Advanced or Metastatic TNBC
This section is intended for people with TNBC that has spread away from the breast and lymph glands nearby into other organs.
This form of breast cancer is sometimes referred to as ‘advanced’ or ‘Stage 4’, but they are all the same thing!
Unlike early or primary triple negative breast cancer, secondary or metastatic breast cancer cannot be cured.
We hope this will help you to understand your treatment options, ask your medical team questions and to cope with the physical and emotional pressures.
What is Metastatic Triple Negative Breast Cancer?
You can see what triple negative breast cancer is, who is more likely to be affected and what it means in terms of your treatment here.
As someone who has been diagnosed with secondary/metastatic triple negative breast cancer you can see what to expect when you are first diagnosed here; this includes how the Stage of your cancer and other features affect the treatments that will be discussed
It is important to understand that metastatic TNBC cannot be cured, but it can be controlled by drug treatment, sometimes with the addition of radiotherapy or surgery.
What drug treatments are used to treat people with Metastatic TNBC?
Chemotherapy is the drug treatment used to treat most people with metastatic triple negative breast cancer.
Some people will also receive immunotherapy, depending on the type of triple negative breast cancer they have. Likewise, others may be offered targeted therapy if they have the BRCA 1 or BRCA 2 gene mutation.
These treatments can shrink or control the cancer, delaying the point at which the cancer starts to get larger or to progress, but they do not cure metastatic disease. Chemotherapy has side effects that can be serious.
Therefore, your medical team will be keen to discuss what you want from treatment and what matters most to you in deciding how best you can be treated.
Finally, because you have triple negative breast cancer and would not benefit from hormone therapies such as tamoxifen or letrozole or treatments targeted at HER2 such as trastuzumab, these will not be discussed with you.
Which chemotherapy drugs are used to treat people with Metastatic TNBC?
Most of the chemotherapy drugs used to treat people with metastatic TNBC are widely used to treat other types of breast cancer and cancers other than breast cancer.
Some chemotherapy drugs appear, however, to be more effective than others in treating triple negative breast cancer. The choice of chemotherapy that is recommended may also depend on what, if any, treatment someone received when their cancer was early or primary.
These include:
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A taxane, most often paclitaxel given intravenously weekly, is most often recommended first (in some people given with immunotherapy as discussed below).
Some people can have an allergic reaction to paclitaxel and may then be offered nab-paclitaxel to overcome this allergy.
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An alternative treatment is with intravenous carboplatin, which appears to be more effective than some other chemotherapies in treating metastatic triple negative breast cancer.
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Eribulin is another intravenous drug that also appears to be more effective than some other chemotherapies in treating metastatic triple negative breast cancer.
It is approved after just a single regimen of chemotherapy for metastatic breast cancer, but only available through the NHS after two lines of chemotherapy for metastatic disease.
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Capecitabine is an alternative, oral chemotherapy.
Other chemotherapies that may be discussed include vinorelbine and gemcitabine, but these are probably less effective than other drugs.
When is chemotherapy for Metastatic TNBC given in combination with other drugs?
Although chemotherapy for metastatic breast cancer is usually given as a single agent, you doctor may discuss giving it in combination with other drugs in certain circumstances.
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Paclitaxel may be given in combination with carboplatin because both drugs are active in many people with TNBC and this is a combination that works well in other cancers such as ovarian cancer.
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Similarly, there are indications that adding gemcitabine to carboplatin chemotherapy may increase the effectiveness of chemotherapy, but at the expense of more side effects.
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Some people with metastatic triple negative breast cancer may benefit from adding immunotherapy to certain chemotherapy treatments as discussed below.
How will I be monitored while receiving chemotherapy to treat Metastatic Triple Negative Breast Cancer?
Your oncologist will typically recommend that treatment continue for as long as you are benefiting and it is controlling your cancer.
While you are on treatment your oncologist will look at how you are coping with the treatment and any side-effects, and whether you appear to be benefiting by monitoring your blood tests (often including tumour markers) and by repeating scans that show whether or not your cancer is under control.
If you experience unpleasant side effects the dose of chemotherapy may be reduced, or that particular treatment stopped. Similarly, if the treatment is no longer working your oncologist will discuss stopping the current treatment.
Either way, your oncologist will then discuss what further treatment options there are for further lines of treatment as they would when treating other types of metastatic breast cancer.
There is more information available on chemotherapy for breast cancer at Cancer Research UK and Macmillan Cancer Support.
What is immunotherapy for Metastatic Triple Negative Breast Cancer?
For a long time there has been a focus on trying to use the body’s own immune system to fight cancerous cells. Over the last 20 years this has led to important improvements in treatment for patients with many types of cancer that often don’t respond to other treatments.
