Breast cancer is the most widespread type of cancer among women. Statistics in this sphere is really frightening. For example, 8 % of women in the USA have a significant risk of developing this disease. Breast cancer can affect men as well, but it is a very rare occurrence. Nevertheless, in case of detection during the early stage of breast cancer, this type of oncology can successfully be treated.
The stage of the disease at the time of diagnosis is one of the most important factors, which influence the choice of treatment options and the future prognosis. During the early stages the disease affects only breasts, while metastatic breast cancer involves injury of nearby and remote organs.
Correct staging is made via comprehensive examination and qualified interpretation of the results. Gene expression tests that are available at the most up-to-date healthcare institutions provide additional information and allow more precise and individual prognosis. Due to well publicised breast cancer awareness campaigns, early breast cancer diagnosis and timely treatment became possible in the last few decades even for women with metastatic breast cancer. Novel stage 4 breast cancer treatment options prolong life and improve its quality.
How is the stage of breast cancer determined?
After the first step – confirmation of breast cancer diagnosis, this is followed by the second step – evaluation of the stage of breast cancer. This process includes additional investigations and consultations of the related specialists. Stage of the disease reflects the extent at which the disease spreads and thus influences preferential treatment options. For example, at the first stage of the disease doctors mainly recommend surgical treatment, while further stages require a combination of surgery with chemotherapy and radiotherapy for breast cancer. Also information about the stage of breast cancer determines prognosis and life expectancy. For example, according to the European statistics for 2017: a five-year survival rate at the first stage of the disease is about 87 %, at the second stage – 75 %, at the third stage – 46 %, and at the fourth stage (i.e. metastatic breast cancer) – 20 %.
Reliable and exact determining of the stage of breast cancer usually requires specific examinations:
- Mammography. Mammography is a kind of X-ray examination, which reveals tumors and other pathological conditions of breasts (like cysts or mastopathy). Depending on the level of healthcare institution, mammography might be traditional (with film screens) or digital (with receiving images of better quality and recording the data on the computer).
- Ultrasound examination of the breasts. Ultrasound examination allows more intricate estimation of the breast tissue state, distinguishing between solid tumors, which may be both benign and malignant, and cysts, which are always benign, but need surveillance.
- MRI of the breasts and other chest organs. MRI is mainly used for revealing the extent of the invasion by the tumor, presence of oncologic process in the other breast and nearby organs, and development of metastatic breast cancer. Under certain circumstances a mammography may be substituted with MRI, as the last one is more precise and gives more diagnostic information in women with metastatic breast cancer. MRI is always performed before planning, surgery, chemotherapy or radiotherapy for breast cancer, chemoembolization for breast cancer.
- Biopsy. Biopsy is the "golden standard" in breast cancer diagnosis. This investigation involves the taking of a sample of tumor or suspicious tissue in metastatic breast cancer and examining it under the microscope or with the help of chemical agents. Biopsy may be performed by thin (it is called "fine needle aspiration", FNA) or wide (it is called "core needle biopsy") needle. Needle biopsy is guided with the help of mammography, ultrasound or MRI. In case a greater amount of tissue is required for the diagnostic purposes, surgical biopsy is performed. Usually surgical biopsy means total removal of the neoplasm, regardless of its origin, and may be complemented with chemotherapy or radiotherapy for breast cancer.
General examinations are also carried out in order to estimate state of a patient and advise the most suitable treatment scheme:
- Complete blood count (to reveal anemia)
- Biochemical blood test (to estimate liver and kidney function, e.g. before chemotherapy for breast cancer)
- Inflammation markers test
- Electrocardiogram (to estimate state of the heart)
Once results of all tests and investigations are ready, it is possible to establish the stage of breast cancer and elaborate individual treatment plan. It is quite natural that stage 4 breast cancer treatment options will differ significantly from the treatment of early-stage breast cancer. Today, there are few classifications and systems of breast cancer staging, we will review all of them.
Stage of breast cancer according to the TNM staging system, stages 0-4
The TNM staging system is widely used in the sphere of oncology. Actually, each type of cancer, except for blood cancer, is always classified with the help of this tool. Principles of the TNM system are common worldwide; this allows cooperative elaborating and implementing into the clinical practice guidelines for cancer treatment.
TNM staging system answers three main questions:
- Where is the primary tumor located? What is the size of the primary tumor?
- Has the oncologic process affected lymphatic nodes? If so, how many of them and where are they located?
