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Trial ‘shatters century of belief’ that all breast cancer axillary nodes must be removed

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September 12, 2017

Sentinel lymph node dissection appeared noninferior to axillary lymph node dissection among women with stage I or II invasive breast cancer and sentinel node metastasis, according to long-term follow-up from the American College of Surgeons Oncology Group Z0011 trial.

As a result, the findings do not support the routine use of axillary lymph node dissection in this patient population.

“Axillary lymph node dissection is an effective method of maintaining regional control but it is associated with a significant risk [for] complications such as lymphedema, numbness, axillary web syndrome and decreased upper-extremity range of motion,” Armando E. Giuliano, MD, from the department of surgery at Cedars-Sinai Medical Center, and colleagues wrote. “Changes in the presentation and management of breast cancer and the selection of systemic therapy based on tumor biology raised questions regarding the necessity of axillary lymph node dissection for some patients with sentinel lymph node metastases.”

The multicenter, randomized phase 3 American College of Surgeons Oncology Group (ACOSOG) Z0011 trial evaluated whether sentinel lymph node dissection alone yielded noninferior survival outcomes to axillary lymph node dissection in women with a limited number of sentinel node metastases undergoing breast-conserving surgery who received adjuvant whole-breast irradiation with adjuvant systemic therapy.

OS served as the primary endpoint. Secondary endpoints included DFS, morbidity and locoregional recurrence.

Initial results after a median follow-up of 6.3 years demonstrated that OS did not differ between groups, with a noninferiority HR margin of 1.3. Researchers also observed no statistically significant difference in DFS, and nodal recurrence occurred in fewer than 1% of patients in either group.

However, the short follow-up of the trial failed to account for late death, particularly because hormone receptor-positive breast cancer is associated with risk for locoregional and systemic relapses after 5 years.

“The majority of patients were postmenopausal with hormone receptor-positive breast cancer, raising concern that additional follow-up beyond 6 years was needed to document noninferiority of OS with sentinel lymph node disease alone in this node-positive cohort,” Giuliano and colleagues wrote.

Of the 891 women (median age, 55 years) enrolled, 436 women who received sentinel lymph node dissection alone and 420 women who received axillary lymph node dissection completed the trial.

At a median follow-up of 9.3 years, 110 deaths occurred (sentinel, n = 51; axillary, n = 59).

A comparable proportion of women achieved 10-year OS in the sentinel lymph node (86.3%; 95% CI, 82.2-89.5) and axillary (83.6%; 95% CI, 79.1-87.1) dissection arms. The unadjusted HR of 0.85 (95% CI, 0-1.16) did not cross the prespecified noninferiority HR margin of 1.3.


Rates of 10-year DFS were 80.2% in the sentinel group compared with 78.2% in the axillary group (HR = 0.85; 95% CI, 0.62-1.17).

“This confirms that although distant recurrence among hormone receptor-positive tumors is a later event, nodal recurrence among these patients is primarily an early event,” Giuliano and colleagues wrote.

One nodal recurrence occurred in the sentinel lymph node dissection group compared with no events in the axillary lymph node dissection group between year 5 and 10 of follow-up.

Those treated with nodal-field irradiation experienced no difference in DFS, OS or locoregional recurrence compared with those not treated with irradiation.

“The long-term outcome of this study provides additional support that axillary dissection is not necessary for long-term disease control and survival for patients with positive sentinel nodes, even for those with generally late recurring hormone receptor-positive tumors,” Giuliano and colleagues wrote.

Despite its controversy, the results from the ACOSOG Z0011 trial had a substantial effect on breast cancer treatment, Edward H. Livingston, MD, and Hsiao Ching Li, MD, both from University of Texas Southwestern Medical Center, wrote in an accompanying editorial.

“Despite the limitations of the study, surgeons around the world felt more comfortable avoiding axillary dissection even if cancer might be present and rates of axillary node dissection declined internationally,” they wrote.

These results have “shattered a century of belief” that physicians must remove all breast cancer-containing axillary lymph nodes, Livingston and Li added.

“Less can be more in clinical medicine, meaning that providing fewer diagnostic tests or treatments may be just as good for patients as when very aggressive interventions are pursued,” they wrote. “The same can be true for clinical research when sometimes less than perfect clinical trials can be interpreted with commonsense instead of statistical purity, resulting in changed clinical practice that improves patient care.” – by Kristie L. Kahl

Disclosures: Giuliano received travel support from ACOSOG; and Cedars-Sinai Medical Center received per capita compensation for patient accrual from ACOSOG. Please see the full study for a list of all other researchers’ relevant financial disclosures. Livingston and Li report no relevant financial disclosures.

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