My doctor told me that the surgeon will remove my sentinel lymph nodes. What does that mean?
This is the question that lingers the minds of many patients diagnosed with Early Stage Breast Cancer. The concept of Sentinel Lymph Node Biopsy has been introduced around the past 50 years now. But it was in the late 1980s and early 1990s that it started becoming widely accepted in the management of various cancers.¹
Studies from the National Cancer Database have shown an exponential increase in the use of sentinel lymph node biopsy in breast cancer from 27 to 77 % between 1998 and 2005 in over 490,000 women in United States.²
To understand the logistics behind this procedure lets go over some of the basic definitions one has to be familiar with…
To begin with...What is a lymph node?
A lymph node is a small oval shaped organ, each connected to the other via vessels called lymphatics. The lymph nodes together with the lymphatics present throughout the human body are dense carriers of white blood cells, thus forming an important part of our immune system by filtering the harmful wastes from the body.
How does cancer spread (metastasize)?
There are mainly three routes by which cancer cells can spread:
· through direct invasion of the surrounding tissue
· via the blood vessels
· via the lymphatics
Many cancers spread through the lymphatic vessels, including breast cancer. As the cancer spreads to the nearby lymph nodes, they enlarge and become firm or hard lumps. In breast cancer, the most common lymph nodes to be involved about 80% of the times are the nodes under the armpit (axillary nodes). Surgical removal of these lymph nodes is called axillary lymphadenectomy or axillary lymph node dissection (ALND). Status of these lymph nodes is very important in determining the likely outcome of the disease (prognosis) especially in patients with early stage breast cancer.
Traditionally. ALND has been the standard treatment of choice for patients with clinically palpable axillary nodes and in whom positive nodes (harboring cancer cells) were found through ultrasound in early stage Breast Cancer. It was used in assessing the spread of cancer to these nodes (nodal staging). However, it involved removal of almost all the lymph nodes in the axilla, causing serious complications, especially to the arm after surgery.
This paved the way for the introduction of sentinel lymph node biopsy in patients with clinically non-palpable nodes, which proved to be associated with fewer complications and was more accurate in nodal staging.²
So what does the word ‘sentinel’ mean?
Sentinel is one that keeps guard.
What is a Sentinel lymph node?
Sentinel lymph node (SLN) is a lymph node or a group of lymph nodes that guards the other lymph nodes by acting as a barrier. It does this by being the first most likely to harbor the cancer cells brought by the lymphatics from a tumor site.²̛ ⁴
What is sentinel lymph node biopsy?
Removal of these lymph nodes and then examining them under the microscope is called Sentinel lymph node biopsy (SLNB). The likelihood of other lymph nodes having cancer cells in highly low when sentinel nodes examined do not show any evidence of cancer spread.²̛ ⁴
SLNB is most commonly employed in Breast Cancer and Melanoma. Some of the other cancers it is used include, cancers of the Vulva, Cervix, Colon, Head and Neck, Thyroid, Lung etc.⁴̛ ⁵
Here, we are mainly going to discuss the role of SLNB in Early Stage Breast Cancer.
Now what is Early Stage Breast Cancer?
There are four stages in breast cancer, Stages I through IV, depending on the size of the tumor, extent, lymph node involvement and distant metastases (spread to other organs like bone, brain, liver etc.). Stages I and II are considered as early stage breast cancer. In Stages I and II, cancer is limited to the breast tissue and may not or minimally involves the lymph nodes.⁹
In whom is SLNB done?
SLNB is most commonly recommended for:
· Patients in early stage breast cancer (T1, T2 tumors) who do not have lymph nodes palpable under the arm (clinically node-negative patients)
· SLNB can also be performed in some patients with Ductal carcinoma in situ (DCIS), male breast cancer, elderly, obese, where as in some other cases it holds doubtful.²̛ ⁶
We shall discuss some of the common clinical scenarios encountered by patients and doctors in another section below.
How is it done?
