Vi The Seed And Soil Hypothesis In Light Of The Macrophage Origin Of Metastasis
It is well documented that metastatic tumor cells do not invade distant organs randomly. Rather, metastatic cancer cells invade in a non-random pattern with lung, liver, and bone as primary sites of metastases., The English surgeon, Stephen Paget, was the first to record this phenomenon in his seed and soil hypothesis of breast cancer metastasis., He proposed that certain tumor cells have a preferential affinity to invade certain organs . None of the current models of metastasis, i.e., the EMT/MET, stem cells, or TAM accessory models, have addressed Pagets seed and soil hypothesis. The origin of metastasis as a macrophage disease, however, can address this phenomenon.
Although the non-random dissemination of metastatic cancer cells has engaged the attention of numerous investigators for decades, no credible genetic mechanism has been able to account for the phenomenon.,, The seed and soil hypothesis is extremely difficult to explain if cancer is viewed as a genetic disease.,, There are simply no clear connections between the non-random invasion of distant organs and the genetic abnormalities found in metastatic cells. On the other hand, a credible explanation of the seed and soil hypothesis emerges if cancer is viewed as a macrophage metabolic disease.
Integrative Therapies For Metastatic Breast Cancer
You may find it beneficial to add integrative therapies;to your treatment plan. There are many evidence-informed integrative modalities to boost the mind and body. Practices like gentle yoga, meditation, massage and music therapy may feel enjoyable and reduce stress and anxiety levels.
To help our patients maintain quality of life after a metastatic breast cancer diagnosis, our team of breast cancer experts may offer supportive care services to help manage side effects of the disease and its treatments. These may include:
Breast Cancer Survival Rate Statistics
In the US, the 5-year survival rate for localized breast cancer diagnoses is situated at 99%.
Furthermore, it is important to point out that 62% of all breast cancer cases in the US are discovered and diagnosed when they are still at a localized stage, which means they havent spread to other parts of the body. In this case, the survival rate for 5 years is situated at 99%, which is an excellent outcome. However, we mustnt forget the remaining 38% of breast cancer cases that are discovered later than optimal, thus leading to lower than 5-year survival rates, according to our statistics on breast cancer.
National Breast Cancer
Research estimates have determined the presence of more than 3.5 million breast cancer survivors living in the US.
Based on this stat, we can conclude that breast cancer is significantly less dangerous when compared to more aggressive and invasive types of the disease. While surgery is generally required, in addition to chemotherapy, and in some cases radiotherapy, breast cancer is definitely survivable.
National Breast Cancer
5 in 6 women that are diagnosed with breast cancer in the UK will survive for at least 5 years.
Based on this, while the;breast cancer rate;is still fairly high, survivability rates are high as well all across the world; especially so in;countries with advanced healthcare systems.;To put things into perspective, only 3 out of 6 women wouldve survived the 5 year period in the 1980s.
Breast Cancer Now Organization
Cancer.net
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Functional Stratification: A New Way To Look At Breast Cancer
As mentioned above, current breast cancer staging is heavily dependent upon the evaluation of pathology specimens. However, recent findings suggest that functional classification of breast tumours may become an important addition to risk prediction and prognosis. Results from preclinical animal models suggest that it might be possible to classify breast cancers on a functional basis, as determined by their ability to promote outgrowth of micrometastatic tumour populations at distant sites. Of note, as presented at the recent Nobel Conference on Breast Cancer, we have the ability to use human tumour cell lines and fresh surgical specimens in our xenograft model to test their ability to promote systemic instigation and/or respond to a protumorigenic host systemic environment .
The ability to determine whether or not a given tumour has the potential to promote the dissemination of tumour cells from the primary tumour, support the proliferation of otherwise indolent disseminated cells or activate systemic signalling pathways that recruit bone marrow cells to the developing tumour stroma of a metastatic lesion would have significant implications for treatment strategies . The ability to use tumour tissue in functional assays to predict tumour behaviour may enable more accurate identification of patients with a high likelihood of future relapse, thereby allowing for potentially curative treatment during the therapeutic window in which the disease can be controlled.
