|Year : 2018 | Volume
| Issue : 1 | Page : 31-39
Assessment of the efficacy and oncological safety of sentinel lymph node biopsy in node-negative breast cancer using methylene blue dye
Rania Elahmady, Sherief M Mohsen MD
Department of General Surgery, Ain Shams University, Cairo, Egypt
|Date of Submission||27-Jul-2017|
|Date of Acceptance||25-Aug-2017|
|Date of Web Publication||14-Feb-2018|
Sherief M Mohsen
Department of Surgery, Ain Shams University, Cairo, 11566
Source of Support: None, Conflict of Interest: None
Background Sentinel lymph node (SLN) biopsy in patients with breast cancer with clinically negative axillary nodes is an innovative technique in the management of the axilla. SLN biopsy has been performed using different techniques including injection of patent blue dye, radioactive colloid, and recently methylene blue dye. The aim of this study was to assess the safety and efficacy of methylene blue dye as a mapping agent for SLN biopsy in clinically axillary node-negative breast carcinoma.
Patients and methods Between January 2014 and October 2016, 50 female patients with established diagnosis of breast carcinoma by tru-cut biopsy and clinically negative ipsilateral axillary lymph nodes were included in the study. All the patients were operated upon in Ain Shams University hospitals. After induction of anesthesia, 3–5 ml of sterile 1% methylene blue was infiltrated into the subareolar tissue on the affected side. The lymph nodes receiving the blue dye were excised as the SLN. Excised specimen with the axillary tissue was sent for histopathological examination. The presence or absence of metastasis in SLN and axillary lymph nodes was compared. Statistical analysis was carried out to know sensitivity, specificity, and accuracy of SLN biopsy in breast cancer.
Results The incidence of breast cancer was highest at 41–50 years. Of our 50 cases, SLN was identified in 44 cases using methylene blue dye. The identification rate was 88%. None of the patients had negative SLN but positive axillary lymph nodes (false negative), and in six cases, SLNs were involved only but not the rest of the axilla (false positive). The sensitivity, specificity, positive predictive value, and negative predictive value were 100, 85.7, 25, and 100%, respectively.
Conclusion This study confirms the safety and efficacy of methylene blue dye as a mapping agent for SLN biopsy in axillary node-negative breast cancer.
Keywords: breast cancer, methylene blue dye, sentinel lymph node biopsy
|How to cite this article:|
Elahmady R, Mohsen SM. Assessment of the efficacy and oncological safety of sentinel lymph node biopsy in node-negative breast cancer using methylene blue dye. Egypt J Surg 2018;37:31-9
|How to cite this URL:|
Elahmady R, Mohsen SM. Assessment of the efficacy and oncological safety of sentinel lymph node biopsy in node-negative breast cancer using methylene blue dye. Egypt J Surg [serial online] 2018 [cited 2018 Aug 19];37:31-9. Available from: http://www.ejs.eg.net/text.asp?2018/37/1/31/225487
| Introduction|| |
Breast carcinoma is the most common cancer of women worldwide, including 23% of all female cancers . Approximately one in nine women will have breast cancer during her lifetime. Breast cancer is the commonest cause of deaths owing to cancer in females throughout the world .
The incidence of breast cancer is increasing. This increase in incidence may be because of screening, self-examination, and awareness. Staging is very important for management of all patients with cancer, and breast cancer is not an exception. Staging of axilla in breast cancer is the single most important prognostic factor for selection of appropriate adjuvant therapy, locoregional recurrence, and long-term survival. Exact staging of axillary lymph nodes can be obtained in two ways: directly by axillary lymph node dissection (ALND) or indirectly by sentinel lymph node biopsy (SLNB). The ALND is drastic and associated with debilitating complications of the ipsilateral arm like lymphedema, seroma, paresthesia, etc.; whereas, SLNB is less drastic and devoid of aforementioned complications ,,.
SLN biopsy by radio-colloid method was first reported by Krag et al.  and by blue dye method by Giuliano et al. . Combined use of radioactive colloid and blue dye injection is considered as gold standard for axillary SLNB in breast cancer, with 97% accuracy rate ,,, but this combined usage does not attain an adequately higher detection rate to defend the cost . However, some researchers have been using blue dye only for identification of SLN with good reliability . The positive results found by using methylene blue dye and by isosulfan blue dye were 99 and 97%, respectively ,. Moreover, another similar study for methylene blue dye was done, showing the sensitivity and specificity of 85.7 and 71.4%, respectively . Therefore, the efficiency of detecting SLN by methylene blue is as good as isosulfan blue with cost-effectiveness and is equal to ALND in breast cancer, but there is difference between the percentages of positive results in different studies .