Personnel involved: An experienced team including a surgeon, radiologist, nuclear medicine physician and a pathologist. This team is called ‘the sentinel node team’.⁹
Preoperative: Injection of the tracers
The sentinel lymph node is identified using either a radioactive colloid (technetium-99m sulfur colloid) or an isosulphane blue dye or both. Studies have proven the combined use of both to be more accurate.³̛ ⁴̛ ¹⁰̛ ¹³ However, use of either one can also produce similar results, depending on the surgeon’s expertise, comfort level and availability of the material.³̛ ¹⁰ You may want to discuss with your surgeon what method suits both you and your surgeon best.
Radio colloid and/or blue dye is injected around the tumor site into the skin or surrounding tissue of the breast. In the combined procedure, optimal time for radio colloid injection is around 1 -3 hours prior to the surgery. The blue dye is later injected about 5 minutes before the procedure.
The patient is asked to gently massage the breast for 5 minutes after injecting each tracer. It dilates the lymphatics and allows easy flow of the tracer.
Once injected, the tracers then travel though the lymphatics and subsequently, flow into the lymph nodes, which could be one or few. The first among them to take up the radioactive colloid and/or the blue dye are termed the SLN.³̛ ¹⁰
In the operating room: Identifying and removing the SLN(s)
The SLN(s) are identified using a gamma probe which detects the most radioactive nodes labeled as “hot spots”. A small incision is then made in the skin around the hot spots and the gamma probe used to guide the surgeons to the labeled nodes.
Nodes that are blue, hot, blue and hot, not stained but found at the end of a blue lymphatic channel found during the procedure are removed (excised).
Care should be taken to remove those lymph nodes that feel firm while doing the procedure even though they haven’t taken up the stain or radio colloid. These are considered SLNs too.
Evaluation of the excised SLN(s): Looking for cancer cells.
The SLNs can be evaluated in the operating room by the pathologist for possible cancer cells. If the specimens do show evidence of cancer cells, a complete ALND can be performed right then. This alleviates the need for a second surgery. However, the accuracy of this procedure is questionable because of loss of some tissue while preparing the slides.³̛ ¹⁰
As a result, many institutions prefer to carry out a more detailed examination of the lymph nodes (permanent sections), results of which are out in a few days and are more accurate.
If no tumor cells are detected (negative SLNB test), then involvement of other nodes is highly unlikely, therefore obviating the need for further surgery.
If tumor cells are detected (positive SLNB test), the patient may have to undergo a second surgery for complete lymph node dissection.³̛ ¹³ The approach to a positive SLNB test is discussed further below.
What are the benefits of this procedure?
· Minimal hospital stay as it is carried out as an outpatient procedure, and doesn’t require a drain like in complete dissection
· It is less invasive, involving minimal tissue damage, early recovery and rapid return to ones daily activities (usually within a week)
· Considerably decreases the long-term disability to the arm in terms of lymphedema (swelling of the arm resulting from blocked lymphatics), numbness, prolonged pain, reduced range of motion
· A more sensitive and accurate technique for nodal staging in early stage breast cancer, which is very helpful in deciding further treatment plan
· May avoid the need for a more extensive surgery in patients with clinically non-palpable nodes, if no cancer cells are detected by the pathologist
· Rates of axillary recurrence have been considerably low in patients who did not undergo full axillary dissection because of a negative SLNB test²̛ ⁴̛ ¹⁰̛ ¹¹̛ ¹³
What are the drawbacks of this procedure?
