Less can be more when removing lymph nodes during breast cancer surgery

A conservative approach to removing lymph nodes is associated with less harm for breast cancer patients and often yields the same results as more radical procedures, researchers at UT Southwestern Medical Center have found.

In the Oct. 2 edition of the Journal of the American Medical Association, lead author Dr. Roshni Rao, associate professor of surgery at UT Southwestern, and other investigators from the Harold C. Simmons Cancer Center reviewed studies on patient outcomes of women who had received various forms of surgical treatment, ranging from removal of one lymph node to prevent the spread of breast cancer to removing the entire network of lymph nodes spanning the armpits.

Until recently, clinical practice guidelines advised complete axillary node dissection -- removal of all 20-30 axillary nodes -- if a woman's sentinel node biopsy was positive. The sentinel node is generally the first node to which cancer cells will spread from a primary tumor. A positive sentinel lymph node biopsy indicates the tumor has metastasized and can be used to determine the stage of the cancer. Axillary lymph nodes are distributed at the edge of the chest muscles and into the armpits and lower neck.

For women with no suspicious axillary nodes who undergo breast-conserving therapy, there is little evidence of benefit in doing a complete axillary node dissection compared with sentinel node biopsy alone, the reviewers reported. Breast conserving therapy is defined as partial mastectomy followed by whole breast radiation.

"In the past, axillary nodal status was a critical factor considered in therapy decisions," said Dr. Rao, a breast cancer surgeon. "With the validation of sentinel lymph node biopsy, the same staging information can be obtained with less morbidity and risk to the patient. And now that decisions regarding chemotherapy are often guided by molecular tumor profiling in an era of personalized medicine, there are other avenues to explore beyond aggressive surgeries."

To assess the effect of the guidelines, Dr. Rao and her colleagues reviewed the risks and benefits of sentinel node biopsy as compared with complete axillary node dissection in previous published research. They also compared these procedures with nonsurgical interventions (i.e., additional radiation) in women with breast cancer who do not have palpable lymph nodes or ultrasound evidence that their cancer has spread to the axillary nodes.

They also reviewed the rate of recurrence of axillary node metastases, mortality, morbidity, and complications associated with each intervention, using online medical databases. In all, more than 1,000 results were examined from 17 studies to write the JAMA review.

Avoiding axillary surgery if possible is important, Dr. Rao said, because it can cause shoulder and arm symptoms including lymphedema, severe pain or numbness, and reduced range of motion, and it generally involves longer stays in the hospital, as opposed to sentinel node surgery.

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UT Southwestern Medical Center

New solution in detecting breast-cancer related lymphedema

Viewed as one of the most feared outcomes of breast cancer treatment, doctors struggle detecting and diagnosing breast-cancer related Lymphedema -- a condition affecting the lymphatic system and causing psychosocial distress and physical challenges for patients.

Now, a team of researchers led by Mei R. Fu, PhD, RN, ACNS-BC, associate professor of Chronic Disease Management at the New York University College of Nursing (NYUCN), offers supporting evidence for using Bioelectrical Impedance Analysis (BIA) ratios to assess Lymphedema. The study, "L-DEX Ratio in Detecting Breast Cancer-Related Lymphedema: Reliability, Sensitivity, and Specificity," published in Lymphology, argues because the low frequency electronic current cannot travel through cell membranes, it provides a direct measure of lymph fluid outside the cells. This allows for a more accurate assessment of lymphedema using a Lymphedema Index named L-Dex ratio.

"To lessen breast cancer survivors' worry about lymphedema development, the BIA may have a role in clinical practice by adding confidence in the detection of arm lymphedema among breast cancer survivors," says Dr. Fu, "even when pre-surgical BIA baseline measures are not available."

The objective of the study was to examine the reliability, sensitivity, and specificity of cross-sectional assessment of BIA in detecting lymphedema in a large metropolitan clinical setting.

