node and bone marrow metastases detected by IHC, found that examination of histologically negative sentinel nodes by IHC adds no prognostic information (Abstract CRA504). These results were presented by Kelly K. Hunt, MD, FACS, of The University of Texas M. D. Anderson Cancer Center during the Breast Cancer — Local-regional and Adjuvant Therapy Oral Abstract Session that took place during ASCO's 2010 Annual Meeting.

Z0010, a prospective multicenter study, enrolled 5,210 eligible and evaluable patients who underwent lumpectomy and sentinel node biopsy as well as bilateral iliac crest bone marrow aspiration. Histologically negative sentinel nodes and bone marrow aspirates were also examined by IHC.

In her presentation, Dr. Hunt said that histologically negative sentinel nodes were identified in 3,995 of 5,210 patients (76%), and 349 patients (10%) had IHC-positive sentinel lymph node micrometastases. Additionally, bone marrow micrometastases were identified in 104 (3.0%) of the 3,413 patients examined.

Median patient age was 56. Eighty percent of patients had ductal-type tumors, approximately 85% of the tumors were smaller than 2 cm, more than 80% were estrogen receptor (ER)-positive, and 68% of tumors were progesterone receptor-positive.

Approximately half of the patients received chemotherapy, 68% underwent hormone therapy, more than 90% received radiotherapy, and more than 98% were given some form of adjuvant therapy.

Dr. Hunt stated that no concordance was observed between IHC-positive bone marrow metastases and IHC-positive sentinel lymph nodes. The larger the tumor size, the more likely sentinel lymph nodes were histologically or IHC-positive, she said. Tumor size was not correlated with IHC-positive bone marrow.

Five-year overall survival was 93% for the group with histologically identified metastases and 96% for the group with IHC-positive sentinel nodes or nodes that contain no IHC metastases (p = 0.0009). For patients with bone marrow metastases, 5-year overall survival was significantly decreased (p = 0.016); however, multivariate analysis (which included estrogen receptor status, progesterone receptor status, tumor grade, tumor size, and age, IHC-positive bone marrow) found that this was not an independent predictor for overall survival.

Z0010 found that histologically positive sentinel nodes were predictive for overall survival on both univariate (p = 0.0003) and multivariate (p = 0.007) analyses; however, IHC-positivity was not predictive for overall survival in either analysis. Other factors that were independent predictors of survival included younger age and tumor size.

Dr. Hunt concluded that routine examination of sentinel nodes by IHC is not warranted for this patient population.

National Surgical Adjuvant Breast and Bowel Project (NSABP) trial NSABP Protocol B-32
Results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-32 found that axillary dissection (AD) provided no additional benefit compared with sentinel lymph node (SN) removal for patients with clinically node-negative breast cancer and a histologically negative SN.

“When the SN is negative, SN surgery alone with no further AD is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes,” said David N. Krag, MD.

Dr. Krag, of the University of Vermont, reported these results during Monday’s Breast Cancer — Local-regional and Adjuvant Therapy Oral Abstract Session. He noted that NSABP B-32 is the largest prospective randomized phase III trial conducted to date and was designed to determine whether SN resection alone results in the same survival and regional control as SN resection plus AD while reducing morbidity for patients with SN-negative disease.

In the trial, 5,611 women with operable, clinically node-negative, invasive breast cancer were randomly assigned to receive SN resection plus AD or SN resection alone, with AD only if SNs were found to be positive. Of the 5,611 patients randomized, 3,989 (71.1%) were SN-negative and were followed for an average of 95 months; 99.9% of follow-up information was obtained.

Primary endpoints of the study were overall survival (OS), disease-free survival (DFS), and regional control. The study was powered to detect a difference of 2% in OS between groups at 5 years. Dr. Krag said the small difference — necessitating a large study size — was chosen because “we did not want to trade off survival for decreased morbidity.”

Comparisons of OS between the two groups showed no statistically significant difference (hazard ratio [HR] 1.20; p = 0.117). Similarly, comparisons of DFS showed no difference (HR 1.05; p = 0.542).

