Every year the Breast Cancer awareness month is celebrated during October. The purpose of this event is to raise funds to research this disease and increase awareness about the disease. By increasing awareness, organizations seek to prevent the progression of the disease. Prevention is a fundamental aspect of controlling this disease due to the mortality of the disease. It is the second most frequent cause of cancer death. About 600,000 women die of breast cancer yearly worldwide.
What is Breast Cancer?
Part of the awareness campaign should include education concerning what is breast cancer? In spite of the constant campaigns, there seems to be confusion when describing breast cancer. People tend to think of breast cancer as a single disease. However, the biology of breast cancer indicates otherwise. Even though the different types of breast cancers share some common characteristics, there are numerous distinctive characteristics within each type (1, 2). Therefore, the classification of breast cancer is essential when describing what defines it.
Summary: Breast Cancer awareness month is celebrated every October. This event helps raise funds for breast cancer cures and advancements. About 600,000 women die every year worldwide of the disease. It is often confused what breast cancer is. It is not a single disease, in fact there are many different types of breast cancers that share common characteristics.
Breast cancer is defined by the direct etymological meaning and the different classifications for this group of diseases (3). The name itself can provide the essential characteristics of all breast cancers. First of all, the term breast is easy to understand. The breast is defined as a structure composed of the tissues in front of the pectoral muscles. All of the breast tissues are found within the anatomical boundaries of the breast (4, 5). Properly defined as the tissue beneath the collar bone down to the level of the 6th rib and media from the axillary region to the sternum. Logically, this defines only one breast, nevertheless, the anatomical boundaries are described in the same way for both breasts.
It is composed of fat and a highly specialized glandular tissue that produces milk. This glandular tissue is arranged into around 20 lobes which contain lobules (6). All of these structures converge into ducts, which converge into larger ducts until they reach the nipple. Additional, to the glandular structure there is connective tissues and ligaments which provide support to the breast. Finally, the breast contains numerous nerves, blood vessels, lymph nodes, and lymph vessels (7, 8).
Summary: The term “breast” is easily understood and defined as the structure composed of tissues in front of the pectoral muscles. It is composed mostly of fat and has specialized glandular tissue to produce milk. It also has many nerves, blood vessels, lymph nodes, and lymph vessels.
Cancer, on the other hand, refers to any histological structure with uncontrolled cell growth and the potential to metastasize or invade other tissues (9, 10). All cancer requires the capacity to grow without regulations to be considered as such. Cancer cells for many reasons begin to multiply abnormally and will grow and often form masses or tumors (11). These cells can multiply abnormally because they avoid programmed cell death, they grow autonomously, avoid immune cells and other characteristics summarized by the hallmarks of cancer (12). However, not all cancer has the capacity to metastasize. Cancer cells with the capacity to metastasize require the development of mechanisms of penetrating the basal membrane and migrate to other areas (13, 14).
Cancer cells are characterized by the hallmarks defined by Hannah and Weinberg in the year 2000 (15). Hannah and Weinberg defined the 6 classical cancer hallmarks as biological capabilities that allow cancer cells to behave the way they do. The six classical hallmarks are resisting cell death, sustaining proliferative signaling, evading growth suppressors, inducing angiogenesis, enabling replicative immortality and activating invasion and metastasis (16, 17). As scientists discover and understand new characteristics of cancer cells new hallmarks are currently being defined, such as deregulating cellular energetics and the evasion of immune destruction (18).
Summary: Cancer refers to uncontrolled cell growth with potential to metastasize into other tissues. Cancer cells can begin to multiply abnormally and grow into masses or tumors. Not all cancer cells can metastasize. Cancer cells resist cell death, sustain proliferative signaling, evade growth suppressors, induce angiogenesis, enable replicative immortality, and activate invasion and metastasis.
The importance of hallmarks when defining what is breast cancer relies on that it allows us to differentiate why are cancerous tumors different from other tumors that could arise in the breast tissue. Among these are the fibrocystic breast disease, intraductal papilloma, fibroadenomas, lipoma, and mastitis (19, 20). These benign breast masses also form from the same breast tissue but develop through different mechanisms. However, it is not possible to observe these mechanisms clinically. This is why physicians rely on the medical history to gather risk factors and the physical exam to identify signs which permit to distinguish a benign mass from a malignant one.
