HER2-Negative Advanced Breast Cancer

What Is HER2-Negative Advanced Breast Cancer?

HER2, also known as human epidermal growth factor receptor 2, is a protein that is generally present on breast cells, which enables the cells to grow and multiply. Sometimes, these HER2 cells start to grow out of control, which leads to HER2-positive breast cancer.

On the other hand, in some cases, these breast cells with the HER2 protein grow very little or stop completely, resulting in HER2-negative breast cancer. When HER2-negative cancer becomes more serious and has reached the last stage, it is referred to as HER2-negative advanced breast cancer.

What Are the Symptoms of HER-2-Negative Advanced Breast Cancer?

HER2-negative breast cancer shows symptoms similar to other breast cancer types. Some common symptoms are as follows:

• You may have swelling or a lump in the breast.

• Dry, red, or thick skin on the nipple or breast.

• Skin dimpling (like an orange peel).

• Nipple turning inward or unusual discharge.

• You will have pain in the breast or nipple, or you will notice changes in breast size or shape.

• Swelling of lymph nodes under your arm or near the collarbone.

If you have or had any of these symptoms, it does not always mean cancer. Sometimes they are caused by noncancerous conditions or hormonal changes. But still be aware of these symptoms and be proactive.

What Are the Types of HER2-Negative Breast Cancer?

Breast cancers are also grouped by whether they have hormone receptors for estrogen or progesterone. The types are:

• HER2-Negative, Hormone Receptor-Positive: This is the most common type. The cancer cells have receptors for estrogen and/or progesterone, meaning these hormones help the cancer grow. Most cases are estrogen receptor-positive.

• HER2-Negative, Hormone Receptor-Negative: If the cancer does not have HER2, estrogen, or progesterone receptors, it is called triple-negative breast cancer (TNBC). This is less common and is more aggressive.

What Are the Diagnostic Methods for HER2?

The diagnosis is done by reviewing your medical history and your family history.

The doctor will also ask whether you have had any symptoms and will diagnose through a breast biopsy. During the procedure, a small piece of the tumor is removed and sent to a laboratory for testing. If the sample shows cancer cells, a pathologist will check it for the HER2 protein. If the cancer cells have a normal or lower amount of HER2 protein or HER2 genes, it means the cancer is HER2-negative.

Some more laboratory tests, the doctor will advise to confirm the diagnosis are:

1. Immunohistochemistry (IHC) Test: This test uses special dyes to look for the HER2 protein on cancer cells under a microscope. The results are reported as:

1. IHC 0 - HER2-negative.

2. IHC1+ - HER2-negative.

3. IHC 2+ - Borderline or unclear result; other tests, like FISH (fluorescence in situ hybridization), are advised to confirm the diagnosis.

4. IHC 3 + - HER2 -positive.

2. Fluorescence in Situ Hybridization (FISH) Test: It gives a more detailed report, but is more expensive and takes longer. It uses fluorescent (glowing) labels that attach to the HER2 gene in the cancer cells. When viewed under a special microscope, these labels help doctors see whether the HER2 gene is present in high amounts.

What Are the Treatment Options for HER2-Negative Advanced Breast Cancer?

Treatment for HER2-negative advanced breast cancer focuses on symptom management and daily living. It is not curable, but your doctor will use systemic treatments to destroy cancer cells throughout the body. The treatment depends on the cancer stage, extent, and hormone receptors. These include:

1. Surgery: For treating HER2-negative advanced breast cancer, surgery is done to remove the tumor, such as a lumpectomy or, if the cancer has spread, then a mastectomy (removal of the breast) is done. Other therapies for HER2 breast cancer are chemotherapy, radiation, targeted, and hormone therapies might be needed before or after surgery.

2. Chemotherapy: This reduces the risk of cancer recurrence, but its benefits must be balanced against possible side effects, especially in older patients or those with other health issues.

For triple-negative breast cancer, surgery and chemotherapy are the main treatments.