At first it seemed that this immunotherapy did not benefit people with breast cancer. Recent clinical trials have shown that some people with secondary or metastatic TNBC do benefit from the addition of immunotherapy, which stimulates the immune system.
Atezolizumab (Taqcentric) and pembrolizumab (Keytruda) are targeted therapies that help the immune system “see” and attack cancer cells that cancer cells use to hide. Although similar, there are differences between the two.
Atezolizumab blocks a protein that cancer cells use to disarm immune cells, whereas pembrolizumab stops the immune cells from being disarmed.
Both atezolizumab and pembrlizumab are more effective against cancers with higher levels of the protein PD-L1.
These immunotherapies add to the benefit of certain chemotherapy drugs in people with secondary or metastatic breast cancer that has high levels of PD-L1 and who have not received prior drug treatment for metastatic disease. They do this by shrinking or control of the cancer for longer than chemotherapy alone, delaying the point at which the cancer starts to get larger or to progress.
The addition of immunotherapy does not, however, cure metastatic disease.
Who should be considered for immunotherapy to treat Metastatic Triple Negative Breast Cancer?
Because immunotherapy, alongside chemotherapy, is only available through the NHS for people who have not received chemotherapy for metastatic disease it needs to be considered as “first-line” treatment.
Both immunotherapy drugs are available to people whose cancers have higher levels of PD-L1, tested either on a piece of the tumour stored earlier or on a new biopsy. The PD-L1 test for the two immunotherapies are, however, different.
Within the NHS, the combination of pembrolizumab with chemotherapy is an alternative treatment for people who cannot have atezolizumab with chemotherapy.
In the NHS, the usual plan is to first do the PD-L1 test for atezolizumab (called SP142)
If this test is positive, the patient can be offered atezolizumab with nab-paclitael chemotherapy
If the SP142 test is negative, do the test for pembrolizumab (SP22C3)
If this test is positive, the patient can be offered pembrolizimab in combination with paclitaxel or nab-paclitaxel.
If both tests are negative, immunotherapy is not an option and people will be offered standard chemotherapy.
How is immunotherapy used to treat Metastatic Triple Negative Breast Cancer?
Atezolizumab is given intravenously every 2 weeks, with nab-paclitaxel chemotherapy
Chemotherapy is given on days 1, 8 and 15 of a 28 day treatment cycle.
Pembrolizumab is given intravenously usually every 3 weeks (but this may be changed to 6-weekly), with paclitaxel or nab-paclitaxel chemotherapy
Chemotherapy is given on days 1, 8 and 15 of a 28 day treatment cycle.
Pembrolizumab is approved, but not funded through the NHS, with gemcitabine plus paclitaxel chemotherapy.
Chemotherapy has side effects and so does immunotherapy that result from the immune system also attacking normal parts of the body such as the bowels, lungs and glands. These side effects can be serious, so you will be monitored closely while receiving atezolizumab or pembrolizumab (with chemotherapy).
The combination of immunotherapy and chemotherapy continues so long as the patient is benefiting and not experiencing significant side effects. If there are side effects one or other (or both) of the immunotherapy and chemotherapy may need to have the dose reduced, treatment omitted or stopped.
There is more information available on immunotherapy for breast cancer at Cancer Research UK and Macmillan Cancer Support.
What if I am a BRCA 1 or BRCA 2 gene mutation carrier?
An altered BRCA 1 or 2 gene can mean breast cancer runs in families. Most breast cancers caused by BRCA1 are triple negative. If you have triple negative breast cancer, you may be offered genetic testing, even if you do not have a family history of breast cancer.
People with Metastatic TNBC who carry BRCA 1 or BRCA 2 mutations make up about 1 in 5 of all those with TNBC triple. If they have previously had certain chemotherapy (unless that treatment is not suitable) they may be offered talazoparib (or Talzenna) a tablet taken as a newly available alternative to chemotherapy through the NHS. This is not chemotherapy or immune-therapy. Rather, it is a targeted therapy, often referred to as a PARP inhibitor because of how it works.
Talazoparib shrinks or controls the cancer for longer than chemotherapy, delaying the point at which the cancer starts to get larger or to progress. Treatment continues so long as talazoparib is not causing too many side effects and is controlling your cancer. Talazoparib does not, however, cure metastatic disease
Although not chemotherapy, talazoparib can have significant side effects that may lead to the dose being reduced, treatment delayed or even stopped.
There is more information available on PARP inhibitors for breast cancer at Cancer Research UK and Macmillan Cancer Support.
Are there other new treatments for Metastatic Triple Negative Breast Cancer?
Another new drug is an “antibody drug conjugate”, a mixture of the conventional and the new.