Measuring lymphedema is challenging because most methods cannot distinguish bone and soft tissues from extracellular fluid. BIA is time-efficient, easy to operate and easy to interpret, making it ideal for clinical practice. Dr. Fu's research collected data from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema, demonstrating that survivors with lymphedema had significantly higher L-Dex ratios, which shows the possibility of using BIA to discriminate between those cohorts of women.

"Our study also demonstrated that using a more sensitive L-Dex cutoff point, this allowed for BIA to catch 34% of the usually missed lymphedema cases," said Dr. Fu. "This allows for earlier treatment, which naturally leads to better outcomes for at-risk patients."

The American Cancer society estimates that in 2013 approximately 232,340 new cases of breast cancer are detected, adding to the already 2.9 million breast cancer survivors, all with a at a lifetime risk of Lymphedema.

"Giving that all the women who are treated for breast cancer are at a life-time risk for lymphedema, using assessment methods that can accurately identify true lymphedema cases among at-risk breast cancer survivors is of the ultimate importance for clinical practice," added Dr. Fu.

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New York University

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Genetic Markers Associated To the Growth of Lymphedema in Breast Cancer Survivors

A new UC San Francisco study has found a clear association between certain genes and the development of lymphedema, a painful and chronic condition that often occurs after breast cancer surgery and some other cancer treatments.
The researchers also learned that the risks of developing lymphedema increased significantly for women who had more advanced breast cancer at the time of diagnosis, more lymph nodes removed or a significantly higher body mass index.
The study is the first to evaluate genetic predictors of lymphedema in a large group of women using a type of technology, bioimpedance spectroscopy, to measure increases in fluid in the arm. Bioimpedance spectroscopy is a noninvasive procedure that allows one to measure body composition including an increase in fluid in an arm or a leg.
The study, which involved some 400 women who were tracked over four to five years, will be published online on April 16 in PLOS ONE.
“The genetic markers found in our study make perfect sense,” said senior author Bradley Aouizerat, PhD, a professor at the UCSF School of Nursing in the department of physiological nursing. “These genes are ‘turned on’ later in the development of our lymph system and blood vessels. They appear to play a role in the ability of our lymphatic system to function on an ongoing basis. It is possible in some individuals who have changes in these genes, that lymphedema could develop after an injury like breast cancer surgery because these genes do not function properly.”

Lymphedema is a swelling or buildup of fluid in the lymphatic tissues, typically in the arms and fingers but also commonly in the patient’s legs and trunk. It can occur after treatment for any form of cancer that affects lymph node drainage. The exact prevalence is unknown, and the onset of the condition can greatly vary, but as many as 56 percent of women who undergo breast cancer surgery develop lymphedema within two years, according to the National Cancer Institute. More than a half-million breast cancer survivors in the United States are estimated to be afflicted with the condition.
Lymphedema can be debilitating, causing scarring, discomfort, disfigurement, difficulty in exercising, walking or other daily activities. Some patients are unable to wear their usual clothing or jewelry because of the increased weight and size of their affected limbs. There’s no cure for the condition – treatment generally centers on controlling pain and reducing swelling.

Genomic Determinants of Lymphedema

To date, much of the research on lymphedema focused on identifying which women were at greater risk for the development of the condition, and relied only on patient self-reporting or on data from their medical charts.
In the new study, the authors hypothesized that genomic determinants were behind some of the variations in the occurrence of lymphedema as well as the time of onset of the condition.
The study involved 410 women who were at least six months post-treatment for breast cancer surgery on one breast, and either had lymphedema in their upper extremity or did not have the condition.
The women were assessed at the Clinical Research Center at the UCSF Medical Center at Mt. Zion, one of eight clinical sites in the Bay Area managed by UCSF’s Clinical and Translational Science Institute.
As part of the research, the women underwent spectroscopy measurements of their arms, and genomic DNA was extracted. Genotyping was performed blinded to the women’s lymphedema status.
The researchers found that women with lymphedema had:

• More advanced breast cancer at the time of diagnosis;
• A higher number of positive lymph nodes;
• Were more likely to have a significantly higher body mass index.
• The authors also found associations between lymphedema and four genes known to play a role in the development of lymphedema.

