Secondary Breast Cancer: What You Need To Know

There are around 55,900 new cases of invasive (stage 2 or higher) breast cancer diagnosed in the UK every year, which is more than 150 every day (CRUK). It is the most common cancer in the UK (15% of cases, mostly people assigned female at birth [AFAB]). Of these cases, 20-30% will develop secondary breast cancer (Medscape). Secondary breast cancer refers to breast cancer which has spread from the breast and local lymph nodes to another site in the body, most commonly the liver, lungs, brain and/or bones. It is also called metastatic breast cancer, advanced breast cancer or stage IV (4) breast cancer. It occurs when the primary tumour or cancer becomes more advanced and sheds some of its cells into the bloodstream or lymphatic system, allowing them to travel around the body and collect at a new site, where they may grow into a secondary tumour. The cancer cells at the new site are still breast cancer, but the disease is not the same. At this stage, breast cancer is no longer curable but may be controlled by treatment to allow survival for several more years. This is well described in an excellent blog here.

Stages of Breast Cancer

What does ‘stage 4 breast cancer’ mean? Breast cancer stages are complex and there is more than one way of calculating them. One method of characterisation describes them as:

• Stage 0: Pre-invasive breast cancer called ductal carcinoma in situ (DCIS). The cancer cells in the primary tumour have not begun to spread into the surrounding breast tissue.
• Stage 1: the cancer is small at this stage and only found in the breast tissue or possibly in lymph nodes close to the breast.  This is also known as early stage breast cancer.
• Stage 2: Breast cancer is either in the breast or in the nearby lymph nodes, or both.
• Stage 3: The breast cancer has spread to the local lymph nodes and possibly to the skin of the breast or to the chest wall.  This is also called locally advanced breast cancer.
• Stage 4: This is advanced, secondary or metastatic cancer, and has spread to other parts of the body.

Metastatic breast cancer is always classified as stage 4, no matter the primary site in which it arises.

Types of Secondary Breast Cancer

Breast cancer can metastasise (spread) to any part of the body (CRUK) but most commonly spreads to the:

• Lungs
• Brain
• Liver
• Bones
• Lymph nodes
• The opposite breast

In each of these places, metastatic cancer will produce its own symptoms.  

According to the Mayo Clinic and CRUK, there are several subtypes of breast cancer, based on whether they are invasive or not, their original location (e.g. duct or lobule), their appearance, and genetics. Cancers in epithelial tissues of the milk duct and lobules are called carcinomas, those occurring in connective tissue are called sarcomas. Types include:

• Invasive breast cancer
• Invasive lobular breast cancer
• Angiosarcoma of the breast
• Phyllodes tumour (sarcoma)
• Inflammatory breast cancer
• Ductal carcinoma in situ
• Lobular carcinoma in situ
• Breast cancer in men
• Paget’s disease of the breast
• Triple negative breast cancer 

The appearance of breast cancer cells is graded according to the following criteria:

• the arrangement of the cells in relation to each other
• whether they form tubules (gland formation)
• how similar they look to normal breast cells (the nuclear grade)
• how many of the cells are dividing (the mitotic count)

In low grade (grade 1) tumours, the cells look very similar to normal breast cells and are slow growing. These are called well differentiated cancers. These cancers tend to grow and spread slowly and have a good outlook for the patient (prognosis).

Intermediate grade (grade 2) cancers have cells that look different to normal breast cells. They are known as moderately differentiated. The outlook (prognosis) is moderately good,  somewhere between grade 1 and grade 3. 

In high grade (grade 3) cancers, the cells are very different to normal breast cells and are faster growing, these are poorly differentiated cancers and have abnormal features. They tend to grow and spread quickly and have a poor prognosis. These cancers are more likely to come back (recur, see below) after they have first been treated.

The genetics of breast cancer cells is very complex. Some breast cancers are driven by hormones, and may express the oestrogen receptor (ER-positive), the progesterone receptor (PR-positive), or may not have hormone receptors (HR-negative), this type being insensitive to hormones.  A biopsy of cancer might also be tested for the presence of too many copies of the HER2 gene.  The HER-2 (human endothelial growth factor receptor-2) protein is associated with a subtype of breast cancer.  Doctors classify breast cancers genetically as:

• Group 1 (luminal A). This group includes tumours that are ER-positive and PR positive, but negative for HER2.
• Group 2 (luminal B). This type includes tumours that are ER-positive, PR negative and HER2 positive.
• Group 3 (HER2 positive). This type includes tumours that are ER negative and PR negative, but HER2 positive.
• Group 4 (basal-like). This type, which is also called triple negative breast cancer, includes tumours that are ER-negative, PR negative and HER2 negative.