· Pain or bruising at the biopsy site
· Infection of the biopsy site
· Sometimes there could be premature opening of the wound along the sutures slowing down the healing process, called wound separation/dehiscence
· There could be formation of seromas (accumulation of clear fluid in the cavity left after surgery) or hematomas (accumulation of blood in the cavity, due to damage of some vessels during surgery)⁶
· Allergic reaction to the blue dye, like skin rash, itching, hives, low blood pressure, rarely severe allergic reaction(anaphylaxis) seen in 0.7-1.1% of the cases³
· Dye induced discoloration of the injection site
· Dye induced discoloration of urine
· Failure of the procedure is 5–10 % , which can be lower by experienced surgeons²̛ ¹³̛ ¹⁴̛¹⁵
· No clear evidence of improved survival or decreased recurrence as compared to ALND⁴
What is the role of SLNB in management of early stage breast cancer?
As we mentioned earlier, SLNB has played a pivotal role in the management of early stage breast cancer. The flow diagram below explains the approach broadly.
When SLNB is positive in clinically node-negative patients, there have been numerous debates regarding management of these patients with complete ALND.
These doubts arise from the fact that the tumor cells found are categorized into three different types depending on the size of the largest tumor deposit in the sentinel node. They are labeled:
Isolated tumor cells: tumor deposits less than 0.2 mm
Micrometastases: tumor deposits between 0.2 and 2 mm
Macrometastases: tumor deposits greater than 2 mm
Depending on the clinical situation of individual patients, further treatment options are planned which may include complete ALND or radiation therapy.²
Isolated tumor cells are proved not to be clinically significant and hence, do not change overall patient survival.⁴ Similar studies have been suggested for micrometastases too⁸, which is discussed further below
What are the current data suggesting?
The most recent guidelines have suggested that there has been more surgery related disability, along with no improvement in overall survival and recurrence rate in complete ALND compared to SLNB alone in patients:
· Who have clinically node negative T1 – T2 tumors
· less than 3 SLNs involved
· undergoing breast conserving surgery and radiation therapy⁷̛ ⁹
There have been various ongoing trials, one among them being the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial which analyzed 1,389 patients over a period of 96 months.⁸
The conclusions drawn suggested patients with macrometastases in the SLNs had poorer survival outcomes as compared to those with micrometastases.
Also, however, the likely outcome of those with micrometastases was no different from those with node-negative breast disease. Thus, further surgery may not be required.
Two other studies, results of which are still pending, include the AMAROS trial and the International Breast Cancer Study Group –Trial 23-01, are in the process of finding the benefit of complete node dissection in clinically node-negative patients with positive SLNs.²
Some of the clinical scenarios encountered…
Doctor, what if I am pregnant?
The use of vital blue stains is contraindicated in pregnant women. The dose of radio colloid used is very minimal to cause any adverse effects to the fetus. Therefore, it still remains a controversial issue. Guidelines go against doing the procedure during pregnancy.²̛ ⁶
What if I underwent a breast reduction surgery or have breast implants?
There is insufficient data to prove the feasibility of the procedure.
Guidelines do not go for or against doing the procedure in these patients.²̛ ⁶
What if I had an axillary surgery before?
Guidelines do not recommend doing the procedure.
However, successful procedure results after surgery are being reported.²̛ ⁶
Can I have the procedure before or after Neoadjuvant chemotherapy?
Neoadjuvant chemotherapy – refers to the drugs that are given before surgery to treat the tumor.
There is again insufficient data to decide the timing of the procedure in case patients have to receive pre operative systemic therapy.
Trials (ACOSOG trial Z1071) are under progress to answer this question.²̛ ⁶
What if I was diagnosed with locally advanced tumor or inflammatory tumor?
Guidelines recommend against using the procedure in T4, locally advanced and inflammatory tumors.
Some patients with T3 tumors with no distant metastases have undergone successful procedure.²̛ ⁶
Doctor said I have multicentric/multifocal disease. Can I have this procedure?
Multicentric disease - multiple tumors arising in different areas of the breast and not originating from one particular tumor
Multifocal disease - multiple tumors in the same area of the breast originating from a single tumor
Guidelines recommend the use of the procedure in both cases.²̛ ⁶
I was diagnosed with DCIS. Can I have this procedure?
