Triple-Negative Breast Cancer: Understanding Treatment Before and After Surgery

A patient diagnosed with breast cancer can have too many questions, especially when they hear some new terms such as "triple-negative breast cancer" (TNBC). TNBC is a type of breast cancer in which the cancer cells do not have three commonly tested treatment targets: estrogen receptors (ER), progesterone receptors (PR), or levels of the HER2 protein. These markers matter because they help doctors choose the treatments most likely to work.

For many people with early-stage TNBC, their treatment may start before surgery, called neoadjuvant therapy, and may help shrink the tumour and give important information about how the cancer responds to treatment. The results of the pathology after surgery can help the health care team determine if more treatment is needed to reduce the risk of cancer returning.

So, in this blog, we will go through the treatment for triple-negative breast cancer and what the treatments actually involve before and after surgery. Understanding the diagnosis, stage, treatment sequence, and role of surgery can help patients and their families better understand cancer care.

What is Triple Negative Breast Cancer (TNBC)?

Triple-negative breast cancer is a type of invasive breast cancer that is characterised by the absence of all three receptors:

Estrogen receptor (ER)
Progesterone receptor (PR)
Human epidermal growth factor receptor 2 (HER2)

In triple-negative breast cancer, all three markers test negative. TNBC is commonly seen in young African American women and Hispanic women who carry a mutation in the BRCA1 gene, or in women who have not gone through menopause. TNBC presents a unique molecular profile, aggressive behavior, different metastatic patterns, and a lack of targeted therapies. TNBC accounts for ~10-20% of invasive breast cancers, with an estimated burden of approximately 170,000 cases worldwide.

What Are the Signs and Symptoms of TNBC?

TNBC symptoms include:

A lump or mass in your breast
Pain in the breast or nipple
Nipple discharge
Nipple retraction (A nipple turning inward)
Dry, flaking, thickened, or red skin of the breast
Swelling of the Breast
Swollen lymph nodes under the arm

Most breast cancers can be detected through regular breast screening, such as mammography, before a woman shows any visible symptoms. Triple-negative breast cancer can occur in younger women (less than 40 years old) before they reach screening age. This highlights the importance of regular breast examination by women of any age, so they can identify any changes, such as a hard lump.

How is Triple-negative Breast Cancer Diagnosed?

Diagnostic Tests

The healthcare provider will consider the above-described symptoms with some diagnostic techniques such as

Imaging tests: depending on the individual condition, the doctor may recommend imaging tests like mammography or breast MRI
Breast biopsy: Confirmation starts with breast biopsy results. It is a procedure where a sample of breast tissue is taken for testing. Your care team will send the tissue to the laboratory to analyse the cell type, cancer cell grade, and whether the cancer cells have hormone receptors (estrogen receptors, progesterone receptor, and human epidermal growth factor receptor 2 (HER2)).

The cells that lack all three receptors can be classified as triple-negative breast cancer. Also

Gene expression profiles can further classify tumors by molecular subtype, such as basal-like, or by specific mutations in genetic susceptibility genes such as BRCA1 or BRCA2.

Understanding Stages of TNBC

The stage of breast cancer describes the extent of the cancer and whether it has spread beyond the breast. Staging considers the size and extent of the primary tumour (T), involvement of nearby lymph nodes (N), and whether the cancer has spread to distant parts of the body (M). Breast cancer staging may also consider tumour grade and biomarkers such as ER, PR, and HER2.

Stage I: The cancer is relatively small and is limited to the breast or may involve a small number of nearby lymph nodes, depending on the specific TNM findings.
Stage II: The cancer may be larger and/or may have spread to certain nearby lymph nodes, depending on the tumour and lymph-node characteristics.
Stage III: The cancer is locally advanced and may involve nearby tissues, the chest wall, skin, or more extensive regional lymph nodes, but it has not spread to distant organs.
Stage IV: The cancer has spread from the breast to distant organs or tissues, such as the bones, liver, lungs, or brain.

For TNBC, the treatment approach depends on the stage, tumour characteristics, lymph-node involvement, overall health, and other factors. Stage IV TNBC is generally managed differently from early-stage or locally advanced TNBC because the cancer has spread to distant parts of the body.

Management and Treatment of TNBC

In some types of breast cancer, chemotherapy is used after surgery and sometimes not at all.

The Therapy Before Surgery:

Shrinking the Tumour: To preserve more natural breast tissue, doctors use therapy to shrink large tumours.
Early Treatment of Small Cancer Cells: This helps target any tiny cancer cells that might have left the breast, lowering the chance of them spreading to other areas.
Instant Monitoring: This acts as an in-body test. The oncology team can monitor whether the tumour is shrinking to confirm whether the chosen medicine is working against your specific cancer cells.

In the case of TNBC triple-negative breast cancer, the vast majority of patients are treated with chemotherapy before surgery. In early-stage TNBC, doctors generally recommend "neoadjuvant therapy."

Chemotherapy: Triple-negative breast cancer usually begins to spread at a microscopic level right from the beginning. This means the cancer must be treated with systemic therapy, a combination of drugs that can be taken orally or through an IV to reach cancer cells in all parts of the body. Chemotherapy uses medicines that destroy or slow cancer cell growth. The exact combination and number of treatment cycles depend on the patient's cancer characteristics and treatment plan. Some combinations include taxanes (like paclitaxel), anthracyclines (like doxorubicin), and platinum compounds (like carboplatin).

