Understanding breast cancer metastasis

Metastasis is a complex process in which malignant
cancer cells from the breast spread into other regions of the body. Once metastasis has occurred, it is much more difficult to effectively treat breast cancer.

If breast cancer has metastasized to other areas of the body, it is termed a ‘Stage IV‘ breast cancer. Sometimes metastasis has occurred at the time the original breast cancer is diagnosed.

However, in other cases, the metastasis of breast cancer is found months or even years after the initial treatment. This would be termed a ‘recurrent’ breast cancer.

How does cancer actually spread from the breast to around the body.

Okay, let’s take a look …

How Do Breast Cancer cells spread around the Body?

Breast cancer cells travel through the body like any other cancer cells. Firstly, cancer cells can invade neighbouring healthy tissue. Following this, the cancer cells then invade local lymph nodes or blood vessels.

When breast cancer spreads to the axillary lymph nodes (under the arm) this is still a relatively early stage of metastasis, and potentially curable.

The cancer cells will typically travel through the lymphatic system or blood vessels to other distant parts of the body.

How do you know if there is cancer in the lymph nodes?

Sometimes the affected lymph nodes will become swollen. However, often there are no symptoms and a biopsy will determine cancer cells in the lymph nodes.

Distant metastasis

Once the breast cancer travels beyond the lymph nodes to other parts of the body, it is termed a ‘distant’ metastasis, and this is not curable.

However, cancer cells can remain inactive for many years at a distant site, causing no problems or symptoms.

If breast cancer has metastasized beyond the lymph nodes it is termed a systemic disease. This means that the whole body must be treated and not just a particular area. The only way to effectively treat the whole body is usually through chemotherapy and hormonal therapy.

Treatment is aimed at slowing the progression of the disease process and controlling symptoms.

Mechanisms of Breast Cancer Metastasis

No one really knows what factors will make a certain patient more or less susceptible to breast cancer metastasis.

There is growing awareness that part of that susceptibility is due to ‘host factors’. The host factors are the characteristics of the non-malignant cells and the general biological environment surrounding the malignant breast tumor.

Sometimes the host factors are referred to as the pre-metastatic niche and it is thought that bone-marrow-derived progenitor cells may directly influence the dissemination of malignant cells to distant areas.

Non-neoplastic ‘host cells’ within the tumor may also play a key role in the regulation of breast cancer metastasis.

Where does the cancer spread to,
Doc?

Well, breast cancer cells can spread to any part of the body. However, say the breast cancer spreads to the bone, the treatment will continue for breast cancer and the cells will still be breast cancer cells rather than bone cells.

Wow! I never knew that!

Breast Cancer Metastasis: Secondary Sites

Over the years there have been significant improvements and advancements in the diagnosis and treatment of breast cancer. Indeed, breast cancer is now considered to be a manageable disease.

However, there are still over half a million deaths worldwide from breast cancer and over 90% of these women die of metastasis. Consequently, research into metastasis is of vital importance in overcoming deaths from metastatic breast cancers.

Stage IV or metastatic breast cancer, as mentioned earlier, are cancer cells that have spread from the breast to distant sites around the body. Common secondary sites are:-

Bone: (Most common secondary site occurring in around 70% of metastatic breast cancer cases).
Lungs
Regional lymph nodes
Brain
Liver

Attitude is a little thing that makes a big difference.

Yes. A positive attitude may not solve everything, but it will annoy enough people to make it worthwhile!

De novo metastatic Breast Cancer and Recurrent Breast Cancer

It is important to understand the two types of Stage IV Breast Cancer and the differences between them:-

De Novo metastatic breast cancer: This term refers to women who are Stage IV at the initial diagnosis of breast cancer. That is, cancer has already spread to other parts of the body. De novo metastatic breast cancer accounts for only around 6% of cases at diagnosis in the US.
Recurrent Breast Cancer: More often, breast cancer returns or spreads after the initial diagnosis and treatment of breast cancer. This recurrence can happen months, or even years, after the first presentation and treatment.

Just when I think I have learned how to live, life changes.

