Second opinion on breast cancer

Among all malignancies, breast cancer (more precisely, a group of malignant breast diseases) is the most frequent among women. The disorder also occurs in men, but much less frequently.

What is it and how does it develop?

The cells of our body (including the breast cells) are subject to an uninterrupted cycle. The old or damaged regularly die out and are replaced by new ones. However, if this cycle goes wrong, the older cells cease to die, and the new cells start dividing uncontrollably, a tumor develops.

Initially, it is confined to the area of a glandular lobule and in this non-invasive (not penetrating further) stage is referred to as carcinoma in situ (CIS). As the disease progresses, however, it can develop into an invasive form, in which the cancer cells grow into adjacent tissue or are spread throughout the body via the lymphatic and blood vessels, eventually forming daughter tumors (metastases) in distant organs.

Where does breast cancer occur most frequently?

The breast is composed of fatty, glandular and connective tissue. Running between them are nerves, blood and lymph vessels. The glandular tissue contains milk ducts and branched glandular lobules. When a child is born, milk is formed in the mother’s glandular lobules, which flows through the milk ducts to the nipple.

Malignant changes usually originate in the tissue of the milk ducts (ductal breast carcinoma) or in the glandular lobules (lobular breast carcinoma).

Breast cancer types and why are they important to know

Modern medicine has many different drugs for the treatment of mammary carcinoma. Some of them have a very specific effect on certain tumor cells structures. Therefore, it is important to describe the mass as precisely as possible, using a number of criteria. This process can be compared to the way a tailor takes measurements before making a garment: the more meticulous the measurements are, the better the clothing fits. Treatment of a malignant breast tumor is similar: the more information about its features and possible "weak points" has been collected, the better the therapy works.

So, a breast tumor can be viewed in terms of:

• Its original site: ductal or lobular.
• Degree of spread beyond the original tissue: non-infiltrating (non-invasive, or carcinoma in situ) and infiltrating (invasive).
• Growth features of cells which constitute the mass: non-specific, mucinous, tubular, medullary, papillary, adenoid cystic, metaplastic.
• Biological properties: the presence of specific biomarkers that determine tumor behavior and are crucial for the development of customized breast cancer therapy concepts.

Breast tumor molecular biology

Special tests on tissue material obtained during biopsy or tumor removal can detect the so-called biological tumor markers (biomarkers). They are divided into prognostic (helping to assess the degree of malignancy of the tumor and, accordingly, the prospects for the disease course) and predictive (providung information on how the tumor can be treated and what therapy is necessary or effective in each individual case).

Biomarkers with proven relevance for breast cancer include:

Hormone receptor status: the ratio of tumor cells and the number of canster-stimulating estrogen and progesterone hormone receptors that they contain. If more than one percent of all cells respond to a special labeling procedure, the tumor is considered hormone-dependent and can be treated with anti-hormone therapy.

HER2 receptor status: a large number of these receptors often causes a more aggressive course of cancer; however they can be blocked with special targeting drugs.

Proliferation marker Ki-67 shows how fast the tumor is growing, which is very important for risk assessment. A Ki-67 of 20% or higher indicates that the disease is aggressive.

Genomic profile

Changes in gene expression in tumor cells serve as an informative indicator of the likelihood of recurrence. Based on their analysis, one can calculate the individual risk of disease recurrence. In hormone-dependent carcinomas, it helps to identify cases where chemotherapy can be avoided.

What can indicate a malignant process?

There are a number of certain symptoms that should definitely alert and become a reason to visit a mammologist. First of all, it is the presence of a thickening, when felt as a dense lump. Other danger signs are changes in the shape or size of the breast, changes in the breast or nipple skin, discharge from the nipple, palpable lymph nodes in the armpit or around the collarbone. They are no reason for panic, because about 90 percent of lumps are benign. However, without a medical examination, it is impossible to distinguish between a malignant and a harmless mass.

Diagnosis

Imaging studies such as mammography, ultrasound or magnetic resonance imaging play an important role in making a diagnosis. If the images give reason to suspect cancer, a tissue sample is taken (a biopsy). Only laboratory examination of biopsy specimens can confirm or deny the cancer diagnosis.

Breast biopsy options

There are various techniques for tissue sampling. The main difference lies in the diameter of the needles or instruments used and, consequently, the volume of the sample obtained.

All techniques are minimally invasive, and the risk of malignant cell “dispersal” followed by new tumor lesion growth is virtually nonexistent thanks to modern technical safety measures.

When the mass to be examined cannot be detected by palpation, imaging is used to guide the needle to the target location. With ultrasound guidance, the doctor follows the movement of the needle on the ultrasound monitor. If the tumor is only visualized on mammography, a stereotactic (under X-ray guidance) biopsy is needed. This requires two mammograms taken from different angles to accurately locate the target.

A fine-needle aspiration biopsy is used primarily when a cyst is suspected. It is performed with a thin needle with a hollow center and is comparable to blood sampling. It is the simplest but least reliable method; if the findings are inconclusive, a more complex procedure may be required.

A core needle biopsy can be used to clarify the nature of virtually any palpable mass or lesion detectable by ultrasound. A special 1.6-millimeter needle is placed directly in front of the tumor and automatically “shot” into the tumor at high speed to take a tissue sample. Typically, at least 3 shots are made. 

Vacuum-assisted biopsy (VAB) is done with a special probe that is inserted only once. Tissue from a suspicious area is drawn into it by vacuum, removed by a rotating cutting device and transferred through the probe to the collection area. More material can be obtained in this way than with a needle.

Incision or extirpation is required if the nature of the mass cannot be determined with the help of minimally invasive techniques. In the first case, a part of the tumor is removed with a surgical scalpel; in the second case, the entire mass is removed.

