Practical Considerations and advantages of the sentinel lymph node biospy used in breast cancer staging.

A Quick overview of the sentinel lymph node biospy technique

A sentinel lymph node biopsy is a relatively new procedure that was developed to identify metastasis of breast cancer to the axillary lymph nodes, but without having to do a traditional axillary lymph node dissection. By way of background, the lymph ducts of the breast usually drain to one lymph node first, before draining through the rest of the lymph nodes underneath the arm. This initial lymph node is called the sentinel lymph node, and a sentinel lymph node biopsy removes this lymph node only. The sentinel lymph node may be identified either by a weak radioactive dye (technetium-labeled sulfur colloid) or by a blue dye (isosulfan blue) that stains the lymph tissue a bright blue color.

Negative Sentinel lymph node biopsy usually means all axillary lymph nodes are cancer free.

The main advantage of the sentinel lymph node biopsy is that a negative result will, in most cases, spare the breast cancer patient the ordeal of axillary node biopsies and dissections. In fact, the SLN biopsy is so accurate the current debate is as to whether or not axillary dissections are necessary at all.

A 'positive' finding, means that malignant cells have been found on the sentinel lymph node, (or that the sentinel lymph is mysteriously absent). Postive sentinel nodes would warrant an immediate follow-up with a thorough axillary node assessment. But, sentinel lymph node biopsies, when negative, indicate that the axillary nodes are cancer free and are now considered to be about 95% accurate. It can be a mixed blessing, however, as there often can discussion and consultation between the breast cancer patient and the treatment team as to whether or not the sentinel lymph node biopsy is 'good enough', which can create a great deal of anxiety.

At which cancer stage would a sentinel lymph node biopsy be requested?

The sentinal node biopsy is a staging procedure used fairly early on when treated breast tumors, and is indicated when a percautaneous needle biopsy shows an infiltrating lesion, but a clinical exam of the axilla is negative.

How 'serious' does a lesion or tumor have to be before getting a SLNB?

The sentinel lymph node biopsy may be requested if the attending physicians feel that breast carcinoma has reached an infiltrating status, or possible when a non-infiltrating lesion has characteristics suggestive of an aggressive cancer. That determination could be due to a variety of variables, which would include high risk factors and histological findings, but the most likely reason to proceed is that the tumor is considered medium to large in size.

Sentinel lymph node biopsies are usually taken when the TNM classification is T1-2 N0 (tumor size 2-5 cm ), but not for T3. At TNM T3, the size of the tumor is greater than 5 cm and there is a very high probability of lymphatic involvement.

The adverse realtionship between tumor size and nodal metastasis is quite consistent, but not a certainty. The correspondance rate varies between 67%-100%, which would tend to suggest that sentinel lymph node findings are less trustworthy in ruling out axillary metastasis as the size of the primary tumor increases. At the same time, other studies suggest that axillary dissection can be avoided in up to 1/3 of patients even with large T2 and T3 tumors if a sentinel lymph node biospy is tried first.

What about 'high risk' DCIS?

The prevailing consensus is that a sentinel lymph node biopsy is unnecessary with DCIS. Critics might argue that 'high risk' DCIS could potentially be 'understaged', and the relative convenience of the SLNB warrants its application from the get-go.

It is likely that the sensitivity of the sentinel lymph node biopsy and specifically the relatively new idea of 'micro-metastasis' on the lymph nodes , has both researchers and breast cancer patients somewhat over-eager to have a SLNB. It must be remembered, however, that up to 90% of all ductal carcinoma can be treated and cured locally.

 

breast cancer micrometastasis to sentinel lymph node

 

Lymph node "micro-metastasis" of breast carcinoma

The term "Micrometastasis" refers to extremely small amounts of malignant cancer cells developing on the lymph nodes or other secondary sites; so small they can only be seen 'microscopically'. It is somewhat of a 'hot topic' in cancer research at the moment. Advocates reason that through the use of specialized pathological techniques such as the 'polymerase chain reaction' method, malignant cells may be found on lymph nodes which traditional methods such as ultrasound, CT, PET, and MRI, would not reveal.

The idea, then, is to perform a rigourous histological evalution of the sentinel lymph node biopsy, specifically searching for micrometastases. The hope is that if malignant cells are found, even in tiny quantities, aggressive treatments can begin right away and prognosis will be improved.

Is it really necessary? Some studies estimate a rate of relapse for node-negative breast cancer patients within five years to be about 30%. Proponents also claim that micro-metastases are found in 9%-30% of negative lymph nodes upon re-examination, and that current histological detection methods may therefore be inadequate for identifying metastatic tumor cells in lymph nodes.