Survival Rates for Stage IV Breast Cancer

Stage of breast cancer at diagnosis is one of the most important prognostic factors. Above is a bar chart from the National Cancer Institute (SEER) statistics for 2012. As we can see, the 5-year survival rate for women diagnosed with Stage IV breast cancer was 22%.

Remember, these figures are still quite dated as it takes 5 years to determine survival rates and treatment is improving all the time.

A recent study found that 37% of women survived for three years after a Stage IV breast cancer diagnosis, although some women do survive longer.

However, although the 5-year survival rates are much higher for earlier stages of breast cancer at diagnosis, there is no predicting which cases will progress to metastatic breast cancer in the future.

I believe that the most recent 5-year survival rate for Stage IV breast cancer is 26% (SEER results 2016).

Although it is important to be realistic regarding the survival of metastatic breast cancer, each individual situation is unique and ultimately, statistics are meaningless.

There is a small subcategory of people with Stage IV breast cancer (about 2%) who beat the odds and live for years. However, it is difficult to predict who will fall into this group.

All that is known is that people in this group have secondary spread to the bones. Furthermore, cancer is often estrogen positive and responds to hormone treatments.

Recurrent Breast Cancer: Facts and Figures

Breast cancer can return at any point after the initial diagnosis and treatment. This is one of the most anxiety-provoking factors for many women after breast cancer diagnosis and treatment.

There are 3 types of cancer recurrence:-

Localized: The cancer returns to the original site where it started.
Regional: The cancer has spread to nearby lymph nodes, tissues or organs
Distant: The cancer has spread to distant body sites such as the bone, brain, liver or lungs.

It is very difficult to predict how many breast cancers of all stages recur, at local, regional and distant sites.

Indeed, breast cancer incidence and mortality rates are documented over the years. However, data on most cancer registries do not document the incidence of recurrence.

Furthermore, a local or regional recurrence does not have the same prognostic impact as distant metastasis. Even more difficult to handle, is that cancer can recur at any given point in time.

Many women who have been initially, successfully treated for breast cancer feel that they are living with a time bomb.

That’s right, 22% to 74% of breast cancer patients fear recurrence (depending on how the question is asked).

Sometimes, I’m scared to be too happy, because that means something bad may happen.

Are there any statistics on Recurrence rates or incidence of Metastasis?

As mentioned, it is very difficult to find statistics on metastatic breast cancer that has recurred after initial diagnosis. However, these cases represent a large proportion of Stage IV breast cancer cases and overall deaths.

Most of the statistical data on Stage IV or metastatic breast cancer is from those women presenting at diagnosis. According to the Metastatic Breast Cancer Network (MBCN) in 2012 new cases of Stage IV breast cancer were between 13,776 to 22,096.

The number of breast cancer recurrences at Stage IV is estimated to be between 20% and 30% of all breast cancer diagnoses.

As a side issue Doc, what do you think of the alkaline diet as a natural eating plan for cancer?

Funny you should ask that.
I have a new post on the alkaline diet with lots of research and here it is.

A note from Dr Halls regarding the Statistics for Metastatic Recurrence in Breast Cancer

The statistic of 20% to 30% for metastatic breast cancer that recurs remain controversial amongst medical experts. The figure of 30% metastatic breast cancer recurrence rate first appears in a 2005 medical study, but no statistical data or sources are cited.

The MBCN take the 18-year relative survival rate from the SEERS data between the years of 1990 to 1994 as 71%. The argument is, that this takes us close to the 30% recurrence rate statistic. However, there are many other factors at play and treatment has advanced so much that recurrence rates may have even halved since then.

It is safe to say that much more data and research into metastatic recurrence rates would be of huge value towards a long-term cancer cure.

Indeed, it has also been suggested that research into the rare group of women who survive many years with metastasis may be of equal importance to understanding recurrence and patterns of breast cancer.

How can you predict which cancers will recur at a later date?

Now that is the million dollar question. The answer is we can’t, exactly, at the moment.

What are the chances of breast cancer recurring?

Despite huge advancements in breast cancer screening, early detection and treatment, a percentage of breast cancers will recur and spread to distant sites.

