In stage III breast cancer, the cancer cells have spread outside the breast tissue to the adiacent lymph nodes or to the thoracic muscles but they have not  moved to the distant organs. Even though in this stage the breast cancer is considered to be advanced, the 5 year survival rates in the USA and European Union countries range from 54 to 67 %.  There are several different forms of breast cancer stage III, depending on the size of the tumor the number of lymph nodes affected, or by the invasion into the chest wall or into the skin.
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Almost all the forms of stage III breast cancer are operable, the only exception being the case in which the cancer cells have spread to the supraclavicular lymph nodes, this form representing the inoperable stage IIIC breast cancer. The stage III breast cancer is divided by most oncologist into other 3 stages. In stage IIIA there are many situations: no tumor can be found in the breast, but cancer has developed in the axillary lymph nodes (which may be either attached to each other or to the surrounding structures), or the cancer can affect the lymph nodes near the sternum.


Another situation in stage IIIA is when the tumor's diameter is up to 2 centimeters and cancer cells have spread to the axillary lymph nodes which may be as in the previously mentioned case attached to each other or to the surrounding tissues or the cancer has spread to the peristernal lymph nodes; or  another situation in which the tumor is has more than 2 to 5 cm in diameter and it  to the axillary  or other peristernal lymph nodes, or the case in which the tumor measures more than 5 centimeters and the cancer spreads to the axilary or peristernal lymphatic structures. The 5 year survival rate for this stage varies from 56% to 67% according to The American Cancer Society.


In stage IIIB, the tumor may have virtually any size and the cancer may have spread to the thoracic wall and/or the skin and it may have affected also axillary and peristernal lymph nodes and other close structures. The 5 year survival rate for stage IIIB breast cancer ranges between 49% and 54%.

In stage IIIC, the tumor may have any size or it may be even absent but it may have affected the chest wall and/or the skin.In this stage the cancer spreads to lymph nodes above and/or below the collarbone and to the lymph nodes in the axilar region and/ or near the breastbone. In operable stage IIIC, the cancer is usually found in 10 or more axillary lymph nodes, in the subclavicular lymph nodes or in the axillary and peristernal lymph nodes. In inoperable stage IIIC, the cancer has affected the supraclavicular lymph nodes (the lymph nodes above the collarbone). The Stage IIIC is considered to have a five-year survival rate of 36 to 50%.

A woman who receives the diagnosis of breast cancer, will first require information concerning the prognosis and survival. Breast cancer mortality has decreased with about 3 percent since 1990 and mortality rates keep dropping as new ways of treating this disease are studied all around the world.

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There are many factors which influence the prognosis of breast cancer. The stage of the cancer, the age of the patient, the cell type found in the tumor, the grade of the cancer, the presence of hormone receptors on the membrane of cancer cells and the oncogene expression.

Stage is a parameter used when referring to the extent (spread) of the breast cancer.  The breast cancer patients are categorized from stage 0 (the very earliest cancer) to stage IV,  (the situations in which the cancer has metastasized to other organs of the body). Several tests including imaging tests and lymph node biopsies should be performed in order to establish the stage of the breast cancer. According to the American Cancer Society the five-year survival rate for the patients with localized breast cancer is 98%. The survival rates  if breast cancer has spread to the toracic wall or lymph nodes is about 80%, and minimum 25% of the patients with metastatic breast cancer will survive five years or more. These statistics will continue to improve as  better ways of treatment will be investigated.

Even though it seems paradoxical,  the survival rate for the women younger than 40 years with breast cancer is slightly lower than the rate for older patients with breast cancer, maybe because of the fact that many younger patients develop more aggressive forms of cancer. There is a gain in survival  rates of 7% in the women over 40 compared to those under 40. In some cases the natural hormones, the estrogen and the progesterone help the division of cancer cells. In case that the tests show that the breast cancer tissue is hormone positive, hormone therapy is necessary in order to block the effects of these two hormones on the cancer, even if the cancer spread to other organs.