It is a bit of a good news/ bad news scenerio, however. The potential for finding micrometastases has created a great deal of fear in women, who now doubt the authenticity and reassurance-value of 'image' staging of the lymph nodes, even when they are clear. Those who specialize in SLN biopsies also point out that the findings can be so sensitive, sometimes able to find spot a single malignant cell among one million normal cells, it is just as likely that the cell in question is just passing through the lymphatic system and will be cleared out by the lymphatics, not ominious indication which requires more surgery or chemotherapy.

 

Should some breast cancer patients should NOT have the sentinel lymph node biopsy?

The sentinel lymph node biopsy has so many positives that it is difficult to find reasons not to use it. There has been a fair bit of discussion as to whether or not factors such as prior breast surgeries and radiation and chemical therapies compromise the results, and the general consensus is no. There are other considerations surrounding allegies or pregnancy, and also as to at which point there is enough evidence of 'clearly aggressive' or metastizing cancers that axillary dissection is mandatory.

Sentinel Lymph node biopsy not advised for pregnant women

Most physicians will advise that a SLNB should not be offered to pregnant women of less than 30 weeks gestation. The fear is that chemical agents in the dyes may have some unexpected effect on either the mother or the fetus. However, there are very few research studies at this time and findings are unclear.

Allergies to the dye agents?

There will be a few breast cancer patients who demonstrate allergic reactions to either the isosulfan blue dye or to the radio colloid. Before the SLN biopsy, women are often asked if they have any allergies to cosmetics, as there can be similarities. In these situations the technologist might have to experiment with alternate dyes or possibly add anti-allergents to the injected compound.

 

ultrasound multifocal breast tumors

 

Multi centric breast tumors contra-indicate the SLNB

A sentinel node biopsy is contraindicated for women with multiple (multicentric ) breast tumors. The reasoning behing this is quite logical. One cannot be sure which breast lesion has or has not metastized to the sentinel lymph nodes. The liklihood of a 'false negative' is therefore very high.

Radiation treatments of breast tumor also compromise the SLNB

It is quite common for ongologists to recommmend radiation treatments to halt of slow cancer metastasis from the breast. The problem with sentinel lymph node biopsies follwoing radiotherapy is that radiation makes normal lymphatic ducts and capillaries lleak at first, then shrivel up. New pathways eventually form, but they often form in odd, jagged paths and not straight lines of drainage anymore, so the sentinel aspect becomes un-reliable.

Is a sentinel lymph node biopsy used following chemotherapy?

The short answer is yes. Around 40%-48% of women with advanced breast cancer who are also taking neoadjunct chemothepary, will not develop axillary metastastis. A sentinel lymph biopy could potentially be spared the inconvenince and body-stress of axillary dissections in just under half of all patients receiving breast chemotherapy.

One concern is that the lymphatic ducts and capilliaries around the breast tumor will be damaged and compromised by the chemical treatments, which might effect the reliability of sentinel lymph node findings. Additionally, chemotherapy often shrinks tumors, leaving scar tissue and fibrosis that can make it hard for surgeons to inject a tracer or dye into the tumor.

There is no hard and fast rule in this regard. Lymphatic drainage patterns are generally considered to be in better shape following chemotherapy as compared to radiation treatments, but they are damaged nonetheless. Lymphatic flow continues through alternate routes, and as time passes and the wound heals, normal lymphatic channels are restored. Lymphatic mapping might be well advised prior to the SLNB, but if there is no evidence of subsequent infiltration at the primary site and a resonable time period has passed since the treatment, there is little reason to doubt the accuracy of the sentinel lymph node biopsy.

The effects of previous breast dissections on sentinel lymph node sensitivity

A hot topic of debate amoung current breast cancer researchers is whether or not prior lumpectomies and mastectomies can compromise the reliability of sentinel lymph node biopsies. The traditional view has been that previous breast surgeries might disrupt the lymphatic flow from the tumor site to the axilla, and lead to higher 'false negative' results. This has not in fact been proven to be true. When lymphatic channels have been surgically comprised, flow continues through new and different routes. As damaged lymphatic channels are gradually repaired, normal lymphatic flow resumes.If the tumor is located in an intact quadrant of the breast... even a recent reductive procedure is unlikely to affect the reliability of the sentinel lymph node biopsy.

