BREAST SENTINEL NODE LOCALISATION & BIOPSY Kirsten Worthington Senior Nuclear Medicine Technologist/MRT Good morning, We have been performing Breast SN Biopsies with Mr Pfeifer, Mr Samson and their teams at Southland Hospital since March 2006. Click.

What is a ‘Sentinel’ lymph node (SLN)? The very first lymph node to receive drainage from a cancer containing area of the breast Typically located in: - Axilla (armpit) but can also be in: - Internal Mammary - Clavicular groups Firstly I will quickly reinforce what is referred to as a breast sentinel node. We know that breast cancer can spread from the breast in a number of ways. One of these ways is for breast cancer cells to escape from the primary tumour and enter into the lymphatic system. In breast cancer, the lymph glands affected are mainly located in the axilla, however other gland groups can also be involved such as the internal mammary situated behind the sternum or the supra & infra clavicular nodes near the clavicle. The ‘Sentinel’ node is classified as any lymph node receiving direct lymph drainage from the primary tumour site. Click. Axillary lymph nodes Internal mammary lymph nodes Supra & infra clavicular lymph nodes

Axillary Clearance (A.C) All axillary lymph nodes removed in patients with breast cancer Pathological lymph node analysis important in ‘staging’ disease Typically 1015 nodes removed (Diehl, Chang) A.C reduces chance of cancer returning to axilla. Gold Standard Procedure In the past, the usual operation for cancer of the breast was to remove most, if not all the lymph glands from the armpit of the affected side. This is known as axillary clearance or dissection. On average 10-15 lymph nodes are removed in this operation, but can be as many as 30 nodes. Pathological analysis of the axillary lymph glands is extremely important in ‘Staging’ the breast disease and the presence of cancerous lymph node involvement determines the treatment pathway for the patient. The main advantage of axillary clearance is that it helps reduce the chance of breast cancer returning in the armpit. Click.

Side Effects from Axillary Clearance Lymphedema +/- - Stiff shoulder - Numbness (nerve damage) - Fluid collection 10-15 cm surgical wound Long recovery period 70% of DCIS breast cancer cases have not metastasized to the lymphatic system (Journal of Nuclear Medicine, Vol. 42 No.8, 2001) Unfortunately the removal of all these axillary lymph nodes can lead to chronic swelling of the arm, otherwise known as lymphedema. Lymphedema may also be associated with the following possible side-effects: Stiffness of the shoulder Numbness of the arm & fluid collection under the arm The patient will also have a 10-15 cm incision and a longer recovery period. A key point to note is that 70% of women with DCIS breast cancer will NOT have cancer in the lymph glands. Click.

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What is ‘Sentinel Lymph Node Biopsy’ (SLNB)? Recent technique checking for lymphatic mets without performing an A.C 13 sentinel node/s removed only Sentinel node/s identified at surgery by: - 99mTc Senti-scint/Geiger probe - Isosulfan Blue Dye Test Preliminary pathological analysis of nodes during surgery Negative biopsy result  operation completed Positive biopsy result  Patient will require A.C Sentinel Lymph Node mapping and biopsy is a diagnostic procedure used to determine whether breast cancer has metastasized to the lymph nodes without having to do a traditional axillary lymph node clearance. The aim of this technique is to identify and remove just the sentinel node/s and no others. The normal variant of Sentinel nodes seen is between 1 & 3 on average. The reasoning behind this technique being that if breast cancer cells were to escape into the lymphatic's, then the first lymph node met will most likely be the first to be affected by metastases. The Sentinel lymph node is identified by a combination of a 99mTc labelled Colloid that can be measured by a hand held radiation detection probe in theatre and a blue dye which stains the lymph tissue bright blue so it can be seen visually at surgery. If the sentinel node or nodes do not contain cancer cells, then an axillary clearance can be avoided. This clinically improves outcome for the patient because it lessens the likelihood of long term complications and side effects from an axillary dissection. Click.

Who can have Sentinel Lymph Node Biopsy? Patients with ‘in-situ’ breast carcinoma - small tumours (DCIS) SDHB: Procedure done in conjunction with lumpectomy or mastectomy So, who will have a SLNB? This technique is performed on patients with early ‘ductal carcinoma in-situ’ breast tumours which are confined within the lining of endothelial cells along the breast duct. This surgical biopsy can be done in conjunction with either a wide excision lumpectomy or full mastectomy. Click.

