Triple Negative Breast Cancer

Triple Negative Breast Cancer is especially significant because the absence of these three receptors means that it doesn’t respond to some of the most common breast cancer treatments. In simpler terms, the treatments that target these receptors won’t work for TNBC patients.

Triple Negative Breast Cancer (TNBC) is a type of breast cancer that is described by what it doesn’t have, rather than what it does. To break it down, TNBC does not have three specific receptors that are commonly found in other types of breast cancer. Let’s understand these three receptors:

  1. Estrogen Receptor (ER): Many breast cancers grow in response to the hormone estrogen. TNBC doesn’t have this receptor.
  2. Progesterone Receptor (PR): Some breast cancers are sensitive to the hormone progesterone. TNBC lacks this receptor too.
  3. HER2/neu Receptor: HER2 is a protein that can promote the growth of cancer cells. Again, in TNBC, this receptor isn’t present.

Types of Triple Negative Breast Cancer

Though TNBC is one category, it’s not uniform. Different subtypes exist:

  1. Basal-like 1 (BL1): Tends to have a higher rate of cell division. Might respond better to chemotherapy.
  2. Basal-like 2 (BL2): Has traits in common with BL1 but with some differences in the cell’s inner machinery.
  3. Immunomodulatory (IM): Contains immune cells. There’s potential for treatments that boost the body’s immunity against cancer.
  4. Mesenchymal (M): These cancer cells are more flexible and can move around easily.
  5. Mesenchymal stem-like (MSL): Similar to M but with fewer immune cells.
  6. Luminal androgen receptor (LAR): Uses male hormones (androgens) for growth. Might be treated with anti-androgen drugs.
  7. Unstable: Has a lot of genetic mistakes and isn’t easily categorized.

Types of Triple Negative Breast Cancer:

  1. Basal-Like TNBC: Basal-like TNBC is the most common subtype. It gets its name because its characteristics are similar to those of basal cells in the breast. This type tends to grow and spread quickly. It often affects younger women and African-American women. Basal-like TNBC has a high grade, which means the cancer cells look very different from normal cells under a microscope.
  2. Immunomodulatory TNBC: Immunomodulatory TNBC is characterized by its interaction with the immune system. This type has a higher presence of immune cells within the tumor. Researchers believe that this subtype might respond better to certain immunotherapy treatments.
  3. Mesenchymal TNBC: Mesenchymal TNBC is a subtype that’s more likely to have spread to other parts of the body at the time of diagnosis. This type is associated with a process called epithelial-to-mesenchymal transition (EMT), where cancer cells take on properties that enable them to move more easily. This movement makes the cancer more aggressive and harder to treat.
  4. LAR (Luminal Androgen Receptor) TNBC: LAR TNBC is influenced by hormones, specifically androgen receptors. While it’s still considered triple negative, it has receptors for androgens, which are typically considered male hormones. This subtype is less aggressive than others and might respond to hormonal therapies.
  5. BRCA1 Mutation-Associated TNBC: Some cases of TNBC are linked to mutations in the BRCA1 gene. This gene is responsible for repairing damaged DNA. Women with BRCA1 mutations have a higher risk of developing TNBC, and these cases often have a better response to certain treatments, like PARP inhibitors.

Causes

While the exact cause of TNBC isn’t fully understood, several factors have been identified that could contribute to its development, we’ll break down these potential causes in simple terms, making it easier for everyone to understand.

1. Genetic Mutations: Genes can sometimes mutate, leading to abnormal cell growth. Mutations in genes like BRCA1, BRCA2, and TP53 are associated with higher TNBC risk.

2. Hormonal Factors: Hormones like estrogen and progesterone play a role in breast cancer. TNBC doesn’t respond to these hormones, but their presence can still influence cancer development.

3. Age: As age increases, the risk of developing TNBC also rises. This is why regular screenings are important, especially for older women.

4. Family History: A family history of breast cancer, particularly TNBC, can increase the likelihood of developing the disease.

5. Race and Ethnicity: Certain racial and ethnic groups have a higher TNBC risk. African American and Hispanic women are more susceptible.

6. Radiation Exposure: Previous exposure to radiation, especially at a young age, can increase the chances of TNBC later in life.

7. Obesity: Carrying excess weight can disrupt hormonal balance and promote inflammation, potentially contributing to TNBC.