Breast cancer cells should be examined  under a microscope in order to determine the grade of the cancer tissue. When the cancer cells are highly similar to normal breast tissue,  cancer is considered to be low grade or highly differentiated. These tumors usually tend to grow and spread slowly.The cancer that look very different  and abnormal are categorized as high grade or poorly differentiated. These cancers tend to grow quickly and a more aggressive therapy is required in order to achieve a good outcome.

The oncogene (the piece of genetic material that may determin the development of normal cells into cancerous ones) expression is another important factor affecting the prognosis.  A very important oncogene in breast cancer is the HER-2 breast cancer oncogene, found in about  1/3 of breast cancer patients. Research has shown that breast cancer patients with the HER-2 oncogene have a tendency towards having earlier cancer recurrences and lower survival rates.

Mammography is a medical imaging procedure used in order to detect and investigate the mass lesions, the areas of parenchymal distortion, and microcalcifications. This procedure requires compression of the breast between two plates and is considered to be quite uncomfortable by many women. Two views (oblique and craniocaudal) of each breast are taken. A dose of less than 1.5 mGy is standard.
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Since breasts are relatively radiodense in younger women  mammography is not usually performed in the women younger than 35 years.

However, all patients with a breast cancer, regardless of age, should have mammography before the surgery because this procedure is extremely valuable in the assessment of the extent of the disease. The modern digital technologies have offered new opportunities in image enhancement, manipulation transmission and storage.

Reading a mammogram may be quite challenging  for a radiologist, because of the variations in the way the breast structures look on a mammogram. Moreover, some breast cancers may determine almost unnoticeable modifications in the mammogram. If a woman has had one or more mammograms in the past, it is extremely important for the radiologist to have either the x-ray films or digital images in order to compare them with the new images . By comparing the pictures even the small changes can be found and cancer will be detected as early as possible. Because getting the older pictures may be difficult, it would best if the woman found a health care facility she is comfortable with and plan to get her regular mammograms in that facility every year so her other pictures will be easily accessible.

In some medical facilities, the mammogram report includes a Breast Imaging Reporting and Data System classification, reflecting the radiologist’s overall impression of the mammogram. This scale goes from one to five, the higher the numbers are a higher possibility of breast cancer is indicated.

The mammogram report will mention any abnormality in breast structure. First breast symmetry, its general density and the distribution of the glandular tissue will be observed. Next densities,  masses, calcifications ,structural distortions and associated findings will be sought. In case that a mass is found,  its  shape, density and borders will be analyzed. Malignant lesions usually have irregular, spiculated margins and have a strong tendency to have  a greater density than the normal breast tissue. In benign lesions such as lipomas , oil cysts and galactoceles there may be observed areas of very low density.

The calcifications associated with malignancy are usually smaller then the benign calcifications; they have less than 0.5 mm in diameter, and for seeing them well a magnifying glass is frequently usefull. They have a strong tendency tend to have heterogeneous shape or a fine granular, a pleiomorphyc shape or branching aspect. The distribution of any calcification should be specified reffering to them such as grouped, diffuse or linear and, depending on the affected area regional or segmental.

The associated findings should also be studied and mentioned in the report. These associated findings are represented by nipple retraction, skin retraction, skin thickening ( focal or diffuse), skin lesions, axillary adenopathy and trabecular thickening.

All multicellular organisms may be affected or have the potential to be afflicted by cancer. Paleopathologists have observed cancerous lesions which occurred even in dinosaur bones long before the apparition of Homo sapiens. The ancient Egyptians observed the  cancer in humans, and in  the Edwin Smith papyrus, a glyph clearly refers clearly to a clinical cancer of the breast. Moreover, the autopsies of mummies have proven the existence of bone tumors and confirmed the probability of other cancerous processes.