Why Does Metastatic Breast Cancer Happen
Most often, metastatic cancer occurs because treatment didnt destroy all the cancer cells. Sometimes, a few cells remain dormant, or are hidden and undetectable. Then, for reasons providers dont fully understand, the cells begin to grow and spread again.
De novo metastatic breast cancer means that at the time of initial diagnosis, the breast cancer has already spread to other parts of the body. In the absence of treatment, the cancer spreads.
There is nothing you can do to keep breast cancer from metastasizing. And metastatic breast cancer doesnt happen because of something you did.
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Myth #: People With Metastatic Breast Cancer Look Sick And Lose Their Hair
You dont look sick. You look so well. Why do you still have your hair? Are you sure you have cancer? These are comments that people with MBC report hearing. But there are many treatment options besides chemotherapy, and people often appear well while taking them.
As NancyHB comments: Id much rather be a poster child for how sometimes we can live with, rather than die from, MBC at least for a while. Instead, I find myself defending against people who are increasingly becoming impatient with my lack of cancer-patient appearance. Im grateful for this time of feeling good, and theyre harshing my buzz.
Some people with MBC report that they actually look better than they feel while in treatment. So they sometimes have to let family and friends know that even though they appear fine, they dont feel well.
Shetland Pony notes: If she looks good, she is good. Nope. Many of us suffer from the invisible disability of fatigue. I would venture to say every available treatment causes us some level of fatigue. We struggle to keep up. It may look like we are doing the bare minimum when we are really giving it our all.
JoE777 of Texas adds: The new normals advertised about therapies on TV are deceiving about the side effects. They talk about side effects while women are skipping through life. not looking to show the harsh side effects but think there is something wrong with me that my life is not like that.
Treatment Options For Metastatic Breast Cancer
Treatment for metastatic breast cancer often is based on systemic therapies, which use drugs rather than surgery or radiation. Metastases treatments are designed to shrink tumors and slow their growth, help ease symptoms and improve quality of life. Treatment may change, such as when one therapy stops working, or the side effects become too uncomfortable. Rather than having only one treatment, most patients undergo several treatments combined to help fight the cancer.
The four broad categories of drug-based treatments are:
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What Type Of Breast Cancer Is Most Likely To Metastasize
Metastatic breast cancer is breast cancer that has spread to other parts of the body. Cancer cells start in the breast and then multiply, invading the rest of the healthy breast tissue and eventually spreading to lymph nodes under the arms or in other organs.
While all types of breast cancer have the potential to metastasize, human epidermal growth factor receptor 2 -positive and triple-negative;cancers;are;more aggressive and more likely to metastasize faster than the other types.
Data Sources And Definitions
The Surveillance Epidemiology and End Results Program collects clinical, demographic, and vital status information on all cancer cases diagnosed in defined geographic areas. Data included in this report are from the SEER-9 and SEER-11 registries obtained using SEER*Stat software version 8.3.2 . SEER-9 covers approximately 11% of the U.S. population and includes Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, and Utah. For survival analyses, we used data from 19922012 from the SEER-11 registries which include SEER-9, Los Angeles and San-Jose Monterey. We only included invasive breast cancers.
Stage at diagnosis was defined using adjusted American Joint Committee on Cancer 6th edition staging classification . This stage definition uses extent of disease information for cases diagnosed in 19882003 and collaborative staging for cases diagnosed in 20042012. De novo MBC was defined as AJCC 6 stage IV which includes only tumors with distant metastasis. Stage IV from previous AJCC editions and distant stage from SEER historical summary staging classification include some locally advanced tumors without distant metastasis, for example, tumors with positive supraclavicular lymph node involvement without distant metastasis. Recurrent MBC was used to designate women initially diagnosed with AJCC stages IIII breast cancer, whose disease later progressed after treatment to distant organs or tissues.