Additional diagnostic methods

If cancer is confirmed, it is necessary to determine how far it has spread before starting treatment. In breast malignancies, the following examinations can be done:

• a chest X-ray (or a chest CT in highly aggressive tumors);
• a bone scan (scintigraphy);
• an ultrasound or a CT scan of the abdominal cavity.

Echocardiography/heart ultrasound is indicated if drugs that could potentially damage the heart are planned to be administered.

Bone densitometry (osteodensitometry) is recommended before starting medications (e.g., aromatase inhibitors) that affect bone tissue.

Malignant breast tumor classification

Based on biopsy and other tests, the mass is classified according to the TNM system. It determines the stage of the disease based on the size of the tumor, whether it has spread to the lymph nodes and whether it has metastasized to other organs. This is very important for planning treatment and assessing the recovery chances.

Breast cancer treatment options

The goal of all therapeutic procedures is a total cure of the disease. If the process has already gone too far and this goal is unattainable, every effort is made to stop further tumor progression. 

Treatment strategy is usually developed by a tumor board. Specialists in different fields discuss the available data and together decide on the next steps. In general, the therapeutic concept is largely determined by the type of cancer and its various characteristics.

Tumor removal surgery

Surgical treatment of breast carcinoma involves removing the tumor as completely as possible. While in the past the entire affected breast was removed, including the lymph nodes in the axilla, today it is often possible to do with a more gentle organ-preserving operation, which is combined with adjuvant radiation therapy. The necessary condition is that is that there is only one, not a very large lesion which has not grown into the skin or chest wall. If a complete amputation (mastectomy) is unavoidable, the breast can in many cases be reconstructed even within the same operation.

Lymph node resection is not always a must

Malignant cells usually first spread through the lymphatic system. Because lymphatic ducts from the breast lead to lymph nodes in the axilla, the latter used to be removed during tumor resection surgery. Today, if the nodes are not suspicious on imaging studies, only the so-called sentinel lymph node, which is closest to the tumor and therefore the first to be affected by its spread, is usually removed. If its examination does not reveal cancer cells, there is no need to remove other lymph nodes in the axilla. This helps to avoid noticeable scars and reduces side effects such as pain, arm mobility limitation or lymphoedema.

Radiotherapy

In addition to surgery, radiotherapy is a common treatment option for breast carcinoma. Its goal is to destroy any remaining malignant cells or tiny metastases in the area of surgery or lymph nodes. For three to six weeks, usually in an outpatient setting, the breast and lymphatic tissues are treated once a day during four to five days a week. Radiotherapy is usually used as adjuvant treatment after conservative therapy if:

• the tumor tissue could not be completely removed during surgery,
• several lymph nodes in the axillary region are affected,
• the mass is too large;
• there are pains caused by metastases (e.g. spinal).

Systemic drug therapy

At certain stages, treatment should be systemic in nature, that is, it should fight malignancy in the entire body, not just in a particular area. For this purpose, drugs with different mechanisms of action are used. Their choice depends on a number of factors, including the hormonal status of the tumor and its molecular biology. Neoadjuvant drug therapy is expected to shrink large masses to such an extent that they can subsequently be operated on with breast preservation. If given after surgery, it is aimed at preventing metastases development.

Antihormonal therapy for breast cancer

The concept of endocrine or antihormonal therapy is based on the fact that the growth of most breast tumors is driven by hormone influence. To eliminate their stimulating effect, special substances are used. These include anti-estrogens such as tamoxifen, which block estrogen receptors, and aromatase inhibitors, which inhibit the body's production of estrogen in fatty tissue in postmenopausal women.

Chemotherapy

The active substances used in chemotherapy (so-called cytostatics) are cytotoxins that interfere in various ways with the division of cancer cells and thus stop their growth or prevent their further spread. Since malignant cells divide particularly frequently, cytostatics primarily act on them, although they can damage healthy cells as well. Chemotherapeutic drugs are administered intravenously or in tablet form, as a combination or using only one substance. Several cycles with intervals for rest are usually given.

Breast cancer targeted therapy with antibodies or inhibitors

Unlike cytostatics, targeted drugs do not affect all cells in the body, but only the cancerous ones. The reason for this selective action is that they aim at specific features that only tumor cells possess, or that are particularly important to their growth. For example, such drugs block receptors for certain substances on the cell surface or inhibit signaling pathways within the cell.

In particular, two antibodies (pertuzumab and trastuzumab), by binding to a specific area of the HER2 receptor found in about one in four breast cancers, inhibit it and thereby cause the body's own immune system to attack the cancer cells. In addition, the second antibody binds to another region of the HER2 receptor, which, in combination with the first one, stops cell growth and promotes activation of the immune response.

Other targeted drugs (“small molecules”, mTOR inhibitors, CDK 4/6 inhibitors) inhibit angiogenesis (the formation of blood vessels supplying tumor cells) or the growth of the cancer cells themselves by disrupting signaling pathways. The so-called PARP inhibitors act against an enzyme that controls the cell cycle and thus prevent the uncontrolled growth of hormone-sensitive tumor cells.

One more opinion is never too much

Yearly, about 2.3 million people are diagnosed with breast cancer. This news can be devastating, but after the initial shock, the question arises: What shall I do next?

There is no universal answer to it. There seem to be as many coping strategies as there are people. Everyone has their own way, but one thing is clear: it is important to get control over your emotions and find the right approach to dealing with the issue. Among other things, this requires knowledge and information. Do not hesitate to seek them from all possible sources - of course, provided they are trustworthy. One of them is a second opinion from a breast cancer specialist.