|Year : 2020 | Volume
| Issue : 1 | Page : 9-15
A study correlating the tumor site and size with the level of axillary lymph node involvement in breast cancer
Prem Chand, Savijot Singh, Goldendeep Singh, Shivanshu Kundal, Anil Ravish
Department of General Surgery, GMC, Patiala, Punjab, India
|Date of Submission||01-Oct-2019|
|Date of Decision||15-Nov-2019|
|Date of Acceptance||18-Dec-2019|
|Date of Web Publication||10-Feb-2020|
Dr. Savijot Singh
230 Phulkian Enclave, Patiala - 147 001, Punjab
Source of Support: None, Conflict of Interest: None
Background: Breast cancer is the leading cancer in women. The most common histologic type of breast cancer is infiltrating ductal carcinoma. The mainstay of the treatment of breast cancer is surgery when the tumor is localized, followed by chemotherapy as well as radiotherapy (when indicated) and in estrogen receptor and progesterone receptor positive tumors, adjuvant hormonal therapy. Aims and Objectives: The aim of this study is to correlate tumor site and size with the level of axillary lymph node involvement (ALNI) in early and locally advanced breast cancer. Materials and Methods: This prospective and observational study was conducted on fifty female patients of carcinoma breast with early and locally advanced breast cancer. Results: The age distribution showed two peaks at 41–50 years and 51–60 years with 42 and 24 patients, respectively, in both the age groups. Preoperative lymph node positivity by ultrasonography matched with postoperative histopathological examination (HPE) report. Preoperative ultrasonographically determined tumor size was similar to the final histopathological T stage. Conclusion: As size of tumor increases, there is an increase in ALNI which suggests that nodal metastasis is indicative of tumor chronology. Ultrasonography is a good tool to objectively measure tumor size and lymph node involvement preoperatively. Quadrant of involvement can emerge as a clinically useful prognostic cancer in breast cancer as there is a higher incidence of lymph node positivity with increasing size of the breast tumor and for tumors located at the upper outer quadrant of the breast.
Keywords: Breast cancer, lymph node, tumor size and site
|How to cite this article:|
Chand P, Singh S, Singh G, Kundal S, Ravish A. A study correlating the tumor site and size with the level of axillary lymph node involvement in breast cancer. Niger J Surg 2020;26:9-15
|How to cite this URL:|
Chand P, Singh S, Singh G, Kundal S, Ravish A. A study correlating the tumor site and size with the level of axillary lymph node involvement in breast cancer. Niger J Surg [serial online] 2020 [cited 2020 Feb 18];26:9-15. Available from: http://www.nigerianjsurg.com/text.asp?2020/26/1/9/277973
| Introduction|| |
Breast cancer is the leading cancer in women, accounting for 25% of all cancer cases worldwide. It is more common in developed countries. Outcomes for breast cancer vary greatly depending on the cancer sub-type, stage of disease, and person's age. The most common histologic type of breast cancer is infiltrating ductal carcinoma. The mainstay of breast cancer treatment is surgery when the tumor is localized, followed by chemotherapy as well as radiotherapy (when indicated) and for estrogen receptor (ER) and progesterone receptor (PR)-positive tumors, adjuvant hormonal therapy.,
More than two-thirds of breast cancer cases are diagnosed in women aged 50 years and older; the majority of these cases are in developed countries. For women aged 15–49 years, twice as many breast cancer cases are diagnosed in developing countries than in developed countries. In countries where mammography is available and affordable, adherence to recommendations for routine screening is associated with reduced mortality from breast cancer.
The increased use of mammographic screening has led to an increase in the detection of breast tumors that measure ≤2.0 cm (American Joint Committee on Cancer [AJCC] classification T1).,,
Axillary node status remains the most important predictor of outcome in breast cancer patients. Data clearly show that women with cancer-free lymph nodes (lymph node-negative) have better survival than women with cancerous nodes (lymph node-positive). As the number of positive nodes increases, survival decreases.