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Common Sites Of Metastasis
- Brain: 7.3%
- All less common sites: 22.4%
Invasive lobular carcinoma;tends to have a significantly different pattern of metastases than ductal breast cancer. In one 2017 study, almost 70% of people with metastases from lobular carcinoma had peritoneal metastases.
For roughly a third of women ,;cancer spreads to multiple organs at the same time.
Reducing The Risk Of Recurrence
Because the factors that influence recurrence rate are so complicated, it is important for each breast cancer patient to discuss her own situation with her doctor. Many women are eligible for hormonal treatments and targeted therapies that reduce recurrence risk. Although more research is needed, it appears that diet and exercise can also play a role in decreasing recurrence. PJ Hamel has written a list of ten ways to reduce the chances of your cancer coming back. It’s easy to get bogged down in worrying about cancer spreading, but it’s better to let that anxiety move you to a healthier life style.
Editor’s note: As of 2017, Phyllis is still doing fine.
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Examples Of Rates Versus Numbers
Say, town A has a population of 100,000 and town B has a population of 1,000. Over a year, say there are 100 breast cancer deaths in town A and 100 breast cancer deaths in town B.
The number of breast cancer deaths in each town is the same. However, many more people live in town A than live in town B. So, the mortality rates are quite different.
In town A, there were 10 breast cancer deaths among 100,000 people. This means the mortality rate was less than 1 percent .
In town B, the mortality rate was 10 percent .
Although the number of deaths was the same in town A and town B, the mortality rate was much higher in town B than in town A .
Lets look at another example. In 2021, its estimated among women there will be :
- 100 breast cancer deaths in Washington, D.C.
- 720 breast cancer deaths in Alabama
- 4,730 breast cancer deaths in California
Of the 3,;California has the highest number of breast cancers. However, that doesnt mean it has the highest breast cancer rate.;These numbers dont take into account the number of women who live in each state. Fewer women live in Alabama and Washington, D.C. than live in California.
Other factors may vary by state as well, such as the age and race/ethnicity of women. So, to compare breast cancer mortality , we need to look at mortality rates.
In 2021, the estimated mortality rates are :
- 26 per 100,000 women in Washington, D.C.
- 22 per 100,000 women in Alabama 22
- 19 per 100,000 women in California 20
Myth #: If Youre Diagnosed With Metastatic Breast Cancer You Did Something Wrong Or Didnt Get The Right Treatment The First Time
When some people hear stage IV breast cancer, they assume something must have been missed along the way to let the cancer get that far. There is a misconception that breast cancer always develops in orderly steps from stages I to II, III, and then IV and that theres plenty of time to catch it early. People with MBC can face misguided assumptions that they must have skipped mammograms or self-exams, or they didnt control risk factors such as not exercising enough, watching their weight, or eating healthy. But a person can do everything right and still get MBC. Although regular screenings increase the odds of diagnosing breast cancer at an earlier stage, they cant guarantee it.
Another major misconception: If youre diagnosed with metastatic cancer after being treated for an early-stage breast cancer, you must have chosen the wrong treatment regimen or it wasnt aggressive enough. But between 20% and 30% of people with an earlier-stage breast cancer will eventually go on to develop MBC and theres often no good explanation as to why. And it can happen to anyone. Treatments can reduce the risk of recurrence, but they cant eliminate it.
As Illimae of Houston notes: that a stage IV diagnosis equals negligence on the part of the patient. In my case, it had spread before I ever felt a lump. I felt it Saturday and saw my doc on Monday, I ignored nothing, sometimes it just happens that fast.