Although at the moment, it is almost impossible to say which cancers will recur and at what time period from diagnosis, there are a few factors that are known to increase the risk for recurrence.

These risk factors include:-

(i) Lymph node involvement and number of lymph nodes affected at the time of diagnosis
(ii) Tumor Size at the time of diagnosis
(iii) A subtype of Breast Cancer and hormonal receptor Status
(iv) The time span from the initial diagnosis to recurrence of breast cancer

Let’s have a more in-depth look at some of these factors

Okay then Doc, I’ll grab the donuts …

(i) Lymph Node Involvment

Whether or not cancer has spread to nearby or distant lymph nodes, is part of the staging process for cancer, and also an important prognostic factor for survival.

Furthermore, the number of lymph nodes affected remains a prognostic factor too with the more lymph nodes affected, the poorer the long-term prognosis.

A 2013 medical study from China examined 2,591 patients with breast cancer, all of whom had adjuvant chemotherapy following surgery.

The 5-year overall survival rates were 89.3% and the 5-year disease-free survival rate was 81.6%. Likewise, the 10-year overall survival rate was 78.8% and the 10-year disease-free survival rate was 83.5%.

This medical study found that the use of the lymph node ratio was an independent predictor of survival for Chinese patients with breast cancers. Furthermore, the lymph node ratio is superior to assessment of the number of positive lymph nodes alone in determining disease prognosis.

The Lymph Node Ratio is defined as:-

“…the number of positive lymph nodes over the total number of lymph nodes removed.“

It’s all about size. How big is TOO big, Doc?

(ii)Tumor Size

In general, the overall survival of women with breast cancer decreases as the size of the tumor increases.

A 2012 review examined 1,894 invasive breast cancer cases in relation to the size of tumor in both lymph node positive and lymph node-negative patients.

The study found that tumor size can be a strong predictor of 15-year survival in breast cancer cases with and without lymph node involvement. However, in some cases, the subtype of cancer plays a role too, with some small tumors behaving in a very aggressive way.

However, Narod found that for every 1 cm decline in tumor size the 15-year mortality rate decreased by 10.3% in the node-positive group and by 2.5% in the node-negative group.

A decline of 1.5 cm in tumor size was associated with a 23% reduction in the node-positive group and 10.8% in the node-negative group.

Although this medical study shows the relevance of tumor size and survival rates, interestingly, the impact of tumor size on 15-year survival was greater in women with node-positive tumors.

What does that mean, Doc. About the node-positive tumors?

This means that breast cancer screening is equally important for women after regional spread.

(iii) Breast Cancer Subtypes, hormonal and HER2 Status

Although the term ‘breast cancer’ is used in general, there are many different sub-types of breast cancers. The sub-types behave in different ways, with some responding better to treatments and some growing and spreading at faster rates.

Obviously, the sub-type of breast cancer affects survival rates.

There are 5 molecular types of breast cancer:-

Luminal A: This type of breast cancer is hormone receptor-positive (ER+ and/or PR+) and HER2 negative. Furthermore, Luminal A cancers tend to be low-grade and slow growing. These tumors respond well to hormone therapy.
Luminal B: These tumors are ER+ and can be HER+ or HER-. Luminal B cancers tend to grow faster, be of a higher grade and larger tumor size.
Triple negative/basal-like. As the name suggests these tumors are ER- PR- and HER-. Triple-negative breast cancers have a poorer prognosis and do not respond as well to treatment.
HER2-enriched: ER- PR- and HER2 positive. These tumors used to have a poor prognosis but since targeted therapy survival rates have improved.
Normal-like: These cancers are hormone receptor positive and HER2 negative. Normal-like breast cancers have a good prognosis.

This is all very complicated, Doc.
What does it mean?

Yes, there are so many factors in trying to predict which breast cancers will spread, when and why.

Breast Cancer Subtypes, hormonal and HER2 Status and Survival Rates

Many research studies over the years have shown that Estrogen-positive (ER+) breast cancers have better survival rates (when adjusted for all factors) than all of the Estrogen-negative (ER-) subtypes.

Progesterone-positive (PR+) breast cancer also appears to have improved survival rates in comparison to progesterone-negative (PR-) cases.

