Metaplastic Breast Carcinoma

Metaplastic breast carcinoma (MBC) is a rare form of breast cancer in which there is a mixture of malignant mesenchymal and epithelial elements. Metaplastic breast cancers are really quite rare, accounting for only about 0.02% of all breast cancers. Metaplastic breast carcinoma is an aggressive cancer, and tends to present at a more advanced stage and has a high propensity for local recurrence.

Often occuring as a combination of epithelial and mesenchymal-derived cancer cells.

Within the normal breast, epithelial cells are the type most commonly found in the duct lining, and the kind of cells most prone to malignant cancer development. (invasive ductal carcinoma). Mesenchymal cells, on the other hand, are immature cells usually associated with smooth muscle and connective tissues, or the so-called 'stromal' breast tissues. Breast stromal tumors are rare, and the cells involved tend to have a 'spindle' appearance. So, essentially with metaplastic carcinoma of the breast, cancerous cells of an 'epithelial cell' origin are found combined with non-specific malignant spindle cells of mesenchymal origin. (The mesenchymal component can also include other types of developments such as fibrosarcoma, leiomyosarcoma or osteogenic sarcoma.) What actually happens is that immature breast glandular epithelial cells 'differentiate'' into nonglandular mesenchymal tissue. These kinds of metaplastic changes, which could also involve squamous cell, spindle cell, and heterologous mesenchymal growth, occur in less than 5% of breast carcinomas.


metaplastic breast cancer microscopic view


Metaplasia (from the Greek: "change in form") is essentially a reversible replacement of one differentiated cell type with another mature differentiated cell type. This is not a normal occurance, but is likely caused by some kind of abnormal stimulus. It is a kind of 'cellular adaptation' in other words. This is in contrast to 'dysplasia' which is a kind of abnormal overgrowth of an immature cell relative to the mature cells they are supposed to form into. Dysplasia is more likely to be an early indication of a neoplastic process, possibly breast cancer development. Metaplasia, on the other hand, is not directly carcinogenic but is an indication of a change in the biological enviroment such as that the cells normally proliferating in a given area, are no longer thriving in that location.


xray of metaplastic carcinoma of the breast


Mammographic and ultrasound features commonly associated with metaplastic breast cancer

On mammographic imaging, most metaplastic breast cancer tumors will either be 'fatty' or heterogenously dense. Most metaplastic breast carcinoma are rarely associated with microcalcifications or architectural distortion. The margins of metaplastic breast tumors tend to be well-circumscribed or microlobulated, and usually without prominent spiculations. However, the borders of metaplastic breast carcinoma tumors may also be ill-defined, or obscured. Metaplastic carcinomas with well-circumscribed margins are more likely to be composed solely of spindle cells.


metaplastic breast carcinoma


On ultrasound, metaplastic breast cancer masses often show microlobulation or sometimes discrete well-circumscribed oval contours. Some metaplastic breast carcinoma tumors show heterogenous echogenicity, which might indicate the presence of both cystic and solid components. At other times the echogenicity might be homogenous, suggesting more of a solid mass.

Metaplastic breast cancer may appear benign on imaging studies

Mammographic and sonographic features of metaplastic breast carcinomas can appear to be benign masses such as breast fibroademona, but other factors such as age and family history, might suggest the possibility of metaplastic breast cancer, which should be investigated histologically.

Histological considerations for metaplastic breast carcinoma

Most metaplastic tumors of the breast are found histologically to be of a 'high grade', suggestive of a more aggressive cancer. Metaplastic breast carcinoma tends to be highly cellular, featuring mitotically active, poorly differentiated, and pleomorphic spindle cells. Microscopically, metaplastic breast cancers may show various sorts of 'cell mixtures'. Quite commonly metaplastic breast tumors show a squamous cell type differentiation. They might also feature prominent 'matrix-producing' type cells, or carcinosarcomatoid cells.(carcinosarcomatoid cells include both epithelial and mesenchymal features) Sometimes metaplastic breast cancer tumors will feature predominently spindle cells or a mixture of spindle cells with matrix-producing cells. If the mass appeared to show 'heterogenous echogenicity' on ultrasound, one could well expect to see necrosis and cystic degeneration at histopathology.