Understanding the genetic and chemical makeup can drive decisions about treatment strategy.  For example there are targeted therapies that only work against HER2 positive cancers, i.e., groups 2 and 3. Triple negative cancers are particularly hard to treat. 

Symptoms of Secondary Breast Cancer

According to CRUK, there are several general symptoms of secondary breast cancer. These are: 

• Feeling tired
• Low energy levels
• Feeling under the weather
• Having less appetite
• Unexplained weight loss

However, all these symptoms could be explained by other illnesses, or by primary cancer if it is still present.

Symptoms of Breast Cancer Spread to the Liver

Symptoms if breast cancer that has spread to the liver might include:

• Tiredness
• Discomfort or pain on the right side of your tummy (abdomen) where the liver is
• Feeling sick (nausea)
• Loss of appetite
• A swollen abdomen
• Yellowing of the skin or itchy skin (jaundice)

Some or all of these symptoms are common in other conditions too, so remember that they could be due to something else, such as cancer treatment or hepatitis. They do not necessarily mean you have secondary cancer.

Symptoms if Breast Cancer has Spread to the Lungs

Symptoms if cancer has spread to the lungs might include:

• A persistent cough
• Shortness of breath
• Ongoing chest infections
• Weight loss
• Chest pain
• Coughing up blood
• A buildup of fluid between the chest wall and the lung (pleural effusion)

A pleural effusion prevents the lungs from expanding fully. When you breathe in, it can cause shortness of breath, achy chest, discomfort and heaviness. These symptoms can also occur in other conditions such as COPD, so if you have them, it would always be wise to consult your doctor.

Symptoms if Breast Cancer has Spread to the Brain

Brain metastases can cause different symptoms depending on which part of the brain is affected, but these could include:

• Headaches
• Weakness or numbness in your limbs
• Memory problems
• Behaving in a way that is unusual for you
• Feeling or being sick
• Seizures (fits)
• Changes to your eyesight such as loss of sight (vision)
• Confusion and difficulty understanding
• Difficulty speaking (dysphasia)

Again, these symptoms don’t necessarily mean you have secondary cancer, but you should consult a doctor if you are worried.

Tests to Diagnose Secondary Breast Cancer 

Tests done to diagnose secondary breast cancer will partly depend on the site of metastasis suspected. Blood tests may be done initially, but with the exception of blood cancers, they generally can't tell whether you have cancer or some other noncancerous condition. However, blood tests can give your doctor clues about what's going on inside your body by including serum chemistry and complete blood counts (CBC), as well as testing for cancer markers. 

There are several different definitive tests you might undergo to diagnose secondary breast  cancer, which often spreads to sites including lymph nodes, liver, lung, bone, and brain:

• Blood tests. Tests might check how well the liver, kidneys or bone marrow are working or to check the level of calcium in your blood. Blood tests can also measure tumour markers for secondary breast cancer.
• Bone x-ray.  If you have painful areas in the bones you may have this test.
• Bone scan. A bone scan can check the results of a bone x-ray.
• Chest x-ray. This will look for secondary breast cancer in the lungs, and also key tell-tales like pleural effusion (fluid around the lungs). It may be followed up by a lung CT scan.
• Liver ultrasound. Likewise, this will examine the liver for secondary cancers.
• MRI scan. MRI scans build up a detailed 3D image of the body using magnetic radiation and can help spot new cancer sites.
• CT scan. A CT scan uses a whole series of x-ray images to build up a 3D picture of the body, or part of the body, like the lungs. It is used to detect metastasis in other organs such as the lungs, brain or lymph nodes.
• PET-CT scan. This scan is a combination of a CT scan and a positron emission tomography (PET) scan, which uses an injected radioactive marker substance to highlight anomalies within the body.
• Biopsy. If a suspected cancer is detected by other tests, the doctor may take a tissue sample of it (biopsy) in order to carry out further tests to identify the cell types present.  This will confirm the cancerous or non-cancerous nature of the anomaly.

What Causes Secondary Breast Cancer?

According to MacMillan, risk factors for secondary breast cancer are the same as for primary breast cancer. These are:

• Age
• History of previous breast cancer
• Certain breast conditions
• Breast tissue density
• Hormonal factors
• Family History or risk of breast cancer
• Smoking
• Alcohol
• Being overweight

However, there are several other factors that increase the overall risk of secondary cancer.  These include:

• More than 40 genes alter susceptibility to secondary cancer.
• Drug-metabolising enzyme polymorphisms, alter cancer drug breakdown and affect toxicity.
• Chemotherapy agents (drugs). The cancers most often linked to chemotherapy are myelodysplastic syndrome (MDS), acute myelogenous leukaemia (AML) and acute lymphocytic leukaemia (ALL). The risk gets higher with higher doses, longer treatment time, and higher dose intensity (more drugs given over a shorter period of time).
• Radiation therapy. Radiation exposure is one risk factor for several kinds of leukaemia, including AML, chronic myelogenous leukaemia (CML), and ALL. There is also an increased risk of solid tumours.

