Node-Negative Breast Cancer - An Overview

Introduction

The early detection of breast cancer and the use of adjuvant systemic therapy have caused a decline in the number of new cases, especially in Western countries. It has also helped to improve the survival rates of this type of cancer. The increase in breast cancer screening programs has caused increased diagnoses of node-negative breast cancers. This article deals with the management of node-negative breast cancer.

What Is Node-Negative Breast Cancer?

Breast cancer is one of the most commonly seen cancers in women or people assigned to be female at birth. When an abnormal cell grows and multiplies without control in the breast, it is called breast cancer. Healthcare professionals use various cancer-staging systems to diagnose and plan appropriate treatments.

The lymph node status helps healthcare experts know the spread of cancer. In breast cancer, it shows if the cancer has spread to the axillary lymph nodes (lymph nodes in the underarm area). When none of the lymph nodes contain cancer, it is called lymph node-negative. On the other hand, if at least one of the lymph nodes contains cancer, it is called lymph node-positive.

In node-negative breast cancers, the chances of survival and a better prognosis with treatment are considered better. The poorer the prognosis tends to be as the number of lymph nodes that become cancerous increases. The number of cancerous lymph nodes helps in planning the appropriate treatment.

How Is Node-Negative Breast Cancer Diagnosed?

To provide the best treatment according to the stage of cancer, it is necessary to diagnose the stage appropriately. A careful assessment of the associated risks should be done to avoid complications. In breast cancer, the most important histopathologic factor for this is the evaluation of lymph node status. The increase in breast cancer screening programs facilitated the earlier diagnosis of the condition. As a result, the number of cases of node-negative breast cancers is increasing compared to other cancers.

• Sentinel Lymph Node Biopsy: The sentinel lymph node biopsy (SLNB) was introduced more than fifteen years ago to evaluate the lymph node status in patients who were clinically diagnosed with node-negative breast cancer. A medical professional removes one or more sentinel nodes during the surgery, and the samples are forwarded to a lab for cancer cell detection. The findings indicate if the malignancy has progressed from the original (primary) tumor. The first lymph node to which cancer cells from a primary tumor are most likely to spread is known as a sentinel lymph node. There may occasionally be more than one sentinel lymph node.

• Tumor Markers: Plenty of tumor markers are available in node-negative breast cancer. According to the American Society of Clinical Oncology (ASCO), estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, urokinase-plasminogen activator (uPA), and plasminogen activator inhibitor 1 (PAI-1) can be potentially used as tumor markers for node-negative breast cancer. However, more research must be done before adopting it as a routine standard.

• Multiparameter Gene Expression Analysis: Advancements in gene expression have provided an opportunity to study the heterogeneous nature of breast cancer. Studies show that tumors ER-positive by immunohistochemistry (a test that uses antibodies to test for certain types of antigens in the sample) can be categorized as good or bad prognostic ones by proliferation-associated genes.

• Role of Immune System: It was very recently that the researchers became aware of the role of the body’s immune system in predicting the prognosis of the condition. Studies show that high expression of lymphocyte-associated genes showed a good prognosis in node-negative ERBB2-positive (erythroblastic oncogene B, a factor that promotes metastatic activity) breast cancer. More research in this field can help in developing novel strategies that can be used to assess the prognosis of node-negative breast cancer.

How Is Node-Negative Breast Cancer Managed?

Regardless of whether the intervention is systemic, surgical, or radiotherapeutic, recent clinical trials have shown the capacity to de-escalate therapy for early-stage breast cancer. These efforts have been driven by the hope that modern therapy will yield better results and the wish to reduce toxicity. Patients with early-stage breast cancer now want to avoid many of the toxicities that have historically come with cytotoxic chemotherapy, in addition to being treated and having their breasts preserved. They also want to prevent lymphedema and needless radiation.

• Trial Assigning Individualized Options for Treatment (TAILORx): This clinical trial uses Oncotype DX assay (a test that shows the possibility of breast cancer spread). The expression of 21 genes is measured by this reverse transcriptase-polymerase chain reaction (RT-PCR) assay using RNA extracted from formalin-fixed, paraffin-embedded tissue samples from primary breast cancer. It assigns treatment for patients that have a low recurrence score (a score that helps to understand the recurrence of node-negative breast cancer) or a high recurrence score. It advises endocrine therapy alone for low-recurrence node-negative breast cancer, while high scores might require chemotherapy along with endocrine therapy. The patients with intermediate scores are randomly allotted either of the treatment modalities.

• Microarray in Node-Negative Disease May Avoid Chemotherapy (MINDACT): This clinical trial is based on the MammaPrint assay. The genome test helps analyze the role of genes in promoting breast cancer. The trial is expected to have at least 6,000 node-negative breast cancer patients, whose risks can be assessed by both traditional methods and novel developing strategies. If the risk is low for both methods, adjuvant chemotherapy is avoided. On the other hand, if the risk is high, adjuvant chemotherapy is mandated.

Conclusion

Following the treatment of node-negative breast cancer, a five-year follow-up consisting of outpatient visits every year should be continued mandatorily. This should include a physical examination of the axilla and a full-field digital mammography (FFDM). Patients older than 60 should undergo FFDM once every two years after five years of follow-up. Younger patients can have it done annually. Any additional diagnostic tests should be done as indicated by the healthcare providers. A clinical suspicion of axillary metastasis (the spread of cancer to the lymph nodes in the underarm) can be confirmed by an axillary ultrasound scan. The questionnaires by the European Organization for the Research and Treatment of Cancer (EORTC QLQ-C30 and QLQ-BR 23) will help to assess the quality of life of the patient.