The axillary lymph nodes (ALN) are staged to aid in determining prognosis and therapy. Sentinel lymph node biopsy (SLNB) is the initial standard axillary staging procedure performed in women with invasive breast cancer. Reports demonstrate a 97.5%–100% concordance between SLNB and complete ALN dissection (ALND).,,,,,
Tumors may be measured clinically or pathologically. Axillary nodal involvement is an essential prognostic factor in patients with breast cancer. The presence of positive ALNs implies the need for systemic adjuvant chemotherapy and locoregional irradiation. Hence, ALND contributes to the accurate staging of the disease.
The characteristics of the primary breast cancer closely associated with ALN metastasis are tumor size, tumor grade, and lymphovascular invasion, but only tumor size can be determined preoperatively.,,
The presence of axillary node metastasis and the size of the primary tumor are the two main prognostic factors used clinically for the evaluation of breast cancer patients. “Clinically node-positive” patients will undergo ALND without undergoing SLNB. “Clinically node-negative” patients with T1 or T2 tumors currently undergo SLNB. If the SLNB results are negative, no further axillary dissection is done because there is no survival benefit for performing ALND in this setting.,,,
The more lymph nodes that contain cancer cells, the more serious cancer might be. Hence, doctors use the number of involved lymph nodes to help make treatment decisions. After the surgery, a pathologist looks at the cells from breast cancer as well as from the lymph nodes.
Influence of tumor location on breast cancer prognosis
The risk of dying increased significantly (up to 21%) with increasing distance of tumor location from the axilla. Survival is significantly better for women with a tumor in the upper lateral quadrant than tumors located elsewhere in the breast.,,
Axillary node involvement is the most significant and durable prognostic factor for women with breast cancer. The use of systemic adjuvant chemotherapy is often determined by the presence or absence of axillary lymph node metastasis.,
| Aims and Objectives|| |
To correlate tumor site and size with the level of ALN involvement (ALNI) (lymph node-positive) in early and locally advanced breast cancer.
| Materials and Methods|| |
This prospective and observational study was conducted on fifty female patients of carcinoma breast in a tertiary level center on 50 females with a confirmed diagnosis of carcinoma breast.
- Early (Stage IIB) and locally advanced breast cancer (Stage IIB till IIIB).
- Metastatic disease
- Tx, Nx patients as per AJCC tumor, node, and metastasis (TNM) staging
- To, N1 patients as per AJCC TNM staging.
Assessment of tumor size
Tumor size was assessed clinically as well as ultrasonographically for all the patients and the longest dimension in length, width, or depth was taken for size consideration. The final size as described by histopathologists on grossing for all the patients was taken into correlation and this parameter was taken finally for all the patients.
Assessment of tumor site
The breast was divided into five regions with the x- and y-axis centered on the nipple which included 4 quadrants and the central nipple-areola complex.
The tumor was assigned to the quadrant where the bulk of it lay, as assessed ultrasonographically.
If tumor site was equivocal and involved more than one quadrant then tumor site was described as diffuse.
Lymph node status of the axilla
The axilla was assessed clinically, ultrasonographically, and intra-operatively for lymph nodes and statistically compared with each other.
Intraoperatively, lymph nodes up to level III of the axilla were dissected with the axillary fat.
The axillary fat was then dissected for visible ALNs.
These nodes were counted and sent for histopathological assessment, and the final status of axilla was taken to be provided by the histopathological assessment.
The patients were then staged according to the TNM staging by AJCC.
Classifying as early or locally advanced
This was a preoperative classification:
- Early Breast Cancer: Node-negative cancer (up to Stage IIB)
- Locally Advanced Breast Cancer: Node-positive cancer (stage IIB till IIIB).
