Correlating site of tumor and nodal positivity

Out of total 200 cases, 5.5%, 58.5%, and 22% tumors belong to T1, T2, and T3, respectively [Table 2]. The most common T size showing N2 and above nodal status was T2 (19.5%) followed by T3 (12.5%) and T1 (0.5%) excluding cases with T4 and T2/T3 with skin invasion.

Correlating size of tumor and nodal positivity

N1 nodal status was seen in 22.5% of cases and is seen with all sizes (T1-6.6%, T2-66.6%, T3-22.4%) excluding T4 and T2/T3 with skin invasion.

In this study, a distance of skin from the tumor was calculated and was correlated with the nodal status [Table 3]. Positive nodes were seen in 67.5% (135) of cases, of which tumor with distance from skin less than 0.3 cm show maximum nodal positivity (87 of 135 = 64.4%) and maximum cases with N2 and N3 disease (66 cases of 135 = 48.%).

Correlation of nodal status with distance of tumor from skin

Most significant was the finding that Table 2 100% with tumor size corresponding in T2 stage with skin invasion either grossly or microscopically in T3 stage tumors were positive for metastatic deposits in axillary region and 10/11 cases (90%) in T4 stage were positive. Hence, showing a positive result to our proposition. One case with T4 stage with negative nodes showed microscopically medullary type of morphology. Furthermore, tumors in outer upper quadrant were an independent predictor of axillary lymph node positivity (75.5%). Correlation of nodal status with Modified Scarf Bloom Richardson grading was also studied [Table 4]. Grade II was associated with maximum nodal positivity percentage (71.2%).

Correlation of nodal status with grading of tumor

Discussion

Several factors are known to affect the biological behavior of breast cancer. These include the clinical and demographic features, pathological characteristics, nodal involvement, and the molecular factors within the breast tumor itself.[13]

The exact role that each of these may have on the biological behavior of breast cancer is an area of increasing interest, including their role in the regional spread of the disease. However, their impact on treatment until now continued to be an area of research interest only.

Although tumor characteristics and molecular markers contribute to the understanding of breast cancer biology, axillary lymph node status remains one of the most reliable prognostic factors and is used as a guide for adjuvant breast cancer treatment.[14],[15],[16]

Identifying preoperative predictors of positive nodes helps guide the neoadjuvant therapy or surgical plan of choice and help patients become better psychologically prepared for axillary lymph node dissection (ALND) if required.

The three-dimensional lymphatic microanatomy of the breast is not well-known, despite the many studies reporting on the lymphatic drainage pathways from the breast and advances in breast sentinel lymphatic mapping particularly the superficial lymphatic drainage. Several reports have proposed that the dermal lymphatic pathway defines the clinically relevant breast cancer metastatic pathway and suggest that lymphatic supply is less abundant or available in the breast parenchyma than that in the superficial dermal and subdermal layers.[17],[18] This hypothesis has been supported by several studies that investigated sentinel lymph node biopsy (SLNB) methods.

Although SLNB is replacing ALND for axillary staging and is emerging as the new standard of care, there is a lack of standardized methodology for the procedure.

Axillary lymph node biopsy remains the best way to evaluate the presence of node metastases. It is also important in locoregional disease control. However, it is associated with complications such as lymphedema, shoulder stiffness, breast edema, seroma formation, upper limb numbness, and brachial plexopathy.[19],[20]

Thus, finding an independent predictor of axillary lymph node positivity is highly valuable preposition both for the treating surgeon as well as the patient.

However, only a few reports have investigated tumor proximity to the skin and evaluated its relationship with axillary node metastasis.[17],[21] In this study, breast cancer distance from the skin <3>

Ansari et al.[21] reported that more superficial tumors are associated with axillary node metastasis at diagnosis. They reviewed 233 breast cancers in T2 and T3 and found that decreasing tumor distance from the skin was significantly associated with positive axillary lymph nodes in a multivariate analysis.

Cunningham et al.[17] reported that tumors closer to the skin are more likely to have metastasis to the axillary nodes. They reviewed 209 T1 and T2 invasive breast cancer cases and determined an apparent threshold of approximately 1.4 cm from the skin. None of the cancers with a distance >1.4 cm (26 cancers) had axillary node metastasis. However, the findings were based on radiological evaluation, unlike our study.

Chao et al.[18] proposed that palpable tumors are closer to the dermal lymphatics compared with nonpalpable tumors, and that this explains why palpable tumors more frequently metastasize to the axillary lymph nodes compared with nonpalpable tumors.

Although tumor palpability is an independent risk factor for axillary node metastasis, it is insufficient to use as a parameter to predict axillary node metastasis as its affected by several other factors, including physician subjectivity, tumor size, breast tumor depth, hardness, ethnicity, body weight, menopausal status, hormone use, and elasticity of the mass and surrounding tissue.[22],[23]

Siddiqui et al.[6] in multivariate analysis observed that only the tumor size, skin and nipple involvement and disease in the outer quadrants of the breast were predictive for axillary node involvement.

Similarly, our study also observed greater axillary lymph node positivity with advanced tumor stage more so in cases with proximity to overlying skin.

Conclusion

We found the distance of skin from underlying tumor as an independent predictive factor in for the presence of axillary lymph node metastases. With this information, either radiologically or intraoperative/postoperation evaluation of mastectomy specimen, we can select women who are likely to be node negative and give better preoperative counseling with information to patients regarding the probability of requiring further axillary dissection. This will empower patients in the participation of the management of their disease and possibility of follow-up surgery.

Not all cases of duct carcinoma will metastasize to lymph nodes. Even tumors of higher nuclear grade may be localized. According to literature, the lymph node metastasis was more commonly associated with tumors of larger size and with obvious lymphovascular emboli. However, it was also noticed that tumors of smaller size can also present with Axillary nodal metastasis. Anatomically, dermis of skin and nipple and areola has a dense network of lymphatics, and tumor close to the skin or nipple and areola may present with metastasis even with a smaller size. Hence tumor with smaller size but closer to skin should be managed as a tumor which is potentially capable of metastasis, and careful examination should be made to evaluate axillary nodal status.

The study is probably the first in Indian population, and more studies need to be conducted on larger patient groups for more conclusive interpretations and outcome.

Conflict of Interest

There are no conflicts of interest.

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Publication History

Article published online:
17 June 2021

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