Metastatic (stage 4)HER2-positive breast canceris not curable—but it istreatable, and options continue to expand and improve.Given the generally aggressive and rapid growth of HER2-positive tumors and the need to uniquely target the human epidermal growth factor receptor 2 (HER2) protein to be most effective, this is promising. In addition, targeted therapies tend to have far fewer side effects than chemotherapy drugs.
The HER2-positive breast cancer treatment that is right for you will depend on several factors, including whether your tumor is also estrogen-receptor positive, where the cancer has metastasized to, and what treatment you received in the past if you were previously HER2-positive.
Verywell / Brianna Gilmartin
Approach to Treatment
You may have learned that you havestage 4 (metastatic) breast cancerwhen you were first diagnosed with the disease, but more commonly, distant metastases occur as a recurrence of a tumor that was initially an early-stage tumor years earlier. As such, the diagnosis often comes as a shock to many.
With HER2-positive cases specifically, HER2 genes overproduce HER2 proteins. Growth factors bind to these receptor proteins on breast cancer cells, causing the growth characteristic of these tumors.
As metastatic HER2-positive breast cancer is both advanced and aggressive, it’s important that treatment addresses the activity of these HER2 proteins so that therapeutic efforts zero in on this important factor in progression both specifically and quickly.
But unlike with early-stage breast cancer—in which several options (surgery, chemotherapy, radiation, etc.) may be used in combination to prevent recurrence, if possible—such treatment of stage 4 breast cancer doesn’t improve survival. It does, however, increase side effects. As such, theleastamount of treatment needed to control the disease is what doctors aim for in metastatic cases.
Receptor Status ChangeMany people are surprised to learn that the receptor status of their cancer changed after it recurred (for example, an HER2-negative status can turn to HER2-positive, and vice versa). This is why a biopsy and re-checking receptor status is so important if you have a distant recurrence of your disease.
Receptor Status Change
Many people are surprised to learn that the receptor status of their cancer changed after it recurred (for example, an HER2-negative status can turn to HER2-positive, and vice versa). This is why a biopsy and re-checking receptor status is so important if you have a distant recurrence of your disease.
Hormone Receptor Status in Breast Cancer
Primary Treatment Options
Until 1998, whenHerceptinwas approved, HER2-positive tumors had a poorer prognosis, especially for those who also had estrogen- and progesterone-receptor-negative tumors. Since that time, other targeted drugs that target HER2 have been developed, leaving options even when one drug (or even two) fails.
First line treatment for metastatic breast cancerdepends largely on receptor status, and if it is a recurrence, both your estrogen and progesterone receptor status and HER2/neu status should be tested.
If your tumor is both estrogen-receptor-positiveandHER2-positive, initial treatment may includehormonal therapy, a HER2-targeted therapy, or both. This decision will depend, in part, on the medications with which you were treated (if you’re experiencing a recurrence).Chemotherapymay also be used for four to six months (usually a Taxane such as Taxol). It’s thought that giving the most active treatments as soon as possible can improve survival in HER2-positive metastatic breast cancer.
If you have not previously been treated with a HER2-targeted drug, treatment is usually started with Herceptin (trastuzumab) or Perjeta (pertuzumab). For those who have previously been treated with Herceptin, another HER2-targeted drug may be used.
If a cancer has progressed on Herceptin or within 12 months of stopping the drug, trastuzumab emtansine (T-DM1) is the preferred option second-line.
Even in people who had progressed on two previous HER2-targeted drugs, treatment with TDM1 improved overall survival more than an oncologist’s choice of other available regimens (including several chemotherapy drugs) in a 2017 study published inLancet Oncology.
Third line optionswill vary depending on prior treatments. For those who haven’t yet been treated with T-DM1, this drug is an option. Perjeta may also be used for those who have not yet received it in combination with Herceptin.
For those who have been treated with Perjeta and T-DM1 and still progressed, options include the combination of Xeloda (capecitabine) and the targeted therapy Tykerb (lapatinib), hormonal therapy for those who have estrogen-receptor-positive tumors, and other chemotherapy regimens in combination with HER2-targeted drugs.
Preliminary findings from the phase III trial (SOPHIA) found that people who had received several treatments for metastatic HER2-positive cancer had better progression-free survival when treated with the investigational monoclonal antibody margetuximab than with the combination of Herceptin and chemotherapy.
Evolving Thoughts on Surgery
When breast cancer is metastatic at the time of diagnosis, surgery has not usually been done, as it was believed that it didn’t improve survival rates. This thought appears to be changing, with evidence that primary surgery in people with stage 4 HER2-positive breast cancer improves overall survival. In addition, when a breast tumor is causingsymptoms(if it is painful, bleeding, draining, or becomes infected), palliative mastectomy may significantly reduce symptoms. In a 2018 study, palliative mastectomy was found to improve quality of life for some people.
