Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer (BC) characterized by rapid tumor growth, early metastasis to distant organs, and a high likelihood of recurrence.

TNBC has a “triple-negative” phenotype. This means that its cancer cells lack specific hormone receptors for estrogen and progesterone and have little to no HER2 (human epidermal growth factor receptor 2). Information about the presence or absence of these receptors is crucial for selecting effective anti-cancer therapy, as TNBC is unresponsive to hormone and targeted therapies used for other BC subtypes.

Prevalence

Breast cancer ranks first among all cancers in women worldwide, affecting over 2 million people. Of these, 15–20% are TNBC cases, predominantly occurring in young women under 40 of African and Latin American descent, as well as carriers of the BRCA genetic mutation.

Risk Factors

Numerous risk factors contribute to TNBC development, categorized into groups:

• Genetic factors: Breast cancer in first-degree relatives (mother or sister); carrying BRCA1, BRCA2, CHEK2 mutations, or other gene mutations such as p53, ATM, NBS1, LKB1; inherited cancer-related dermatoses like Bloom syndrome and Cowden syndrome.
• Reproductive factors: Early menstruation (menarche); late menopause; underutilized or unrealized reproductive potential (e.g., infertility, late age at first full-term pregnancy, many pregnancies not resulting in childbirth), including lack of breastfeeding.
• Hormonal and metabolic factors: High levels of estrogen and prolactin; low thyroid hormone levels; benign hormonal overgrowth of breast gland tissue; obesity; gynecological and metabolic conditions such as diabetes or atherosclerosis.

Genetic mutations, whether inherited or caused by various factors, decrease cell resilience, disrupt their structure, and lead to the formation of malignant cells.

If you notice similar symptoms, consult a doctor. Avoid self-medication—it can be harmful to your health.

Symptoms

Symptoms depend on the disease stage and may vary slightly among patients. Here are the common signs you can think about.

In the early stages, TNBC may cause little discomfort or manifest as mild breast pain. Over time, a lump may develop, which can sometimes be self-detected. Not all TNBC patients can feel the tumor, but they may experience worsening general health, neurological issues, skin yellowing, pathological bone fractures, breathing difficulty, or coughing.

If these symptoms arise, seek medical advice and evaluation promptly, as early detection and treatment greatly improve the chances of recovery.

Pathogenesis

Breast structure

Each breast consists of 15–20 cone-shaped lobes converging toward the nipple. Lobes are surrounded by loose connective and fatty tissue, and each is formed from glandular tissue with a milk duct. The ducts enlarge near the nipple and open into milk sinuses on the nipple’s tip, which is encircled by pigmented skin (areola).

Breast structure changes with age and physiological conditions, such as pregnancy and lactation.

TNBC development mechanism

Breast tumors are classified into lobular and ductal types based on morphology. Trigger factors transform epithelial breast cells into malignant stem cells, which then form tumors.

TNBC is a distinct BC subtype with unclear pathogenesis. Studies suggest it involves gene expression disruptions (conversion of genetic information into proteins) and functional alterations. Mutations in BRCA1 and BRCA2, tumor-suppressor genes, are particularly linked to TNBC. These mutations hinder tumor suppression, increasing cancer development and recurrence risk.

While TNBC pathogenesis requires further research, current findings help identify its unique characteristics and guide treatment and prevention strategies.

Classification

Classification by Morphological Structure:

1. Basal-like type 1 and 2
2. Immunomodulatory
3. Mesenchymal
4. Mesenchymal-like
5. Androgen receptor-positive ductal type

The basal-like type accounts for 70% of TNBC cases and 8–20% of all BC cases, mostly affecting young women. It is characterized by high proliferation rates (rapid tumor growth) and aggressive progression with early metastasis.

Other TNBC types are primarily of scientific interest without notable distinctions.