For adopting SLNB technique, it is a well-recognized accepted fact that a multidisciplinary team, which includes surgery, nuclear medicine, and surgical pathology departments, is required to work in close cooperation. Each of these disciplines plays a crucial role in achieving success, and the surgeon cannot embark upon a successful SLNB program without cooperation from other disciplines.
In this study, we had chosen the subareolar technique in detection of sentinel lymph nodes (SLNs) using methylene blue dye only, together with the assessment of its accuracy, efficacy, and oncological safety in clinically node-negative patients.
| Patients and methods|| |
Between January 2014 and October 2016, a series of 50 consecutive female patients presenting with breast cancer proven with true-cut biopsy, and clinically node-negative axilla, were included in this prospective study. Patients with palpable axillary lymph nodes, distant metastasis, previous breast cancer surgery, neoadjuvant treatment, inflammatory breast cancer, pregnant females, male patients, and patients unwilling to participate in the study were excluded. Local ethical committee approval was given for the study, and written informed consent was obtained from all participants. This study was performed in Ain Shams University hospitals in Cairo, Egypt.
All patients underwent bilateral sono-mammographic examination, routine preoperative investigation, (complete blood count, prothrombin time and concentration, renal function test, and liver function test), and ECG for assessment for surgical fitness. Metastatic workup was done, including chest radiography, abdomen and pelvis ultrasonography, and isotope bone scan, to exclude presence of distant metastasis.
The procedure is carried out under general anesthesia with the patient supine on the operating table and the arm abducted at 90° from the body. After draping, 5 ml of 1% methylene blue dye was injected in the subareolar region, divided in three injections times ([Figure 1]). Massage was done for 10–15 min in a clockwise direction. A useful anatomical landmark is made to place the incision 1 cm below the hairline of the axilla. Skin and subcutaneous tissue were dissected followed by dissection of clavipectoral fascia to enter the axilla, and blue-stained lymphatics were identified. Following the stained lymphatics, identification of the blue colored node(s) is made, which presented mainly below the pectoralis minor muscle ([Figure 2]). These nodes, together with perilymphatic tissue, were dissected and were labeled separately, and then, planned procedure, either modified radical mastectomy (MRM) ([Figure 3]) or wide local excision (WLE), was performed. The breast tissue or excised mass along with the remaining axillary lymph nodes were histopathologically examined separately from sentinel lymph nodes. The presence or absence of metastasis in SLN and axillary lymph nodes was compared. Statistical analysis was carried out to know sensitivity, specificity, and accuracy of SLN.
|Figure 2 (a,b) Identification and dissection of sentinel lymph node in the axilla stained with methylene blue dye.|
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|Figure 3 Modified radical mastectomy specimen together with remaining axillary specimen after dissection of sentinel lymph node.|
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| Results|| |
Age of the study group
The age of the 50 female patients included in the study ranged between 30 and 70 years, with a mean age of 45.7±1.0 years. A total of 13 (26%) patients were between the age of 30 and 40 years. Patients between the ages of 41 and 50 years represented the highest percentage with 18 (36%) cases, followed by patients between the age of 51 and 60 years, with 12 (24%) cases, and finally, those older than 60 years, with seven (14%) cases ([Table 1] and [Figure 4]).
Size and stage of the tumor
In our study, the size of the tumor ranged between 1.5 and 5.5 cm, with a mean size of 3.4 cm. A total of 38 (76%) patients had tumor size ranging from 2 to 4 cm (T2N0M0) and nine (18%) patients had tumor size ranging from 4 to 5.5 cm (T3N0M0), and finally, three (6%) patients presented with tumor less than 2 cm (T1N0M0). None of the patients had palpable axillary lymph nodes or distant metastasis ([Table 2] and [Figure 5]).
Site of the tumor
The outer upper quadrant was the most common site in 29 (58%) patients, the lower outer quadrant was involved in 14 (28%) patients, the upper inner quadrant in five (10%) patients, and central lesion in two (4%) patients ([Table 3]). A total of 30 (60%) patients presented with left-sided breast cancer, and the rest (20 patients) presented with right-sided breast cancer (40%) ([Figure 6]).