Who Shouldn’t have a SLNB? Women with large carcinomas - >5 cm Had R/T or surgery to breast/axilla area Present with enlarged axillary lymph glands Multifocal tumour Occult Malignancy This slide shows that a SLNB is not for every woman diagnosed with breast cancer. Some patients are still best treated with the traditional operation of full axillary clearance. Such groups of patients include: Those with large breast tumours greater than 5 cm in diameter. Others who have had previous radiation therapy or surgery to breast or axilla. Another group are those with enlarged lymph glands felt in the armpit before surgery. Then there those with multifocal tumours And lastly occult Malignancy where the primary breast tumour is not found. Click.

Possible Side Effects from SLNB Blue urine  24 hrs Breast stained blue  2 weeks - Mild reaction to dye: 1-2% risk (NSW Breast Cancer Institute) - Severe reaction: rare Wounds in breast, armpit & sternum Lymphedema: 1-2% risk (NSW Breast Cancer Institute) Numbness False negative result possible Like all examinations, possible side effects may be evitable. For SLNB these may include: Patient peeing blue urine. The skin over the breast will be stained blue. The patient also has a 1-2% chance of a mild allergic reaction to the blue dye, with a rare risk of severe anaphylaxis. They will have wounds in their armpit, breast and maybe sternum. There is a 1-2% risk of lymphedema associated with SLN Biopsy as opposed to 7% risk with axillary clearance. Possible nerve damage causing numbness. And lastly a false negative result. Click.

Advantages of SLNB (over Axillary Clearance) Reduced hospital stay Smaller axillary scar Quicker recovery time Reduced risk of lymphedema, pain & numbness The advantages of a SLN Bx approach over axillary clearance are: Shorter stay in hospital. The patient will have a smaller scar Quicker recovery time As fewer lymph nodes are removed, this in turn reduces the risk of lymphedema, pain and numbness. Click.

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How is the breast SN mapped in Nuclear Medicine? Technique 1 Affected breast  4 x injections 99mTc Senti-scint Radioactive injections are placed tumour quadrant around areolar (about o’clock position) So what happens in Nuc Med? There are 2 imaging techniques which can be implemented to localise a SLN. The first and easiest approach is to administer 4 small sub-cutaneous radioactive injections of technetium labelled ‘Senti-scint’. The majority of the time at Southland Hospital we place the injections around the darkened areolar in the quadrant of the breast carcinoma. For example, if the tumour lies in the left breast at 2 O’clock as identified on the diagram on your left, by the red cross, then four separate injections would be spaced evenly in the upper outer quadrant at 12, 1, 2 & 3 O’clock positions. This is better illustrated by the photo on your right. The NM MRT will administer the radioactive injections for this procedure. Click.

How is the breast SN mapped in Nuclear Medicine? Technique 2 2 x injections 99mTc Senti-scint placed either side of breast tumour Require Radiologist + ultrasound machine A further technique is possible whereby 2 x peri-tumoral injections can be positioned either side of the breast carcinoma under the guidance of U/S and we do implement this technique when a patient presents with a medial breast tumour. This is imperative to establish if the tumour is draining into the intra-mammary chain as opposed the axillary lymph nodes. A Radiologist is required to administer the radio-isotope in this instance and an US booking for the use of their machine is also necessary. Click.

Senti-scint Localisation in Lymph Node Radioactivity travels freely in lymph vessels but trapped in lymph nodes Isotope travels from tumour location to Sentinel Node Breast massage encourages flow of radio-tracer Scanning occurs & lymph node is identified The properties of the senti-scint injections allow the radio-colloid particles to be filtered into the lymphatic capillaries and then in turn move freely along the lymph vessels until it is trapped into the reticular cells of functionary lymph nodes. This is how the tracer travels the pathway from the tumour to the sentinel node/s. We have found that breast massage just after the injections helps expedite this process. Scanning protocols differ drastically from one Dept to another in NZ & Australia, but essentially scanning can commence immediately, but must be done within a 6 hour window. Click.

Nuclear Medicine SLN Images Peri-areolar Technique Node/s marked on patient’s skin Patient ready to proceed to surgery Node/s identified - Anterior + 57Co Flood Field - Lateral + 57Co Flood Field Static images are acquired anteriorly and laterally of the affected breast. The images are acquired with a 57Co flood field which outlines the patients body habitus. For this slide, the injections were done peri-areolar. At completion of imaging in both planes we mark the patients skin with a permanent pen over the sentinel nodes in both projections. These markings become the ‘guide’ or map to the sentinel node at surgery. Lymphatic mapping can be performed either on the day preceding or a few hours prior to surgery. The tracer dose must be calculated accordingly to surgery time. Click.