A prudent measure might be to combine the sentinel lymph node biopsy with a pre-operative lymphoscinitigraph or other lymphatic mapping (LM) method, just to make sure the flow is sound. The SLNB technique has been around since about 2001 and there is enough experience now to assert that the effect of breast surgery itself on lymphatic flow is negligible.

Bear in mind that for all breast conserving therpies, the cancer will recur locally (along the breast or chest wall) 10-15% of time, and metastize to the lymph nodes or other distant areas at about the same rate. One can never really be attribute metastasis; false positives, and false negatives, specifically to 'this or that' procedure.

 

Should SLNB be trusted after 'local recurrence' of breast cancer following surgery?

Lymph node assessment will be on ongoing part of breast cancer staging and treatment. The sentinel lymph node biopsy is typically something which occurs as you treat the cancer in an early stage, either before or after any necessary breast dissection. Following breast surgery, a 'local recurrence' means that the cancer has subsquently developed somewhere on the chest wall of breast. It can still be treated and possibly 'cured' locally, however. Local recurrence of breast cancer would tend to rule out the use of the SLNB, because the cancer is cleary aggressive and traditional axillary node biopsies would be a mandatory follow up.

Other evidence of axillary metastasis precludes SLNB

Obviously, if a clinical evaluation indicates metastasis to the lymph nodes ( the finding a palpable mass ) the technique would be redundant. Excisional biopsies and possibly a 'complete lymph node dissection' (CLND) of level I and level II axillary nodes would be a likely course of action. (The 'levels' of axillary lymph nodes refer to their anatomical location.)

It has been speculated that a SLN biopsy could be a helpful prognostic indicator, even after a confirmed clinically positive axilla (NI) from needle or core biopsies. The problem with this notion is that the path of the dye or the radio-colloid agent may be blocked from tumor cells infiltrating the lymph vessels. This could prevent the identification of true sentinel nodes and produce false positive results.

So you have a positive SLN. then what?

Sentinel lymph node biopsies are very accurate and reliable (around 90-95%) when they are negative for tumor cells. But if there is a positive result there is still lack of clarity regarding the prognostic indications. If the sentinel lymph node is tumor-positive, it does not necessarily mean that the cancer will metastize to the other 'non-sentinel' lymph nodes.

If results show a 'mix' of negative (clear) nodes and positive (cancerous)nodes, the risk of spread to the axillary lymph nodes is still considered quite low, at around 10%. A CLND ( Completion lymph node dissection ) may not be required, but cannot be conclusively ruled out.

Other factors that tend to suggest an increased probability of involvement of the other lymph nodes include the size of the lesion on affected sentinel node, and also the size of the primary tumor. Other factors which can help predict additional nodal metastasis include the presence or absence of lymphovascular invasion in the primary tumor, and the number of lymph nodes that were removed.

 

Reliability of other non-invasive methods in predicting breast cancer metastasis to axillary nodes

Assuming that the axillary nodes are not yet clinically palpable on a physical exam. It is estimated that either preoperative ultrasound imaging or a fine needle aspiration biopsy can determine the malignant status of the axillary nodes about 40% of the time. That is not a particularly high rate, so in the absense of a sentinal node biopsy, routine follow-up scans are usually recommended at relatively short intervals.

 

Is it best to give women a choice regarding the SLNB?

Women undergoing breast cancer treatment often get the impression that every choice is theirs to make. Certainly, there are some important choices to be made in consultation, and these difficult decisions usually revolve around the potential cancer-fighting benefits of a procedure versus the strain on the body and quality of life during and after. A decision to reject axillary surgery and have a sentinal node biopsy instead is not necessarily the most prudent one, even thought the success rate is so high and the side effects are so minimal. Some modern breast cancer treatment centers have access to clinical trials of the newest, best chemotherapy agents, but those clinical trials often require the highest degree of staging.


Overall,the Sentinel Lymph node biopsy is a major 'plus' for breat cancer treatment.

 

Now that the SLNB is in widespread use, the challenge for researchers is to refine the groups of patients who will most benefit from the technique. The main benefit is in identifying patients with less aggressive cancers, who may not need complete lymph node dissection. Additional benefits of bypassing axillary dissection, from a purely medical perspective, is that the normal flow of lymph is relatively undisturbed. This ios to the benefit of preventative chemical and radiation therapies already underway.

For all breast cancers, between 70%-80% of patients will not develop axillary lymph node metastasis. But, for breast cancer patients undergoing multimodal therapies and with histologically negative sentinel lymph nodes, the rate of recurrent disease is extremely low.

