ASCO Issues First Guidelines for Metastatic HER2-positive Breast Cancer

Breast Cancer News
July 3, 2014
Robin Warshaw, Contributing Writer
Reviewed By: 
Nancy U. Lin, MD

To help doctors recommend treatment options based on research evidence and expert consensus, the American Society of Clinical Oncology released its first guidelines on treating metastatic HER2-positive breast cancer.

ASCO issued two clinical practice guidelines for this breast cancer type. One advises on systemic (whole body) therapies for HER2-positive breast cancer that has advanced outside of the breast, other than to the brain. The other recommends specifics on treating brain metastases.


Breast cancer treatment options depend, in part, on tumor characteristics. These include the presence or absence of the HER2 (human epidermal growth factor) protein on the surface of breast cells. If tests show the cancer has too much of this protein – and about 20 percent of breast cancers do – it is called HER2-positive breast cancer. When HER2 positive disease spreads, or metastasizes, beyond the breast and local lymph nodes, it is called metastatic HER2-positive breast cancer.

Some targeted or biologic therapies recognize the HER2 protein and block its actions. These systemic treatments are trastuzumab (Herceptin), lapatinib (Tykerb), pertuzumab (Perjeta) and ado-trastuzumab emtansine, or T-DM1 (Kadcyla). Using these against HER2-positive metastatic breast cancer has improved survival. Yet some of these treatments may have difficulty getting into the brain, so may not work as well there as they do in the rest of the body. No systemic therapies are FDA approved for brain metastases.

Why and How Guidelines Were Created

ASCO guidelines give cancer doctors the most up-to-date information and treatment recommendations. The process of creating guidelines uses a panel of experts, who review recent research and clinical practice findings.

For the guideline on systemic treatment of HER2-positive breast cancer, the panel identified multiple well designed phase III trials to guide treatment, and developed guidelines based on the evidence from those trials.

For the guideline on brain metastasis, 19 phase III and several phase II trials were reviewed. These studies were not specific enough to write a new guideline because many included people with various cancers, not just breast cancer. So, the panel wrote recommendations that were then reviewed and rated by themselves and other experts who treat brain mets.

Recommendations From The Two Guidelines

To treat the whole body for metastatic, HER2-positive breast cancer that is not in the brain, ASCO recommends

  • first treatment
    • a combination of pertuzumab, trastuzumab and taxane chemotherapy as the preferred option for most
    • in some people, such as those with no symptoms and who have very little disease, hormonal therapy with or without trastuzumab or lapatinib may be used in place of chemotherapy if the cancer is also hormone receptor-positive,
    • if chemotherapy is given, it should last for 4 to 6 months, with HER2-targeted therapy and hormonal therapy continuing afterwar
    • In those treated with trastuzumab for early-stage breast cancer and whose cancer spread while on or within 12 months of stopping trastuzumab, T-DM1 is recommended instead of the options above
  • second treatment
    • T-DM1 for metastatic disease that worsened or returned
  • third treatment or more
    • T-DM1 for those who have not received it before
    • pertuzumab, if not already received, in combination with trastuzumab
    • for those not eligible for the above, lapatinib with capecitabine (Xeloda), other chemotherapy and HER2-targeted therapy combinations or hormonal therapy

For brain metastases in HER2-positive breast cancer, the guideline recommends

  • Brain MRI done quickly for symptoms like new or worsening headaches, unexplained nausea, weakness in one part of the body and seizures, because brain mets occur more often in this type of breast cancer
    • routine brain MRI in those without known brain metastases and without symptoms is not recommended
  • surgery or stereotactic radiosurgery, a form of localized radiation therapy, may be considered for one or a few metastases depending on size, location and symptoms
    • surgery is usually followed by radiation therapy
    • stereotactic radiosurgery should be given as one high radiation dose or smaller, daily doses and may be given alone, or with whole-brain radiation therapy (WBRT)
  • WBRT for mets that are more widely spread in the brain
  • additional treatment if brain mets worsen through initial treatment
    • may include one of the above, plus or with systemic medicine that has shown some action in the brain, such as lapatinib and capecitabine
  • continued treatment for metastatic HER2-positive disease in other parts of the body
    • a HER2-targeted therapy also may be added or changed
    • if only the brain mets grow, cancer in other parts of the body remain the same, and the mets can be treated with surgery, radiosurgery, or WBRT, the previous HER2-targeted therapy can be continued rather than switched

You may also get treatment through a clinical trial. Go to to search for trials matching your diagnosis.

What This Means for You

There are treatment options for metastatic HER2-positive breast cancer that have been shown to lengthen survival and improve quality of life.

The ASCO guidelines will help you and your doctor talk about your treatment goals, the benefits and risks of your options, and how to manage side effects. If you have brain metastases, the related guideline offers direction to reduce symptoms and protect brain function.

You can find out more about metastatic breast cancer and connect with others at

Giordano, SH, Temin, S, Kirshner, JJ et al. Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology. 2014; doi: 10.1200/JCO.2013.54.0955

Ramakrishna, N, Temin, S, Chandarlapaty, S et al. Recommendations on Disease Management for Patients With Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology. 2014; doi: 10.1200/JCO.2013.54.0948

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