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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 3  |  Page : 282-285
 

A clinical study to assess the pathological involvement of occult supraclavicular lymphnode metastasis in case of locally advanced operable breast carcinoma


Department Surgical Oncology, Bhagwan mahaveer Cancer Hospital and Research Centre, JLN Marg, Jaipur, Rajasthan, India

Date of Web Publication18-Feb-2016

Correspondence Address:
S J Virani
Department Surgical Oncology, Bhagwan mahaveer Cancer Hospital and Research Centre, JLN Marg, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.176711

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 » Abstract 

Purpose: The prognosis of ipsilateral supraclavicular lymph node (SCLN) recurrence after early breast cancer appears to be worse than for other locoregional recurrences, but better than for distant metastases. Prophylactic radiotherapy (RT) to supraclavicular region decreases risk of ipsilateral SCLN recurrence. Currently, all patients with locally advanced breast cancer are considered high-risk for SCLN metastasis and treated with prophylactic RT. This study is carried out to identify risk factors associated with occult SCLN metastases in locally advanced breast cancer. Materials And Methods: Total 48 female patients of all ages presenting with locally advanced carcinoma of breast who were operable by protocol criteria were included in the study. All the patients underwent modified radical mastectomy with supraclavicular lymphnode dissection. The resected specimen was processed for the histopathological analysis. Results: Occult SCLN metastases are found in 25% (12/48) of the patients in this study. Eleven factors were identified and analyzed to know whether or not they are associated with SCLN metastasis. Of those only pathological N stage (7% for <pN3 vs and 52% for pN3 stage) and level axillary nodal involvement (7% for patients without Level III involvement and 52% for with Level III involvement) are significantly associated with high-risk for occult supraclavicular lymphnode metastasis. Other factors such as age, menopausal status, T stage, pathologic grade, lymphovascular invasion, extracapsular extension, hormone receptor, and Her2 neu receptor status are not associated with risk for SCLN metastasis. Conclusion: Our study has shown that only high axillary disease burden in terms of more than 10 node positivity or more than 75% positive node out of total dissected nodes is associated with occult supraclavicular lymphnode metastasis breast cancer.


Keywords: Locally advanced breast cancer, occult supraclavicular lymph node metastasis, prophylactic supraclavicular radiotherapy, supraclavicular recurrence


How to cite this article:
Virani S J, Patni S, Shah R. A clinical study to assess the pathological involvement of occult supraclavicular lymphnode metastasis in case of locally advanced operable breast carcinoma. Indian J Cancer 2015;52:282-5

How to cite this URL:
Virani S J, Patni S, Shah R. A clinical study to assess the pathological involvement of occult supraclavicular lymphnode metastasis in case of locally advanced operable breast carcinoma. Indian J Cancer [serial online] 2015 [cited 2019 Jun 26];52:282-5. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/282/176711



 » Introduction Top


The incidence of supraclavicular lymph node (SCLN) metastasis after definite surgery for breast cancer is low around 1%, but SCLN metastasis is as common as axillary nodal failure in patients after complete axillary dissection.[1],[2] SCLN metastasis in breast cancer is usually considered as almost invariable signal of micrometastasis with a grave prognosis.[3],[4] A wide variety of treatments are used for SCLN metastasis, including radiotherapy (RT), chemotherapy, and surgery.[5],[6],[7] The lack of a consensus on treatment indicates that is a difficult problem, although RT is considered mandatory.[8] A world-wide overview of post-mastectomy RT showed a significant survival benefit and based on this data prophylactic supraclavicular RT is indicated in locally advanced breast cancer.[9],[10] Moreover, the benefits of aggressive local therapy such as RT must be balanced against the potential morbidities, including radiation pneumonitis,[11] brachial plexus injury,[12] lymphedema,[13] and second tumor occurrence.[14] To our knowledge, no report has studied the prediction of SCLN metastasis and then selected high-risk patients for additional systemic or local treatment. The retrospective study by Chen et al.,[15] attempted to define the risk factors for SCLN metastasis and select high risk patients for whom aggressive local treatment like RT is indicated.

Here, we had evaluated incidence of occult metastasis in SCLN from locally advanced breast cancer, which are technically operable in our prospective study and analyzed risk factors related to SCLN metastases.


