Treatments for advanced breast cancer

Advanced breast cancer can be treated using systemic treatments including endocrine therapy, targeted/biological therapy and chemotherapy. Local treatment including surgery and radiation therapy is used mainly for symptom relief. 

Treatments for ABC

• Endocrine therapy
• Chemotherapy
• Targeted therapy
• Radiation therapy

Surgery is not typically used in ABC treatment, as tumours are not confined to one site. Removal of the primary tumour has not been shown to improve ABC survival. However, surgery may be used as a treatment to alleviate symptoms (e.g. repairing or strengthening weakened or fractured bones). In selected cases, surgery may be used to remove oligometastases in the liver or brain. Oophorectomy for ovarian suppression may also be performed.

Clinical trials

Clinical trials are a way of accessing new therapies, drugs, or novel ways of receiving treatment not otherwise available through the public health system. Patients receive the same standard of care as they would outside of a clinical trial. Breast Cancer Foundation NZ hosts a database of recruiting and pending trials in Australia and New Zealand that are regularly updated. Visit the database here.

Endocrine therapy is the recommended first-line treatment for patients with hormone receptor-positive ABC, even if they have been previously treated with endocrine therapy. The type of therapy is determined by the patient’s menopausal status and prior treatment.

Anti-oestrogens:

• Tamoxifen is used to treat both pre- and post-menopausal women. It is taken daily in tablet form.
• Aromatase inhibitors (AIs) include anastrozole, exemestane and letrozole for post-menopausal women. They are taken daily as a tablet. 
• Fulvestrant (Faslodex) is indicated for post-menopausal women and is given as an intramuscular injection.
• Ibrance is a CDK4/6 inhibitor and is used to treat HER2 negative and ER positive ABC. It is taken daily as a tablet, in conjunction with an AI.

Ovarian suppression:

Goserelin suppresses oestrogen production in the ovaries. It is indicated for pre-menopausal women and can be used alone or in combination with tamoxifen or AIs. It is a small implant given as subcutaneous injection in the abdomen every 28 days or in three-month intervals. 

Monitoring for complications/side effects:

The most common side effects of endocrine therapy are menopausal symptoms, such as:

• Hot flushes
• Night sweats
• Vaginal dryness
• Loss of bone density
• Reduced libido
• Mood changes

Other side effects include:

• Joint/muscle pain or stiffness
• Headaches
• Nausea
• Tiredness or fatigue

Rarely, tamoxifen is associated with:

• Blood clots
• PV blood loss
• Uterine bleeding

Chemotherapy is one of the main treatments for ABC. The first chemotherapy drug used is known as first-line treatment. When ABC no longer responds to the current course of treatment, sequential treatments (second- and third-line treatments) are used.

Chemotherapy may be given after endocrine therapy, or it may be used as a first-line treatment if:

• The cancer is hormone receptor-negative
• The cancer has metastasised to the liver or lungs
• The cancer is aggressive.

Common chemotherapy regimens for ABC include:

• Capecitabine (Xeloda)
• Carboplatin
• Cyclophosphamide
• Docetaxel (Taxotere)
• Doxorubin (Adriamycin)
• Epirubicin (Pharmorubicin)
• Gemictabine (Gemzar)
• Paclitaxel (Taxol)
• Vinorelbine (Navelbine).

Chemotherapy can be delivered via intravenous infusion or as a tablet.

Side effects of chemotherapy

Some common side effects are:

• A sore mouth
• Nausea and vomiting
• Fatigue
• Hair loss
• Peripheral neuropathy or numbness, tingling and pain in the hands and feet
• Neutropenia

Managing side effects

Chemotherapy side effects are closely monitored by the specialist treatment team. Patients and GPs are encouraged to report concerning symptoms through the hospital's chemotherapy urgent care service.

Targeted therapies for hormone receptor positive advanced breast cancer

CDK4/6 inhibitors

This treatment is a small molecule that targets cyclin-dependent kinases (CDK4/6). These are proteins that inhibit cell proliferation and help mediate endocrine resistance.

Palbociclib (Ibrance)
Palbociclib is indicated for use in post-menopausal women with ER+, HER2- locally advanced or metastatic breast cancer. It is given in conjunction with an aromatase inhibitor. In women who have had prior endocrine therapy it is given with fulvestrant. This therapy is delivered as a tablet, taken once a day on a four weekly cycle, three weeks on, one week off.

Ribociclib (Kisqali) 
Ribociclib can be used in combination with an aromatase inhibitor as initial therapy to treat advanced HR+, HER2-negative breast cancer in postmenopausal women. In women who have had prior endocrine therapy it is given with fulvestrant. This therapy is delivered as a tablet, taken once a day on a four weekly cycle, three weeks on, one week off. 

Abemaciclib (Verzenio)
Abemaciclib stops the proliferation of cancer cells in HR+, HER2- locally advanced or metastatic breast cancer. It can be used as a first or second-line treatment. It is registered, but not funded, in New Zealand.