Therefore, in general, breast cancer is defined as a group of diseases resulting from the abnormal proliferation of breast tissue (21). Given that the breast is composed of several types of cells, the subtypes of cancer can be defined by the type of cells from which the cancer cell originated. Regarding the type of cancer, an important way to classify breast cancer is its capacity to invade other tissues (22). Additionally, in clinical settings breast cancer can be classified into independent grades and staging groups. New classification divides breast cancer groups related to the molecular receptors in the cancer cells.
Summary: Cancerous tumors differ from other tumors that arise in the breast. Physicians gather information on medical history and physical exams to identify whether a mass is benign or malignant. Breast cancer is defined as a group of diseases resulting from the abnormal proliferation of breast tissue. Therefore, there are many different types, subtypes, and classifications.
Histological classification divides breast cancer into cancer from the stroma and mammary glandular tissue (23). The stroma is the tissue found between the glandular tissue composed of cells, proteins, blood vessels, and other supporting structures (24). Cancers originating from the stroma are called sarcomas (25), which are not frequent in the breast tissues. On the other hand, the mammary glandular tissue is the most common site of breast cancer. Glandular tissue is composed of epithelial tissues and cancers originating from epithelial tissues are labeled carcinomas (26).
Breast carcinomas are further divided into those originating in the lobules or those coming from the ducts. Most of the breast carcinoma originates from the ducts, causing about 80-85% of breast cancers (27). On the other hand, breast carcinomas coming from the lobules make up 10-15% of breast cancers. Clinically both cancer subtypes will behave similarly, having the same treatment and prognosis. However, while ductal breast cancer tends to clump together, different from lobular breast cancer does not and forms long stretches of cancer cells (28). This results in the possibility that lobular breast cancer can be larger than expected.
Summary: Histological classification divides breast cancer into stroma and mammary glandular tissue. Cancers from stroma are called sarcomas and aren’t as frequent in the breast tissues. Mammary glandular tissue is the most common site of breast cancer and are called carcinomas. Carcinomas are further divided into the lobules or those coming from the ducts. Most cancer originates in the ducts.
Breast cancer can also be classified by the capacity to invade other tissues. The division according to this capacity is simple, there are cancers that can invade other tissues and cancers which cannot invade other tissues (29). This is mainly going to be defined by the invasion of the basal membrane, which functions as a barrier to most cancers (30). Cancer cells that cannot penetrate the basal membrane will continue to grow regardless of this. This results in incredibly large but benign cancer cell masses.
Those who can invade other tissues are also called infiltrating cancers. Infiltrating breast cancer not only penetrates the basal membrane but also need access to blood vessels and lymph vessels (31, 32). Access to both types of vessels will provide a mechanism by which cancer cells can move around the body to invade distal tissues. In contrast, noninvasive breast cancer can also be called in situ cancer, intraductal cancer or preinvasive cancer (33). This type of cancer has not penetrated the basal membrane, therefore it lacks access to the lymph and blood vessels required to move around the body.
Summary: Cancer cells that cannot penetrate the basal membrane will continue to grow into benign masses. Infiltrating cancers can penetrate the basal membrane and access blood and lymph vessels. This provides infiltrating cancer cells ability to move and invade other tissues in the body. Noninvasive breast cancers (situ cancer), has not penetrated the basal membrane and cannot move around.
Often in pathological reports, the histological and invasive classification are described together. When describing breast cancer, the pathologist first describes the invasiveness if it’s an invasive breast cancer but will describe the histological type first if it’s an in situ breast cancer. This will provide descriptions such as invasive ductal carcinoma or ductal carcinoma in situ.
The capacity to invade relates to therapeutically relevant classification methods for breast cancer or the staging of breast cancer. However, the staging also depends on the size of the main tumor and the evaluation of the nearby lymph nodes. Together, all these factors compose the TNM staging system. (T referring to the tumor size, N for the lymph nodes, and M for tumor metastasis) (34, 35). After the individual study of each factor, the breast cancer stage is determined. The stages range from stage 0 to stage 4. The staging of the patient´s breast cancer will describe and categorize it according to its behavior. On one end, a stage 0 breast cancer is defined as a small in situ with a good prognosis. On the other, stage 4 represents cancer that has disseminated accord the body with a poor prognosis.