Stage 4 Breast Cancer Survival Rates
Metastasis-Specific Treatment
When breast cancer spreads to other organs, such as the bones, brain, liver, and lungs, it is cancerous breast cancer cells that spread in those organs. This means that the disease is different than if the cancer originated in these areas.
Treatment is decided on accordingly, and an approach for metastases of breast cancer to any site usually involves hormonal drugs, HER2-positive-targeted therapies, or chemotherapy.
That said, treatments that are “metastasis-specific” may be used as well. These are treatments that specifically address the area to which the cancer has spread.
Bone Metastases
Bone metastases with breast cancerare very common, found in around 70 percent of people with metastatic disease.In addition to systemic treatment options addressing breast cancer itself, metastasis-specific treatment for bones can reduce pain and also improve survival (overall, bone metastases have a better prognosis than other sites of metastatic disease).
Of note is that the complications of bone metastases, such as fractures, become extra important as many of the treatments for breast cancer can lead to bone loss.
Options include:
Liver Metastases
Liver metastases from breast cancerare the second most common site of metastases and occur more often among people with HER2-positive tumors.
Radiation therapyis commonly used in addition to other treatments for the cancer. Other treatments such asembolizationmay be considered as well. In this treatment, an injection causes blockage in an artery to the liver that supplies the area that contains tumor, resulting in death of the tissue.
If there are only a few sites of metastasis (oligometastases), surgical removal orstereotactic body radiotherapy(SBRT)can improve survival. SBRT differs from conventional radiation therapy in that a very high dose of radiation is delivered to a precise area of tumor with the intent of eradicating the metastasis.
Liver metastases often causeascites(abdominal swelling) andparacentesis, removing the fluid in the abdomen through a long thin needle, is often needed to reduce discomfort. Itching is also very common with liver metastases and treatment to manage this symptom can improve quality of life.
Brain Metastases
While metastases from breast cancer are often treated as part of general metastatic breast cancer treatment, brain metastases can pose a unique challenge. Theblood-brain barrieris a collection of tightly knit capillaries that prevents many toxins and medications, including many chemotherapy drugs, from accessing the brain. Thankfully, some drugs are able to cross over.
A 2017 review of the literature found that Herceptin (trastuzumab) clearly improves survival for those with HER2-positive breast cancer with brain metastases. Trastuzumab emtansine (T-DM1) and Perjeta (pertuzumab) are also promising. In contrast, Tykerb (lapatinib) appears to have little effect on brain metastases and has a high toxicity profile. When lapatinib is combined with chemotherapy, however, the response rates are better.
Lung Metastases
Lung metastases from breast cancer are primarily treated with general measures to treat the breast cancer, such as hormonal therapies, HER2-targeted drugs, and chemotherapy, rather than any specific treatments.
When only a few metastases are present, treating these with surgery or SBRT may be considered, but studies have not yet shown an increased survival rate from this practice.
Other Distant Metastases
Breast cancer can spread to many other distant regions of the body as well, including the skin, muscle, fatty tissue, and bone marrow. Most of the time, these distant metastases are treated with general treatment for metastatic HER2-positive cancer, but when isolated metastases occur, options such as surgery or radiation therapy may be considered.