Detection of sentinel lymph node(s)
The detected SLNs were identified in 44 (88%) of 50 patients. The number of SLNs was as follows: one lymph node detected in 16 (32%) patients, two lymph nodes in 19 (38%) patients, and three lymph nodes in nine (18%) patients ([Table 4]).
In 47 (94%) patients, SLN biopsies were found in level I alone, and in three (6%) patients, SLN biopsies were found in both levels I and II.
Comparison between axillary and sentinel lymph nodes
When status of axillary lymph node was compared with SLNs, the result was as follow: 36 (81.8%) of the 44 patients with identified SLN showed negative result for metastasis. In this group, we found that none of them showed axillary metastasis.
In eight (18.2%) of the 44 SLNs cases, metastasis was found in the nodes. Of these eight cases, two (25%) cases contained metastasis in the remainder axillary lymph nodes whereas in the other six (75%) cases, the results of the axillary lymph nodes were negative ([Table 5]).
The relation between axillary and SLNs is statistically significant ([Figure 7]).
Result of lymph node localization
The identification rate for lymph node localization was 44/50 (88%).
Failure rate of the technique was 6/50 (12%).
- The number of true-positive cases (positive sentinel and positive axillary) was 2.
- The number of true-negative cases (negative sentinel and negative axillary) was 36.
- The number of false-positive cases (positive sentinel and negative axillary) was 6.
- The number of false-negative cases (negative sentinel and positive axillary) was 0.
- Positive predictive value=2/(2+6)=25%.
- Negative predictive value=36/(36+0)=100%.
Operation done for the patients
Overall, 16 (32%) patients underwent MRM, whereas 34 (68%) underwent wide local excision.
Histological type showed that 47 (94%) patients had invasive ductal carcinoma, whereas three (6%) patients had invasive lobular carcinoma.
Postoperative morbidity results showed that three (6%) patients developed seroma, one (2%) patient developed hematoma, and one (2%) patient developed infection and necrosis. The remaining 45 (90%) patients had no postoperative complications. No complications related to the use of the dye, such as cutaneous and urine staining or allergic reactions, occurred in any of our patients ([Table 6]).
| Discussion|| |
Management and staging of breast cancer according to axillary nodal status has been the subject of intense debate and controversy . The study of NSABP B-04, which randomized patients with clinically uninvolved axillary nodes to radical mastectomy, total mastectomy plus radiotherapy, or total mastectomy alone, demonstrated that axillary treatment with either dissection or regional radiotherapy reduced axillary recurrence rates from 18.6 to 1–2%. However, there was no benefit to axillary treatment in terms of distant disease-free survival ,.
Sentinel lymph node dissection (SLND) alone is widely accepted as an axillary management for women with clinically node-negative breast cancer. SLND makes axillary procedure more conservative, less morbid, and improves the quality of life, with reduction in pain, lymphedema, and shoulder stiffness .
In this study, we conducted a validation study on the accuracy of SLND using methylene blue dye technique alone in patients with nodal negative breast cancer, using a simple, available, and cheap technique.
In our study, we did not expose our patients to oncological risk because we completed ALND after detection of SLN.
In this study, we excluded patients who received neoadjuvant chemotherapy because this produces an inflammatory response and fibrosis. Therefore, it is not surprising that identification and dissection of sentinel nodes is a more difficult procedure after neoadjuvant chemotherapy , and the sentinel lymph node biopsy identification rate is too low for routine use, and that the false-negative rate is also too high .
By contrast, there are those who believe that the advantages to the patient in reducing an unnecessary axillary clearance is such that SLNB has a definite role after neoadjuvant chemotherapy .
Moreover, we excluded node-positive patients (clinically and radiologically) because positive nodes may be blocked, and it prohibits accurate mapping leading to a false-negative result. This agrees with the studies performed by Lyman et al.  and Hoar and Stonelake .
In contrast, some authors report that clinically positive axilla is subject to false-positive result, so SLNB deserves wider consideration as an alternative to ALND in clinically positive patients ,.
Inflammatory breast cancer was also excluded. The false-negative rate for patients with inflammatory breast cancer is unacceptably high, hence SLNB is not recommended in such situation until more data are available .
Pregnant women with breast cancer were excluded because vital dyes should not be administered to pregnant women .