8. Reproductive History: Starting menstruation early, having late menopause, or not having children can influence TNBC risk.

9. Alcohol Consumption: Regular alcohol consumption is linked to an increased risk of TNBC.

10. Environmental Factors: Exposure to certain environmental toxins and pollutants might play a role in TNBC development.

11. Lack of Physical Activity: A sedentary lifestyle can contribute to obesity and hormonal imbalances, potentially raising TNBC risk.

12. High Sugar Diets: Diets high in sugar and refined carbohydrates may promote inflammation and cancer growth.

13. Lack of Breastfeeding: Breastfeeding can reduce the risk of various types of breast cancer, including TNBC.

14. Hormone Replacement Therapy: Certain hormone therapies used during menopause may increase TNBC risk.

15. Inherited Mutations: Inherited gene mutations, not just BRCA mutations, can increase TNBC susceptibility.

16. Inflammation: Chronic inflammation in breast tissue might contribute to cancer development.

17. Chemical Exposures: Exposure to certain chemicals found in plastics, cosmetics, and pesticides may raise TNBC risk.

18. Diabetes: Uncontrolled diabetes could potentially influence TNBC development.

19. Sleep Patterns: Disrupted sleep patterns or lack of quality sleep may impact the immune system’s ability to prevent cancer.

20. Stress: Chronic stress can weaken the immune system and potentially contribute to cancer growth.

21. Viral Infections: Some viral infections, like the human papillomavirus (HPV), might be linked to TNBC.

22. Autoimmune Diseases: Certain autoimmune conditions could increase the risk of TNBC.

23. Lack of Sunlight Exposure: Low levels of vitamin D due to limited sunlight exposure may play a role in cancer development.

24. Air Pollution: Living in areas with high air pollution might be associated with increased TNBC risk.

25. Hormonal Disruptors: Chemicals that mimic hormones (endocrine disruptors) could potentially affect TNBC development.

26. Unhealthy Fats: Diets high in unhealthy fats might contribute to inflammation and cancer growth.

27. Socioeconomic Status: Limited access to healthcare and resources could impact early detection and treatment.

28. Chemical Industry Occupations: Certain jobs with chemical exposure could raise the risk of TNBC.

29. Lack of Screening: Not undergoing regular breast cancer screenings can lead to late-stage diagnosis.

30. Personal History of Cancer: Having a history of other cancers might increase TNBC susceptibility.

Symptoms

Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer that doesn’t have the three common receptors: estrogen, progesterone, and HER2/neu. Understanding its symptoms is crucial for early detection and treatment.

1. Lump in the breast: The most common sign. If you feel a hard knot or thickening in your breast or underarm, it’s essential to see a doctor.

2. Change in breast size or shape: Any unexplained change can be a signal. It’s different from the normal size fluctuation many women experience during their menstrual cycle.

3. Breast pain: Not all breast pain is cancer-related, but if it’s persistent or unusual, it’s worth checking.

4. Skin dimpling: Imagine an orange peel’s texture. If your breast looks like that, it’s a cause for concern.

5. Redness or darkening: If your breast becomes red or darker and it’s not due to an injury, it’s essential to consult with a medical professional.

6. Nipple discharge: Any unexpected liquid (that’s not breast milk) coming out of the nipple might be a sign.

7. Nipple retraction: If your nipple suddenly starts to pull inwards, it could be due to an underlying issue.

8. Scaly skin around the nipple: A rough, flaky patch of skin here could be more than just dry skin.

9. Itchy breasts: Persistent itching that doesn’t go away with regular moisturizing should be noted.

10. Swollen lymph nodes: Found in your armpits or neck, these can swell if your body is fighting an illness – or due to cancer.

11. Unexplained weight loss: Losing weight without trying can sometimes signal a medical issue, including cancer.

12. Fatigue: Feeling constantly tired, even with plenty of sleep, can be associated with many conditions, including TNBC.

