Another Major Trial Challenges Axillary Dissection Practice

Nick Mulcahy

December 08, 2011

December 8, 2011 (San Antonio, Texas) — More evidence suggests that there is no price to pay for forgoing axillary dissection (AD) in patients with breast cancer who have minimal lymph node involvement.

The surgery has been the long-standing standard treatment when there has been any — including minimal — disease spread to the lymph nodes in the axillary region.

However, a landmark trial from the United States recently indicated that in women with 1 or 2 positive sentinel nodes, forgoing axillary dissection did not produce inferior results in the setting of modern clinical practice.

The latest data challenging this surgery come from the International Breast Cancer Study Group (IBCSG) Trial 23-01 and were presented here today at the 34th Annual San Antonio Breast Cancer Symposium (SABCS).

The 931 women in the new study had clinically node-negative breast cancer and micrometastases in a sentinel node or nodes. Most of the women (85%) had only 1 or 2 positive sentinel nodes. Most (67%) had metastases less than 1.0 mm, and none had metastases greater than 2 mm.

The patients were randomly assigned to AD or no AD.

The 5-year rate of disease-free survival was 87.3% for AD and 88.4% for no AD (P = .48), with a median follow-up of 57 months, report Vivianna Galimberti, MD, and colleagues from the IBCSG. Dr. Galimberti is from the European Institute of Oncology in Milan, Italy, which was 1 of the 27 centers participating in the 23-01 trial.

The 5-year overall survival rate was 97.6% for AD and 98% for no AD (P = .35).

The findings are consistent with those of the Z11 trial.

"The findings are consistent with those of the Z11 trial," Dr. Galimberti told the meeting audience, referring to the recent American College of Surgery Oncology Group Z0011 trial. In both trials, patients underwent surgery, radiation therapy, and adjuvant systemic therapy, including hormone therapy.

"I hope everyone will go home and stop doing axillary dissection on people with clinically negative [nodes] but a positive sentinel node in the operating room," commented Laura Esserman, MD, from the University of California at San Francisco. Her comment from the floor brought a round of applause from the usually staid San Antonio gathering.

The new presentation was of "preliminary" findings, said Dr. Galimberti — the median follow-up is a few months short of its study goal.

She also explained that the trial, which did not meet its accrual goal, had to adjust its statistical design. The accrual target was 1960 patients in order to provide 90% power to detect nonequivalence if 5-year disease-free survival was 64% for group B and 70% for group A. However, the trial closed enrollment because the projected time to complete accrual was too long, and the aggregate event rate at 30-month median follow-up was much lower than anticipated.

At 57 months, 46 events (9.9%) occurred in the no-AD group and 52 (11%) occurred in the AD group. The disease-free survival results translated into a hazard ratio of 0.87; 80% confidence interval, 0.67 - 1.12. The result was below the noninferiority boundary of 1.25. "No axillary dissection is not inferior to axillary dissection," summarized Dr. Galimberti.

Lost Importance

"Minimal axillary lymph node involvement has lost its importance in the decision-making process," Dr. Galimberti told Medscape Medical News in an interview after her presentation. "The impact of its prognostic significance has diminished as adjuvant treatments are tailored more and more on the biological features of the disease."

She also pointed out that axillary dissection is not a curative procedure but instead is a staging procedure.

Still, at the American Society of Clinical Oncology meeting in 2010, the lead investigator of the Z0011 trial admitted that leaving behind some cancer in the axilla was "counterintuitive."

When the results of the Z0011 trial were published, an accompanying editorial attempted to explain why the residual disease is not problematic. "Adjuvant radiation and systemic therapy likely treated the low-volume nodal metastasis in this study," wrote Grant Walter Carlson, MD, and William Wood, MD, from the Winship Cancer Institute of Emory University in Atlanta, Georgia.

Dr. Galimberti concurred with the hypothesis.

The new IBCSG 23-01 trial, which included only patients with micrometastatic disease, is different from the Z0011 trial insofar as the US study included patients with both micro- and macrometastases.

The trials had a few other differences. The US trial included only patients treated with breast-conserving therapy. In the new international study, 90% of the patients underwent breast-conserving therapy and 10% had mastectomy.

The mean patient age at entry was 54 years (range, 26 to 81 years). More postmenopausal (56%) than premenopausal (44%) patients participated. Sixty-seven percent of patients had breast tumors less than 2 cm, and 7% had tumors 3 cm or greater; 26% had grade 3 disease.

Tumors were estrogen receptor positive in 89% of patients and progesterone receptor positive in 75%. Most (96%) patients underwent lymphoscintigraphy. A previous excision biopsy was performed in 16%.

Adjuvant radiation therapy was performed in 90% of the AD group and 92% of the no-AD group and hormone therapy in 63% and 67%, respectively. Only 7% of the AD group and 9% of the no-AD group had chemotherapy.

Dr. Galimberti has disclosed no relevant financial relationships.

34th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S3-1. Presented December 8, 2011.


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