 » Materials and Methods Top


After ethics committee approval, this study was conducted at our center. This is a prospective study. Female patients of all ages presenting with locally advanced carcinoma of breast from March, 2010 to March, 2012 and who were operable by protocol criteria were included in the study, these were patient with Tumor size >5 cm with or without single or multiple mobile non matted axillary nodes with clinically negative SCLN or patient of carcinoma breast with skin involvement who can be primarily operated with adequate safe skin margin and with the primary closure. Following patients were excluded from study (1) patients with primary tumor with chest wall involvement (T4a), (2) patients with primary tumor with skin involvement who are not candidate for primary surgery (primary closure with safe margins not possible), (3) patients with matted/fixed axillary lymph nodes (N2), (4) patients who have received prior chemotherapy or RT, (5) patients with early breast cancer. That is (Stage I and IIA), (6) patients with metastatic breast cancer. Total 48 patients were included in this study of those 20 patients were premenopausal and less than 45 years while 28 patients were postmenopausal and more than 45 years. Only three patients were nulliparous and 45 patients were multiparous.

All the patients underwent modified radical mastectomy with the supraclavicular lymphnode dissection. Level I, II and III lymph nodes are dissected by retracting pectoralis minor muscle (Auchinclau's method). SCLN dissection carried out with separate incision in neck. The extent of supraclavicular lymphnode dissection were inferior belly of omohyoid superiorly, clavicle inferiorly, lateral border of stern mastoid laterally, and midline medially [Figure 1].
Figure 1: Extent of supraclavicular lymph node dissection

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The resected specimen was processed for histopathological analysis including SCLN analysis by routine histopathological protocol (4-5 micron section) and correlated nodal spread in the supraclavicular nodes in respect to T stage, size of tumor, N stage, level of positive axillary nodes, and histological grade of tumor, lymphovascular invasion, hormone receptor status and Her2 neu receptor status. The statistical significance of factors was studied with the Chi-square test.


 » Results Top


Occult SCLN metastases are found in 25% (12/48) of the patients in this study. An analysis of four clinical factors including age, menopausal status, clinical T stage, and location of tumor were performed to know whether or not they are associated with SCLN metastasis. However, none of these four factors was significantly associated with SCLN metastasis [Table 1].
Table 1: Clinical risk factors for occult supraclavicular lymph node metastasis in locally advanced breast cancer

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Seven pathological factors were analyzed to see for the prediction of occult SCLN metastasis [Table 2]. In this study, 40% patients had occult SLNM in patients with grade I tumor and 15.2% patients had occult SCLN metastasis in patients with grade II tumor. Thus, higher rate of occult SCLN metastasis in low grade tumors observed as compared to high grade tumors. Only 9.1% patients had occult SCLN metastasis in patients with nodes with extracapsular extension while 38.4% patients had occult SCLN metastasis patients without nodes with extracapsular extension. Twenty five percent patients had occult SCLN metastasis in both lymphovascular invasion positive and negative group (P = 0.7000). Thus, all these three factors do not predict for occult SCLN metastasis.
Table 2: Pathological risk factors for occult supraclavicular lymph node metastasis in locally advanced breast cancer

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In this study, 33% patients had occult SCLN metastasis in patients with 1-3 positive axillary nodes (pN1 group) and 6.6% patients had occult SCLN metastasis in patients with 4-9 positive axillary nodes (pN2 group). However, 52.6% patients had occult SCLN metastasis in patients with more than 10 positive axillary nodes (pN3 group). Thus, when entire study group divided into two groups, patients with less than or more than 10 positive axillary nodes, a significantly higher incidence of occult SCLN metastasis occurred in patients with >10 axillary nodes compared with the patients with less than 10 positive nodes (52% vs. 7%). This difference does reach statistically significant P value (P = 0.002). Only 7% patients had occult SCLN metastasis in patients who had less than 75% positive nodes and 55.5% patients had occult SCLN metastasis in patients who had more than 75% positive nodes. No patient had occult SCLN metastasis in clinically negative axillary node and 11% patients had occult SCLN metastasis with only Level I and II involvement without Level III involvement. While 52.6% patients had occult SCLN metastasis in patients with Level I, II and III involvement (P = 0.001). Thus, in this study out of 12 patients who had positive occult SCLN metastasis only one patient had skip metastasis that is without Level III involvement, which is statistically non-significant.

Other two factors including hormone receptor status and Her2 neu receptor status which independently associated with prognosis of breast cancer were analyzed, but not significantly associated with occult SCLN metastasis.


 » Discussion Top


Breast cancer is one of most common cancer in females. Locally advanced breast cancer refers to a diverse and heterogeneous group of breast cancers and represents only 2-5% of all breast cancers in the United States; however, locally advanced breast cancer is more prevalent in India. Subdividing these patients into three broad groups (1) those with operable disease at presentation-cancer/American Joint Committee on Cancer (AJCC) clinical Stage T3N0 to N1M0,2) inoperable disease at presentation-AJCC clinical Stage T4 or N2 to 3M0 or both, and 3) inflammatory disease-AJCC clinical Stage T4dN0 to N3M0 facilitates clinical management. Generally clinically operable breast cancer is treated first by surgery followed by adjuvant therapy including RT to chest wall and supraclavicular region with or without axillary RT depending on disease burden in axilla. Although, other two groups are treated with neoadjuvant chemotherapy first followed by local treatment.