Immunotherapy: Another systemic therapy used to treat triple-negative breast cancer is immunotherapy, drugs that help your immune system identify and kill cancer cells.For early-stage TNBC, approved immunotherapy may be given with chemotherapy before surgery and then continued after surgery for appropriate patients.

The Major Goal: Pathological Complete Response (pCR)

The main goal in neoadjuvant treatment is to attain a Pathological Complete Response(pCR).

A pCR indicates that after the surgeon removes the remaining breast tissue and lymph nodes, the pathologist observes no active cancer cells remaining under the microscope. Attaining a pCR strongly suggests a favourable long-term prognosis and a reduced risk of cancer returning.

The Surgical Step

After completing neoadjuvant therapy, the doctor will recommend repeating the imaging tests (such as an ultrasound or MRI) to evaluate how much the tumour has shrunk, followed by surgery.

Main surgical options:

Lumpectomy (Breast-Conserving Surgery): The surgeon removes only the lump or tumour site and surrounding tissue, preserving most of the breast.
Mastectomy: The entire breast tissue is removed.

Checking the Lymph Nodes

During surgery, the surgeon checks the adjacent lymph nodes for involvement.

Sentinel Lymph Node Biopsy (SLNB): Removing the first few lymph nodes that drain the breast to check for cancer cells.
Axillary Lymph Node Dissection: Removing additional lymph nodes if cancer was confirmed in multiple nodes prior to or after systemic therapy.

After surgery, the removed tissue goes straight to the pathology lab. Based on the pathology report, the post-surgery treatment plan is advised.

Treatment After Surgery: What Next?

The treatment received after surgery is called adjuvant therapy and aims to eliminate tiny remaining cancer cells and decrease the chance of the cancer coming back.

Continuing immunotherapy

For patients who received neoadjuvant chemotherapy as part of an appropriate treatment plan, it may be continued after surgery.

Radiation therapy

Radiation therapy uses powerful radiation to kill cancer cells that might stay in the treated area. It is often recommended after breast-conserving surgery and sometimes after mastectomy, depending on factors like tumor size, lymph node involvement, and surgical results.

Why Does Treatment Vary for Each Individual with TNBC?

Every person has different physiological conditions, due to which the doctor uses different approaches and different treatment plans to treat patients with triple-negative breast cancer

Some factors considered, such as:

Stage of the cancer
The size and location of the tumour
The grade of the tumour.
BRCA1/BRCA2 or other relevant genetic findings
Overall health of the patient.
Response to neoadjuvant therapy.
Whether cancer remains after surgery
Previous treatment and possible side effects

Managing Life During and After Treatment

Treating TNBC requires adequate time. Healing involves caring for your physical comfort, mental health, and everyday emotional well-being.

Managing Treatment Side Effects: Chemotherapy and immunotherapy often cause some side effects like fatigue, temporary hair loss, nausea, tingling in the fingers and toes, or immune-related inflammation. Tell your care team about any new symptom. Modern supportive medications like anti-nausea medications and gentle therapies for nerve pain can make a real difference in how you feel.
Emotional and Peer Support: Dealing with cancer can be emotionally tough. Support from psycho-oncology counsellors, patient navigators, and TNBC communities can connect you with others who understand what you're experiencing.
Follow-up: After active treatment ends, you'll follow a surveillance schedule. This usually includes clinic visits every few months, regular physical exams, and yearly imaging tests to check your health.

Conclusion

Receiving a diagnosis of triple-negative breast cancer can be daunting, but advancements in medicine have significantly changed the outlook. Modern cancer treatment involves planning therapy before surgery to reduce the tumour and see how it responds to drugs, and after surgery to remove leftover cells and prevent the cancer from returning. This approach uses targeted, effective methods to eliminate the disease.

You don't have to make these decisions by yourself. Talk with your healthcare team, including your cancer doctor, breast surgeon, and radiation doctor, to understand how each part of your treatment fits your health and recovery.

References

Frequently Asked Questions

Not everyone receives the same treatment; management depends on the individual's condition, including the tumor's size, location, and grade. For many people with early-stage TNBC, doctors may recommend chemotherapy before surgery, especially when the tumour is larger or the cancer has a higher risk of spreading.

Early-stage TNBC can be treated with the goal of a cure. However, an individual's condition depends on factors such as the stage, tumour characteristics, treatment response, and overall health. Your oncologist can provide information based on your specific diagnosis.

If surgery reveals no remaining invasive cancer, it is referred to as a pathological complete response. Nonetheless, your doctor will review the complete pathology and treatment history to determine if further treatment is necessary.

Genetic testing might be suggested for certain individuals with TNBC, especially if factors like age, family history, or other clinical traits indicate a potential inherited mutation related to cancer risk. Consult your doctor or a genetic counsellor to determine if testing is suitable for you.

Your next treatment depends on your pre-surgery treatment, surgical outcomes, and pathology results. Additional options may include immunotherapy, chemotherapy, radiation, or other medicines, selected based on individual factors.