Stages

Despite TNBC heterogeneity, treatment principles depend only on the stage, determined by tumor size and spread (regional lymph nodes or distant organs):

• Stage 0 (in situ): Cancer cells are confined to breast ducts without invading surrounding tissue. Usually symptom-free, detected via mammography or ultrasound.
• Stage 1: Cancer spreads beyond ducts into nearby tissue, forming a lump ≤2 cm with no lymph node involvement. Detected through imaging or self-exam.
• Stage 2: Tumor grows to 2–5 cm, possibly affecting regional lymph nodes. Women may notice breast lumps or enlarged lymph nodes under the arm.
• Stage 3: Metastasis involves lymph nodes under the arm, near the sternum, or above/below the collarbone. Symptoms include breast pain and shape or size changes.
• Stage 4: Cancer metastasizes to distant organs (e.g., liver, lungs, bones). Symptoms range from general deterioration and weight loss to organ-specific signs like jaundice or vomiting (liver involvement).

Staging requires additional tests, including biopsies, lymph node assessment, and imaging such as chest X-rays, CT scans, or abdominal and pelvic MRI/ultrasound.

Complications

The most serious complication is rapid metastasis to other body parts, including the lungs, liver, brain, or bones. As triple-negative breast cancer (TNBC) resists hormone and HER2-targeted therapies, it has a higher metastatic potential. Untreated cases often involve organ damage and debilitating symptoms.

• Liver metastasis: ellowing skin, vomiting, appetite loss, abdominal swelling (ascites).
• Lung metastasis: Shortness of breath, chest pain, coughing, and bloody sputum.
• Bone metastasis: Sudden fractures, local pain, and sensory issues from nerve compression.
• Brain metastasis: Headaches, dizziness, vision problems, memory and speech loss, or coordination impairment.

TNBC patients also face psychological challenges, including stress, anxiety, and depression, necessitating continuous emotional support.

Diagnosis

Diagnosis involves identifying the disease and staging it. Early detection significantly improves outcomes.

Initial visits include symptom reviews, family cancer history, and reproductive health assessments.

At the initial appointment, the doctor will definitely ask about complaints and previous symptoms, clarify whether any close blood relatives had cancer, gather an obstetric and gynecological history (information about menstruation, sexual activity, gynecological diseases, pregnancies, and childbirth), and examine the breasts.

Patients with triple-negative breast cancer (TNBC) often have specific characteristics, such as younger age, African or Latin American ancestry, and a family history of cancer.

The goal at this stage is to identify patients with a high risk of developing cancer and detect early symptoms that may indicate the presence of a malignant breast tumor. Based on the symptoms and anatomical and physiological features, the doctor will refer the patient for further testing.

To detect a lesion or suspicious area in the breast, a comprehensive approach involving various types of studies is required.

Mammographic examination

This is the most informative method for diagnosing breast oncopathology, based on X-ray imaging. Mammography allows the detection of tumors as well as microcalcifications, which can serve as markers of a malignant process, enabling timely treatment.

Mammography is recommended for women over 40 years of age because, from this age, glandular breast tissue begins to be replaced by fat. X-rays penetrate fat tissue more effectively.

Ultrasound of the mammary glands

Since triple-negative breast cancer (TNBC) most often develops in patients under 40 years of age, cancer diagnostics should include other methods. Breast ultrasound allows the detection of masses and suspicious structures in cases with a high gland-to-fat tissue ratio. However, identifying microcalcifications using this method is challenging.

Depending on the clinical case, the oncologist may also prescribe:

• Tomosynthesis: An X-ray examination in which a series of images (30 to 80) are taken through the entire thickness of the breast at steps of 1 to 5 mm.
• Breast MRI: This can be performed if the patient has breast implants or if mammography or tomosynthesis cannot be done.

Biopsy

The diagnostic methods mentioned above only allow suspicion of a malignant tumor process. To confirm the diagnosis of “breast cancer,” a puncture biopsy must be performed, i.e., a tissue sample from the tumor is taken and sent for histological examination.

Immunohistochemical study

If breast cancer is confirmed, the tumor tissue samples are sent for immunohistochemical analysis to determine whether the tumor cells have estrogen, progesterone, and HER-2 receptors. If all three types of receptors are absent, it is triple-negative breast cancer (TNBC).