“These findings suggest that complex interactions may exist between a variety of patient characteristics and genetic markers that place some women at higher risk for the development of lymphedema,’’ said lead author Christine Miaskowski, RN, PhD, a professor at the UCSF School of Nursing in the department of physiological nursing. “Our hope is that once our findings are confirmed in a future study, we will be able to identify women at higher risk for lymphedema prior to breast cancer surgery, and initiate measures to prevent the development of this devastating condition.”
The study was funded by grants from the National Cancer Institute (CA107091 and CA118658) and the American Cancer Society.

Researchers Advocate Exercise for Breast Cancer Survivors, Lymphedema Patients

Lymphedema, a chronic swelling condition common in breast cancer survivors, affects three million people in the U.S. In the past, most people believed that exercise might induce or worsen lymphedema. After reviewing the literature, University of Missouri researchers say the benefits of exercise outweigh the risks for breast cancer survivors and patients with lymphedema. Jane Armer, professor in the Sinclair School of Nursing, says patients at risk for lymphedema can exercise if they closely monitor their activities.

"Exercise can be beneficial and not harmful for breast cancer survivors," Armer said. "Each individual should balance the pros and cons of the activity she chooses, but keep in mind that being sedentary has risks and being active is beneficial in many ways, including possibly reducing the risk of cancer recurrence."

Lymphedema can occur any time after cancer treatment and is usually caused by the removal or radiation of lymph nodes as part of the treatment process. Armer found that patients who exercise had no greater risk for developing lymphedema than those who do not exercise. In addition, patients with lymphedema did not worsen their condition by exercising. She says future research is needed to determine whether exercise prevents the condition.

"Breast cancer survivors do not need to restrict their activity as we once thought," Armer said. "If patients want to be active, they should carefully condition their bodies by increasing repetitions of resistance exercises under proper supervision."

In another new literature review, Armer and her colleagues examined published literature pertaining to the surgical treatment of lymphedema. They found that in most studies surgery did not eliminate the need for traditional compression garments in patients with lymphedema.

"Many people think surgery will correct the underlying lymphatic problem, but that is not correct," Armer said. "There are several surgical techniques that may reduce the swelling associated with lymphedema. In most cases, it is recommended that patients undergo traditional therapy using specialized massage and compression garments and bandages to reduce fluid and swelling before considering surgery."

The literature reviews were the first two in a series of thirteen reviews to be published in conjunction with the American Lymphedema Framework Project (ALFP). Established in 2008, the ALFP aims to increase awareness of lymphedema, improve patient care and enhance training for professionals caring for persons at risk or with cancer-related lymphedema. The ALFP has two main goals: maintain up-to-date best practices supported with evidence-based lymphedema treatment guidelines for health practitioners, and create a minimum data set of all available lymphedema research and clinical data.

The first article, "Exercise in patients with lymphedema: A systematic review of the contemporary literature," was published in the Journal of Cancer Survivorship. The second, "The surgical treatment of lymphedema: A systematic review of the contemporary literature," was published in Annals of Surgical Oncology.

Liver Cells, Insulin-Producing Cells, Thymus Can Be Developed in Lymph Nodes, Team Discovers

Lymph nodes can provide a suitable home for a variety of cells and tissues from other organs, suggesting that a cell-based alternative to whole organ transplantation might one day be feasible, according to researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine. In a report recently published online in Nature Biotechnology, the research team showed for the first time that liver cells, thymus tissue and insulin-producing pancreatic islet cells, in an animal model, can thrive in lymph nodes despite being displaced from their natural sites.