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By the era of Hippocrates in the 4 th century B.C., breast cancer was clinically recognized and described and Hippocrates considered that in many cases  it was very important that one of his cardinal rules, Primum non nocere (first do no harm) be applied, since little could be done for the patient. Hippocrates establishes the use of the term carcinoma when referring to tumors "that spread and destroyed the patient "and advances a theory according to which cancer is determined by the excess of "black bile". Hippocrates (and after him many other doctors in the following 2000 years) tended not to treat the deep-seated or ulcerated cancers, because “if treated, the patients die quickly; but if not treated, they hold out for a long time.”



About six hundred years later, Galen makes another classification describing “tumors according to nature” (the normal enlargement of the breast with female maturation or during pregnancy and "tumors contrary to nature" (benign and malign tumors). Galen also was the one who suggested the slight similarity between a crab and cancer.

During the Middle Ages the medical practice has been dominated by the concepts of Galen and Hippocrate. The Renaissance and the 17th and the 18th century brought a new perspective on the disease. The “black bile” theory of the cause of cancer has been disputed by an increasing number of physicians (one of the most important being Ramazzini) and the surgery of neoplasms appeared. There were written treatises on mastectomies for breast cancer some of them mentioning the dissection of regional lymph nodes. Ramazzini also attributed the high prevalence of breast cancer among nuns to their celibate life. This observation withstood the test of time.



In the nineteenth century the medical community and the scientists began to study cancer systematically and intensively. The anatomist Bichat is the one who extended the principles of Galen. Bichat (1821) described the anatomy of many neoplasms and is the one who suggested that  cancer was an “accidental formation” of tissue built up in the same way as any other portion of the organism. Seventeen years later, Johannes Müller extended these observations through the use of the microscope. Although the cellular theory was just being formulated and little was known about the cell at that time, Müller demonstrated independently that the cancer tissue was made up of cells. Rudolf Virchow (1863), a student of Muller extended our descriptive knowledge of cancer;  he came up with a number of theories that were later disproved but he was the first one who pointed out a relation between chronic irritation and some cancers.

As major advances have been made in biology, many advances have been also made in the study of cancer. In 1829, Recamier introduced the term "metastases" in his work Recherces du Cancer  and described clearly how cancer spreads by metastasis. Another important advance in cancer study was the demonstration by Waldeyer (1872) that the metastases were the result of the fact that some cells from primary cancers infiltrated lymphatic vessels.Other important advances in oncology were based on the work of Novinsky (1877), Doven and Shimkin (1970) .

Inflammatory Breast Cancer or shorter, IBC is a highly aggressive type of breast cancer. In this form of the disease the cancer cells block the lymphatic network in the skin of the breast. This form of  cancer is named  “inflammatory” due to the swollen , red ( “inflamed”) aspect of the breast which may occur overnight and can sometimes be misdiagnosed as another breast disease, mastitis. The edematous swelling of the breast occurs due to the impaired lymphatic drainage determined by the invasion of the regional lymphatic ducts.. Because the suspensory ligament of Cooper tethers the skin of the breast , a dimply appearance of the skin, similar to an orange peel (peau d'orange ) may occur, due to fluid accumulation.
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Unlike in the other forms of breast cancer , the inflammatory breast cancer does not manifest as a lump, ( although in many cases a dominant mass may be observed)  the cancer cells forming sheets or nest, affecting the subcutaneous lymph vessels (diffuse infiltration) ; basically it looks like a rash or an infection .

Another symptom of this disease is breast pain, without a cyclical pattern, and which may be either constant, or stabbing. This symptom is one of the main reasons why inflammatory breast cancer is misdiagnosed as an infection and treated with antibiotics so, if a woman has been taking an antibiotic treatment for more than 7 days without any form of response a breasy biopsy or / and a refferal to a breast specialist should be considered.

The peau d'orange aspect has an important diagnostic value, but other skin modifications may also occur. Skin discoloration, represented by an erythematous (red, pink or dark color of the skin) is highly common, and in many cases it is accompanied by pruritus, which does not relieve or decreases in intensity, not even after the use of topical agents or oral medication. The skin also presents ridges, and some areas seem thickened.