Site, size, and axillary involvement descriptors for patients who receive neoadjuvant chemotherapy
- T: Done by clinical examination and ultrasonography for evidence of size
- N: Done by clinical examination and ultrasonography for evidence of nodal status.
(For Internal Mammary lymph nodes, chest X-ray PA view was done, if it showed widened mediastinum, then contrast enhanced computed tomography chest was done).
Locally advanced cancer was described before starting neoadjuvant chemotherapy.
| Results|| |
The present study was undertaken between September 2015 and April 2017. A total of 50 cases of early and locally advanced breast cancer were included in the study to develop a correlation between site and size of tumor with lymph node involvement based on clinical examination, ultrasound findings, intraoperative findings, and postoperative histopathological reports. The Chi-square test was applied for statistical analysis.
The study for clinical examination for nodes was found to be nonsignificant whereas that for ultrasonography for nodes was found to be highly significant indicating that preoperative ultrasonography is a significant predictor of lymph node positivity.
In this study, it was observed that out of the two patients with tumor size <2 cm, none had the involvement of lymph nodes. While among 45 cases with size between 2 cm and 5 cm, 7 cases had no lymph nodes involved, 6 had 1–3, 22 had 3–9, and 10 cases had more than 10 lymph nodes involved. Of 3 patients with tumor size more than 5 cm, all had more than 10 lymph nodes involved. The study was found to be highly significant. Thus, predicting that with an increase in tumor size, number of lymph nodes involved increases.
As per our study, patients with tumor present in the upper outer quadrant had more number of lymph nodes involved. On analyzing the data, our study was found to be significant with P = 0.042.
Using the Pearson Correlation test, we found that preoperative ultrasonographic-determined tumor size had a positive correlation of 0.890 to the final histopathological Tumor size (P < 0.001), which implies that ultrasound was a good tool to objectively measure tumor size before the surgery.
| Discussion|| |
The present study of breast carcinoma showed that 46% of cases belonged to 51–60 years of age group, 42% to 40–50 years age group and 12% to < 60 years age group. These findings showed that most of the breast cancer in our study was of the age group 40–60 years (88%) and locally advanced type. In a study by Chopra et al. conducted in 100 patients of histopathologically confirmed breast cancer, the mean age of patients was 51 years (standard deviation = 10.48). The age distribution showed two peaks at 41–50 years and 51–60 years with 42 and 24 patients, respectively, in both the age groups [Table 1].
The ALNI increased significantly (P = 0.008) as the tumor size increased as shown by our study [Table 2].
|Table 2: Correlation between size of tumor and lymph node involvement determined by clinical examination and sonomammography|
Click here to view
In a study by Kumar and Mukherjee when lymph node status and size of the tumor were correlated, it was found that 26 out of 50 (52%) patients were of N1. T2, T3, and T4 showed an increase in lymph node positivity as three out of five (60%) in the T3 were of N2 lymph node status, whereas all of T4 were of N3 lymph node status.
Legha et al. found that as the average size of the breast tumor increases, so does the average number of lymph nodes, both clinically as well as histopathologically positive for metastasis. It was also seen that as the number of lymph nodes increased, so did the size of the tumor by both clinical and histopathological examination.
We have seen a close relationship between tumor size and ALNI. The risk of ALN metastasis increases as tumor size increases which suggests that nodal metastasis is indicative of tumor chronology. T stage was significantly associated with nodal positivity. Larger tumor size was found to be an independent predictor of node positive disease in our study, concurring with data from several other centers.,
It was also observed that the majority of cases 45 fell into T2 stage, 11 (24.44%) out of these were of N3 nodal status which is quite high in relation to the T stage. This shows that there may be high nodal involvement even in smaller-sized tumors. Hence, there is a need for early screening programs as even small-sized tumors may have already metastasized at the time of presentation.