Hepatitis virus infection, alcoholic cirrhosis and other diseases can cause so much damage that liver transplantation is the only way to save the patient, noted senior investigator Eric Lagasse, Pharm. D., Ph.D., associate professor, Department of Pathology, Pitt School of Medicine. Children with DiGeorge syndrome lack functional thymus glands to produce essential immune cells, and diabetes can be cured with a pancreas transplant.

"However, the scarcity of donor organs means many people will not survive the wait for transplantation," said Dr. Lagasse, whose lab is at the McGowan Institute. "Cell therapies are being explored, but introducing cells into tissue already ravaged by disease decreases the likelihood of successful engraftment and restoration of function."

In the study, his team tested the possibility of using lymph nodes, which are abundant throughout the body and have a rich blood supply, as a new home for cells from other organs in what is called an "ectopic" transplant.

They injected healthy liver cells from a genetically-identical donor animal into lymph nodes of mice at various locations. The result was an enlarged, liver-like node that functioned akin to the liver; in fact, a single hepatized lymph node rescued mice that were in danger of dying from a lethal metabolic liver disease. Likewise, thymus tissue transplanted into the lymph node of mice that lacked the organ generated functional immune systems, and pancreatic islet cell transplants restored normal blood sugar control in diabetic animals.

"Our goal is not necessarily to replace the entire liver, for example, but to provide sufficient cell mass to stabilize liver function and sustain the patient's life," Dr. Lagasse said. "That could buy time until a donor organ can be transplanted. Perhaps, in some cases, ectopic cell transplantation in the lymph node might allow the diseased organ to recover."

Best Ways To Manage Lymphedema: Exercise And Complete Decongestive Therapy

Nearly 40 percent of breast cancer survivors suffer from lymphedema, a chronic condition that causes body limbs to swell from fluid buildup, as a result of lymph node removal and radiation therapy. A cure for lymphedema does not exist, so individuals with the condition must find ways to manage the symptoms throughout their lifetimes. Now, a team of researchers and clinicians working with a University of Missouri lymphedema expert has found that full-body exercise and complete decongestive therapy (CDT) are the best ways for patients to minimize their symptoms and maintain their quality of life.

"There's a sense of empowerment - of autonomy - that comes from meeting the challenge of living with lymphedema," said Jane Armer, an MU nursing professor. "Some breast cancer survivors say that they've become a new person after cancer because they met a challenge, and they like the stronger person they've become. The challenge of lymphedema is similar. It's something that is pervasive in every part of life. It takes problem solving and persistence to manage the condition without letting it interfere with their goals."

Armer and her colleagues reviewed published research about lymphedema self-management in order to determine which practices were most effective in managing the condition. The researchers found that full-body exercise, such as weight lifting and stretching, was likely to be effective in minimizing lymphedema symptoms. In addition, the researchers concluded that complete decongestive therapy (CDT), a comprehensive treatment approach that incorporates skin care, exercise, manual lymphatic drainage and bandaging of swollen limbs, also helps patients effectively manage the condition.

"Previous research suggests that, the earlier the interventions, the better the outcomes," Armer said. "If patients can learn how to successfully manage the condition early on, then they can continue those processes throughout their lives, and their outcomes will be better than those of individuals who resist participating in self-care."

New Guideline Offers Evidence-Based Testimonials On Function Of Sentinel Lymph Node Biopsy For Melanoma Staging In The U.S.A.

The American Society of Clinical Oncology (ASCO) and the Society for Surgical Oncology (SSO) have issued their first evidence-based clinical practice guideline on the use of sentinel lymph node biopsy (SLNB) to stage patients with newly diagnosed melanoma. Although SLNB has proven to be an important tool for determining prognosis and selecting treatment for many patients with melanoma, recent studies suggest that the procedure is inconsistently used. The new guideline recommendations, based on a review of all available evidence, are intended to clarify which patients should receive the procedure.

