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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 04/26/2013

Women with Breast Cancer Micrometastases in Their Sentinel Lymph Nodes May Not Need Axillary Dissection

Summary

In a randomized clinical trial, women with breast cancer and only small numbers of cancer cells (micrometastases) in their sentinel lymph nodes who received axillary lymph node dissection (ALND) had more side effects but no improvement in disease-free survival compared with women who had no further lymph node surgery.

Source

Lancet Oncology March 11, 2013 (See the journal abstract.)

Background

Until the early 2000s, when a woman had surgery for breast cancer the surgeon would also remove a large number of axillary lymph nodes (lymph nodes located in the armpit) in a procedure called axillary lymph node dissection (ALND). Knowing whether the cancer had spread to the axillary lymph nodes would help her doctors determine whether the woman would also need systemic therapy, such as chemotherapy or hormone therapy. However, ALND can have major long-term side effects, including lymphedema, pain, and impaired arm mobility.                                           

Since the early 2000s, sentinel lymph node biopsy (SLNB) has been the standard of care for staging disease in women with invasive breast cancer. In this procedure, which is associated with fewer long-term side effects than ALND, only the first lymph nodes to which cancer is likely to spread (sentinel lymph nodes) are removed and checked for the presence of cancer cells. If no cancer cells are found in the sentinel lymph nodes, no other nodes are removed.

But it was unclear whether ALND is always necessary if cancer cells are found in the sentinel lymph nodes. In 2011, results from a clinical trial, called ACOSOG Z0011, indicated that certain women with breast cancer cells in their sentinel nodes could avoid ALND without reducing the likelihood of survival. The IBCSG 23-01 trial further explored the value of ALND in women with sentinel lymph node metastases.

The Study

The IBCSG 23-01 trial was launched about 3 years after ACOSOG Z0011. Like that trial, IBCSG 23-01 randomly assigned women who had undergone surgery and SLNB to receive ALND or no further lymph node dissection. Both trials were limited to women with an invasive breast tumor 5 cm or smaller and no palpable lymph nodes. 

There were also some differences in eligibility between the two trials. Women having either breast-conserving surgery or mastectomy could participate in IBCSG 23-01, whereas the ACOSOG Z0011 trial excluded patients who underwent mastectomy. IBCSG 23-01 was restricted to women with metastases no larger than 2 mm (micrometastases) in their sentinel lymph nodes, whereas participants in ACOSOG Z0011 could have larger sentinel lymph node metastases. Finally, participants in ACOSOG Z0011 could have no more than two positive sentinel lymph nodes.  

From 2001 to 2010, the researchers randomly assigned 931 women to undergo ALND (n = 464) or to receive no further lymph node surgery (n = 467). The primary endpoint of the trial was disease-free survival—the time from randomization to the return of their disease (either in the breast or elsewhere in the body), a second primary breast tumor, or death.                                                                                 

All of the women returned for follow-up visits every 4 months for the first year and every 6 months after that for up to 5 years.

Results

Tumor characteristics were similar between groups. Overall, about 70 percent of the women had primary tumors that were smaller than 2 cm, and 90 percent of tumors were estrogen receptor-positive. Most women (91 percent) had breast-conserving surgery, and 98 percent of those women received radiation therapy. Nearly all of the women in both groups received hormone therapy, chemotherapy, or a combination of both treatments.

After 5 years of follow-up, about 84 percent of women who underwent ALND were alive and disease free, compared with about 88 percent of those who had SLNB only. The rate of axillary recurrence was also very low in both groups. These equivalent outcomes were achieved even though 13 percent of patients in the ALND group were found to have cancer cells in axillary lymph nodes other than the sentinel nodes, indicating that some women in the group that did not undergo ALND likely also had cancer cells in their axillary nodes.

As expected, women who underwent ALND had more side effects than women who did not. For example, lymphedema occurred in 13 percent of women who underwent ALND but only in 3 percent of women who had no further surgery.

Limitations

Both ACOSOG Z0011 and IBCSG 23-01 recruited fewer participants than planned, which may limit the strength of their findings. And women and their doctors should be careful not to extrapolate the findings from these two trials to populations that were not included in the studies.

Comment

“These results of IBCSG 23-10 are practice-changing when co-interpreted with those of Z0011,” wrote John R. Benson, MD, of the Cambridge University Teaching Hospitals Trust in an accompanying editorial. “In the aftermath of Z0011, many breast cancer centers have already abandoned [ALND] for patients positive for sentinel lymph node biopsy with micrometastatic foci only; results from IBCSG 1-23 support this change in practice and provide justification for omission of [ALND] in selected patients who undergo mastectomy.”

The authors noted that although metastases may have been present in the lymph nodes of some patients who did not undergo ALND in IBSCG 23-01, almost all patients had some form of additional treatment that could have helped eliminate remaining cancer cells. In the group that did not undergo ALND, 98 percent of women who had breast-conserving surgery had radiation therapy. In addition, 95 percent of those who did not undergo ALND had either chemotherapy, hormone therapy, or both, which can kill cancer cells throughout the body.

“Patients should discuss these findings with their doctors,” said Jo Anne Zujewski, MD, head of breast cancer therapeutics at NCI. “Some patients, especially those for whom radiation therapy plus chemotherapy and/or hormonal therapy is planned, may be able to avoid an axillary lymph node dissection.”