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*Corresponding Author: Anil Heroor, Head of Department, Surgical Oncology, Fortis Hospital, Mulund, Mumbai, India
Citation: Yadhukrishnan T.P., Aysha Khan, Ziaul Rahman, Arul Vanan, Hitesh Singhavi, Anil Heroor (2021) Clinical Value of Size, quadrant, and Hormonal Status in Predicting Axillary Node Metastasis in Early Clinico-Radiologically Negative Indian Breast Cancer- A Hospital Based Prospective Observational Study. J, Surgical Case Reports and Images 4(8); DOI: 10.31579/2690-1897/082
Copyright: © 2021, Anil Heroor, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 27 May 2021 | Accepted: 10 August 2021 | Published: 23 October 2021
Keywords: sentinel node biopsy, breast cancer, axillary node metastasis, sentinel node metastasis
Background: Sentinel lymph node biopsy (SLNB) is standard of care in clinico- radiologically negative axilla in early breast cancer case. It’s an oncologically safe alternative to Axillary lymph node dissection (ALND), however factors predicting sentinel node metastasis in Indian population is lacking.
Methods: A prospective observational study which recruited 80 patients with breast cancer who underwent SLNB with or without ALND, with evaluation of predictive factors including size, type and quadrant , hormonal status of breast this characteristics were prospectively analyzed to predict the axillary metastasis and need of SLNB .
Result: Mean age of the patients included in our study was 52.4 years. On univariate analysis, size (p<0.013), upper outer quadrant (UOQ) (p<0.038), central quadrant (CQ) (0.07) were significantly associated with axillary node metastasis in T2 tumors. While on multivariate analysis, UOQ (P<0.009), CQ (p<0.02) metastasis were associated with axillary node metastasis in T2 tumors. Overall sensitivity, specificity, positive predictive valve (PPV) and negative predictive valve (NPV) of SLNB in predicting axillary node status was 77.59%, 100%, 100% and 62.86% respectively. The overall accuracy was 83.7%.
Conclusion: Upper outer quadrant, central quadrant and size of the tumors are important prognostic factors to predict axillary node metastasis without the need of sentinel node biopsy in early breast cancers.
Sentinel lymph node (SLNB) mapping and dissection is a sensitive and accurate technique for nodal evaluation and has been applied to staging of axillary lymph nodes in patients with breast cancer [1]. It has prognostic value, least invasive and less surgical morbidity than with axillary lymph node dissection (ALND), it’s also important prognostic indicator of overall survival in patients with breast cancer. However, SNB has its own limitation. Its false negative rate is 5 percent according to Amersi et al, there is increase the risk of recurrence and its controversial in pregnancy, vital blue dye is contraindicated in pregnant patients, or use of radioactive colloid alone to map this subgroup of patients [2].Similarly other relative disadvantages of SNB includes its implication of finding micro metastases in the sentinel nodes, and its effectiveness after neo adjuvant therapy, and in staging of axilla in locally recurrent breast cancer following breast surgery with or without prior axillary surgery. The British journal on cancer, published a study which show the model estimated that SLNB results in 1.1 more axillary recurrences per 1000 patients at 5 years, and 1.9 more axillary recurrences per 1000 patients at 20 years than ALND [3, 4].
We need to find out usefulness of SLNB in a patient with high risk of axillary metastasis. Patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably higher incidence of axillary disease. There are many studies around the globe regarding the controversies of axillary lymph node dissection and sentinel lymph node biopsy However data of Indian population with respect to site (quadrant) of breast cancer influencing axillary metastasis and axillary dissection without sentinel lymph node biopsy in early breast cancer is scarce.
In those specific high risk cases of early stage, usefulness of SNB may be questionable. Therefore, we decided to study those specific cases in which axillary node dissection can be performed in resource constrain settings. We also aimed to find out site and size-specific incidence of ALNM depending on the quadrant of the breast involved.