13. Bone pain: An aching sensation in your bones that doesn’t result from a known injury should be addressed.

14. Shortness of breath: Finding it hard to breathe, even after light activity, isn’t normal.

15. Persistent cough: A cough that doesn’t go away might be more than just a cold.

16. Headaches: Constant or very intense headaches can be concerning, especially if they’re unusual for you.

17. Double vision or blurry vision: If your sight changes suddenly or without explanation, consult a doctor.

18. Loss of appetite: Suddenly not feeling hungry or being put off by foods you loved can indicate a health issue.

19. Abdominal pain: Pain or discomfort in the stomach area that persists could be a sign.

20. Jaundice: Yellowing of the skin or eyes suggests liver problems, which can sometimes be related to advanced breast cancer.

21. Swelling or fluid build-up: Unexpected swelling in the body, especially around the abdomen, can be concerning.

22. Difficulty walking or balancing: If you’re struggling with balance or walking without a clear reason, it might be a symptom of something serious.

Diagnosis

Diagnosis and Testing for Triple Negative Breast Cancer: A Simplified Guide

  1. Clinical Examination: Your doctor will begin by conducting a thorough physical examination to check for any lumps, changes in breast size, or skin abnormalities.
  2. Mammogram: This is an X-ray of the breast tissue. It helps identify any unusual masses or changes that might indicate cancer.
  3. Ultrasound: Using sound waves, an ultrasound creates images of the breast tissue. It can help differentiate between solid masses and fluid-filled cysts.
  4. Biopsy: If an abnormality is detected, a biopsy is performed. This involves removing a small sample of tissue for further testing.
  5. Fine Needle Aspiration (FNA): A thin needle is used to extract a sample of cells from the lump. These cells are then examined under a microscope.
  6. Core Needle Biopsy: A larger needle is used to remove a small core of tissue from the suspicious area. This provides a more comprehensive sample for testing.
  7. Surgical Biopsy: In some cases, a surgical procedure is needed to remove a larger portion of the tumor or the entire lump.
  8. Imaging Tests: If cancer is confirmed, imaging tests such as CT scans, MRI scans, and PET scans may be performed to determine the extent of the cancer’s spread.
  9. Estrogen Receptor Test: This test checks whether the cancer cells have estrogen receptors. In TNBC, these receptors are absent.
  10. Progesterone Receptor Test: Similar to the estrogen receptor test, this determines the presence of progesterone receptors in the cancer cells.
  11. HER2/neu Test: HER2/neu is a protein that promotes the growth of cancer cells. This test checks if it’s present in the cancer cells.
  12. Ki-67 Test: This test measures how quickly cancer cells are dividing. A higher Ki-67 percentage might indicate a more aggressive cancer.
  13. BRCA Gene Testing: Genetic testing to check for mutations in the BRCA1 and BRCA2 genes, which are linked to a higher risk of breast cancer.
  14. TNM Staging System: This system categorizes the cancer’s size, lymph node involvement, and whether it has spread to other parts of the body.
  15. Lymph Node Biopsy: To determine if cancer has spread to the lymph nodes, a sample of lymph nodes may be removed and examined.
  16. Circulating Tumor Cell Test: This test detects cancer cells in the blood, helping to monitor the effectiveness of treatment.
  17. Gene Expression Profiling: Tests like Oncotype DX and Mammaprint analyze the activity of certain genes to predict the likelihood of cancer recurrence.
  18. CTC Enumeration: Counting the number of circulating tumor cells in the blood can provide insight into the cancer’s aggressiveness.
  19. Sentinel Node Biopsy: Involves injecting a dye near the tumor to identify the first lymph node the cancer is likely to spread to.
  20. MRI-Guided Biopsy: If MRI scans show suspicious areas, this technique allows for precise biopsy guidance.
  21. PET-CT Scan: A combined PET and CT scan helps visualize areas with high metabolic activity, indicating possible cancer spread.
  22. Bone Scan: To check if cancer has spread to the bones, a small amount of radioactive substance is injected, and a scan is performed.
  23. Liver Function Tests: These blood tests help assess the health of the liver, which is a common site for cancer spread.
  24. Chest X-ray: This can help determine if cancer has spread to the lungs.
  25. Breast MRI: Provides detailed images of the breast tissue and helps identify any additional tumors.
  26. Tumor Marker Tests: Blood tests that measure certain proteins associated with cancer, such as CA 15-3 and CA 27-29.
  27. Lung Function Tests: Assess lung health and capacity, important if cancer might have spread to the lungs.
  28. Abdominal Ultrasound: To check for cancer spread to the liver or other abdominal organs.
  29. Bone Marrow Biopsy: Rarely, a bone marrow biopsy might be done to check for cancer involvement.
  30. Complete Blood Count (CBC): This blood test checks for abnormalities in the blood, which might indicate cancer-related issues.