In our study, we excluded male breast cancer cases because of the rarity and no sufficient previous studies about drawback of SLNB in breast cancer in men. However, there are studies that encourage SLNB in men .
In our study, we found that among the series of 50 patients, the number of patients between ages of 30 and 40 years was 13 (26%), the number of patients between age of 41–50 years − which was the highest − was 18 (36%), the number of patients between the age of 51–60 years was 12 (24%), and finally, the number of patients older than 60 years was seven (14%). This was a similar figure to the study performed by Mahadevan et al. , where the highest number of breast cancer cases fell in the age group of 41–50 years (33.1%), followed by 31–40 years (27.8%) and 51–60 years (20.4%).
In our study, 38 (76%) patients were staged as IIA (T2 N0 M0) with a tumor size of 2–4 cm, and nine (18%) patients as stage IIB (T3 N0 M0) with a tumor size of 4–5.5 cm, and finally three (6%) patients as stage I (T1 N0 M0) with a tumor size less than 2 cm. This pattern coincides with the pattern in the study by Ravichandran et al.  where 151 patients had stage I, 315 patients had stage II, and excluded patients with higher stages of breast cancer.
We found that the outer upper quadrant was the most common site in 29 (58%) patients, the lower outer quadrant in 14 (28%) patients, the upper inner quadrant in five (10%) patients, and central lesion in two (4%) patients. A total of 30 patients presented with left-sided breast cancer (60%), and the rest (20 patients) presented with right-sided breast cancer (40%).
Moreover, Wilting and Hagedorn reported in their study that left-oriented breast cancer (especially upper outer quadrant) showed 45.8% positivity, having a 10% lead over the right orientation, and this was in consonance with the report by Tulinius and colleagues. Wilting and Hagedorn showed that the left side of the body is prone to carcinomas, especially breast cancer (5–10%) ,.
Regarding the site of the dye injection, we favored the subareolar injection, as it can access the subareolar lymphatic plexus of Sappey, drainage is independent of tumor size, requires less amount of the dye, and increases identification rate as compared with other methods of injection as demonstrated by McMasters et al. , D’Eredita et al. , and Povoski et al. .
In our study, SLNs were identified in 44 (88%) patients. The number of SLNs was as follows: one lymph node detected in 16 (32%) patients, two lymph nodes in 19 (38%) patients, and three lymph nodes in nine (18%) patients. The mean number of identified lymph nodes in our study was 1.6, and this finding matched with other studies such as Montumora et al. , Cox et al. , and Padmanabh et al. , where the mean number of identified lymph nodes was 1.8, 1.9, and 1.6, respectively.
In 47 (94%) patients, SLN biopsies were found in level I alone, and in three (6%) patients, SLN biopsies were found in both levels I and II. This matches with SLN report by Arima et al. , who postulated that axillary nodes with breast cancer have a relatively low rate of involvement of level II or level III nodes in the absence of involved level I nodes (called skip metastases), and there is a 2–4% rate of skip metastases above axillary levels I and II.
In our study, we did not find skip metastasis mostly owing to small number of patients (50) and detected SLN in 39 patients. This matches with an Indian study done by Padmanabh et al. , in which the number of patients was 35.
Overall, 34 (68%) of our patients underwent WLE and ALND, whereas 16 (32%) underwent modified radical mastectomy. Most patients underwent MRM upon their wishes, and two patients had multicentric lesions and two patients showed multiple positive margins after WLE.
Time needed for WLE ranged from 65 to 90 min, including frozen section of the mass and SLN examinations. On the contrary, time needed for MRM ranged from 60 to 105 min.
Drains after surgery were left for 48–72 h for observation of reactionary hemorrhage. The mean amount of seroma in the first day was 250 cm3, second day was 150 cm3, and third day was 50 cm3.
Postoperative morbidity showed that three (6%) patients developed seroma. These patients were treated conservatively by continuous aspiration under US guidance and coverage of antibiotics. Seroma subsided in 10–15 days. Moreover, one (2%) patient developed hematoma. This patient was treated conservatively, and hematoma subsided within 13 days. Another patient (2%) developed infection and necrosis. This patient underwent debridement of necrotic tissue after 1 week of conservative management, and the wound healed within 10 days. The remaining 45 (90%) patients had no postoperative complications.