Nuclear Medicine SLN Images Peri-tumoral Technique Axillary nodes - Multiple IM node positive As you can see the quality of this image hasn’t magnified very well. Often images can also be confusing. This patient had 2 peri-tumoral injections and subsequent results show us multiple nodes in the axilla with the largest node highlighted in the circle. There was a much smaller and less intense node identified in the intra-mammary chain, as indicated by the oval. Click.

SPECT / CT Images 3D volume rendered SPECT/CT CT (top line) This IM node is better seen in the hybrid images of the Nuc Med SPECT data which has been fused with anatomical CT for precise localisation. The red circle triangulates on the IM node and shows that it is situated beside the sternal angle. If the surgeon is unable to harvest this node at surgery time, then Radiotherapy can be delivered to the node in an attempt to irradiate cancer cells. The overall aim with SLN localisation and biopsy is to identify all SLN’s so that we can ensure the patient has Improved staging A more accurate prognosis And better tailored management of their breast disease. Click. CT (top line) SPECT data (middle line) Fused data (bottom line)

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Surgery/Biopsy of SN Blue dye injected at commencement of surgery  turns SN blue Geiger probe detects radioactivity in SN Success of biopsy depends greatly on experience of breast Surgeon Incision at SN position and blue node removed SN analysed for metastatic spread A small amount of blue dye is injected around the breast nipple at the beginning of surgery. This dye quickly moves into the lymphatic channels and turns the sentinel nodes blue. A hand-held gamma probe is used by the surgeon to pinpoint radioactivity in the sentinel node by emitting an audible tone and thus revealing its location. A small incision is made and when the blue node is found, it is removed and examined under a microscope. Click.

SLNB Results Pathological analysis categorizes nodes in groups: Negative (no cancer cells)  axilla treatment finished Positive (contains cancer) or Indeterminate (uncertain of cancer cells) A.C required Pathologist report authorised The results. The excised nodes are examined by a Pathologist post surgery and categorised into the following groups: The negative group where no further treatment of the armpit is required. Then there are the indeterminate or positive groups. From here an axillary dissection will be required because other lymph nodes in the armpit may be affected by metastases. Click.

False-negative Result Occurs when SN has no cancer cells, but another node in axilla does Metastatic spread will go undetected 8% risk of this result with SLNB (NSW Breast Cancer Institute) Patient is undertreated as they won’t receive chemotherapy at time of biopsy ? Significance to progress of disease ? Further lumps of cancer in axilla What does this result mean? A false-negative finding occurs when the lymph nodes removed as the sentinel node do not contain cancer cells when, in fact, another lymph node that does contain cancer cells is left in the armpit. Clinical trials, on average show that there is an approx. 8% chance of this occurring. Potentially this group of women are then undertreated and won’t receive chemotherapy. Long term consequences of leaving the cancerous cells behind in the axilla are not known yet due to the short longevity of clinical trials. It is possible that these cells could eventually form ‘lumps’ of cancer that could be felt in the axilla. These lumps can be removed by a full axillary clearance. Click.

Clinical Trials Global research on SLNB has been under way for quite some time and is still on-going 18 years research for SLN Biopsy Sentinel Lymph Node Biopsy is being studied in large research trials globally and these have been underway for approximately 18 years. Click.

Conclusion Results show that SLNB is a safe & reliable technique in appropriately selected patients Determines who should or should not require A.C In conclusion the overall results thus far have shown that SLN Biopsy in appropriately selected patients, is a safe and reliable technique of deciding which patients go on to have full axillary clearance. Click.

Thanks Thank-you. Pause 2 sec. Click.

References Bova D, Dillehay G, Halama J, Karesh S, Wagner R, Zimmer A (2006) Nuclear Medicine (2nd Ed). China: Mosby Elsevier. Diehl KM, Chang AE. Sentinel Node Biopsy: What Breast Cancer Patients Need to Know. Available: [online] http://www.cancernews.com/printer.asp?aid=202 Imaginis (updated Jan 31, 2008) Sentinel Lymph Node Biopsy. Available: [online] http://www.imaginis.com/breasthealth/sentinelnode.asp Mariani G, Moresco L, Viale G, Vialla G, Bagnasco M, Canavese G, Buscombe J, Strauss HW, Paganelli G (2001) Radioguided Sentinel Lymph Node Biopsy in Breast Cancer Surgery. Journal of Nuclear Medicine. Vol. 42 No. 8, P1198-1215. The NSW Breast Cancer Institute, Sentinel Node Biopsy, An Information Guide for Patients (Jan 2008). Available: [online] http://www.bci.org.au Pause 2 sec. Click.

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