How Breast Cancer Can Be Misdiagnosed
11 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.American Cancer Society.Treatment of Stage IV (Metastatic) Breast Cancer.Pernas S, Tolaney SM.HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance.Ther Adv Med Oncol. 2019;11:1758835919833519. doi:10.1177/1758835919833519Krop IE, Kim S-B, Martin AG, et al.Trastuzumab emtansine versus treatment of physicians choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial.The Lancet Oncology. 2017;18(6):743-754. doi:10.1016/s1470-2045(17)30313-3.Food and Drug Administration.Enhertu label.Kai M, Kubo M, Kawaji H, et al.QOL-enhancing surgery for patients with HER2-positive metastatic breast cancer.BMJ Supportive & Palliative Care. 2018;9(2):151-154. doi:10.1136/bmjspcare-2018-001622.Pulido C, Vendrell I, Ferreira AR, et al.Bone metastasis risk factors in breast cancer.Ecancermedicalscience. 2017;11:715. doi:10.3332/ecancer.2017.715American Cancer Society.Treating Bone Metastases.Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990–27996. doi:10.18632/oncotarget.15856American Cancer Society.Radiation Therapy for Liver Cancer.Laakmann E, Müller V, Schmidt M, Witzel I.Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review.Breast Care (Basel).2017;12(3):168-171. doi:10.1159/000467387Lee YH, Kang KM, Choi HS, et al.Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in patients with pulmonary metastases.Thorac Cancer. 2018;9(12):1671–1679. doi:10.1111/1759-7714.12880
11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.American Cancer Society.Treatment of Stage IV (Metastatic) Breast Cancer.Pernas S, Tolaney SM.HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance.Ther Adv Med Oncol. 2019;11:1758835919833519. doi:10.1177/1758835919833519Krop IE, Kim S-B, Martin AG, et al.Trastuzumab emtansine versus treatment of physicians choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial.The Lancet Oncology. 2017;18(6):743-754. doi:10.1016/s1470-2045(17)30313-3.Food and Drug Administration.Enhertu label.Kai M, Kubo M, Kawaji H, et al.QOL-enhancing surgery for patients with HER2-positive metastatic breast cancer.BMJ Supportive & Palliative Care. 2018;9(2):151-154. doi:10.1136/bmjspcare-2018-001622.Pulido C, Vendrell I, Ferreira AR, et al.Bone metastasis risk factors in breast cancer.Ecancermedicalscience. 2017;11:715. doi:10.3332/ecancer.2017.715American Cancer Society.Treating Bone Metastases.Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990–27996. doi:10.18632/oncotarget.15856American Cancer Society.Radiation Therapy for Liver Cancer.Laakmann E, Müller V, Schmidt M, Witzel I.Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review.Breast Care (Basel).2017;12(3):168-171. doi:10.1159/000467387Lee YH, Kang KM, Choi HS, et al.Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in patients with pulmonary metastases.Thorac Cancer. 2018;9(12):1671–1679. doi:10.1111/1759-7714.12880
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
American Cancer Society.Treatment of Stage IV (Metastatic) Breast Cancer.Pernas S, Tolaney SM.HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance.Ther Adv Med Oncol. 2019;11:1758835919833519. doi:10.1177/1758835919833519Krop IE, Kim S-B, Martin AG, et al.Trastuzumab emtansine versus treatment of physicians choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial.The Lancet Oncology. 2017;18(6):743-754. doi:10.1016/s1470-2045(17)30313-3.Food and Drug Administration.Enhertu label.Kai M, Kubo M, Kawaji H, et al.QOL-enhancing surgery for patients with HER2-positive metastatic breast cancer.BMJ Supportive & Palliative Care. 2018;9(2):151-154. doi:10.1136/bmjspcare-2018-001622.Pulido C, Vendrell I, Ferreira AR, et al.Bone metastasis risk factors in breast cancer.Ecancermedicalscience. 2017;11:715. doi:10.3332/ecancer.2017.715American Cancer Society.Treating Bone Metastases.Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990–27996. doi:10.18632/oncotarget.15856American Cancer Society.Radiation Therapy for Liver Cancer.Laakmann E, Müller V, Schmidt M, Witzel I.Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review.Breast Care (Basel).2017;12(3):168-171. doi:10.1159/000467387Lee YH, Kang KM, Choi HS, et al.Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in patients with pulmonary metastases.Thorac Cancer. 2018;9(12):1671–1679. doi:10.1111/1759-7714.12880
American Cancer Society.Treatment of Stage IV (Metastatic) Breast Cancer.
Pernas S, Tolaney SM.HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance.Ther Adv Med Oncol. 2019;11:1758835919833519. doi:10.1177/1758835919833519
Krop IE, Kim S-B, Martin AG, et al.Trastuzumab emtansine versus treatment of physicians choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial.The Lancet Oncology. 2017;18(6):743-754. doi:10.1016/s1470-2045(17)30313-3.
Food and Drug Administration.Enhertu label.
Kai M, Kubo M, Kawaji H, et al.QOL-enhancing surgery for patients with HER2-positive metastatic breast cancer.BMJ Supportive & Palliative Care. 2018;9(2):151-154. doi:10.1136/bmjspcare-2018-001622.
Pulido C, Vendrell I, Ferreira AR, et al.Bone metastasis risk factors in breast cancer.Ecancermedicalscience. 2017;11:715. doi:10.3332/ecancer.2017.715
American Cancer Society.Treating Bone Metastases.
Wu Q, Li J, Zhu S, et al.Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study.Oncotarget. 2017;8(17):27990–27996. doi:10.18632/oncotarget.15856
American Cancer Society.Radiation Therapy for Liver Cancer.
Laakmann E, Müller V, Schmidt M, Witzel I.Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review.Breast Care (Basel).2017;12(3):168-171. doi:10.1159/000467387
Lee YH, Kang KM, Choi HS, et al.Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in patients with pulmonary metastases.Thorac Cancer. 2018;9(12):1671–1679. doi:10.1111/1759-7714.12880
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