Treatment of Advanced HER2-Negative Breast Cancer

September 2, 2014

To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) asks its medical experts to develop evidence-based recommendations about specific topics in cancer care. These recommendations are for the treatment of human epidermal receptor 2 (HER2)-negative breast cancer that has spread beyond the breast to areas either nearby the breast or to distant parts of the body. This guide for patients and caregivers is based on ASCO's recommendations.

Key Messages:

  • Several treatments are currently available that can help women with HER2-negative breast cancer continue to live and function well after diagnosis, even if the cancer has spread.
  • Treatment of HER2-negative breast cancer that has spread usually includes hormonal therapy, but may also include chemotherapy and/or targeted therapy.
  • Treatments to manage the symptoms of metastatic breast cancer and the side effects of treatment, called palliative care, are also an important part of each patient’s treatment plan.
  • Clinical trials are another treatment option to consider at any time during cancer care.


Advanced breast cancer is cancer that is locally advanced, has spread from the breast to another part of the body, or has come back in another location within the same or the other breast. Locally advanced breast cancer is disease that has spread from the breast to areas nearby, such as the chest wall or many underarm lymph nodes. The area where cancer has spread is called a metastasis, or metastases if there are multiple areas of spread. Breast cancer most commonly spreads to the bone, lungs, liver, and brain. It is important to remember that breast cancer that spreads to these other organs is still considered breast cancer and treated similarly.

Treatment options for metastatic breast cancer depend on several factors, including where the cancer has spread, the patient’s overall health, and the levels of hormone receptors and HER2 in the tumor. Both hormone receptors and HER2 are specialized proteins. Hormone receptors are found inside breast cells, and HER2 is found on the surface of breast cells. Cancers with detectable hormone receptors, called hormone receptor-positive, use the hormones estrogen and progesterone to grow and spread. When a breast cell has abnormally high levels of the HER2 gene or the HER2 protein, it is called HER2- positive. The cancer is called HER2-negative when it does not have high levels of the HER2 gene or the HER2 protein.

Most patients with metastatic breast cancer have HER2-negative breast cancer. If HER2-negative breast cancer is also hormone receptor positive, the most common treatment is hormonal therapy, but chemotherapy or targeted therapy may also be given.

In addition to treatment to slow, stop, or eliminate the cancer, an important part of cancer care, particularly for those with metastatic cancer, is relieving the symptoms and side effects. This is called palliative care, and it includes supporting the patient and family with their physical, emotional, spiritual, and social needs.


Hormonal therapy is considered the standard initial treatment for HER2-negative metastatic breast cancer that is also hormone receptor positive. However, chemotherapy may also be given. ASCO’s specific recommendations on chemotherapy for metastatic breast cancer are listed below.

  • There is no specific type of chemotherapy recommended for this type of breast cancer. Many drugs are available, including types of drugs called taxanes and anthracyclines. In addition, platinum-based drugs, as well as the drugs capecitabine (Xeloda), eribulin (Halaven), gemcitabine (Gemzar), ixabepilone (Ixempra), and vinorelbine (Navelbine) may be used.
  • Drugs should be given sequentially, which means one drug after another, rather than as a combination, which is more than one drug at the same time. However, a combination of drugs may be an option for patients with cancer that is immediately life threatening.
  • Generally, chemotherapy should continue until the disease worsens if a patient is not experiencing unmanageable side effects. At some point, chemotherapy may no longer be able to control the cancer’s growth. When this happens, patients may choose to stop chemotherapy while continuing to receive palliative care.
  • The best chemotherapy option for each patient depends on several factors, including the previous treatments received, potential side effects, overall health, and the patient’s preference.

In addition to chemotherapy, the targeted therapy bevacizumab (Avastin) in combination with chemotherapy may be an option if a patient has severe symptoms. Currently, bevacizumab is not approved by the U.S. Food and Drug Administration for patients with breast cancer, so it may not be available to all patients.

What This Means for Patients

For most patients, a diagnosis of metastatic cancer is very stressful and, at times, difficult to bear. It is important to remember that people with an advanced cancer such as metastatic breast cancer continue to have treatment options and can maintain a good quality of life.

How well treatment works depends on many factors, including how widespread the cancer is and what treatments have already been used. Be sure to talk with your doctor about the goals of treatment, the next steps if the cancer worsens, and the best options to help maintain your quality of life. You may want to ask a caregiver or family member to come to appointments with you to help ask questions and write down or record the answers. That will allow you to read or listen to the information later, taking the time you need to process it. It may also help to talk about the way you are feeling with doctors, nurses, social workers, other members of the health care team, or a support group.

Questions to Ask the Doctor

Consider asking your doctor the following questions about metastatic breast cancer:

  • Where has the cancer spread?
  • What is the HER2 status of the cancer? What does this mean?
  • What is the hormone-receptor status of the cancer? What does this mean?
  • What is my prognosis (chance of recovery)? Is it possible for me to fully recover from the cancer?
  • What treatments have I already received?
  • What are my treatment options?
  • What are the benefits and risks of each option?
  • What clinical trials are open to me? Where are they located, and how do I find out more about them?
  • Is there any research I can participate in that could help other patients with metastatic breast cancer in the future?
  • What treatment plan do you recommend? Why?
  • What is the goal of each treatment? Is it to eliminate the cancer, help me feel better, or both?
  • If I’m worried about managing the costs related to my cancer care, who can help me with these concerns?
  • How will we know the treatment is working?
  • How will my quality of life change over time?
  • What are the next steps if the cancer worsens or comes back?
  • What side effects of the treatments are most common?
  • How can the symptoms and side effects be managed?
  • Where can I find emotional support for me and my family?

More Information

Read the entire clinical practice guidelines at a separate ASCO website.

Guide to Breast Cancer

HER2 Testing for Breast Cancer

ASCO Recommends Palliative Care as a Part of Cancer Treatment

Navigating Challenges Video Series: Talking with Your Cancer Care Team, Making Decisions about Your Cancer Treatment, Managing the Cost of Your Cancer Care, and Finding Emotional Support after a Cancer Diagnosis

Advanced Cancer Care Planning