HER2-Negative Breast Cancer: Causes, Risk Factors, and Symptoms

Breast cancer is the abnormal growth of breast cells that can spread to other parts of the body if not detected and controlled early. Treatment depends on the stage, type, and other factors, and may include surgery, chemotherapy, radiation therapy, immunotherapy, or hormone therapy.

This section focuses on HER2-negative breast cancer, its causes, risk factors, and symptoms.

What is HER2 in Breast Cancer?

HER2 (human epidermal growth factor receptor 2) is a protein that can promote the rapid growth of breast cancer cells.

HER2-positive breast cancer: Cells have higher-than-normal levels of HER2, which often leads to faster growth and spread. These cancers are usually more responsive to drugs targeting HER2.
HER2-negative breast cancer: Cells do not have high levels of HER2.

All invasive breast cancers should be tested for HER2 levels, either through a biopsy or after surgical removal of the tumor, according to the American Cancer Society.

Understanding HER2 status helps doctors determine the most suitable treatment for each patient.

What Is HER2-Negative Breast Cancer?

HER2-negative breast cancer occurs when cancerous breast cells do not overexpress HER2 protein.

In many breast cancers, hormones and/or HER2 drive tumor growth.
HER2-negative cancers are classified based on other tumor characteristics.
Your doctor will determine HER2 status as part of your diagnosis.

Knowing the biological markers of the cancer helps guide targeted and effective treatment (Cleveland Clinic).

Symptoms of HER2-Negative Breast Cancer

Symptoms are similar to those of breast cancer in general:

Changes in breast size or shape.
A new lump or firm area in the breast or underarm that does not change with the menstrual cycle.
Skin changes on the breast or nipple: dimpling, wrinkling, scaling, itching, or color changes.
Nipple discharge, which may be bloody or clear.
Nipple inversion or pulling inward.

Note: Breast cancer does not always cause noticeable changes, and many of these symptoms can also occur with benign conditions. Regular screenings are essential for early detection.

Causes of HER2-Negative Breast Cancer

HER2-negative breast cancer develops when the DNA in breast cells changes, causing cells to grow uncontrollably and form tumors.

Risk Factors for HER2-Negative Breast Cancer

While the exact causes of the mutations leading to HER2-negative tumors are not fully understood, several factors may increase risk:

Inherited genetic mutations:
- No mutation specifically causes HER2-negative breast cancer.
- Mutations in BRCA1 or BRCA2 increase overall breast cancer risk.
Personal or family history of breast cancer:
- Previous breast cancer diagnosis increases risk.
- Having close relatives (parents, siblings, or children) with breast cancer also increases risk.
Long-term exposure to estrogen or progesterone:
- Early menstruation or late menopause increases lifetime hormone exposure.
Certain hormone therapies:
- Some hormone-based treatments may also raise the risk of developing breast cancer.