The areola (the pigmented skin surrounding the nipple) is affected by the disease and its color and texture changes and nipple abnormalities occur as well. In inflammatory breas cancer the nipple is retracted (flattened) and in many cases, a serous or bloody nipple discharge has been observed.The skin of the nipple may also be swollen or it may presents crusts.

The breast may increase rapidly in size (a cup in a matter of days,), be warmer than usual, and many women notice that the breast is also harder and/ or firmer than before.

Since the disease affects the subcutaneous lymph nodes, it will lead to a swelling of the ipsilateral axilary lymph nodes or even supraclavicular lymphatic group. The lymphedema (the swelling of the arm ) occurs more rarely (only 7% of cases) and a decrease in breast size has also been documented.

After the diagnosis of a breast cancer has been established, an experienced clinician should inform the patient in a compassionate manner and reffer her to a breast care expert, who will provide more information and support and help establishing new contact. Knowing the extent of disease is extremely important in order to determine the most adequate management plan. The prognosis in breast cancer is highly related to the stage of the disease at presentation.
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The purpose of staging is to determine which patients are suitable for a radical, potentially curative combination of regional treatments and appropriate adjuvant systemic therapy from the patients with metastatic disease, who are usually and primarily treated with systemic therapy. The clinical examination is the first way of providing some amount of information of the size of the lesion, the presence of the involvement of the thoracic wall or the skin, the presence of a spontaneous nipple discharge and whether the cancer presents inflammatory features.

For an  easier management, breast cancer can be classified, based on the extent of the disease into three separate groups: early or operable breast cancer, locally advanced disease, and metastatic breast cancer.

A more complex and elaborate classification is the one established by UICC (Union Internationale Contre le Cancre), known as TNM (Tumour / Node/ Metastasis). This classification, however is considered by some clinicians to be "not ideally suited to breast cancer". According to TNM classification breast cancer stages are defined by three parameters: tumor, lymph nodes and metastasis.

Depending on the tumor (T), breast cancer staging is classified in: TX (primary tumor which cannot be assessed, T0 (there is no evidence of primary tumor), Tis (tumor in situ), T1 (tumor of up to 2 cm in diameter), T2 (tumor diameter is between 2 and 5 cm), T3 (tumor larger than 5 cm) and T4 (tumor of any size with direct extension to toracic wall or skin or inflammatory carcinoma).

Depending on the involvement of regional lymph nodes the breast cancer may be characterised as: NX (the lymph nodes cannot be assessed), N0 (with no regional lymph node metastasis), N1 (metastasis to the ipsilateral axillary node / nodes), N2 (metastasis to ipsilateral axillary node/ nodes fixed to one another or to other adiacent structures, or clinically apparent ipsilateral internal mammary nodes with no evidence of axillary node metastasis) and N3 (metastasis to the  ipsilateral infraclavicular node / nodes or ipsilateral internal mammary lymph node/ nodes associated with axillary lymph node metastasis, or metastasis in ipsilateral supraclavicular lymph node / nodes.

M, or distant metastasis is another important parameter in evaluating the stage of a breast cancer. Depending on it, breast cancer may be evaluated as MX (in which distant metastasis cannot be assessed) M0 (there is no distant metastasis) or M1(in which distant metastasis is present).

Depending on these parameters the staging of breast cancer can be summarized as: stage 0 (carcinoma in situ, intraductal carcinoma, Paget’s disease of  the nipple with no tumor or lobular carcinoma in situ), Stage I (in which the tumor does not involve axilar lymph nodes) stage IIa (T2, N0, or T 1 and N positive) stage IIb (T3, N0, or T 2–5 cm and N positive (<4 axillary ipsilateral nodes), stage IIIA (T 3, N positive, or T2 with 4 or more axillary nodes involved), stage IIIB (T4 spread to less than 10 axillary nodes), stage IIIC (in whic the tumor  has affected more than 10 axillary nodes, one  or more supraclavicular or infraclavicular lymph nodes, or internal mammary nodes) and stage IV (defined by any form of distal metastasis).