Causes and Risk Factors of HER2+ Metastatic Breast Cancer

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When breast cancer spreads from outside of the breast to distant areas of the body, such as the liver, brain, bones, or lung, it is called metastatic breast cancer.

HER2-positive breast cancer means that the breast cancer cells have extra HER2 (human epidermal growth factor receptor 2) proteins on the outside of them. These HER2 receptors can signal the cancer cells to grow quickly and out of control. Breast cancer can be metastatic when it is diagnosed or can come back years later. 

This article will review the causes and risk factors associated with HER2-positive metastatic breast cancer. 

HER2+ Breast Cancer Risk Factors - VWH illustration by Ellen Lindner

Verywell / Ellen Lindner

Common Causes 

In many cases, the exact reason why HER2-positive breast cancer starts is unknown, although there have been some connections made between risk factors and being diagnosed with breast cancer. 

HER2-positive breast cancer typically develops due to an overproduction of the HER2 gene. As a result, the gene makes excess HER2 proteins, which cause abnormal and out-of-control growth of the breast cancer cells. 

HER2-positive breast cancer has been shown to potentially relapse or metastasize sooner after treatment than other types of breast cancer, usually within five years after being diagnosed.

When cancer spreads, incredibly small cells escape from the original tumor and travel through the body via the lymphatic system or the blood vessels. These cells then stay in other areas of the body. When and why they eventually start to grow is not well understood. 


HER2-positive metastatic breast cancer is not a genetic disease, in that it is not inherited from a parent.

However, a mutation or change to the HER2 gene is what causes too many HER2 proteins to develop. These extra proteins signal the cancer cells to grow out of control. Treatments used for HER2-positive breast cancer target that protein specifically and block it to slow the growth of the cancer.

There are genes that increase the risk of developing breast cancer that can be passed from parents to their children. These genes include:

  • BRCA1
  • BRCA2
  • PALB2
  • PTEN
  • TP53
  • ATM
  • CDH1
  • CHEK2
  • NBN
  • NF1
  • STK11

Lifestyle Risk Factors 

Some risk factors associated with the development of breast cancer include:

  • Being overweight
  • Not exercising or being too sedentary 
  • Smoking cigarettes or using other tobacco products
  • Taking hormonal therapy
  • Drinking alcohol

Other Risk Factors

There are some risk factors that unlike lifestyle risk factors, can’t be changed. 

One of these risk factors is being born female. Although men can be diagnosed with breast cancer, the majority of breast cancer patients are female. 

Females who have never had a baby or have had a baby after the age of 30 have an increased risk of developing breast cancer. 

Although HER2-positive breast cancer is not due to a gene that can be passed from parents to children, having a family history of breast cancer can increase the risk of getting breast cancer. 

Other risk factors that cannot be altered include:

  • Having Ashkenazi Jewish descent
  • Male breast cancer in your family
  • Strong family history of other cancers 
  • Increasing age
  • Starting menstrual cycle at an earlier age
  • Having dense breast tissue
  • History of getting radiation therapy to the chest


Why metastatic HER2-positive breast cancer develops may never be known. And there are many factors that can’t be avoided that may increase someone’s risk of getting this type of cancer.

However, there are some risks that can be reduced, some of which include decreasing alcohol intake, maintaining a healthy weight, and getting exercise. 

A Word From Verywell

If you have a diagnosis of metastatic HER2-positive breast cancer, you may be wondering exactly what caused the disease. Unfortunately, that may never be known. If you have some risk factors for developing breast cancer, keep in mind the things you can do to help reduce your personal risk, including exercising regularly, eating a nourishing diet, and maintaining a healthy weight.

7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Cancer Society. Breast cancer HER2 status.

  2. Medline Plus. HER2 (breast cancer) testing.

  3. Riggio AI, Varley KE, Welm AL. The lingering mysteries of metastatic recurrence in breast cancer. Br J Cancer. 2021;124(1):13-26. doi: 10.1038/s41416-020-01161-4

  4. National Cancer Institute. HER2 genetic link to breast cancer.

  5. Genetics.

  6. Centers for Disease Control and Prevention. What are the risk factors for breast cancer?

  7. Moffit Cancer Center. HER2 positive breast cancer risk factors.

By Julie Scott, MSN, ANP-BC, AOCNP
Julie is an Adult Nurse Practitioner with oncology certification and a healthcare freelance writer with an interest in educating patients and the healthcare community.