Advances & Insights: Cancer
What the news means for you
Heather Wright, MD
New study will change current practices
The first important study evaluating the importance of axillary lymph node dissection (ALND) was the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial, begun in the 1970s. In that study, patients with breast cancer who did not have axillary lymph nodes that could be felt on physical examination were selected randomly to undergo radical mastectomy, total mastectomy plus nodal irradiation, or total mastectomy with delayed ALND if there was nodal recurrence.
“Patients who undergo a lumpectomy for a stage T1 or T2 cancer, followed by whole-breast irradiation and systemic therapy, probably do not need more than [sentinel lymph node dissection] SLND.”
Will leaving lymph nodes involved with cancer affect survival?
There was no survival difference between the groups, suggesting that removal of axillary lymph nodes in patients with breast cancer had no effect on overall survival. That study was conducted at a time when no chemotherapy was available. So the question became, now that we do have systemic therapy, will leaving behind axillary lymph nodes involved with cancer make a difference in survival?
The American College of Oncology Surgeons study is a very important one that is going to change practice. What we can extract from the findings is that patients who undergo a lumpectomy for a stage T1 or T2 cancer, followed by whole-breast irradiation and systemic therapy, probably do not need more than SLND to evaluate the axilla. This practice would decrease morbidity. Following ALND, the risk of lymphedema is around 20 percent. It is much lower following SLND.
“Survival depends less on the size of the tumor and number of lymph nodes involved and more on the biology of the tumor and how well it responds to systemic therapy.”
Breast cancer treatment is constantly evolving. In the future, there may be no need to remove lymph nodes. We have other tools now on which to base our systemic therapy recommendations.
For example, for hormone-receptor positive breast cancers, there is a test called an Oncotype DX assay, in which RNA is extracted from the tumor. The genes of the cancer are then examined and the patient's likelihood of distant recurrence at 10 years is determined. Patients who fall in the low-risk category do not benefit from chemotherapy. This does not mean they have no risk of recurrence, but rather we do not change that risk by administering chemotherapy. If the patient is high-risk, we know that there will be a benefit from chemotherapy.
Biology of cancer
There are three reasons why lymph nodes are removed from cancer patients: possible survival benefit, local control and staging to determine further recommendations regarding adjuvant therapy. The results of the Z0011l and NSABP B-04 trials suggest that removing lymph nodes likely does not improve survival. In the Z0011 trial, the rate of recurrence within the breast or axillary lymph nodes at five years was only 2.5 percent.
Whether the patient has one or more positive lymph nodes does not affect the recommendations for systemic therapy. Furthermore, with tests like the Oncotype DX assay, which focuses more on the biology of the cancer, we are relying less on the traditional TNM (tumor, node, metastasis) staging. We are finding survival depends less on the size of the tumor and number of lymph nodes involved and more on the biology of the tumor and how well it responds to systemic therapy.
Choosing the less invasive SLND
Based on this new study, I would feel comfortable – in a select group of patients with tumors no more than 5 centimeters who plan to undergo lumpectomy followed by whole breast irradiation – performing only SLND and not proceeding to ALND in patients with up to two sentinel lymph nodes involved with metastatic disease. With this new evidence, similar trials will likely be performed to evaluate whether this less invasive approach can be utilized in a broader patient population.
Women with breast cancer are often among the most informed, proactive patients. They are driven by awareness of advances in research. Many are very concerned about removal of lymph nodes. There is no cure for lymphedema. Research findings have enabled us to make surgery less invasive, and it seems that surgery to evaluate the lymph nodes will be the next frontier.
Dr. Wright is medical director of the Comprehensive Breast Cancer Center at the UK Markey Cancer Center and an assistant professor of surgery at the UK College of Medicine.
Less radical breast cancer surgery often just as effective, study shows
A better understanding of breast cancer biology over the last 40 years has led to a reduction in aggressive surgery for the disease. The standard treatment has evolved away from radical mastectomy, in which the entire breast is removed along with adjacent musculature and lymph nodes. Nevertheless, axillary lymph node dissection (ALND) – removal of the lymph nodes from the area under the arm – has remained a standard way to examine lymph nodes for metastases (the spread of cancer from the initial site to another part of the body).
Research suggests women can now skip this aggressive surgery [ALND] without impacting their chances for survival or recurrence.
However, ALND can have debilitating side effects, including long-lasting arm swelling, stiffness and pain. As a result, sentinel lymph node dissection (SLND) – removal of one or two nodes to which cancer first spreads – was developed.
The sentinel lymph nodes are the first lymph nodes that receive drainage and thus those most likely to be involved with cancer. These nodes can be identified by injecting a tracer or dye into the breast that then travels to the lymph nodes. They can then be removed and carefully examined to determine whether there is any lymph node involvement. If no cancer identified in the sentinel lymph nodes, no additional nodes need to be removed.
Approximately 24,000 of the 180,000 women diagnosed with breast cancer each year have limited spread to nearby nodes. However, it is not known whether removing additional nodes after breast cancer spread has been identified by SLND increases chances of survival.
The American College of Surgeons Oncology Group in 1999 began the multicenter Z0011 trial to determine the effect of ALND on overall survival of patients with cancer that has spread to the sentinel lymph nodes. Recently released results suggest that thousands of women can now skip this aggressive surgery without impacting their chances for survival or recurrence.
The trial, published in the Feb. 9, 2011, issue of JAMA, the journal of the American Medical Association, was conducted at 115 sites over a five-year period. Subjects were women with early-stage breast cancer (tumors measuring no greater than 5cm) that had spread to only one or two sentinel nodes, identified by SLND. All had undergone lumpectomy, followed by radiation therapy.
“The results clearly showed that ALND [axillary lymph node dissection] was not beneficial.”
They were randomized into two groups of 445 each: one group having SLND only, the other having SLND followed by ALND. The ALND group underwent of 10 or more nodes. Most of the women in both groups also received chemotherapy. The results clearly showed that ALND was not beneficial. The five-year overall survival was similar in both groups – 91.8 percent in the ALND group and 92.5 percent in the SLND-only group.
The trial closed early because the survival rate was vastly better than expected and accrual to the study was slow. The rate of recurrence was also comparable: 83.9 percent in the SLND-alone group and 82.2 percent in the ALND group were disease free after five years.
In an editorial accompanying the JAMA article, Grant Walter Carlson, MD, and William C. Wood, MD, called the Z0011 trial "an important contribution to the surgical management of SLN metastasis in breast cancer." Taken along with findings from other investigations, they conclude, there is "strong evidence that patients undergoing partial mastectomy, whole-breast irradiation, and systemic therapy for early breast cancer with microscopic SLN metastasis can be treated effectively and safely without ALND."
For more information, see:
- Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis, JAMA, v. 305, no. 6, February 9, 2011, pp. 569-575,
- Some women may not need more extensive lymph node surgery for breast cancer, NCI Cancer Bulletin, National Cancer Institute, February 22, 2011
- Breast cancer, Health Information, UK HealthCare
- Lymphedema, Dictionary of Cancer Terms, National Cancer Institute
- Lumpectomy, Health Information, UK HealthCare
- Comprehensive Breast Care Center, Fact Sheet, Markey Cancer Center, UK HealthCare
UK HealthCare Cancer Services - Markey Cancer Center
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