This is a prospective observational study done in our tertiary care center from January 2019 – January 2020. Early stage, clinic-radiological negative patients with Fine needle aspiration cytology or true cut biopsy positive patients were included in the study. Patient receiving any definitive prior treatment were excluded. All patients underwent surgery as a definitive treatment. They underwent breast conservative therapy or modified radical mastectomy with sentinel node biopsy followed by Axillary node dissection. A pretested proform was used to collect relevant information (patient data, detailed history, clinical examination, FNAC/Trucut biopsy, USG breast and axilla, mammography and chest x-ray, lab investigations, etc.) from all selected patient was assessed. All patient underwent required preoperative investigations, informed consent from all participating patients and after ensuring fitness for surgery, these patients were taken for SLNB along with wide local excision with axillary clearance or modified radical mastectomy. Methylene blue dye was injected in sub areolar region 2 minutes prior to surgery. Intra operatively, sentinel lymph node was searched after raising superior flap. Axillary node dissection was done to detect stained node. All blue nodes and any node receiving a blue lymphatic channel was considered as sentinel nodes. After excising the stained lymph nodes, nodes were sent for frozen section examination and complete axillary clearance was done. In node positive, removal of breast tissue was done. Further histopathological examination and pathological data including histopathological type, size of the tumor, ER/PR status, HeR2Neu status, and lymph node status in sentinel and non-sentinel lymph nodes was collected. SLNs were routinely examined by serial sectioning with two sections of 200 microns each were stained, one with routine hematoxylin and eosin (H&E) and one by IHC using cytokeratin. Lymph nodes were examined by H&E staining. Negative lymph node was additionally stained with IHC.
Demographic, histopathological data was categorically. To analyze the effect of presence of breast cancer (site), size, ER, PR and HER’s-2 status on the presence of ALNM and SNLM. Univariate analysis was done using chi-square test. Multivariate analysis was performed using logistic regression analysis for those factors which were significant on Univariate analysis. Odds ratios and p-values were calculated with 95% confidence intervals (CI). All p-values less than 0.05 were used for statistical significance. Statistical analyses for evaluating sensitivity, specificity, accuracy, and positive and negative predictive values of SLNB were performed in comparison to ALND. False-negative sentinel lymph nodes localization was defined as negative sentinel lymph nodes with other nodes in the basin positive for metastatic breast cancer. Sensitivity was calculated by the number of patients in whom the histological characteristics of the sentinel lymph nodes reflected the histological characteristics of the rest of the nodes in the basin. All analyses were performed using SPSS software version 20.0 (IBM Corp., Armonk, NY, USA).
The study included 80 cases of early breast cancer, of which 44 (55 %) showed axillary metastasis. Mean age of the patient at the time of surgery was 52.84 years which ranged from 30-70 years. 32 patients were below 50 years of age. The tumor size was T2 (2–5 cm) in 65 patients and T1 (<2>
39 patients (48.75%) had grade II tumors which were the most common. ER was positive in 54 patients while PR was positive in 42 patients. On ER and PR immunohistochemistry, it was not significantly associated with low risk of ALNM (p < 0.002 Table 2). Quadrant- wise location of breast cancer is presented in Table 1. To identify the clinical traits affecting SNLM, Univariate analysis was performed on all candidate predictors. The results showed that T2 has higher significance on SLNM (p<0>Table 2). Features statistically significant in the Univariate logistic regression model were included in the multivariable logistic regression model. The results showed that size, UO and central quadrant were independent risk factors of SLNM. (P<0>
UOQ= Upper outer quadrant
UIQ= Upper outer quadrant
LO=Lower outer
LI=Lower inner
CQ=Central quadrant
T1 = tumor less than or equal to 2 cm
T2=size 2cm-5cm
ER=Estrogen receptor
PR=Progesterone receptor
Her 2 neu=Human epidermal receptor
To identify the clinical traits affecting ALNM, Univariate logistic regression was performed on all clinical factors influencing ALNM. The results showed that T2 (P < 0 value =0.015), value =0.08),>Table 2). Features statistically significant in the univariate analysis model were included in the multivariable logistic regression model. The results showed that size, UOQ, and CQ were independent risk factors of ALNM. (p<0>