Breast cancer with ipsilateral SCLN (AJCC Stage IIIC) is unique clinical entity comprising of 1% of all breast cancer. SCLN drainage is a part of continuum drainage of Level I, II and III axillary lymphnode drainage. Skip metastasis can occur commonly from upper quadrant tumor or patients with internal mammary node metastasis. Patients with breast cancer who present with supraclavicular metastases have a poor prognosis, especially when treated with surgery or RT alone. The presence of supraclavicular metastases was one of the original signs of inoperability identified by Haagensen and Stout. In 1987, the International Union Against Cancer/AJCC tumor-node-metastasis staging system changed the classification of patients with supraclavicular metastases from N3 to M1 to reflect the poor prognosis of patients with this presentation. Recently, Brito et al.[16] reported on a pooled analysis of three M.D. Anderson Hospital protocols and found that patients with regional Stage IV disease had better outcomes than patients with visceral Stage IV disease. Recently, the AJCC has further amended the staging classification to include patients with supraclavicular metastases at diagnosis in the IIIC category. This staging change came into effect from January 1, 2003. However, there is no consensus on the treatment of supraclavicular lymphnode metastasis.

The retrospective study by Chen et al.[15] attempted to define the risk factors for SCLN metastasis and select high-risk patients for whom aggressive local treatment such as RT is indicated. In this study, between 1990 and 1998, 2658 consecutive invasive breast cancer patients underwent surgery and adjuvant therapy in the hospital. The median age was 47 years (range 22-92). The median follow-up period was 39 months. In their study, 113 (4.3%) out of 2658 patients developed SCLN metastasis during this period. Young age (< or = 40 years), tumor size >3cm, high histologic grade, angiolymphatic invasion, negative estrogen receptor status, synthetic phase fraction >4%, >4 positive nodes, and Level II or III involved nodes were all significant for predicting neck metastasis in the univariate analysis. Of these three predictive factors were significant after multivariate analysis: High histologic grade, >4 positive nodes and axillary Level II or III involved nodes. However, in our study none of the clinicopathological factors excluding axillary nodal burden such as including age, menopausal status, and clinical T stage, location of tumor, high histologic grade, angiolymphatic invasion, negative hormone or Her2 neu receptor status were associated with occult SCLN metastasis.

Axillary nodal status was the most important factor relating to adjuvant therapy and correlated well with survival and regional nodal failure. Kiricuta et al.[3] 72% of the patients who developed SCLN metastasis had positive axillary nodes when the primary tumor was diagnosed. McKinna et al.[4] found that 22 of the 27 patients who had positive axillary nodes at presentation developed SCLN metastasis. The number of positive axillary nodes also correlated with the development of SCLN metastasis. Galper et al.[2] showed that 10% of 3 positive axillary node patients developed SCLN metastasis compared with only 2% of the node-negative breast cancer patients. Chen et al.[15] only 1.9% of the node-negative patients and 4.5% of the 1-4-positive node patients developed SCLN metastasis; however, for the patients with 4 positive axillary nodes, the incidence of SCLN metastasis was 10.0%. Based on this results prophylactic supraclavicular RT is recommended in locally advanced breast cancer though it is not associated with improvement in survival. The study by Tai et al.[17] was to evaluate the role of supraclavicular and axillary radiotherapy (SART) according to the nodal ratio (NR) (nodal positivity to total examined nodes-NR). They categorized whole study group into three NR groups-low (< or = 25%), medium (>25% to < or = 75%), and high (> 75%) nodal involvement, respectively. In their study, for a low NR, the 10-year overall survival rate with and without SART was 57% and 58% (P = 0.18), and the cause-specific survival rate was 68% and 71% (P = 0.32), respectively. For a medium NR, the 10-year overall survival rate with and without SART was 48% and 34% (P = 0.007), and the cause-specific survival rate was 57% and 43% (P = 0.002), respectively. For a high NR, the 10-year overall survival rate with and without SART was 19% and 10% (P = 0.005), and the cause-specific survival rate was 26% and 14% (P = 0.005), respectively. Thus, not all patients with locally advanced breast cancer will be benefited with adjuvant RT except those are with high axillary disease burden. In our study 55% of patients with high nodal ratio (>75%) had occult SCLN metastasis as compared to only 7% occult SCLN metastasis in patients with nodal ratio <75%. This observation confirms the attribution of high axillary disease burden as a risk factor for occult SCLN metastasis.