- Is this metastatic breast cancer? Has the oncologic process metastasized to remote organs and tissues? If so, where and to which extent?
As a matter of fact, there are two types of TNM staging when it comes to breast cancer. The first one is the clinical stage. The clinical stage of breast cancer is based on the primary results of the non-invasive investigations and biopsy before the surgery. The second one is the pathologic stage, which takes into consideration pathology reports after examination of the surgically removed breast tissue and lymphatic nodes. Pathologic stage of breast cancer is more precise, as oncologic changes may be invisible to the naked eye, but not to the microscope. "T" in the TNM staging system stands for "tumor". This point describes the size of the initial tumor and its interrelation with nearby tissues and organs.
"T" may be assessed in the following ways:
- TX – size of the primary tumor cannot be determined due to objective reasons.
- T0 – there are no signs of the primary tumor.
- Tis – this is usually carcinoma in situ or Paget disease; carcinoma in situ is small and superficial. Chemoembolization for breast cancer may substitute surgery at this stage.
- T1 the primary tumor is under 2 cm in maximum size; this stage of breast cancer may be divided into stages T1a, T1b and T1c if a doctor needs more precise information. At this stage doctors also use both surgery and chemoembolization for breast cancer.
- T2 the primary tumor is more than 2 cm, but less than 5 cm in size. Chemoembolization for breast cancer can still be carried out as the safer and more sparing surgery alternative.
- T3 the primary tumor is more than 5 cm in size. At this stage surgery comes to the fore, as chemoembolization for breast cancer may be ineffective. However, in certain women chemoembolization for breast cancer can reduce tumor size and stop its growth.
- T4 – the primary tumor may have any size, but it affects skin or chest wall. Symbol T4a means spreading on the chest wall, symbol T4b – spreading on the skin and edema of the involved breast, symbol T4c – affecting both chest wall and skin, symbol T4d – inflammatory oncologic process with edema, pain and redness of the skin.
"N" in the TNM staging system stands for "nodes". This point describes spreading of the oncologic process on the nearby or remote lymphatic nodes. Earlier removed lymphatic nodes were investigated under the light microscope, but improvement of technical basis gradually gave the possibility to find out the tiniest changes in the tissues. As it is not actually clear, whether such changes are clinically significant or not, doctors take into consideration only focuses of 200 and more oncologic cells or 0.2 and more mm in size. When such focuses are less than 2 mm in size, they are called micrometastases.
"N" may be assessed in the following ways:
- Nx – it is impossible to assess nearby lymphatic nodes.
- N0 – there are no signs of oncologic process in the nearby lymphatic nodes. To be more precise, stage N0(i+) is distinguished in case of revealing focuses consisting of less than 200 cells or less than 0.2 mm in size and stage N0(mol+) is distinguished in case of revealing cancer cells only with the help of molecular tests (RT-PCR).
- N1 – cancer process has spread to 1-3 lymphatic nodes in the underarm region (axillary lymphatic nodes) and / or near the breast bone (internal mammary lymphatic nodes). To estimate the process more accurate, stage N1mi means presence of micrometastases in the axillary lymphatic nodes, stage N1a – involving into the process 1-3 lymphatic nodes with presence of at least one macrometastasis, stage N1b – involving into the process internal mammary lymphatic nodes on the same side (without their enlargement), stage N1c – presence of stages N1a and N1b signs.
- N2 – cancer process has spread to 4-9 axillary lymphatic nodes or has led to the enlargement of internal mammary lymphatic nodes. Stage N2 is divided into stage N2a – 4-9 axillary lymphatic nodes are involved into the process with presence of at least one macrometastasis, and stage N2b – cancer has spread to internal mammary lymphatic nodes and they are visually enlarged.
- N3 is divided into stage N3a, when oncologic signs are present in more than 10 axillary lymphatic nodes or other lymphatic nodes below the clavicle; stage N3b, when both axillary and internal mammary lymphatic nodes are affected with macrometastases; stage N3c, when lymphatic nodes above the clavicle are involved into oncologic process.
"M" in the TNM staging system stands for "metastases". This point describes the metastatic breast cancer with spreading of the process to the distant organs – brain, bones, bone marrow, lungs, liver.
"M" has the following meanings:
- Mx – it is impossible to assess the presence of metastatic breast cancer.
- M0 – metastases are absent according to physical examination or imaging investigations (X-ray, CT, MRI). Stage M0(i+) is distinguished when oncologic focuses of less than 200 cells or less than 0.2 mm in size are revealed.