Other targeted therapies

Everolimus (Afinitor)
Everolimus belongs to a class of drugs known as mTOR inhibitors, which target the mTOR proteins that fuel cancer cell growth and division. It can be used in post-menopausal women with metastatic HR+, HER2- breast cancer, in conjunction with exemestane (Aromasin), but only if the patient has previously been treated with AI. It is taken orally. It is not funded in New Zealand.

Targeted therapy for HER2+ advanced breast cancer

There are a number of targeted therapies available to treat advanced HER2+ breast cancer.

The standard first line treatment is dual anti-HER2 therapy (trastuzumab + pertuzumab) with chemotherapy.

Trastuzumab (Herceptin/Herzuma)

Trastuzumab is the most widely used targeted therapy to treat HER2+ ABC. It can be given with other chemotherapy drugs and is administered every three weeks via IV infusion (funded), or SC injection (unfunded), for as long as the patient continues to benefit. For more information about Herzuma and possible side effects see the Medsafe consumer information booklet.

Pertuzumab (Perjeta)

This is another monoclonal antibody treatment that is used to treat advanced HER2+ breast cancer. It is given by intravenous infusion and is administered every three weeks. Perjeta is used at the same time as Herceptin and docetaxel chemotherapy. Perjeta is currently indicated for patients with HER2+ metastatic breast cancer who have not received previous anti-HER2 therapy or chemotherapy for their advanced disease. As of January 2017, Perjeta is funded for use in the New Zealand public health system. For more information about Perjeta and possible side effects see the Medsafe consumer information.

Trastuzumab emtansine /T-DM1 (Kadcyla)

Kadcyla is widely used as second line treatment in advanced HER2+ breast cancer. It is an antibody drug conjugate, combining an antibody and a chemotherapy drug. Kadcyla uses the monoclonal antibody in trastuzumab to deliver DM1 directly to the inside of the cancer cells while minimising the effects on healthy tissues. It is delivered every three weeks via IV infusion. For more information about Kadcyla and possible side effects see the Medsafe consumer information.

Trastuzumab deruxtecan/T-Dxd (Enhertu)

T-Dxd is an antibody-drug conjugate approved for pre-treated metastatic HER2-positive and HER2-low breast cancer. It was evaluated in the DESTINY Breast06 trial as the first therapy for patients with HR-positive, HER2-low, and HER2-ultralow breast cancer after prior endocrine therapy. Medsafe consumer information

Lapatinib (Tykerb)

Lapatinib is a small-molecule drug belonging to a group known as Tyrosine Kinase Inhibitors, which target both HER2 and epidermal growth factor receptor (EGFR) pathways. It is only publicly funded in New Zealand for people with HER2+ advanced breast cancer that have not been treated with Herceptin, or for those who have not been able to tolerate Herceptin. Lapatinib is an oral chemotherapy, given in combination with capecitabine (Xeloda) or paclitaxel (Taxol). It can also be given with an aromatase inhibitor. Treatment can continue after chemotherapy for as long as the cancer responds. Due to decreasing demand for Lapatinib, Novartis made the decision to discontinue the drug on 1 April 2021. Since this date, no new patients have been started on Lapatinib, and it will eventually be delisted from Pharmac's schedule. There is ample supply of the drug to allow patients already on it to continue taking it. For more information about Lapatinib (Tykerb) and possible side effects see the Medsafe consumer information. 

Targeted therapy for triple negative breast cancer (TNBC)

From 1 October, pembrolizumab (Keytruda) will be funded for advanced TNBC. Patients can also access targeted therapies through cost share programmes or clinical trials. GPs can also access unfunded medicines on behalf of their patients. Patients may benefit from clinical trials to identify treatments that would otherwise not be available through the public health system.

Pembrolizumab (Keytruda)

Keytruda (pembrolizumab) may be given alongside chemotherapy in advanced triple negative breast cancer and where the tumour also expresses the PD-L1 protein. Keytruda is an immune checkpoint inhibitor that binds to the protein PD-1 to help immune cells recognise and kill cancer cells. 

Sacituzumab Govitecan (Trodelvy)

Trodelvy is another drug for metastatic triple negative breast cancer. It has been submitted to Pharmac but has not been registered in NZ by the drug company.  It is used as a 2^nd or 3^rd
line treatment for TNBC.

Atezolizumab (Tecentriq)

Atezolizumab is an immunotherapy treatment and is used in combination with chemotherapy. It works by attaching to a protein called programmed death-ligand 1 (PD-L1), which is found on some tumour cells, and this makes it easier for the immune system to target cancer cells. It can be used in patients with advanced triple negative breast cancer, and is given intravenously every two weeks. Atezolimuzab is not publicly funded in New Zealand, although Roche offers a Cost Share Programme to assist with the cost of the medicine.

Radiation therapy

Palliative radiation therapy is used to treat local metastatic deposits in the bones, brain or skin to relieve pain, control the growth at a specific site or to reduce the risk of bone fracture.

Using radiation therapy to achieve a survival benefit is an interesting area but is not yet proven. 

For example, stereotactic ablative radiation (SABR) for the treatment of early oligometastatic disease (one or more small secondary breast cancers),usually contained in one site in the body is currently being trialled and used in a limited capacity in clinical practise in New Zealand. SABR is commonly used to treat brain metastases, but can also be used in the lungs and liver.