Govitecan is a chemotherapy drug that kills cancer cells but also normal cells so that it cannot be used on its own. Sacituzumab is a monoclonal antibody that homes in on a protein present on the surface of many cancer cells; although triple negative cancer cells lack ER, PR and HER2 they often do have the TROP-2 receptor on their surface, which sacituzumab targets.
Together, as the drug sacituzumab govitecan (Trodelvy), the cytotoxic is delivered mainly to TNBC cells while sparing normal cells. Sacituzumab govitecan can, however, cause side effects including a fall in the blood count with a risk of infection, and diarrhea that you should discuss with your cancer team.
Sacituzumab govitecan is given intravenously every 3 weeks and is more effective than “ordinary” chemotherapy, with patients on average living longer.
Sacituzumab govitecan is available through the NHS for people with metastatic TNBC without the need for any extra special tests; they must, however, have received 1 or 2 previous lines of chemotherapy for metastatic disease. Your cancer team will explain what this means for you.
You can find more information available on antibody drug conjugates, including sacituzumab govitecan breast cancer, on the Cancer Research UK and Macmillan Cancer Support web-sites.
Why is the treatment of Metastatic Triple Negative Breast Cancer so complicated?
It’s complicated, at least in part, because we now realise that there are different types of triple negative breast cancer, with more and different treatments becoming available.
If PD-L1 levels in the cancer are high, atezolizumab or pembrolizumab (given with chemotherapy) should be considered. For patients carrying an altered BRCA 1 or BRCA 2 gene talazoparib is now available as an alternative to chemotherapy. And we also have the option of targeted chemotherapy with sacituzumab govitecan in people who have already received conventional chemotherapy.
These new treatments are adding to the options open to people with TNBC because, in addition, we still have conventional chemotherapy that can be used whatever the type of TNBC. Moreover, we have a better understanding of which of those chemotherapy drugs are more likely to control metastatic triple negative breast cancer.
This is all good news because it means there are more, and better new treatments becoming available, although there is not a “one size fits all” approach to treating people with metastatic TNBC.
There is more to do, but we are entering an era when people with metastatic TNBC are living longer and living better than before!
Frequently asked questions about advanced/metastatic TNBC
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When cancer has spread to a part of the body outside the breast, it is called advanced or metastatic breast cancer, sometimes called Stage 4.
Like other types of advanced breast cancers, advanced/metastatic triple negative breast cancer cannot be cured; it can, however, be treated and controlled.
The main treatment is chemotherapy, and it is now better understood which chemotherapy drugs are likely to work best in people with triple negative breast cancer.
It is also possible to be tested to show if the addition of immunotherapy would be of benefit. In people with advanced/metastatic TNBC immunotherapy increases the efficacy of chemotherapy in people whose cancers test positive for PD-L1; this test can be carried out in local laboratories. These immunotherapy drugs, atezolizumab or pembrolizamab, work best when used with chemotherapy as the first line of treatment for advanced/metastatic TNBC.
There is also a new targeted chemotherapy treatment, sacituzumab govitecan, for people with TNBC who have already received other chemotherapy for advanced/metastatic disease.
For people whose cancers test positive for BRCA1 or 2 gene mutations, a new oral targeted drug treatment , talazoparib, is available.
Other treatments are being tested in clinical trials, for which you may be eligible.
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When you have been told your triple negative breast cancer has spread outside the breast, and has become ‘advanced’ or metastatic, as a parent or carer, one of the first things you may think about is ‘how am I going to tell the children’?
The Ruth Strauss Foundation Family Support Team are there to support and guide you through those very difficult conversations.
You can self-refer to the Family Support team via their website. They support families across the UK and their support is free.
Or you may just want to look at their helpful Guide to starting conversations.
Visit the Ruth Strauss Foundation Foundation website here for more information.
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Treatment for early stage/primary triple negative breast cancer will, for many people, result in them being cured. However, for others, the cancer can return and spread outside the breast area. This is because some of the ‘seedlings’ or metastases from the original breast cancer had spread into the blood stream, and eluded (neo)adjuvant drug therapy.
These seedlings or metastases can grow and develop in different parts of the body but it will usually still be triple negative breast cancer. Other types of early/primary breast cancer can spread in this way, but it happens more often with TNBC. This is why TBNC is sometimes said to be more “aggressive”.
There are many and varied symptoms for advanced breast cancers depending on where it has spread to. A comprehensive description of what to look for is available on make2ndscount.co.uk.
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Advanced or metastatic TNBC, like other types of advanced/metastatic breast cancer, is not curable. It can, however, be treated and controlled to provide as long and fulfilled a life as possible.