- M1 – implies presence of metastatic breast cancer with lesions in any of distant organs. M1 stage requires systemic treatments, e.g. chemotherapy for breast cancer.
Additional factors of staging: hormone receptor status
Tissue samples taken during biopsy or surgical intervention are always investigated with the help of histological and immunohistochemical techniques. Histological examination gives us information about the type of tumor and degree of malignancy, while immunohistochemical methods reveal important biochemical and molecular signs of the tumor.
When it comes to breast cancer, immunohistochemical examination of the tumor includes analyses for hormone receptors. Breasts` development and growth are tightly controlled by female hormones – estrogen and progesterone. To receive an approach to the breasts` tissue and be able to act here, these hormones need to find their own specific receptors on the outer part of cells. Receptor is a special protein, which "sees" only selected molecules. Thus, estrogen receptors "see" only estrogens and can`t be activated by other substances. The same is true for progesterone receptors. Once receptors are activated by hormones, they start stimulating growth and the division of breasts` cells. Unfortunately, tumor cells may have the same receptors and receive the same signals. Thus, normal hormone levels of the woman may cause progression of breast cancer.
That is why testing for the presence of hormone receptors is significant for elaboration of the individual treatment plan and receiving personalized therapy. Tumor cells may contain one or both of these receptors on their surface. Such cells and cancer types are called ER-positive (for estrogen receptors) and PR-positive (for progesterone receptors)respectively. Hormone therapy is highly effective for these kinds of cancer, as depriving receptors of their hormones prevents cancer from advancing and transforming into metastatic breast cancer. There are few types of drugs, which are used for hormone receptor-positive cancer treatment: they lower hormone levels or simply inactivate receptors.
In case immunohistochemical examination reveals no receptors on cancer cells, cancer is classified as hormone receptor-negative. This type of cancer doesn`t require administration of hormone treatment. In general, hormone receptor-positive cancer grows more slowly and responds to the treatment better, but it tends to succumb to long-term relapses (in years after treatment completion).
Additional factors of staging: HER2/neu status, score 0-3+
Another part of immunohistochemical examination is determining HER2 (human epidermal growth receptor 2) status. HER2/neu, which is often shortly called HER2, is a specific protein on the membrane of breast cancer cells. This receptor is responsible for growth and spreading of cancer. As a matter of fact, HER2 is present in all cells, as it helps tissues to grow and develop normally. Risks arise only in revealing excessive amount of this protein.
There are two techniques for HER2 status assessment: immunohistochemical (IHC) straining and fluorescent in situ hybridization (FISH). Both of them are performed in vitro, using the tissue samples taken during the biopsy or surgical intervention. The IHC test is performed first, as it gives results in the relatively short period of time.
Possible results include the following:
- Score is 0 or 1+ the result is negative, cancer is considered to be HER2-negative. Such types of cancer do not need additional administration of drugs that target HER2.
- Score is 2+ the result is intermediate; the pathologist is not able to come to the precise conclusion. In this case an additional FISH test is performed to receive more exact information.
- Score is 3+ the result is positive, cancer is considered to be HER2-positive. Such types of cancer are more aggressive, but can be effectively treated with the help of drugs that target HER2. This group of drugs includes different monoclonal antibodies (trastuzumab, pertuzumab) and kinase inhibitors (lapatinib, neratinib). Specific target treatment may be provided as the monotherapy or combined with chemotherapy and radiotherapy for breast cancer.
Additional factors of staging: determining grade, grade 1-3
Tumor grade mainly characterizes cancer cells structure and degree of their abnormality. Correct grade determination is significant for estimating risk of cancer growth and development of metastatic breast cancer. Usually three biopsy samples or samples of tissue removed during the surgical intervention are required for the analysis. Each grade has a specific number. Low grade number (1) implies low degree of malignancy, slow growth and minimal tendency to the development of metastatic breast cancer. And vice versa, high grade number (3) means that the tumor cells have severe abnormalities and signs of malignancy, tumor growth rate is fast and tends to spread to remote organs and tissues.
According to the summarized score, or Bloom-Richardson Grade in Nottingham modification, the following groups are distinguished:
- Grade 1 (the score is 3-5). The tumor is well differentiated and looks like normal breast tissue. The risk of metastatic breast cancer development is quite low.
- Grade 2 (the score is 6-7). The tumor is moderately differentiated. It is mainly an intermediate state between grades 1 and 3, when the pathologist is unsure about the interpretation of the result.