Treatment

This aggressive form lacks the three common receptors targeted by many breast cancer treatments, making it more challenging to treat. However, medical science has made significant strides in developing effective treatments for TNBC. In this guide, we’ll break down treatments for Triple Negative Breast Cancer in simple terms, ensuring you understand your options clearly.

1. Surgery: Surgery involves removing the tumor and nearby tissues. A lumpectomy removes only the tumor, while mastectomy removes the entire breast. Lymph node removal may also be necessary.

2. Chemotherapy: Chemotherapy uses strong medications to destroy cancer cells. It’s often given before surgery to shrink tumors or after to eliminate remaining cancer cells.

3. Radiation Therapy: Radiation therapy targets cancer cells with high-energy rays to prevent them from growing or spreading. It’s typically used after surgery.

4. Targeted Therapy: Targeted therapy focuses on specific molecules involved in cancer growth. In TNBC, PARP inhibitors are used to disrupt cancer cells’ ability to repair themselves.

5. Immunotherapy: Immunotherapy boosts the body’s immune system to fight cancer cells. Checkpoint inhibitors like Pembrolizumab are used to block proteins that prevent immune cells from attacking cancer.

6. Neoadjuvant Therapy: Given before surgery, neoadjuvant therapy shrinks tumors, increasing the chance of successful surgery.

7. Adjuvant Therapy: Adjuvant therapy follows surgery to kill any remaining cancer cells. It can include chemotherapy, targeted therapy, or radiation.

8. Anthracycline Chemotherapy: A potent type of chemotherapy, anthracyclines damage cancer cells’ DNA, hindering their ability to multiply.

9. Taxane Chemotherapy: Taxanes disrupt cell division, preventing cancer cells from growing. Paclitaxel and Docetaxel are common examples.

10. Platinum-Based Chemotherapy: Platinum-based drugs like Carboplatin interfere with cancer cell DNA, impeding their replication.

11. HER2-Targeted Therapy: If TNBC is HER2-positive, drugs like Trastuzumab can be used to target HER2 proteins on cancer cells.

12. Angiogenesis Inhibitors: These medications block the formation of new blood vessels that supply tumors, starving them of nutrients.

13. Clinical Trials: Participating in clinical trials gives access to cutting-edge treatments being tested for TNBC.

14. PARP Inhibitors: PARP inhibitors target DNA repair processes, making it difficult for cancer cells to survive.

15. COX-2 Inhibitors: These drugs can potentially slow down cancer cell growth by inhibiting COX-2 enzymes.

16. MEK Inhibitors: MEK inhibitors disrupt cancer cell signaling, slowing down their growth.

17. PI3K Inhibitors: These inhibitors target a protein pathway that promotes cancer cell growth.

18. HDAC Inhibitors: HDAC inhibitors affect how genes are expressed in cancer cells, slowing their growth.

19. mTOR Inhibitors: mTOR inhibitors block a protein that helps cancer cells grow and divide.

20. Aromatase Inhibitors: In postmenopausal women with TNBC, aromatase inhibitors can be used to lower estrogen levels that fuel some tumors.

21. Stereotactic Radiosurgery: This focused radiation technique delivers high doses of radiation to small areas with precision.

22. Cryoablation: Cryoablation uses extreme cold to freeze and destroy cancer cells.

23. Nanoparticle-Based Therapies: Tiny particles deliver drugs directly to cancer cells, minimizing damage to healthy tissue.

24. Liposomal Delivery: Liposomes carry drugs to cancer cells, improving drug effectiveness and reducing side effects.

25. Gene Expression Profiling: This helps tailor treatment plans by analyzing how genes are active in a tumor.

26. Personalized Vaccines: Vaccines are created from a patient’s tumor to stimulate the immune system against cancer cells.

27. Stem Cell Transplant: High-dose chemotherapy is followed by a stem cell transplant to restore bone marrow.

28. Hormone Therapy: In rare cases, hormone therapy may be used to block estrogen receptors if present.

29. Tumor-Infiltrating Lymphocytes (TILs): TILs are immune cells harvested, multiplied, and re-infused to target cancer cells.