Chemotherapy is known to be a greater risk factor than radiation therapy in causing leukaemia. 

Local and Regional Recurrence

When cancer comes back after treatment, this is called a recurrence. There is more than one type of recurrence (BreastCancerNow):

• Local recurrence: if cancer recurs in the chest, breast, armpit area or the skin near the original site or surgery scar, this does not mean cancer has spread.
• Regional recurrence: also known as locally advanced breast cancer.  If breast cancer has spread to the chest wall or skin of the breast, or the lymph nodes around the chest, neck and under the breast bone, but has not spread to other areas of the body, it’s called a regional recurrence. Sometimes, when breast cancer is diagnosed, it is already locally advanced.
• Secondary breast cancer: when the breast cancer recurs but at a different site, perhaps because a few cancer cells were left viable after treatment and spread around the body.

A recurrence, after breast-conserving surgery or a mastectomy, with or without reconstruction, might manifest in the chest area, on either side, as:

• swelling on your chest, in your armpit or around your collarbone
• a change in shape or size
• a change in skin texture, such as puckering or dimpling
• redness or a rash on or around the nipple or on the skin
• liquid (discharge) that comes from the nipple without squeezing it
• the nipple has become inverted (pulled in) or looks different, for example, changed its position or shape
• swelling in the arm or hand
• a lump or thickening that feels different (with your treated breast this could be on or away from the scar line)

Symptoms of a recurrence at another site in the body are described above under ‘Symptoms of Secondary Breast Cancer.

Tests done if a recurrence is suspected in the breast or chest area include:

• mammogram
• ultrasound scan
• core biopsy
• punch biopsy
• fine needle aspiration (FNA)

If a secondary recurrence is suspected, the tests will be as described under ‘Tests to Diagnose Secondary Breast Cancer.

Living with Secondary Breast Cancer

Survival rates for breast cancer are very high (CRUK). Five year survival rate after diagnosis for stage 1 breast cancer is now 98-99%. Survival for breast cancer in general is now 75% at ten years. Generally, the more advanced the cancer, the lower the survivability, but even at stage 4 it is 25% after five years. At this stage, the cancer can’t be cured but it can be managed with treatment. 

This means that the needs and concerns of those living with metastatic breast cancer in the longer term becomes a significant consideration. Fortunately there are many online resources and support groups to help with this. Living with secondary breast cancer is physically, financially, and emotionally demanding (Macmillan), involving physical changes to the body, doctor visits, and the side effects of cancer therapies, plus the added stresses of paying bills when you may not be able to work. For some, the shock of the initial diagnosis is the worst. The uncertainty of living with secondary breast cancer can be the hardest part for many people. You may experience stress, anxiety, and even depression as a result of these feelings. 

There may be long periods between treatments when the cancer is under control and some semblance of normal daily life can return. During these times it is important to care for yourself and get emotional support. Make sure you get enough rest and exercise. All of these will improve your quality of life. In addition, you might need to seek emotional support. This could come from family and friends, healthcare professionals, counselling,  support groups, or online forums. When symptoms recur, principally pain, fatigue, and breathlessness, it is time to turn to your clinical team for help as all these can be managed.

You can get much more detailed advice and information about living with secondary breast cancer at the Breast Cancer Now website and Breastcancer.org. You might also find it helpful to read this blog on FredHutch.org.

FAQs

• Can metastatic breast cancer go into remission?
  • While metastatic breast cancer may not go away completely, treatment may control it for a number of years. Cancer can be active sometimes and then go into remission at other times.
• What is the wide window of relapse in breast cancer?
  • In contrast with other cancers like lung cancer, where relapse and recurrence can occur within weeks of surgery, the metastatic recurrence of breast cancer typically spans months to decades after surgery. The reasons for the width of the window are still unclear but may be related to the different subtypes of breast cancer, e.g., HER2 positive and luminal cancer.¹ 
• How long can you live with secondary breast cancer?
  • After five years, 25% of women with metastatic breast cancer are still alive.
• Is secondary breast cancer always terminal?
  • Secondary breast cancer can be controlled, often for many years, but it cannot be cured. Because of new and improved treatments, women with secondary breast cancer are living longer.
• Where is the first place breast cancer spreads to?
  • The lymph nodes under your arm, inside your breast, and near your collarbone are among the first places breast cancer spreads. It's only “metastatic” if it spreads to other parts of your body.
• How likely is secondary breast cancer?
  • Between 20% and 30% of women with a primary diagnosis of breast cancer will go on to develop secondary breast cancer.