The role of locoregional RT after mastectomy or BCS bresat conserving surgery in patients with intermediate-risk disease, particularly in those with T1-2 breast cancer with 1-3 positive nodes, is more controversial. Yau et al.[18] reviewed locoregional recurrence patterns associated with their institution's policy in 838 patients treated with mastectomy. In this series, high-risk disease was defined as tumors ≥4 cm with 1-3 positives nodes, any tumor with >3 positive nodes, or positive surgical margins; “intermediate-risk” disease was defined as tumors <4 cm with 1-3 positive nodes, or node-negative tumors with at least one risk factor, i.e., large tumors ≥4 cm, lymphovascular invasion, or margins ≤2 mm. Patients with node-negative tumors without these factors were considered low risk and did not receive adjuvant RT. At a median follow-up time of 5.5 years, the low-risk group treated without RT experienced significantly higher locoregional recurrence versus the intermediate-risk group treated with RT. In the low-risk subgroup, age <50 and grade III histology were significant prognostic indicators for higher locoregional recurrence. Due to its high locoregional recurrence, RT is routinely considered in this intermediate risk group patients. However, in our study all these risk factors, which categories patients into intermediate risk groups including young age, high grade histology, lymphovascular invasion, larger tumor size, 1-3 positive axillary nodes not significantly associated with occult SCLN metastasis. However, larger prospective study should be carried out to confirm these findings.


 » Conclusion Top


All the studies carried out before either evaluated risk factors related to supraclavicular metastasis retrospectively after development of the same or evaluated efficacy of prophylactic RT in prevention of supraclavicular metastasis. Moreover, the benefits of aggressive local therapy such as RT must be balanced against the potential morbidities, including radiation pneumonitis,[11] brachial plexus injury,[12] lymphedema,[13] and second tumor occurrence.[14] No prospective study until the date identified high-risk group for SCLN metastases. In our study, 25% of patients shows occult SCLN metastasis in locally advanced breast cancer who are candidates for adjuvant RT including RT to supraclavicular region. Thus, theoretically 75% patients are extra irradiated. Thus, it is important to identify the patients at high-risk for the supraclavicular metastasis. Our study has shown that the extent of axillary node involvement as well as the number of positive nodes, is independent factors in predicting occult SCLN metastasis. Patients with >10 positive nodes in the axilla or involvement at Level III or >75% positive axillary nodes of total dissected nodes are at high-risk for occult SCLN metastasis. There is statistically non-significant association of tumor size and clinical T stage and location of tumor with occult SCLN metastasis in locally advanced breast cancer. No other factors such as age, menopausal status, histological grade, lymphovascular invasion, extracapsular extension, and hormone receptor or Her2 receptor status have any predictive value for occult SCLN metastasis.

Although a small number of cases were examined in this single center study, this is the only prospective study of this kind. Furthermore, our study population can be followed for extended period to know the effect of prophylactic supraclavicular lymphnode dissection on survival.

 
 » References Top

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Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956-62.  Back to cited text no. 10
    
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Larson D, Weinstein M, Goldberg I, Silver B, Recht A, Cady B, et al. Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy. Int J Radiat Oncol Biol Phys 1986;12:1575-82.  Back to cited text no. 13
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Neugut AI, Robinson E, Lee WC, Murray T, Karwoski K, Kutcher GJ. Lung cancer after radiation therapy for breast cancer. Cancer 1993;71:3054-7.  Back to cited text no. 14
    
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Chen SC, Chen MF, Hwang TL, Chao TC, Lo YF, Hsueh S, et al. Prediction of supraclavicular lymph node metastasis in breast carcinoma. Int J Radiat Oncol Biol Phys 2002;52:614-9.  Back to cited text no. 15
    
16.
Brito RA, Valero V, Buzdar AU, Booser DJ, Ames F, Strom E, et al. Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience. J Clin Oncol 2001;19:628-33.  Back to cited text no. 16
    
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Tai P, Joseph K, Sadikov E, Mahmood S, Lien F, Yu E. Nodal ratios in node-positive breast cancer: Long-term study to clarify discrepancy of role of supraclavicular and axillary regional radiotherapy. Int J Radiat Oncol Biol Phys 2007;68:662-6.  Back to cited text no. 17
    
18.
Yau TK, Chang TY, Soong S. Postmastectomy locoregional recurrence in Hong Kong: low risk patients without radiotherapy have more failures than intermediate risk patients with radiotherapy. Breast Cancer Res Treat 2007;106 suppl 1:S198.  Back to cited text no. 18
    


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