Long-term results from a large clinical trial confirm that, for some women with early-stage breast cancer who have lumpectomy as their surgical treatment, a less extensive lymph node biopsy approach is sufficient.
The trial showed that women with early-stage breast cancer who have cancer cells in one or two sentinel lymph nodes can skip axillary lymph node dissection (ALND) after breast-conserving surgery without affecting their long-term survival.
The findings are important for patients because ALND can cause chronic side effects such as numbness, decreased range of motion in the upper body, and lymphedema, said Armando Giuliano, M.D., of Cedars-Sinai Medical Center in Los Angeles, who led the trial.
Dr. Giuliano said he now feels comfortable telling patients that, in the long term, they would “suffer more from the axillary dissection than from the omission of the axillary dissection.”
The trial results were published September 12 in JAMA.
Changing Views on Breast Cancer Metastasis
The axillary lymph nodes run from the breast tissue into the armpit. Early theories of breast-cancer metastasis held that cancer cells that had broken free from the main tumor would first travel through these lymph nodes on their way to other organs. That led doctors to believe that removing the axillary lymph nodes could reduce the risk of both cancer recurrence and metastases.
However, more-recent research has suggested that breast cancer may metastasize to other areas of the body through several different routes, explained Dr. Giuliano.
Also, modern treatment for early-stage breast cancer typically includes radiation therapy—which targets some of the same lymph nodes—along with breast-conserving surgery, Dr. Giuliano added.
Most patients additionally receive some sort of systemic treatment, such as hormone therapy, chemotherapy, and, more recently, targeted therapy, all of which can kill cancer cells throughout the body.
Less Lymph Node Surgery, Equivalent Survival
The trial, called ACOSOG Z0011, was designed to compare whether sentinel lymph node biopsy (SLNB) alone provided equivalent survival benefits to ALND after breast-conserving surgery among a subset of women who also received radiation and systemic therapy. The research team enrolled 891 participants into the study from 1999 to 2004.
Women who had stage I or II cancer and metastases in only one or two sentinel nodes were eligible to join the study. All women had undergone SLNB at the time of breast-conserving surgery.
Half of the trial participants received no further surgery, and the other half underwent ALND. Almost 90% of women in both groups had radiation therapy after surgery, and almost all received some type of systemic therapy.
In the initial results from the trial, published in 2010 and 2011, women who had only SLNB did not have worse overall survival than women who underwent full ALND. The two groups also had similar rates of disease-free survival and cancer recurrence in the lymph nodes.
These early results “were absolutely practice changing, and at this point the overwhelming majority of surgeons are not doing a full axillary lymph node dissection in patients with one or two positive [sentinel] nodes,” said Larissa Korde, M.D., head of Breast Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis.
However, the cancer research community had lingering concerns about the trial, the authors of the new paper explained.
For example, the trial recruited fewer participants than initially planned. In addition, far fewer women than expected in both arms of the trial had any recurrence of their disease, making statistical comparisons between the groups difficult.
Most participants also had hormone receptor-positive breast cancer, which can recur many years after initial treatment.
However, after 10 years of follow-up, the initial results held: only about 50 women had died from any cause in each group. Overall survival was 86.3% in the SLNB group and 83.6% in the ALND group.
“It appears that less surgery, in the current era, is safe,” said Dr. Korde. Having the long-term data from the ACOSOG trial “makes us have a little more confidence in something we’ve been doing for quite a while,” she added.
Rates of negative side effects from surgery were much higher in the ALND group, with 70 percent of women experiencing wound infection, delayed healing, or pain compared with 25 percent of women in the SLNB-alone group. In addition, more women in the ALND group reported lymphedema. (The researchers reported complete data on side effects seen during the trial in a previous paper.)
A Lot to Learn about ALND in Other Patients
It’s important for doctors and patients to understand that these results can only be applied to women whose breast cancer and treatment regimen match those of the participants in the trial, the papers’ authors cautioned.
The results should not be used to direct the care of women with palpable axillary lymph nodes, women who had breast tumors larger than 5 cm in diameter, women with three or more positive sentinel lymph nodes, women who received chemotherapy or hormone therapy before surgery, and women who underwent mastectomy instead of breast-conserving surgery with radiation, they wrote.
“We still have a lot to learn about [the need for] ALND in other [treatment] settings,” commented Dr. Giuliano.
One trial, currently underway in Europe, is examining whether ALND can be skipped in some women who have a mastectomy for early-stage breast cancer, but results are not expected for years.
But for now, according to Edward Livingston, M.D., and Hsiao Ching Li, M.D., of the University of Texas Southwestern Medical Center, authors of an accompanying editorial, “The ACOSOG Z0011 trial has shattered a century of belief that all cancer containing axillary lymph nodes must be removed in women with breast cancer.”