We hear about breast cancer on almost a daily basis, yet many people have never heard of secondary breast cancer even though the disease kills on average 1,000 people every single month in the UK alone.
In 2018, 2019, 2020, & 2021 breast cancer was the leading cause of death for females aged 35 to 49 in England and Wales. In Scotland, breast cancer is the most common cancer in women and in 2020 and 2021 was the second most common cause of cancer death in women.
What is secondary breast cancer?
Secondary breast cancer, also known as metastatic, advanced or stage 4 breast cancer, is breast cancer that has spread beyond the breast to other parts of the body. It occurs when the initial breast cancer cells (primary breast cancer) spread through the blood stream or lymphatic system to other parts of the body and this process is called metastasis.
Parts of the body affected are usually the bones, liver, lungs, brain or the skin. Secondary breast cancer may be diagnosed years after primary breast cancer. Researchers estimate that 35% of people with primary breast cancer will develop secondary breast cancer within 10 years of their initial diagnosis. It is estimated that approximately 5% of people with breast cancer already have secondary tumours at the point of diagnosis. This is classified as being diagnosed ‘de novo’.
Secondary breast cancer can be treated but it cannot be cured. Treatments aim to control and slow down the growth and spread of the disease to enable patients to have the best possible quality of life for as long as possible.
Invasive ductal carcinoma (IDC)
Invasive ductal carcinoma (IDC) is the most common type of invasive breast cancer and starts in the milk ducts of the breast. Cancer cells can break through the wall of the milk duct and begin growing into nearby breast tissues. From here the cancer cells can spread through the lymphatic system and bloodstream to other parts of the body. IDC most commonly metastasises to the bones, lungs, brain and liver.
Invasive lobular carcinoma (ILC)
Invasive lobular carcinoma (ILC) is another common invasive breast cancer that begins in the breasts milk producing glands (lobules). ILC can metastasise to the same sites as IDC, as well as the gastrointestinal tract, reproductive organs, abdominal lining, as well as other sites. Unfortunately, the risk of primary breast cancer metastasising is not fully understood or easy to predict.
How are metastases formed?
Metastasis is when cancer cells spread to other sites in the body. Any new tumours that grow at new sites are called metastases, which is the plural term for metastasis. For metastases to develop, cancer cells must go through a complicated process, this is referred to as the metastatic pathway (Figure 1). It involves the following steps:
- The cancer cells break away from the primary tumour site and invade the nearby normal tissue.
- The cancer cells enter the blood or lymphatic system.
- The cancer cells travel through the blood or lymphatic vessels until they reach the target site, such as the bones, lungs, liver, brain etc.
- Once at the target site, the cancer cells leave the blood or lymphatic vessels and start to grow, forming secondary tumours.
Figure 1. The metastatic pathway: 1) Cancer cells detach from the primary tumour site and invade the surrounding area of normal tissue 2) cancer cells invade the blood or lymphatic system 3) cancer cells travel through the blood or lymphatic vessels to reach target sites 4) cancer cells exit the blood or lymphatic vessels and form a secondary tumour at the target site e.g. the lungs.
During this process many cancer cells often die along the way. However, if conditions are right at each step of the process, cancer cells may be able to form tumours at new sites in the body. Once cancer cells reach a secondary site they do not always turn into aggressive tumours, they can stay inactive for a while, or permanently.
How many patients are living with secondary breast cancer?
The exact number of secondary breast cancer patients living in the UK is currently unknown as no central registry is kept. An NHS funded National Metastatic Breast Cancer Audit is planned for England and Wales. Northern Ireland is also planning an audit and Scotland might plan one in 2023.
A recent research estimate from NHS England data estimates that the number of patients living with secondary breast cancer in England was over 57,000 in 2021. The findings of this study showed that estimates for the number of secondary breast cancer patients have increased steadily and risen from 38,350 patients in 2016-2017.
How is secondary breast cancer diagnosed?
Medical imaging techniques are tests that can be done to see if the cancer has spread. These tests are helpful for your care team to understand how far and where the cancer has spread. Some commonly used imaging techniques include:
- X-ray: This takes pictures of the inside of your body to look for cancer in tissues, bones and organs.
- Ultrasound: This uses sound waves to create pictures of your body and can help find tumours that do not show up well on X-rays.
- PET scans: This test shows the differences in the activity of certain tissues in the body and highlights active cancer cells.
- CT scans: This creates a 3D image of any part of the body and can help to determine tumour shape and size.
- PET-CT scans: This test combines PET and CT scans to identify areas in the body with increased cell activity and creates a detailed 3D image of these areas.
- MRI scans: A strong magnet and radio waves are used to identify cancer and look for signs of metastasis.
A tumour biopsy helps your care team to understand characteristics of the metastatic breast cancer. It involves a small sample of tissue being taken from the secondary tumour and looking at it under a microscope. The sample can be taken from many parts of the body, including lymph nodes, lungs, liver, bone, skin or bodily fluids. Owise has a blog to help with understanding your pathology report.
Why do I need a biopsy?
In metastatic breast cancer, tumour biopsies are done to check if the features of the cancer have changed since the primary diagnosis. The cancer cells in the secondary tumour might have different features compared to the primary tumour, such as oestrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) present on the cell surface. This is important information as treatment decisions based on the receptors of the primary breast cancer may not always be suitable for the treatment of the secondary breast cancer.
Types of biopsy
Although tissue biopsies are more common, it is also possible to have a liquid biopsy. This involves taking a sample of bodily fluid (e.g. blood, saliva) to detect and analyse cancer cells or cancer cell DNA. Liquid biopsies can find genetic mutations in cancer cells, see if certain treatments are suitable, and monitor how well treatment is working22. They are useful when a tissue biopsy cannot be done or when quick results are needed. However, results from a liquid biopsy are often used along with tissue biopsy results to guide the treatment decisions.
What is de novo metastatic breast cancer?
It is important to note that in some cases patients can be diagnosed with secondary breast cancer at the initial diagnosis,this is called de novo metastatic breast cancer. Research has found that 3.8% of women were diagnosed with de novo metastatic breast cancer, compared to 5.8% of men. Male breast cancer forms 1% of all breast cancer diagnoses but their breast cancer is often diagnosed at later stages. Tissue biopsies are useful in this scenario to determine the features of the cancer and develop a treatment strategy.
Molecular testing involves testing a biopsy sample for biomarkers that are associated with cancer growth and spread. These biomarkers can include genes, proteins, or other material. This may provide further insights about what characteristics could be targeted with treatment (Table 1).
How are genetic/genomic tests useful?
Tumour genomic tests can be used to measure the expression of certain genes in a biopsy sample. Measuring the expression of genes is useful to determine how likely a gene is to affect the behaviour of the cancer, including how likely it is to grow and spread.
For secondary breast cancer, genetic tests such as next generation sequencing (NGS) or sequencing panels are being developed. These tests can provide information about the weaknesses or vulnerabilities of the tumour. They can also help determine if certain changes in genes can make a person eligible for specific treatment. For example, a mutation in the PIK3CA gene could make a secondary HR+/HER2- patient eligible for treatment with alpelisib (Piqray®, Table 1).
What are the treatment options for secondary breast cancer?
Although secondary breast cancer cannot be cured, there are treatment options that can help to manage the spread of the cancer, improve quality of life, and maintain overall health and wellbeing. The treatment approach depends on factors such as the type of breast cancer, where it has spread, genetic factors, and previous treatments received. Keep an eye out for our later blog posts in this series for more information on specific treatment options for secondary breast cancer.