The presence of axillary disease is the most important prognostic factor in breast cancer. Axillary metastasis indicates biological aggressiveness and extent of tumor involvement, often with systemic spread [18]. SNB has replaced axillary lymph node dissection (ALND) in clinically node negative axilla. Multiple randomized trials have demonstrated that when the SLN is tumor-free, observation alone confers similar regional control and survival compared to SNB followed by ALND [5-8] .Women with operable breast cancer and multicentric tumors, with ductal carcinoma in situ, and planned for mastectomy, with previous breast and/or axillary surgery, or who received preoperative/neoadjuvant systemic therapy may be offered SNB, however SNB is thought to be safer before chemotherapy due to its systemic therapy induced lymphatic changes. Also,SNB for patients with ductal carcinoma in situ (DCIS) is controversial. While women with large or locally advanced invasive breast cancer (tumor size T3/T4), inflammatory breast cancer, or ductal carcinoma in situ (when breast-conserving surgery is planned) or are pregnant should not undergo SNLB [9]. In NSABP-B32, pathologically negative SLNs, 99.9% on follow-up at 95.6 months, there was no statistically significant difference between the SNB plus ALND group and the SNB-only group with respect to regional recurrence (RR) , 8-year overall survival (OS) and 8-year disease-free survival (DFS) [10] Gary H et al suggested that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown [11]. Meanwhile, high-frequency ultrasonography, the first-line imaging modality in breast cancer diagnosis, can show the rich morphological features of breast tumor, associated with ALNM. [13-20]. Previous studies have shown that clinico-pathological features such as size, age at diagnosis, palpable mass or not, body mass index (BMI) and hormone receptors are related to ALNM [21-22]. However, in our study, we aimed to compare the incidence of SLNM and ALNM based on the quadrant of breast and size of tumor in breast cancer. We found that different quadrant of breast involvement had differential incidence of SLNM and ALNM.In our study Upper outer quadrant had significantly higher incidence of breast cancer. We also found that incidence of SLNM and ALNM was significantly higher for this specific quadrant. It was interesting to note that there was no significant difference between the SLNM and ALNM. Thus, axillary node can be addressed in the patient having disease in the outer upper quadrant without the need of sentinel node biopsy especially in low resource settings. Another study led by Franco et al has shown that USG guided FNAC can be an effective alternative to SLNB with frozen section of nodes [23]. It concluded that USG guided FNAC had better specificity, cost reduction and reduction in false positive results. Lee et al in 2002 published a study stated that tumor size and Lymphovascular invasion LVI were the only variables independently predictive of positive SLNB results [22].
In our study, we found that T2 breast lesion had significantly higher number of SNM and ALNM.Similar results were concluded in the study led by Jong Hong Lee et al. [12]. Thus according to our study, quadrant of breast and size of tumor can be consider as a clinically valuable marker for axillary metastasis and reducing the use of SLNB. This can not only help us in cost reduction avoiding the use of radioactive tracer but also in reducing intraoperative timing and need for second surgery. This algorithm will help us in reducing the false negative cases improving overall survival without compromising oncological safety. Indian study led by Nandu [23] showed the Sensitivity of SLNB is 90.48%, specificity is 85.71%, PPV of is 90.48%, NPV is 85.71%, and accuracy is 88.57% comparable to our sensitivity, specificity, PPV, NPV and accuracy of 77.59%, 100%,100%, 62.86% ,83.7% respectively.
Limitation: Lymphovascular invasion, perineural invasion were not taken into consideration for SLNM and ALNM as our study limited to clinical factors influencing the metastasis. Our study is first of its kind Indian study to state the importance of site of early breast cancer in influencing SLNM and ALNM.
Upper outer quadrant, central quadrant and size of the tumors are important prognostic factors to predict axillary node metastasis without the need of sentinel node biopsy in early breast cancers.
None.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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