The technique of SLNB, as any surgical manoeuver, is not devoid of complications related to technique as mentioned before or complications related to dye such as cutaneous staining, staining of urine, and allergic reaction, which was not reported in any case in our study.
Histological examination showed that 47 (94%) patients had invasive ductal carcinoma, whereas three (6%) patients had invasive lobular carcinoma. This was in agreement with Vahdaninia and Montazeri  who found that more than three-quarters (77.5%) of patients were diagnosed with ductal carcinoma and 41.7% of tumors were moderately and well-differentiated.
When we compared status of axillary lymph node with SLNs, the result was as follow: 36 (81.8%) patients of the 44 patients with identified SLN were negative for metastasis, and none of them showed axillary metastasis. In the rest of eight (18.2%) cases, metastasis was found. Of these eight cases, two cases contained metastasis in the remainder axillary lymph nodes (25%) whereas in the other six cases, the axillary lymph nodes were negative (75%). Moreover, Fraile et al.  reported that 1–15% of patients with negative SLNB had nodal metastasis in the same region, and the false-negative rate of SLNB has improved over time and is probably under 5% now in most experienced group .
In our study, SLNs were not identified in six cases, with a failure rate of 12%. This failure corresponded to many factors as following:
First, there is a well-documented learning curve of operator to SLNB. Successful identification of SLNB is directly related to surgeon experience . In this study, we cannot identify 5/6 in the first 25 cases with percentage of 83.3% of failed cases. To decrease the failure rate that related to learning curve, we should take into consideration the multidisciplinary approach between the surgeon, the radiologist, the pathologist, and nursing acquiring the knowledge and skills to enable successful technique. In UK, a structured training programme called NEW START has been developed to standardize technique. This programme includes training of surgeon on five cases followed by performing a series of 25 cases of SLNB and immediate ALND. The aim is to identify SLNB with high rate and more importantly a low false-negative rate . The American Society of Breast Surgeons  recommends that surgeons must perform at least 20 SLNB procedures before doing it therapeutically.Second cause is a metastatic lymph node causing a blockage to the lymphatic flow, which was found in four (66.6%) of six cases. To avoid this, careful palpation and an efficient ultrasonic examination should be provided .
Third cause is the age of the cases. We found that all six cases were older than 55 years .
The technique of SLNB can be applied in most of Egyptian hospitals that could not provide the supplies for SLNB mapping using Tc99m dye and gamma camera as a safe, cheap, reliable, and cost-effectiveness technique.
In our study, SLN was identified in 44 cases using methylene blue dye. The identification rate was 88%. None of the patients had negative SLN but had positive axillary lymph nodes (false negative), and in six cases SLN were involved only but not the rest of the axilla (false positive). The sensitivity, specificity, positive predictive value, and negative predictive value were 100, 85.7, 25, and 100%, respectively, and the overall efficacy was 92.9%.
These results should be compared with the study done by Mukherr and colleagues in 2014, where the identification rate was 88.9%. The sensitivity, specificity, positive predictive value, negative predictive value, and efficacy were 81.8, 100, 100,86, and 90.9%, respectively .
Our results are also comparable with the study performed by Chintamani et al.  where SLN identification rate was 100%, the sensitivity of SLNB was 86.6%, and the accuracy was 93.3%.
Our results showed that the technique of SLNB using methylene blue dye alone is reliable to detect the state of axillary lymph node, so we can avoid an unnecessary lymph node dissection in nodal negative breast cancer and its associated complications.
The technique of SLNB preserves a functioning limb, especially in developing countries as Egypt, where the women in rural area do their work manually.
| Conclusion and recommendations|| |
SLNB using methylene blue dye is a suitable, cheap, safe, and accurate technique in staging of the axilla and an alternative to in early stages of breast cancer. Moreover, it is associated with less morbidity.
Our breast surgeons should be trained on this simple technique to achieve high accuracy and lower false negative rate, and our institutes involved in breast cancer surgery should encourage this method because of its advantages regarding safety, feasibility, and economic advantages.
There are still many unanswered questions about SLND that should be answered in on-going trials.
- The first one is accuracy of SLNB in large and multifocal tumors.
- The second one is accuracy of SLNB after neoadjuvant chemotherapy.
- Role of SLNB in nodal positive patients.
- Overall disease-free survival.
- Role of SLNB in recurrent breast cancer and in male patients.