There were no statistically significant differences in local or regional recurrences between the groups. Axillary recurrence occurred in two patients (0.1%) in the SN resection plus AD group and eight patients (0.3%) in the SN resection alone group. Morbidity was lower in the SN resection alone group by all measures used, Dr. Krag said.

ACOSOG: Z0011
Another ACOSOG study, Z0011, found no benefit from axillary lymph node dissection for women with clinically node-negative breast cancer who have a positive sentinel node biopsy. Armando E. Giuliano, MD, of John Wayne Cancer Institute, reported these findings from Abstract CRA506 on behalf of his colleagues.

Z0011 enrolled 891 women with clinically node-negative disease who had three or fewer sentinel nodes with metastases as detected by hematoxylin and eosin staining. Of these, 446 patients were randomly assigned to undergo no further axillary treatment and 445 were assigned to undergo axillary node dissection. As a result of withdrawals, the intent-to-treat population was reduced to 436 and 420, respectively. The two groups were similar with regard to age, tumor size, Bloom-Richardson score, estrogen receptor status, adjuvant systemic therapy, tumor type, and tumor stage. The median number of nodes removed in the axillary dissection group was 17 compared with two in the SN group. One hundred six patients (27.4%) who underwent axillary dissection had additional positive nodes removed beyond the sentinel node. Median follow-up was 6.3 years.
. Dr. Giuliano stated that no difference was observed between the two groups in terms of 5-year in-breast, nodal or total locoregional recurrence. Independent predictors on multivariate analyses for locoregional recurrence were younger age (p = 0.026) and higher Bloom-Richardson scores (p = 0.0258). No difference was found between the groups with regard to disease-free survival (Fig. 1), and independent predictors of survival were estrogen receptor status (p = 0.007) and adjuvant systemic therapy (p = 0.006), he added.

Five-year overall survival was the same for both groups, and independent predictors included age (p = 0.006), estrogen receptor status (p = 0.013), and adjuvant therapy (p = 0.025). No differences in locoregional recurrence or survival were seen when patients with ER-positive and ER-negative disease were analyzed separately.

In closing, Dr. Giuliano stated that although the study closed early because of low accrual, it is the largest phase III study of axillary lymph node dissection for sentinel node-positive women, and it demonstrates no trend toward clinical benefit of axillary dissection for this patient population He added that despite the widely held belief that axillary lymph node dissection improves survival, this study showed no signifi cant difference for women with sentinel node-positive disease.

Summary of Trial Results
Discussant William C. Wood, MD, of Emory University, indicated that these data are “practice-changing” for breast cancer.

He also said ACOSOG Z0010 has demonstrated that IHC provides no added benefit for patients with histologically negative sentinel nodes. According to Dr. Wood, another important finding of the study was that although bone marrow metastasis determined by IHC has both analytical and clinical validity, it is not an independent predictor; therefore, he said, it lacks clinical utility.

In his discussion of Abstract LBA505, Dr. Wood stated that Protocol B-32 provides evidence to support that axillary lymph node dissection does not add benefit to SN biopsy alone in clinically node-negative patients.

In closing, Dr. Wood told attendees that results from ACOSOG Z0011 suggest that axillary clearance does not improve survival for women with clinically node-negative disease who will receive whole breast radiotherapy and systemic adjuvant therapy as needed.

[das]

Thank you for this posting! I am having surgery next week and have 'clinically' negative lymph nodes - nothing seen on MRI, ultrasound or by exam. I would like to propose to my team that if the first sentinel node is positive they just stop there since the research doesn't support an added survival benefit from further removal of nodes. Any advise for me??

[tricia keegan]

My nodes looked clear on scans and exam, but nine were removed and three were positive which even surprised my surgeon who had told me before the op he was certain they were clear!

[das]

Hi, thanks for the reply. I guess I will find out about the nodes on Tuesday. We had a tough time deciding between chemotherapy before surgery or after. Decided on after so that the cancer could be staged at the beginning. Were you offered this option? Also, why did you decide to have an oophorectomy?