Classifying individually the aggressiveness cancer. Staging can be done by a physical exam or through several tests. Through the physical exam, the main tumor mass size can be estimated, invasion of lymph nodes identified, and the presence of metastasis located. However, the physical exam does not provide enough precision in breast cancer staging. Through diverse imaging test, the size and presences of masses can be precisely measured and localized. After locating the masses, some can be sampled and studied histologically to determine if they are cancerous or not.
Summary: A pathologist first describes the invasiveness of breast cancer if it’s invasive, or the histological type if it’s in situ (noninvasive). The TNM (tumor size, lymph nodes, tumor metastasis) describes the tumor and staging system, ranging from stage 0-4. Staging can be done by a physical exam or several tests. Diverse imaging tests can be more precise in determining size and localization.
If staging a breast cancer describes its behavior, grading breast cancer describes how does it look. Grading is determined solely through a pathological analysis of biopsies of the tumor mass (36). Grading describes how mature do cells look. Maturity in most tissues is considered a regular finding. In contrast, immature cells in most tissues are considered signs of abnormal cell growth (37). Maturity in cells is called differentiation and to classify the level of differentiation, they are divided into three degrees of differentiation. The first-degree representing well-differentiated cells, the second-degree cell representing moderate differentiation, and the third degree meaning poor cellular differentiation.
Summary: Staging breast cancer describes its behavior, grading describes how it looks. Grading is determined through analysis of biopsies and looks at maturity of cells. Immature cells are considered abnormal cell growth. Maturity is called differentiation and is divided into 3 categories: first (well), second (moderate), and third (poor) degree.
Recently, with the advent of molecular biology techniques and genomics, molecular subtypes have been described. Breast cancer will be defined by three receptors, the estrogen receptors, progesterone receptors, and HER2 receptors (38). The presence or absence of these receptors will determine which category the cancer is classified into. There are 4 molecular subtypes of breast cancer, luminal A, luminal B, HER2 positive and basal-like (39). Luminal A can have either or both estrogen and progesterone receptors without the HER2 receptors. In contrast, luminal B have either or both the estrogen and progesterone receptors with the HER2 receptors. The HER2 positive only has the HER2 receptors, while the basal-like have none of the receptors. The basal-like breast cancer is popularly known as triple-negative breast cancer (40).
The identification of molecular subtypes of breast cancers has provided a new classification scheme which also aids in the treatment of this disease. Each receptor is a molecular target of the recently created biological methods of inhibiting cell growth. Evidently, the absence of the receptor is a definite sign that these novel treatments will not work. This is why it is becoming common knowledge, even in the general population, that the presence of triple-negative breast cancer is a bad omen (41, 42).
Summary: Molecular subtypes have been identified in breast cancer. There are 3 receptors (estrogen, progesterone, or HER2) that are classified. The presence or absence of these determine the category of the cancer. Luminal A or B, HER2 positive, and basal-like are the 4 subtypes of cancer that provide even more classification and help determine treatment.
In order to know what things are it is essential to note the common characteristics, the differences with other things and between the types of illnesses. Breast cancer is not an excuse for this, as a patient, a family member and especially a physician, everyone, in general, should understand the general notion in what defines breast cancer. A cancer disease characterized by uncontrollable cell division resulting from the convergence of multiple pathways are known as the hallmarks of cancer. The word breast cancer indicates what type of tissue the cancer cells originate and what are the anatomical boundaries define the location of the initial cancerous mass.
When someone is diagnosed with breast cancer, this is only the first part of the physician’s job. This is the first part of identifying what is going on with the patient. Properly identifying which breast cancer will rely on all the classification methods previously mentioned. Only through the correct identification will a physician develop an adequate treatment plan. Additionally, the combination of the treatment plan and the description of the type of breast cancer will determine the prognosis of the patient diagnosed with breast cancer.
Summary: A physician can develop an adequate treatment plan after the breast cancer is first identified, followed by its classification. The combination of a treatment plan and the description of the type will determine the prognosis of the patient as well.
Because of the possible prognosis, breast cancer also carries an emotional meaning to lots of people. Many people know at least someone who has a family member suffering from this illness. Additionally, it can be shocking that what used to be an organ that gave life can later take it in a terrible way. Perhaps this is the reason many countries support the pink ribbon campaign, in hopes that perhaps the fund’s gather could provide new testing technologies or therapeutical methods that can aid increase the quality of life and save the life others. Another way the campaigns are contributing to saving lives is by raising awareness of what is breast cancer. Because the only way to solve a problem is by understanding the nature of this problem which in this case is breast cancer.