Sentinel lymph node mets and survival in early BC

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Janette
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Sentinel lymph node mets and survival in early BC

Postby Janette » Sun Aug 21, 2011 9:46 pm

(MedPage Today) -- Sentinel lymph node (SLN) metastasis does not adversely affect survival in early-stage breast cancer, according to results of a large multicenter cohort study.

Women with conservatively treated early breast cancer had a five-year overall survival of 95% to 96% regardless of whether they had SLN metastasis by immunohistochemistry (IHC).

Bone marrow metastases, though uncommon, doubled the mortality hazard, but the effect no longer remained statistically significant in a multivariable analysis, investigators reported in the July 27 issue of JAMA.

"Data from [the study] show that occult metastases detected by immunohistochemistry are not associated with survival differences in patients with the earliest stages of breast cancer," Armando Giuliano, MD, of Cedars-Sinai Medical Center in Los Angeles, and coauthors wrote.

"Bone marrow examination with immunocytochemistry may identify high-risk women; however, the incidence in [this study] was too low to recommend incorporating bone marrow aspiration biopsy into routine practice for patients with the earliest stages of breast cancer," they added.

SLN dissection has afforded women with conservatively treated, early-stage breast cancer the opportunity for less invasive axillary staging, and more intensive evaluation of the SLN. SLN dissection also has led to the detection of micrometastases and isolated tumor cells, the significance of which has remained unclear.

Older retrospective studies suggested that occult micrometastases reduced survival, but many patients were treated with regimens that are no longer considered standard of care, the authors noted in the background material.

Other evidence has pointed to no increased hazard associated with micrometastases. A trial conducted by the National Surgical Adjuvant Breast and Bowel Project showed a statistically significant 1.2% decrease in five-year survival in patients with occult metastases (N Engl J Med. 2011;364:412-421).

In an effort to resolve the uncertainty surrounding SLN micrometastases, the American College of Surgeons Oncology Group conducted the Z0010 trial to determine the prevalence and clinical significance of occult metastases in SLNs and in bone marrow. Eligible patients had clinical T1 or T2 node-negative breast cancer, treated by breast-conserving surgery, SLN dissection, and whole-breast irradiation.

Bone marrow aspiration biopsy initially was optional, but became mandatory two years into the trial. The biopsy was performed immediately before SLN dissection and lumpectomy.

SLNs were evaluated by hematoxylin-eosin (H&E) staining, and negative nodes underwent further examination by IHC. Bone marrow aspirates underwent immunocytochemical staining at a central laboratory.

Patients treated with neoadjuvant therapy were ineligible for the study. Adjuvant systemic therapy was determined at the discretion of the treating physician.

The primary endpoint was overall survival from the time of diagnosis.

From May 1999 to May 2003, investigators at 126 centers enrolled 5,210 eligible patients, 5,119 of whom had SLNs identified. H&E results showed that 1,215 SLNs harbored metastases. Of the 3,904 patients with H&E-negative nodes, 3,326 had specimens evaluated by IHC, which revealed occult metastases in 349 cases.

Bone marrow biopsies revealed occult metastases in 104 cases.

After a median follow up of 6.3 years, 435 patients had died, and 376 had disease recurrence. Among patients with H&E-negative, IHC-positive SLNs, five-year overall survival was 95.1% versus 95.7% for patients with IHC-negative results. The five-year disease-free survival was 90.4% among patients with IHC-positive SLNs and 92.2% for women with IHC-negative SLNs (P=0.82).

Bone marrow metastases were associated with an increased mortality hazard but not an increased risk of recurrence.

The five-year mortality was 5% for patients without metastases and 9.9% for patients with occult bone marrow metastases (P=0.01). Five-year disease-free survival was 90.8% for patients with negative bone marrow specimens and 86.7% for those with positive marrow (P=0.22).

Multivariable analysis showed that the increased mortality hazard associated with bone marrow metastases was limited to women older than 50 and those who had tumors larger than 1 cm.

Overall, univariable analysis showed a 1.94 hazard ratio for mortality in patients with bone marrow metastases (P=0.04).

A fully adjusted multivariable analysis yielded a hazard ratio of 1.83, which was no longer statistically significant (P=0.15).

The Z0010 trial provided valuable insight that will help guide clinical practice, the authors of an accompanying editorial wrote. Additionally, the trial demonstrated that a well-designed observational study can address relevant clinical questions that could not be resolved by a randomized clinical trial.

"Randomized controlled trials [RCTs] should not be considered the de facto and sole source of high-level evidence," wrote Ryan P. Merkow, MD of Northwestern University in Chicago, and Clifford Y. Ko, MD, of the University of California Los Angeles.

"By considering RCTs and observational study designs complementary, and recognizing the opportunities to use observational research when appropriate, it might be possible to address questions faster, cheaper, and perhaps even better than either approach alone," they stated.

The study was supported by NIH and by the American College of Surgeons Oncology Group.

Coauthor Karla V. Ballman disclosed relationships with AstraZeneca, Lilly, and Novartis. Giuliano and the other coauthors had no disclosures related to commercial interests.

Merkow and Ko had no relevant disclosures.

Primary source: JAMA Source reference: Giuliano AE et al. "Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer." JAMA 2011;306:385-393.Additional source: JAMASource reference: Merkow RP, Ko CY. "Evidence-based medicine in surgery. The importance of both experimental and observational study designs." JAMA 2011;306:436-437.
Janette


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