Similar to the findings of Chan et al., we also found that preoperative ultrasonographically determined tumor size was similar to the final histopathological T stage which implies that ultrasound was a good tool to objectively measure tumor size before thesurgery and this is particularly useful in hospitals without radio nuclear medicine expertise for SLN imaging. Furthermore, the preoperative determination of tumor size with ultrasound correlates well with the actual level of ALNI. Therefore, tumor size can be used to guide the surgeon to more limited axillary dissection as an alternative to SLNB for T1-node negative breast cancers [Table 3].
|Table 3: Correlation of preoperative tumor size (ultrasonography) with lymph node involvement determined on postoperative HPE|
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From our study, it was also seen that preoperative lymph node positivity by ultrasonography matched with postoperative HPE report, indicating that ultrasonography was a significant predictor of lymph node involvement.
In this study, the site of tumor and lymph node status were correlated. It was observed that out of the majority of cases had tumor involving upper outer quadrant of the breast, among which 14 cases had N2 lymph node status and 11 had N3 lymph node status [Table 4].
|Table 4: Correlation of preoperative tumor site (ultrasonography) with lymph node involvement determined on postoperative HPE|
Click here to view
Legha et al. also found that the upper and outer quadrant of the breast was involved in 62% cases. The second most common site was upper and inner (16%) followed by lower outer in 6% and diffuse, i.e., more than 2 quadrants involved in 12% cases. This may be attributed to a greater amount of breast tissue in the upper outer quadrant than other sectors of the breast.
We have observed that ALN positivity correlates with the location of the primary tumor. The presence or absence of ALNI is the most important prognostic indicator for patients with breast cancer. Increase in the number of involved ALNs is associated with an increased probability of recurrence and mortality. Hence, quadrant of involvement can emerge as a clinically useful prognostic factor in breast cancer.
Although women with tumors in the upper outer quadrant are likely to have more number of ALNs and predictably poorer outcome, but they are also likely to have the most complete surgical management of the tumor burden where axillary Level I and II dissection is a standard procedure. Compared to these patients, women with tumor in the inner quadrant, which may have drainage also to other lymph nodes outside Level I and II of the axilla (mostly internal mammary chain), may have a higher likelihood of having regional undiscovered metastatic spread after standard surgical treatment.,,,, Thus, incomplete removal of tumor tissue among women with tumors located away from the axilla may explain why survival disadvantage is observed in them.
Similar to a study by Kumar and Mukherjee, our results also showed that lymph node involvement is more in hormone receptor negative tumors as compared to other subtypes. Although Luminal A was the most common subtype but 5 out of a total of 6 patients in Triple negative type had N3 lymph node status. Some studies contradict this finding,, as they found that triple-negative subtype was associated with a lower risk of lymph node metastasis as compared to other subtypes. Hence, it can be assumed that other factors might also play a role in determining the relation between receptor status and lymph node status and further research may be required to determine them. In future, molecular classification of early-stage breast cancer using immunohistochemistry may help in predicting the probability of developing ALN metastasis [Table 5].
Limiting factor in our study was nonavailability of SLNB at our institute. Hence, all the cases of doubtful lymph nodes had to undergo ALND to decrease the risk of missed nodal metastasis.
This study was designed to develop a correlation between site and size of carcinoma breast with ALNI based on clinical examination, ultrasound findings, intra-operative findings, and post-operative histopathological reports.
As the size of tumor increases, there is an increase in ALNI which suggests that there may be high nodal involvement even in T2 tumors, so there is a need for early screening. Tumor size can be used as a guide for more limited axillary dissection as an alternative to SLNB for T1 node negative tumors. Quadrant of involvement can emerge as a clinically useful prognostic cancer in breast cancer. The increasing use of SLNB may reduce the complications of ALND at the expense of increasing the risk of missed nodal metastasis. The decision of doing SLNB or ALND in early node-negative tumors should be based on individual patient needs. Molecular classification of early-stage breast cancer using IHC may help in predicting the probability of developing ALN metastasis. It provides a survival advantage for patients with ER + PR + tumors as a treatment in the form of adjuvant hormonal therapy is available easily and is cost-effective.
| Conclusion|| |
This study concludes that there is a higher incidence of lymph node positivity with increasing size of the breast tumor as well as for tumors located at the upper outer quadrant of the breast.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Stewart WB, Wild CP. Cancer worldwide. In: The Global and Regional Burden of Cancer. World Cancer Report 2014. Vol. 1.1. Lyon, France: World Health Organization; 2014. p. 16.