A recent research study combines hormone receptivity, HER2 status and stage and found some interesting results:-

For ER+ sub-types (ER+ PR+ HER2-) survival rates were significantly better than all other subtypes. For example, at stage 1b,

ER+ PR+ HER2- 5-year survival rates were 98.6%
ER+ PR- HER2+ 5-year survival rates were 97.3%

The subtype triple negative (ER- PR- HER2-) breast cancer had the worst survival rates over all three stages. At stage I the 5-year survival rate was 92.9% and at stage III 48.9%.

(iv) Disease Free Intervals and Prognosis in Metastasis

The time that passes between the primary diagnosis and treatment of breast cancer and a diagnosis of metastasis is also of prognostic significance.

A 2015 medical study from the Netherlands looked at 815 patients with metastatic breast cancer between 2007 and 2009 in eight hospitals.

Of these 815 patients, 154 had metastatic spread (Stage IV) at diagnosis. 176 patients had a metastatic free interval of less than 2 years and 485 patients had been metastasis-free for longer than 2 years.

The ladies presenting with metastatic breast cancer at diagnosis had a longer survival rate than those who experienced a recurrence at distant sites in under 2 years from the initial diagnosis of breast cancer.

However, there were no differences in survival rates between those diagnosed at Stage IV and those women who had metastatic spread over 2 years after an original breast cancer diagnosis and treatment.

Furthermore, some medical studies show that survival rates vary for different types and subtypes of breast tumors according to the time intervals of recurrence. So, for example, breast cancer survival rates comparing two cancers may be better at a 5-year interval for some cancers but even out over 15 years.

I try to be an optimist. When life gives me lemons, I make lemonade … and spike it with vodka.

Questions and Answers

Can any type of cancer form a metastatic tumor?

Virtually all cancers, including the cancers of the blood and the lymphatic system, can form metastatic tumors. Although rare, the metastasis of blood and lymphatic system cancers to the lung, heart, central nervous system, and other tissues have been reported.

What are the symptoms of metastatic cancer?

The symptoms produced by metastatic breast cancer vary depending on the location of the metastases.

For example, metastatic disease to the bone causes severe, progressive pain, and less commonly, pathological fracture, erythema (redness) over the affected bone and swelling.

Breast cancer cells that have spread to the brain cause persistent, progressively worsening headache, visual changes, seizures, nausea, vomiting, vertigo, behavioral and personality changes and increased intracranial pressure.

Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting.

Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest x-ray, and chest pain.

In addition, general, non-specific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss and poor appetite.

Can someone have a metastatic tumor without having primary cancer?

No. A metastatic tumor is always caused by cancer cells from another part of the body.

If a person who was previously treated for cancer gets diagnosed with cancer a second time, is the new cancer a new primary cancer or metastatic cancer?

The cancer may be a new primary cancer, but in most cases it is metastatic cancer.

What treatments are used for metastatic cancer?

Metastatic cancer may be treated with chemotherapy, biological therapy, targeted therapy, hormonal therapy, radiation therapy, surgery, or a combination of these treatments.

The choice of treatment generally depends on the type of primary cancer; the size, location, and the number of metastatic tumors. Also, the patient’s age and general health and the types of treatment the patient has had in the past.

Are new treatments for metastatic cancer being developed?

Yes. Researchers are now studying new ways to kill or stop the growth of primary cancer cells and metastatic cancer cells. One new area of research includes ways to boost the strength of the immune response against tumors.

Regulatory T-cells and RANKL proteins may play a role in breast cancer metastasis
Recent breast cancer research suggests that the body’s regulatory T cells, which are an integral part of the immune response system, may play a key role in metastasis.

It is speculated that the T cells produce a protein which seems to accelerate the spread of breast cancer cells to other areas of the body. The inflammatory protein RANKL seems to influence the T-cells’ ability to spread cancer cells to distant areas of the body.

It is believed that by interfering with RANKL’s ability to interact with the T-cells, the early metastasis of breast cancer cells can be significantly inhibited

Remember ladies, chocolate doesn’t ask silly questions … chocolate understands.

Understanding breast cancer metastasis