- Grade 3 (the score is 8-9). The tumor is poorly differentiated. Tumors with this grade need additional attention in terms of possible invasive growth and development of metastatic breast cancer.
Additional peculiarity of the tumor, which becomes visible under the microscope, is the ploidy of cells. Ploidy reflects the different number of chromosomes in breast cancer cells. Normal cells are diploid, which means presence of 46 chromosomes. Breast cancer cells may become aneuploid, with the abnormal amount of chromosomes. Aneuploid cells are more malignant and aggressive; tumors with aneuploid cells should be treated as soon, as possible. Specific targeted therapy or chemotherapy for breast cancer may be administered after detecting aneuploid cells in the neoplasm.
Comprehensive stage grouping, stages 0-4
When results of all the above mentioned investigations are ready and all separate grades / stages are determined, doctors proceed to comprehensive assessment of the data. The process is called "stage grouping" and, as a result, the doctor is able to assign the overall clinical and pathologic stage of breast cancer. This is a final diagnosis, which precedes the start of treatment.
The first stage of breast cancer, stage 0, is carcinoma in situ – the most favorable variant of breast cancer. Stage 0 is described as TisN0M0.
Stage 1 is divided into stages 1A and 1B. At the stage 1A tumor is small (less than 2 cm in size) and there are no signs of lymphatic nodes involvement. Stage 1A is described as T1N0M0. Stage 1B implies the presence of a small tumor (less than 2 cm in size) along with micrometastases in lymphatic nodes. Stage 1B is described as T0/T1N1(mi)M0.
Stage 2 is also divided into stages 2A and 2B. At the stage 2A initial tumor might be visible or not, but it affects axillary lymphatic nodes (T0/T1N1M0). Another variant is revealing tumors from 2 to 5 cm in size with healthy lymphatic nodes (T1N0M0). Stage 2B means that the tumor is 2-5 cm in size with spreading to 1-3 axillary lymphatic nodes (T2N1M0); or tumor exceeds 5 cm in size, but axillary lymphatic nodes remain intact (T3N0M0).
Stage 3 includes more advanced variants of breast cancer. Comprehensive data assessment gives few interpretations of the third stage of breast cancer:
- Stage 3A is assigned to the tumor of any size in case of affecting 4-9 axillary lymphatic nodes and remote metastases absence (T0/T1/T2/T3N2M0). The second variant is a tumor over 5 cm in size spreading to 1-3 axillary lymphatic nodes (T3N1M0).
- Stage 3B means that the tumor is larger in size and more invasive, as it affects the skin or the chest wall. There may be signs of tumor in axillary lymphatic nodes (any number), but remote metastases are not found (T4N0/N1/N2M0).
- Stage 3C mainly takes into consideration the state of lymphatic nodes. At this stage of breast cancer the tumor may have any size, but it spreads to 10 or more axillary lymphatic nodes or lymphatic nodes in other regions. Remote metastases are absent as well (T0/T1/T2/T3N3M0).
Stage 4 is the metastatic stage of breast cancer. The main sign of this stage of breast cancer is presence of remote metastases in the brain, bones, bone marrow, lungs or liver. Size of the initial tumor and state of lymphatic nodes are not really important at stage 4. Stage 4 breast cancer treatment is aimed not at removing the primary tumor, but at fighting metastases and maintaining good general health condition. Stage 4 breast cancer treatment options include hormone therapy, immunotherapy, targeted therapy and chemotherapy for breast cancer. Surgery, chemoembolization for breast cancer, and proton therapy for stage 4 breast cancer are used in certain clinical situations. Duration and types of chosen treatments determine the cost of treatment for cancer stage 4.
It has to be noted that recurrent breast cancer may change stage and even certain characteristics. In case of relapse all examinations and tests are performed once more to receive actual information.
Treatment schedule and cost of treatment for cancer stage 4-1
It is quite obvious that only thorough laboratory analyses, examination with the help of up-to-date medical equipment, qualified performing of needle biopsy and surgery, and comprehensive assessment of the received data by skilled doctors may ensure elaboration of individual, harmless and effective treatment regimen. Both the technical part and the experience of healthcare professionals are of great importance, as they complete each other.