Some cancer treatment centers, particularly those in less affluent parts of the world, have gone so far as to replace all other diagnostic measures for axillary metastasis with the sentinel lymph node biopsy. It is reliable and accurate, and long term quality of life by avoiding axillary dissection is better. This is of course somewhat of a radical conclusion, but points to the practical and ethical dilemmas women sometimes encounter during breast cancer treatment. The best advice is to develop good relationships with an experience, multidisciplinary breast cancer treatment team, and to trust their judgement.

 


References

  1. Evaluation of Sentinel Lymph Nodes in Breast Cancer. Histopathology 2005, 46, 697-706
  2. Kelley MC, Hansen N, McMasters KM. Lymphatic Mapping and Sentinel Lymphadenectomy for Breast Cancer. American Journal of Surgery. 188 (2004) 49-61.
  3. Vijayakumar V, Boerner PS, Vani AB, Vijayakumar S. A Critical Review of Variables Affecting the Accuracy and False-Negative Rate of Sentinel Node Biopsy Procedures in Early Breast Cancer. Nuclear Medicine Communication 2005; 26: 395-405.
  4. Bass SS, Cox CE, Ku NN, Berman C, Reintgen D. The Role of Sentinel Lymph Node Biopsy in Breast Cancer. J. Am. Coll. of Surgery Vol. 189, no 2, August 1999, 183-194.
  5. Breslin, T.M., Cohen, L. , Sahin, A., Fleming, J.B., Kuerer, H.M., Newman, L.A., Delpassand, E.S., House, R., Ames, F.C., Feig, B.W., Ross, M.I., Singletary, S.E., Buzdar, A. U., Hortobagyi, G.N., Hunt, K.K.; Sentinel Lymph Node Biopsy Is Accurate After Neoadjuvant Chemotherapy for Breast Cancer . Journal of Clinical Oncology, Vol 18, Issue 20 (October), 2000: 3480-3486
  6. Filippakis, G., and Zografos, G., Contraindications of sentinel lymph node biopsy: Are there any really? World Journal of surgical oncology 2007, 5:10. (January 2007)
  7. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997 Jul;15(7):2483-93.
  8. Jakub, James W., Pendas, Solange., and Reintgen, Douglas S. Current Status of Sentinel Lymph Node Mapping and Biopsy: Facts and Controversies The Oncologist, Vol. 8, No. 1, 59-68, February 2003
  9. Kaleya, R., Heckman, J., Most, M., Zager, J. Lymphatic mapping and sentinel node biopsy: A surgical perspective. Seminars in Nuclear Medicine, Volume 35, Issue 2, Pages 129-134
  10. Elias, N., Tanabe, K., Sober, A.J., Gadd, M.A., Mihm, M.C., Goodspeed, B., Cosimi, A.B., Is Completion Lymphadenectomy After a Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma Always Necessary? Arch Surg. 2004;139:400-405.
  11. Taback, B., Hansen, N., Conway, K., Giuliano, A., Recurrence patterns following a negative sentinel lymph node biopsy in patients with early-stage breast cancer. Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
    Vol 22, No 14S (July 15 Supplement), 2004: 560
  12. Bembenek A, Kettelhack C, reuhl T et al: Sentinel" lymph node biopsy in breast carcinoma. Current experiences. Zentralbl Chir 2000;125:817-821
  13. Moran CJ, Kell Mr, Flanagan FL et al: role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients. Am J Surg 2007;194:172-175
  14. Mansel R.E, Fallowfield L, Kissin M et al: randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: The ALMANAC Trial. J Natl Cancer Inst 2006;98:599-609
  15. Coombs N, Chen w, Taylor r, Boyages J: A decision tool for predicting sentinel node accuracy from breast tumor size and
    grade. Breast J 2007;13:593-598.
  16. Moghimi, M., Ghoddosi, I., Rahimabadi, A.E., Sheikhvatan, M., Accuracy of Sentinel Node Biopsy in breast cancer patients with a high peralence of axillary metastases. Scandinavian Journal of Surgery 98: 30-33, 2009
  17. Cao, Q. Wang, S., Liu, X. Lin, L., Zhao, J. Sentinel lymph node micrometastasis detection using immunohistochemistry and reverse transcription-polymerase chain reaction for cytokeratin 19 in breast cancer. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 11074
  18. Aasvold JN., Alazraki NP. Update on Detection of Sentinel Lymph Nodes in Patients With Breast Cancer. Seminars in Nuclear Medicine. 35: 116-128. 2005




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Copyright Steven B. Halls, MD Last edited 25-December-2010

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