When a malignant lesion is confirmed, further tests are conducted to determine whether the cancer has spread to other organs.

An oncologist may prescribe:

• General Chest X-ray or Contrast-Enhanced CT
• CT or Ultrasound of the Abdominal and Pelvic Organs
• Bone Scintigraphy: Used to examine the skeleton for metastases, especially in cases of elevated alkaline phosphatase levels or locally advanced breast cancer.
• Contrast-Enhanced Brain MRI: Recommended if there are signs of brain metastases.

Treatment

The treatment of TNBC is a complex and multifaceted process requiring an integrated approach and collaboration among medical specialists from various fields. Treatment methods for this aggressive form of cancer include surgery, neoadjuvant (pre-surgical) and adjuvant (post-surgical) chemotherapy, as well as immunotherapy. However, triple-negative breast cancer differs from other breast cancer forms in that it does not respond to hormone or targeted therapies, making it more challenging to treat.

The method and scope of treatment directly depend on the stage:

• Early Stages: When the tumor is small, and there are no distant metastases, surgical treatment is performed. Surgery aims to remove the tumor from the breast and surrounding tissues. Radical resection, removing part of the breast with the tumor, is often recommended.
• Advanced Stages: For larger tumors, radical mastectomy is performed, removing the entire breast and axillary lymph nodes. This reduces recurrence risks and improves the prognosis.

To shrink the tumor before surgery, neoadjuvant chemotherapy is used alongside surgery. This reduces the spread of the cancer process, enhances surgery effectiveness, and helps evaluate tumor sensitivity to treatment, aiding post-surgical drug therapy selection.

However, neoadjuvant chemotherapy is not always effective for triple-negative breast cancer (TNBC), leading to increased adoption of advanced treatment methods like immunotherapy. Immunotherapy aims to strengthen the patient’s immune system to combat cancer cells effectively. This is achieved through medications that activate immune cells and stimulate their fight against malignant tumors.

Overall, each TNBC treatment method has its specific features and advantages, but their combined application achieves the best outcomes. Patients’ adherence to recommendations is equally crucial in combating breast cancer.

Rehabilitation after mastectomy

From the first days after surgery, women are encouraged to perform special exercises regularly. The recovery period lasts at least four weeks, but even after this, heavy lifting (more than 2.5–5 kg) on the operated side should be avoided for a prolonged period. This reduces the risk of post-mastectomy syndrome (arm pain and swelling), which can occur due to disrupted lymphatic flow after lymph node removal.

Breast reconstruction

It is possible to insert implants in place of the removed breast tissue. This restores breast shape and volume and helps alleviate psychological discomfort that may arise after organ removal. Such reconstructive surgery can be performed immediately after mastectomy or a year after treatment completion, depending on the treatment scope and disease course.

Prognosis

TNBC tends to progress rapidly, complicating its treatment and prognosis. The survival prognosis for TNBC patients is generally less favorable than for other breast cancer types.

Patient survival primarily depends on early detection and effective treatment. If detected early and fully treated, the five-year survival rate for Triple-negative breast cancer is about 70%, meaning 70 out of 100 patients will survive five years after diagnosis. However, individual prognoses vary based on factors like age, disease stage, and other conditions.

Despite significant advancements, TNBC treatment remains challenging. A deeper understanding of TNBC biology and new treatment methods are key research priorities.

Prevention

The main preventive measures include regular screenings (breast ultrasound for young women, mammography, and ultrasound after age 40), mammologist examinations, and breast self-examinations. These help detect tumors early and start treatment, increasing recovery chances.

An additional prevention strategy is lifestyle modification, including healthy eating, increased physical activity, and avoiding smoking and alcohol.

Prevention and treatment plans should be tailored individually in collaboration with a doctor, who can consider the patient’s unique characteristics and disease specifics.

In conclusion, the prognosis and prevention of TNBC pose significant medical challenges requiring a systematic approach. It is essential for governments and the medical community to disseminate information about prevention methods. At the same time, individuals must understand their responsibility for their health. Only through joint efforts by patients, doctors, and the state can significant progress be made in the fight against breast cancer.