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Systemic Promotion Of Angiogenesis
The significance of angiogenesis in supporting tumour growth is well established , and the role of the angiogenic switch in facilitating outgrowth of dormant metastases continues to be an active area of investigation . It is noteworthy that the vascular endothelial growth factor inhibitor bevacizumab was initially approved by the US Food and Drug Administration for treatment of metastatic breast cancer in 2008 . However, approval was revoked in late 2011 after further studies failed to show significant benefit on long-term survival or quality of life . The results of large-scale studies utilizing bevacizumab to treat breast cancer patients were disappointing given the overwhelming laboratory data pointing to a central role for angiogenesis in metastatic growth. Current translational research efforts are now focusing on studies to define more precisely the patient population in which the benefits of anti-angiogenic therapy are likely to outweigh the risks.
Cryoablation For Metastatic Breast Cancer
Cryoablation may be an option to treat small, isolated metastatic breast cancer tumors in women who arent good candidates for surgery. Guided by imaging , cryoablation inserts a special freezing probe through the skin and to the tumor to be treated. Once the tip of the probe is in the right spot inside the tumor core, pressurized argon gas is injected through the probe into the tumor, freezing and destroying the cancerous tissue. Cryoablation techniques may vary from one cancer treatment facility to another. Cryoablation is more common in cases where the breast cancer is being well-controlled by systemic treatments such as chemotherapy and hormonal therapy.
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Tumour Dormancy And Reawakening
Tumour dormancy is generally defined as a prolonged state of asymptomatic micrometastatic disease. In cancer of the breast or prostate, cancer cells can remain dormant for years and even decades before recurring as metastatic disease. During this latent period, patients are considered to be disease-free due to the lack of any symptoms of illness and because they have no detectable neoplasms by clinical imaging. Often described as one of the most wicked cancer;cell misbehaviours, tumour dormancy shares many features in common with chronic diseases. Yet, its nature appears to be reversible, as myriad mechanisms have been shown to induce a switch to reawaken indolent DTCs . Furthermore, tumour dormancy is not exclusively a phenomenon of end-stage tumorigenesis, as it can apply to the presence of occult neoplasms until clinical diagnosis , and/or to MRD left behind after treatment . Attention, however, must be paid to the molecular underpinnings of these two scenarios as mechanistic differences between primary and metastatic dormancy might exist.
Disseminated Tumour Cells As Culprits For Metastatic Recurrence
Metastatic relapse is attributed to the outgrowth of cancer cells that have escaped from the primary tumour and take up residence in secondary sites. Cancer cells that physically detach from a primary source and seed distant sites are known as disseminated tumour cells . The process whereby DTCs transform a localised cancer into a systemic disease is called the metastatic cascade . In the next few sections, the seven key steps comprising this complex biological process are discussed with the goal to shed light on the when and how of DTC dissemination. Importantly, while depicting the metastatic cascade as an orderly series of sequential eventsstarting from the primary tumour and ending in a distant metastatic siteit should be noted that DTC spread can take place through multiple routes and different directions. Accordingly, clinical evidence of self-seedingwhereby a metastatic cell re-infiltrates its primary tumourand of metastasis-to-metastasis spread, has been documented, with one such study in HR+ breast;cancer patients reporting a common origin between lymph;node and distant metastases in up to 25% of cases.
Fig. 2: Tumour cell dissemination: the route to metastatic success or failure.
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Metastatic Breast Cancer Is Terminal
Metastatic breast cancer cant be cured and it is terminal. One thing I didnt know when I was first diagnosed is that breast cancer can only kill you if you have metastatic breast cancer, says Rosen, who explains that if your cancer remains in the breast, the tumor can be removed, but metastatic means it has spread outside the breast.
MBC is almost like a different disease than early-stage breast cancer, adds Ann Silberman, 60, from Sacramento, California, who was diagnosed in 2009. We are going to die. Our concerns are much different from those of a person who has a treatment that will be over . Someone in an earlier stage may worry about losing their hair which is understandable but they will return to their normal life at some point.
People with metastatic breast cancer expect to be on treatment for the rest of their lives. I dont think everyone understands that, Silberman says. I still get, When will your treatment be over? Well, its never going to be over.