As it was mentioned above, surgery, radiation therapy, and systemic treatments (i.e. chemotherapy, immunotherapy, targeted and hormone therapy) are used for breast cancer treatment. Most often, doctors give preference to combinations of few techniques. For instance, chemoembolization for breast cancer may be followed by one of the systemic treatments. Proton therapy for stage 4 breast cancer may be followed by surgical intervention.
Treatment of the advanced cancer stages is the most challenging task. However, there are several novel medicines and efficient techniques. As for today, stage 4 breast cancer treatment options include:
- Chemotherapy for breast cancer
- Chemoembolization for breast cancer (in eligible women)
- Targeted therapy and immunotherapy
- Hormone therapy
Rarely used stage 4 breast cancer treatment options are surgery and proton therapy for stage 4 breast cancer. A surgery or proton therapy for stage 4 breast cancer are performed in order to relieve pain or other worrying symptoms (as the palliative therapy), to prevent bone fractures, to destroy solitary metastases in the brain or spinal cord, to reduce pressure on the spinal cord, to treat open wounds. The proton therapy for stage 4 breast cancer is the safest irradiation mode, as it does not damage the heart, lungs and nervous system.
The cost of treatment for cancer stage 4 is as follows:
- Cost of treatment for breast cancer stage 4 with radical mastectomy – from 4,140 EUR
- Cost of treatment for breast cancer stage 4 with chemotherapy – from 2,483 EUR
- Cost of treatment for breast cancer stage 4 with radiotherapy – from 13,800 EUR
- Cost of treatment for breast cancer stage 4 with proton therapy – from 44,526 EUR
- Oncological rehabilitation – from 951 EUR per day
Treatment of early-stage and metastatic breast cancer abroad
Oncologic disorders rarely give patients the second chance and time to try few variants of treatment. And even if it is so, each next attempt is more exhausting in medical and psychological aspects. That is why it is important to choose an appropriate healthcare institution with the most up-to-date technical basis and qualified doctors. Today we have the opportunity to search for diagnostic and treatment not only in one’s native country, but also in foreign countries all over the world. Patients investigate information about most equipped hospitals and, which is even more significant, doctors with high accreditation and best results in diagnosing and treatment methods. All information is clear and available with free access. One can even compare the cost of treatment for cancer stage 4 in different countries or healthcare facilities, as the estimated cost of treatment for breast cancer stage 4 may influence the choice of the hospital significantly.
When it comes to determining a proper breast cancer diagnosis as well as the accurate staging of breast cancer, Germany is at the top of the list due to the quality of investigations and rating of professors. Fortunately, Germany is open for foreign patients and provides them with all kinds of examination, consultations and treatment for the early-stage and metastatic breast cancer. The main handicap may consist in getting the appointment in the desirable hospital and planning non-medical details of the trip for the patient and his relatives. You should also be prepared financially, as hospitals may ask for a deposit in addition to the estimated cost of treatment for cancer stage 4. This is connected with possible health risks at this stage of cancer.
To make the trip effective and pleasant in all aspects, it is better to use the help of a reputable company such as Booking Health. Booking Health is the medical tourism company, which is expertly equipped to advise and help thousands of patients with early-stage and metastatic breast cancer breast cancer to go through diagnostics and receive treatment. The company has an international quality control ISO certificate in this field of work, which ensures reliability and compliance with the highest international demands.
Booking Health provides comprehensive help:
- Recommending the best doctor and clinic for your case
- Booking an appointment at a convenient date
- Organizing a comprehensive examination program
- Organizing treatment for early-stage or metastatic breast cancer, paying additional attention to stage 4 breast cancer treatment options
- Arranging treatment with specific desired techniques, e.g. proton therapy for stage 4 breast cancer, chemotherapy for breast cancer or chemoembolization for breast cancer, etc.
- Organizing consultations with all necessary specialists, e.g. stage 4 breast cancer treatment options are discussed by the multidisciplinary tumor board
- Excluding extra fees and additional coefficients for non-residents, i.e. even the cost of treatment for cancer stage 4 for you will be lower
- Providing you with transfer, an interpreter and medical coordinator, if necessary
- Providing you with medical insurance against complications
- Preparing for you all the medical reports and further recommendations
To start planning your diagnostic program, as well as treatment of early-stage or metastatic breast cancer you should leave a request on the website of Booking Health. Our highly informed case manager or medical advisor will get in touch with you on the same day to discuss all the details, so, please, be ready. You will be pleasantly satisfied with the helpful recommendations of our team, and rest assured that your medical care will be in good hands.
Choose treatment abroad and you will for sure get the best results!