3. Targeted Therapy: It focuses on specific changes in cancer cells. For HER2-negative advanced breast cancer, these include:

• PARP (poly (ADP-ribose) polymerase) inhibitors such as Olaparib and Talazoparib work in cancer with BRCA gene mutations by blocking the PARP protein, stopping cancer cells from repairing themselves.

• Everolimus blocks the mTOR protein, slowing cancer cell growth and stopping new blood vessels from feeding the tumor.

• CDK4/6 (cyclin-dependent kinase 4 and 6) inhibitors slow down cancer growth by blocking certain enzymes.

• Alpelisib works on cancers with PI3KCA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) gene mutations, which are found in about 40 percent of cases, by blocking the PI3K (phosphoinositide 3-kinase) protein.

• Antibody-drug conjugates target the Trop-2 (type I transmembrane glycoprotein) protein, delivering chemotherapy directly to cancer cells while leaving the healthy ones.

4. Hormonal Therapy: It is often the first choice for women with HER2-negative, hormone receptor-positive advanced breast cancer. These cancers depend on estrogen or progesterone to grow. Hormonal treatments work by lowering the body’s estrogen level and blocking hormones from attaching to cancer cells. This helps stop the cancer growth and progression.

5. Immunotherapy: This helps your immune system recognize and attack cancer cells. Some advanced breast cancers are treated with immune checkpoint inhibitors. These are drugs that block certain proteins that the cancer cells use to hide from immune cells. For example, Atezolizumab blocks PD-L1 (programmed death-ligand 1), a protein that prevents immune T cells from attacking cancer. By blocking PD-L1, the immune system finds and destroys cancer cells.

The goal of cancer treatment is to help patients live longer and to manage symptoms and side effects so that they can manage daily activities comfortably.

Can HER2-Negative Advanced Breast Cancer Be Cured Completely?

Unfortunately, advanced HER2-negative breast cancer cannot be cured completely. The available treatments focus on removing tumors and controlling the disease to improve life quality. Many patients with breast cancer have a good life expectancy while managing it with ongoing treatments. In rare cases, the cancer may go into long-term remission, but there is always a chance it could recur. Even after successful tumor removal, side effects and recurrence risks remain.

What Is the Prognosis for HER2-Negative Advanced Breast Cancer?

The prognosis for HER2-negative breast cancer depends on when the cancer is detected and whether it has hormone receptors. For HER2-negative breast cancer that is limited to the breast, the five-year survival rate is similar to that of someone without cancer, especially if it is hormone receptor-positive.

However, triple-negative breast cancer, which lacks HER2 and hormone receptors, is often more aggressive and harder to treat.

According to the National Cancer Institute, the five-year relative survival rates are approximately:

Hr-Positive or HER2-Negative:

• 100 % - if the cancer is only in the breast.

• 90 % - if it has spread to nearby lymph nodes.

• 31 % - if it has spread to distant parts of the body.

Triple-Negative Breast Cancer:

• -91 % - if the cancer is only in the breast.

• 65 % - if it has spread to nearby lymph nodes.

• 12 % - if it has spread to other body parts.

These scores can vary depending on age, health condition, and response to cancer treatment.

Conclusion:

HER2-negative advanced breast cancer is a cancer type that is common and is easily managed with the right treatment approach. While advanced or serious grades are not curable, early diagnosis and treatment improve the outcome and life expectancy. Ongoing treatments like chemotherapy, radiation therapy, hormonal therapy, immunotherapy, and targeted therapy offer hope and control disease progression. To learn more about HER2-negative advanced breast cancer, consult an oncologist or specialist at iCliniq.

A Key Takeaway/Note From iCliniq:

• HER2-negative advanced breast cancer is caused by changes in the HER2 protein in the breast cells.

• It causes symptoms such as a lump in the breast, sore breast, nipple changes, or discharge.

• It is diagnosed with a biopsy or specific tests like immunohistochemistry or the FISH test.