Stewart WB, Wild CP. Breast cancer. In: World Cancer Report 2014. Vol. 5.2. Lyon, France: World Health Organization; 2014. p. 362.
Paymaster JC, Gangadharan JC. Epidemiology of breast cancer in India. J Natl Cancer Inst 1972;48:1021-24.
World Health Organization. Cancer Control: Knowledge Into Action: WHO Guide for Effective Programmes: Module 4: Diagnosis and Treatment. Geneva: World Health Organization; 2008. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK179050/
. [Last accessed on 2019 Jul 28].
Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, et al
. Breast and cervical cancer in 187 countries between 1980 and 2010: A systematic analysis. Lancet 2011;378:1461-84.
Lin PP, Allison DC, Wainstock J, Miller KD, Dooley WC, Friedman N, et al
. Impact of axillary lymph node dissection on the therapy of breast cancer patients. J Clin Oncol 1993;11:1536-44.
Danforth DN Jr., Findlay PA, McDonald HD, Lippman ME, Reichert CM, d'Angelo T, et al
. Complete axillary lymph node dissection for stage I-II carcinoma of the breast. J Clin Oncol 1986;4:655-62.
Chevinsky AH, Ferrara J, James AG, Minton JP, Young D, Farrar WB. Prospective evaluation of clinical and pathologic detection of axillary metastases in patients with carcinoma of the breast. Surgery 1990;108:612-7.
Greco M, Agresti R, Cascinelli N, Casalini P, Giovanazzi R, Maucione A, et al
. Breast cancer patients treated without axillary surgery: Clinical implications and biologic analysis. Ann Surg 2000;232:1-7.
Kern KA. Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye. J Am Coll Surg 1999;189:539-45.
Rubio IT, Korourian S, Cowan C, Krag DN, Colvert M, Klimberg VS. Sentinel lymph node biopsy for staging breast cancer. Am J Surg 1998;176:532-7.
Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni M, et al
. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1997;349:1864-7.
Albertini JJ, Lyman GH, Cox C, Yeatman T, Balducci L, Ku N, et al
. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 1996;276:1818-22.
Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg VS, Shriver C, et al
. The sentinel node in breast cancer – A multicenter validation study. N Engl J Med 1998;339:941-6.
Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S, et al
. Sentinel lymph node biopsy and axillary dissection in breast cancer: Results in a large series. J Natl Cancer Inst 1999;91:368-73.
Cutuli B, Velten M, Martin C. Assessment of axillary lymph node involvement in small breast cancer: Analysis of 893 cases. Clin Breast Cancer 2001;2:59-65.
Barth A, Craig PH, Silverstein MJ. Predictors of axillary lymph node metastases in patients with T1 breast carcinoma. Cancer 1997;79:1918-22.
Guarnieri A, Neri A, Correale PP, Lottini M, Testa M, Mariani F, et al
. Prediction of lymph node status by analysis of prognostic factors and possible indications for elective axillary dissection in T1 breast cancers. Eur J Surg 2001;167:255-9.
Mitsuyama S, Anan K, Toyoshima S, Nishihara K, Abe Y, Iwashita T, et al
. Histopathological Predictors of Axillary Lymph Node Metastases in Patients with Breast Cancer. Breast Cancer 1999;6:237-41.
Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd
, 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;23:7703-20.
Kleer CG, Sabel MS. Prognostic and predictive factors in breast cancer. In: Kuerer HM, editor. Kuerer's Breast Surgical Oncology. New York: McGraw-Hill; 2010. p. 244.