Financial support and sponsorship
Conflicts of interest
| References|| |
Benson JR, Jatoi I. The Global Breast Cancer burden. Future Oncol 2012; 8:697–702.
Wingo PA, Cardinez CJ, Landis SH, Greenlee RT, Ries LA, Anderson RN et al.
Long-term trends in cancer mortality in the United States, 1930–1998. Cancer 2003; 97:3133–3175.
Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V et al.
A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349:546–553.
Schrenk P, Rieger R, Shamiyeh A, Wayand W. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma. Cancer 2000; 88:608–614.
Peintinger F, Reitsamer R, Stranzl H, Ralph G. Comparison of quality of life and arm complaints after axillary lymph node dissection vs sentinel lymph node biopsy in breast cancer patients. Br J Cancer 2003; 89:648–652.
Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymphnode in breast cancer using a gamma probe. Surg Oncol 1993; 2:335–340.
Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994; 220:391–401.
Ishikawa T, Momiyama N, Hamaguchi Y, Tanabe M, Tomita S, Ichikawa Y et al.
Blue dye technique complements four-node sampling for early breast cancer. Eur J Surg Oncol 2005; 31:1119–1124.
Lamichhane N, Pradhan M, Neupane PR, Shrestha BM, Dhakal HP, Thakur BK et al.
Initial experience in a cancer hospital in Nepal with sentinel lymph node mapping and biopsy for evaluation of axillary lymph node status in palpable invasive breast cancer. Nepal Med Coll J 2007; 9:22–26.
Kavallaris A, Camara O, Runnebaum IB. Subareolar blue dye only injection sentinel lymph node biopsy could reduce the numbers of standard axillary lymph node dissection in environments without access to nuclear medicine. J Cancer Res Clin Oncol 2008; 134:667–672.
East JM, Valentine CS, Kanchev E, Blake GO. Sentinel lymph node biopsy for breast cancer using methylene blue dye manifests a short learning curve among experienced surgeons: a prospective tabular cumulative sum (CUSUM) analysis. BMC Surg 2009; 9:2.
Narui K, Ishikawa T, Kito A, Shimizu D, Chishima T, Momiyama N et al.
Observational study of blue dye-assisted four-node sampling for axillary staging in early breast cancer. Eur J Surg Oncol 2010; 36:731–736.
Mathelin C, Croce S, Brasse D, Gairard B, Gharbi M et al.
Methylene blue dye, an accurate dye for sentinel lymph node identification in early breast cancer. Anticancer Res 2009; 29:4119–4125.
Vohra LM, Memon AA, Khaliq T, Lehri AA. Sentinel lymph node biopsy in breast cancer by using isosulfan blue. Pak J Med Sci 2009; 25:786–790.
Ollila DW, Brennan MB, Giuliano AE. The role of intraoperative lymphatic mapping and sentinel lymphadenectomy in the management of patients with breast cancer. Adv Surg 1999; 32:349–364.
Ahlgren J, Holmberg L, Bergh J, Liljegren G. Five-node biopsy of the axilla: an alternative to axillary dissection of level I–II in operable breast cancer. Eur J Surg Oncol 2002; 28:97–102.
Fisher B, Jeong J, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follw-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2000; 34:567–575.
Galimberti V, Cole B, Zurrida S, Viale G, Luini A, Veronesi P et al.
Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol 2013; 14:297–305.
Clarke D, Newcombe R, Mansel R. The learning curve in sentinel node biopsy: the ALMANAC experience. Ann Surg Oncol 2004; 11:211s–215s.
Lyman G. Appropriate role for sentinel node biopsy after neoadjuvant chemotherapy in patients with early-stage breast cancer. J Clin Oncol 2015; 33:232–234.
Dixon J. Role of sentinel node biopsy in patients having neoadjuvant chemotherapy. Eur J Surg Oncol 2010; 36:511–513.
Lyman G, Giuliano A, Somerfield M, Benson AB, Bodurka DC, Burstein HJ et al.
American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 2005; 23:7703–7720.
Hoar F, Stonelake P. A prospective study of the value of axillary nodesampling in addition to sentinel lymph node biopsyin patients with breast cancer. Eur J Surg Oncol 2003; 29:526–531.
Specht M, Fey J, Borgen PI, Cody HS. Is the clinically positive axilla in breast cancer really a contraindication to sentinel lymph node biopsy? J Am Coll Surg 2005; 200:10–14.