SLNB is a minimally invasive surgical technique that enables doctors to determine whether cancer has spread, a key factor in determining the appropriate surgical and drug treatments, and establishing a patient's eligibility for clinical trials. In the procedure, the "sentinel" lymph node - the node close to the tumor, to which cancer cells are most likely to spread - is removed and examined under a microscope for evidence of cancer. If cancer is found, additional surrounding lymph nodes are removed to accurately assess, or "stage," the disease and prevent further cancer spread. In most cases, however, no cancer is detected in the sentinel node and no additional lymph nodes need to be removed, allowing patients to avoid further pain, discomfort, expense, and possible side effects from a more extensive operation.

"When used for the right patients at the right time, sentinel lymph node biopsy is one of our best tools for personalizing melanoma treatment, and for sparing patients from unnecessary procedures or therapies," explained Sandra L. Wong, MD, lead author and Co-chair of the guideline panel and Assistant Professor of Surgery at the University of Michigan. "But we know this procedure is used inconsistently in the United States. We hope this guideline will provide the clarity physicians need to make the most of the procedure and further improve care for patients with melanoma."

The new clinical practice guideline was developed by a multidisciplinary panel of 14 clinical and methodological experts convened by ASCO and SSO. The panel reviewed literature published between January 1990 and August 2011, analyzing 73 studies that included more than 25,000 patients.

The guideline recommendations state the following:

SLNB is recommended for all patients with melanoma tumors of intermediate thickness (between 1 and 4 mm): Studies have shown that the technique is useful for identifying small nearby metastases in these patients, who account for about one-third of all melanoma cases. SLNB detects cancer in the sentinel node in about 18 to 26 percent of these patients, according to the guideline authors.

Evidence is insufficient to recommend routine SLNB for patients with thin melanoma tumors (less than 1 mm): Thin melanomas are the most common form of melanoma, and can usually be cured through surgical removal of the primary tumor. While SNLB is not necessary in most cases, the guideline recommendations note that it may be considered in select patients with thin melanomas who have certain high-risk factors, such as an ulcerated tumor or rapidly dividing cancer cells.

SLNB for patients with thick melanoma tumors (greater than 4 mm) may be recommended: Thick melanomas are more uncommon than the above two types, but are considered more likely to spread elsewhere in the body. While there are few studies focusing on the use of SLNB in patients with thick melanomas, use of SLN biopsy in this population may be recommended for staging purposes and to facilitate regional disease control.

Completion lymph node dissection is recommended for all patients with a positive SLNB: Complete removal of the remaining lymph nodes has been shown to prevent or limit further cancer spread in these patients. While it is not yet known whether this approach improves survival, the authors note that an ongoing study, the Multicenter Selective Lymphadenectomy Trial II, is expected to help resolve that question.

The guideline concludes that doctors should discuss SLNB as part of a comprehensive treatment planning process with their patients with melanoma. This discussion should address the risks and benefits of the procedure, and patients' individual values and preferences, so patients can make fully informed decisions.

"Our rapidly growing understanding of the biology of melanoma is driving development of more effective treatments with fewer side effects for patients," said Gary H. Lyman, MD, MPH, guideline Co-chair and Professor of Medicine and Director of Comparative Effectiveness and Outcomes Research at Duke University School of Medicine and the Duke Cancer Institute. "But to take advantage of this progress, we need to know the true extent of the disease from the start. This guideline will help ensure that sentinel lymph node biopsy is used appropriately whenever it can provide that vital information while avoiding unnecessary procedures in patients who are unlikely to benefit."

More information on the new guideline can be found at: http://www.asco.org/guidelines/snbmelanoma, and at http://www.surgonc.org--policy/practice-management/clinical-guidelines/clinical- guidelines---melanoma.aspx. A patient-oriented view of the guideline, "What to Know: ASCO/SSO Guideline on Use of Sentinel Lymph Node Biopsy for Melanoma Staging," can be found on ASCO's award-winning patient information website, http://www.cancer.net.