Carlson GW, Wood WC. Management of axillary lymph node metastasis in breast cancer: Making progress. JAMA 2011;305:606-7.
Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2002;347:567-75.
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Ashikaga T, et al
. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: Results from the NSABP B-32 randomised phase III trial. Lancet Oncol 2007;8:881-8.
Vendrell-Torné E, Setoain-Quinquer J, Doménech-Torné FM. Study of normal mammary lymphatic drainage using radioactive isotopes. J Nucl Med 1972;13:801-5.
Ohsumi S, Sakamoto G, Takashima S, Koyama H, Shin E, Suemasu K, et al
. Long-term results of breast-conserving treatment for early-stage breast cancer in Japanese women from multicenter investigation. Jpn J Clin Oncol 2003;33:61-7.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Ver. 1. National Comprehensive Cancer Network; 2010.
Donegan WL. Tumor-related prognostic factors for breast cancer. CA Cancer J Clin 1997;47:28-51.
Hortobagyi GN, Buzdar AU. Current status of adjuvant systemic therapy for primary breast cancer: Progress and controversy. CA Cancer J Clin 1995;45:199-226.
Chopra B, Kaur V, Singh K. Age shift: Breast cancer is occurring in younger age groups: Is it true? Clin Cancer Investig J 2014;3:526-9.9.
Kumar N, Mukherjee S. Correlation of various prognostic factors in breast cancer. Int J Sci Eng Res 2013;3:1-4.
Legha MP, Gandhi A, Gaur R, Bansal P, Chauhan SP. Carcinoma breast: Correlation study between tumor size, number of lymph nodes and metastasis. Int J Gen Can 2015;2:1-8.
Hartveit F. Axillary metastasis in breast cancer: When, how, and why? Semin Surg Oncol 1989;5:126-36.
Chua B, Ung O, Taylor R, Boyages J. Frequency and predictors of axillary lymph node metastases in invasive breast cancer. ANZ J Surg 2001;71:723-8.
Yiangou C, Shousha S, Sinnett HD. Primary tumour characteristics and axillary lymph node status in breast cancer. Br J Cancer 1999;80:1974-8.
Chan GS, Ho GH, Yeo AW, Wong CY. Correlation between breast tumour size and level of axillary lymph node involvement. Asian J Surg 2005;28:97-9.
Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Mazzarol G, Pruneri G, et al
. Size of breast cancer metastases in axillary lymph nodes: Clinical relevance of minimal lymph node involvement. J Clin Oncol 2005;23:1379-89.
Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989;63:181-7.
Lacour J, Lê MG, Hill C, Kramar A, Contesso G, Sarrazin D. Is it useful to remove internal mammary nodes in operable breast cancer? Eur J Surg Oncol 1987;13:309-14.
Lê MG, Arriagada R, de Vathaire F, Dewar J, Fontaine F, Lacour J, et al
. Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes? Cancer 1990;66:2313-8.
Veronesi U, Cascinelli N, Bufalino R, Morabito A, Greco M, Galluzzo D, et al
. Risk of internal mammary lymph node metastases and its relevance on prognosis of breast cancer patients. Ann Surg 1983;198:681-4.
Meier P, Ferguson DJ, Karrison T. A controlled trial of extended radical mastectomy. Cancer 1985;55:880-91.
He ZY, Wu SG, Yang Q, Sun JY, Li FY, Lin Q, et al
. breast cancer subtype is associated with axillary lymph node metastasis: A retrospective cohort study. Medicine (Baltimore) 2015;94:e2213.
de Oliveira Filho HR, Dória MT, Piato JR, Soares Junior JM, Filassi JR, Baracat EC, et al
. Criteria for prediction of metastatic axillary lymph nodes in early-stage breast cancer. Rev Bras Ginecol Obstet 2015;37:308-13.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]