30. Supportive Care: Managing side effects and emotional well-being is crucial. Supportive care includes pain management, counseling, and nutrition guidance.

Medications

Drugs that have been used in its treatment. For anyone seeking this information, it’s essential to understand that choosing the right treatment should always be done under the guidance of a medical professional.

1. Chemotherapy: What is it?
Chemotherapy uses drugs to kill or slow down the growth of cancer cells.
Examples:
a. Doxorubicin
b. Cyclophosphamide
c. Taxanes (like Paclitaxel and Docetaxel)
d. Carboplatin
e. Gemcitabine

2. PARP Inhibitors: What are they?
PARP inhibitors target specific weaknesses in cancer cells, especially in patients with BRCA mutations.
Example:
a. Olaparib
b. Talazoparib

3. Immunotherapy: What is it?
Immunotherapy boosts the body’s immune system to help it fight cancer.
Examples:
a. Atezolizumab
b. Pembrolizumab

4. Antibody-drug conjugates: What are they?
These are drugs that combine an antibody with a chemotherapy drug, ensuring chemotherapy targets cancer cells more precisely.
Example:
a. Sacituzumab govitecan

5. EGFR inhibitors:
What are they?
These inhibit the Epidermal Growth Factor Receptor, which some TNBC cells have in excess.
Example:
a. Cetuximab

6. Androgen Receptor Drugs:
What are they?
Some TNBCs have androgen receptors, and these drugs stop them from helping the cancer grow.
Example:
a. Enzalutamide
b. Bicalutamide

7. Checkpoint Inhibitors:
What are they?
These boost the immune system by blocking proteins that stop the immune system from attacking cancer cells.
Example:
a. Nivolumab

8. mTOR Inhibitors:
What are they?
These target the mTOR protein which can affect cancer cell growth and survival.
Example:
a. Everolimus

9. AKT Inhibitors:
What are they?
They target the AKT protein, stopping cancer cells from growing.
Example:
a. Capivasertib

10. Platinum agents:
What are they?
These are chemotherapy drugs that have shown promise against TNBC.
Example:
a. Cisplatin

According to receptors

8. VEGF Inhibitors (Bevacizumab): These drugs cut off the blood supply to tumors, hindering their growth.

9. EGFR Inhibitors (Cetuximab): EGFR inhibitors block signals that stimulate cancer cell growth.

10. mTOR Inhibitors (Everolimus): mTOR inhibitors interfere with cancer cell growth signals.

11. CDK4/6 Inhibitors (Palbociclib, Ribociclib): These drugs slow down cell division, delaying cancer progression.

12. Androgen Receptor Blockers (Enzalutamide): Used if TNBC tests positive for androgen receptors, these drugs block their activity.

13. PI3K Inhibitors (Alpelisib): PI3K inhibitors disrupt signals that drive cancer growth.

14. HER2-Targeted Therapy (Ado-Trastuzumab Emtansine): If TNBC overexpresses HER2, this drug targets it to stop cancer growth.

15. Checkpoint Inhibitors (Atezolizumab): These drugs release the brakes on the immune system, allowing it to attack cancer cells.

16. Liposomal Anthracyclines (Nanoliposomal Doxorubicin): Similar to regular anthracyclines, but with reduced side effects.

17. HDAC Inhibitors (Entinostat): HDAC inhibitors modify gene activity, slowing cancer cell growth.

18. Antibody-Drug Conjugates (Trastuzumab Deruxtecan): These combine targeted antibodies with chemotherapy, delivering treatment directly to cancer cells.

19. BCL-2 Inhibitors (Venetoclax): BCL-2 inhibitors promote cancer cell death by targeting a specific protein.

20. Src Inhibitors (Dasatinib): Src inhibitors interfere with signals that promote cancer growth.

Conclusion:

Facing Triple Negative Breast Cancer can be overwhelming, but there are numerous treatment options available. From surgery and chemotherapy to targeted therapies and immunotherapy, medical science continues to evolve, offering hope for patients. Understanding these 30 treatments empowers you to make informed decisions about your journey toward recovery. Remember, each individual’s situation is unique, so consulting with healthcare professionals is essential to determine the best treatment plan for you.

References