DCIS – Abnormal cells found in the lining of the breast duct, and have not spread to the breast tissue. In some cases, the cells may spread, calling it invasive DCIS. Since DCIS usually does not involve the axillary nodes, sentinel node biopsy is not routinely performed. However if the disease is extensive or suspected to be invasive, biopsy is done for axillary staging.
If you are undergoing mastectomy, biopsy can be done during the procedure.
If breast conserving surgery is an option, biopsy is not required.²̛ ⁶̛ ¹²̛ ¹³
Doctor told me my internal mammary nodes are involved. Do I need the biopsy?
Internal mammary nodes are the lymph nodes present around your breast bone between both breasts. These can also be the SLNs.
However, the presence of these nodes has not significantly altered the clinical outcome of patients, thus, biopsying them remains controversial.²
I am an elderly patient. Can I undergo this procedure?
Even though the procedure can be technically challenging, elderly patients are not contraindicated for this procedure.⁶̛ ¹¹
I am an obese patient. Can I undergo this procedure?
Same as above
We thus come to the conclusion that the use of SLNB has proved to be quite efficient in the management of patients with early stage breast cancer.
An experienced sentinel node team can greatly reduce the failure rate of the procedure resulting in better patient outcome from the surgery.
SLNB has been studied to have greater than 90% and 95 % identification rate and accuracy, respectively.¹³ Continuous and endless efforts are being undertaken to understand its role in early breast disease and improve survival of many.
1. Tanis PJ, Nieweg OE, Valdés Olmos RA et al. History of sentinel node and validation of the technique. Breast Cancer Res. 2001; 3(2): 109–112
2. Harlow SP, Weaver DL. Sentinel lymph node biopsy for breast cancer: Indications and outcomes, Uptodate, June 13, 2011
3. Harlow SP, Weaver DL. Sentinel lymph node biopsy for breast cancer: Techniques, Uptodate, September 2, 2010
4. Lyman GH, Giuliano AE, Somerfield MR et al. American Society of Clinical Oncology Guideline, Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. Journal of Clinical Oncology, Vol 23, No 30 (October 20), 2005: pp. 7703-7720
5. October 17, 2009. Available at: http//www.mayoclinic.com/health/sentinel-node-biopsy/MY00828
6. Giuliano AE, Mabry H. Sentinel Lymph Nodes in Breast Cancer: Evolving Indications. Breast Cancer Annual Update 2005, Module 4, Clinical Care Options
7. Edge S. Diagnosis, Staging and Initial therapy. Breast Cancer and 2010 San Antonio Breast Cancer Symposium Review, February 5, 2011
8. Burstein HJ. Management of Early Breast Cancer. Clinical Advances in Hematology and Oncology. May 2011, volume 9, issue 5, supplement 11
9. NCCN Guidelines, Version 2.2011 Invasive Breast Cancer
10. Hayashi A. Provincial Guidelines for Lymphatic Mapping and Sentinel Node Biopsy for Breast Cancer. BC Surgical Oncology Network. October 2003
11. Smith BL. Multidisciplinary Approach in the Treatment of Early Breast Cancer, Surgical Management. In: Taghian AG, Smith BL, Erban J. Breast Cancer, A Multidisciplinary Approach to Diagnosis and Management. New York: Demos Medical Publishers; 2010. p. 121-22
12. Racsa M, Hirsch AE, Macdonald SM. Multidisciplinary Approach in the Treatment of Ductal carcinoma in Situ, Radiation Treatment of DCIS. In: Taghian AG, Smith BL, Erban J. Breast Cancer, A Multidisciplinary Approach to Diagnosis and Management. New York: Demos Medical Publishers; 2010. p. 101
13. Chen SL, Iddings DM, Scheri RP, Bilchik AJ. Lymphatic Mapping and Sentinel Node Analysis: Current Concepts and Applications. CA Cancer J Clin 2006; 56:292–309
Visiting Medical student at UIC,
Kasturba Medical College, Manipal, India
Divyesh G Mehta, MD