Rachna R, Jasprit S, Eddie M. Sentinel node biopsy alone versus completion axillary node dissection in node positive breast cancer: systematic review and meta-analysis. Int J Breast Cancer 2014; 2014:513780.
Rovera F, Fritting F, Marelli M, Corben AD, Dionigi G, Boni L, Dionigi R. Axillary sentinel lymph node biopsy: an overview. Int J Surg 2008; 6:S109–S112.
Oreste G, Eduardo C, Stefano Z, Intra M, De Cicco C, Gatti G et al.
Sentinel lymph node biopsy in male patients with early breast cancer. Oncologist 2007; 12:512–515.
Mahadevan G, Balamuthu K. A retrospective analysis of the incidence of breast cancer at a tertiary care hospital in South india. J Acad Ind Res 2016; 8:199–202.
Ravichandran K, Hamdan N, Dyab A. Population based survival of female breast cancer cases in Riyadh Region, Saudi Arabia. Asian Pac J Cancer Prev 2005; 6:72–76.
Wilting J, Hagedorn M. Left-right asymmetry in embryonic development and breast cancer: common molecular determinants? Curr Med Chem 2011; 18:5519–5527.
Tulinius H, Sigvaldason H, Olafsdóttir G. Left and right sided breast cancer. Pathol Res Pract 1990; 186:92–94.
McMaster S. Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J Clin Oncol 2000; 18:2560–2566.
D’Eredita’ G, Ferrarese F, Cecere V, Massa ST, de Carne F, Fabiano G. Subareolar injection may be more accurate than other techniques for sentinel lymph node biopsy in breast cancer. Ann Surg Oncol 2003; 10:942–947.
Povoski S. Prospective randomized clinical trial comparing intradermal, intraparenchymal, and Subareolar injection routes for sentinel lymph node mapping and biopsy in breast cancer. Ann Surg Oncol 2006; 13:1412–1421.
Motomura K, Inaji H, Komoike Y, Kasugai T, Nagumo S, Noguchi S, Koyama H et al.
Sentinel node biopsy in breast cancer patients with clinically negative lymph nodes. Breast Cancer 1999; 6:259–262.
Cox C, Pendas S, Cox J, Joseph E, Shons AR, Yeatman T et al.
Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998; 227:645–651. (discussion 651–653)
Padmanabh I, Garima M, Jayapraksh J. Predictability and reliability of sentinel lymph node biopsy in women with early breast cancer using patent blue dye. Int J Healthcare Biomed Res 2013; 1:150–160.
Arima H, Natsugoe S, Uenosono Y. Area of nodal metastasis and radioisotope uptake in sentinel nodes of upper gastrointestinal cancer. J Surg Res 2006; 135:250–254.
Sener S, Winchester D, Brinkmann E, Winchester DP, Alwawi E, Nickolov A et al.
Failure of sentinel lymph node mapping in patients with breast cancer. J Am Coll Surg 2004; 198:732–736.
Vahdaninia M, Montazeri A. Breast cancer in Iran: survival analysis. Asian Pac J Cancer Prev 2004; 5:223–225.
Fraile M, Rull M, Julian F, Fusté F, Barnadas A, Llatjós M et al.
Sentinel node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients: an approach to its validity. Ann Oncol 2000; 11:701–705.
Veronesi U, Paganelli G, Viale G. Sentinel lymph-node biopsy as a staging procedure in breast cancer: update of a randomized controlled study. Lancet Oncol 2006; 7:983–990.
American Society of Breast Surgeons. Performance and practice guidelines in sentinel lymphnode biopsy in breast cancer patient; 2014.
Straalman K, Kristoffersen U, Galatius H, Lanng C. Factors influencing sentinel lymph node identification failure in breast cancer surgery. Breast 2008; 17:167–171.
Mukherjee A, Kharkwal S, Charak KS. Assessment of the efficacy and safety of methylene blue dye for sentinel lymph node mapping in early breast cancer with clinically negative axilla. Arch Int Surg 2014; 4:6–10. [Full text]
Chintamani XX, Megha T, Ashwani M, Usha AL, Sunita S. Sentinel lymph node biopsy using dye alone method is reliable and accurate even after neo-adjuvant chemotherapy in locally advanced breast cancer – a prospective study. World J Surg Oncol 2011; 9:19.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]