Fine needle biopsies are usually sufficient for diagnosis

Fine needle aspiration biopsy tends to be an acceptable diagnostic approach with metaplastic breast tumors, as the chances of finding a distinct carcinomatous epithelial component from anywhere in the tumor are good. And, unlike malignant myoepithelioma, the mesenchymal component in metaplastic carcinomas will express epithelial markers, at least focally. However, some physicians will still prefer to take an excisional biopsy in suspected metaplastic breast cancer, especially in cases where there is a possibility of associated necrosis or hemorrhage.

Hormone receptor status of metaplastic breast cancers

The majority of all breast carcinomas have positive status for certain hormone receptors. Estrogen receptors are found in about 75% of breast cancers, and progesterone receptors in about 55%. The HER2 receptor is overexpressed less commonly, found in approximately 25% of all breast carcinomas. This can have quite a bearing on prognisis and treatment strategies, and generally speaking a higher level of hormone receptor positivity leads to a more favorable outcome. Adjuvant hormonal therapy and chemotherapy is largerly based upon the receptor status of the primary tumor.

Metaplastic breat tumors tend to be ER and PR negative

With most metaplastic carcinomas of the breast, however, estrogen and progesterone receptors are not very evident. Her-2 is also typically absent in metaplastic breast tumors. Most metaplastic breast carcinomas are therefore 'triple negative' so to speak. However, metaplastic breast tumors do tend to express the HER1/EGFR (epidermal growth factor) receptor at a considerably higher rate than most other types of breast carcinoma, and this is a somewhat unique histological identifier for this type of breast cancer, and may lead to some new and potentially beneficial treatment strategies.

Triple negative and non triple negative status

Metaplastic breast carcinomas are frequently negative for the HER2 protein, and frequently occur without ER and PR receptors as well, and carcinomas which are either lacking or very low in all three types of receptors are sometimes called 'triple negative'. 'Triple-negative' cancers in generally form a potential subtype of breast carcinoma as the cancer cells behave in an aggressive fashion with somewhat distinctive patterns of metastasis.(including to the brain). Triple negative tumors often seem initially receptive to chemical therapy, but are also prone to early relapse.

Triple negative breast tumors are slightly harder to treat

Generally speaking, breast cancer–specific survival rates among patients with a triple-negative breast tumors is lower than for non-triple-negative breast cancers. Recent studies suggest that women with triple-negative breast cancer have higher rates of recurrence and higher mortality rates than those without. In addition, triple negative breast cancers are much more likely to experience recurrence during the first 3 years following therapy, with rapid decline following recurrence, as opposed to a more consistent follow-up course for breast cancers that are not triple negative.

Triple negative metaplastic breast carcinomas tend to have a higher-than-expected prognosis.

What is interesting about metaplastic breast carcinoma is that the outlook and prognosis with respect to 'triple-negative' status is contrary to the norm. Recent studies have shown, contrary to a generally accepted view, that a non-triple-negative metaplastic breast carcinoma actually has a poorer prognosis when compared with the triple-negative metaplastic breast carcinoma.

Carcinosarcoma of the breast: rare subtype of metaplastic breast cancer

Carcinosarcoma is a subgroup of metaplastic carcinoma, and it is probably the rarest of all primary malignancy of the breast, found in only about 0.1% of all cases. Carcinosarcoma describes a malignant tumor that is a mixture of carcinoma (cancer of epithelial tissue,(commonly skin and duct or organ lining tissue) and sarcoma (cancer of connective tissues, such as bone, cartilage, and fat). Carcinosarcomas are aggressive tumors that can arise in various sites of the body, but most commonly in the female uterus or the male urinary bladder. The cells of origin for breast carcinosarcoma are not yet agreed upon fully, but many researchers feel that they are of myoepithelial origin. Breast carcinosarcomas may themselves present in a variety of mixtures, such as homogeneously adenosquamous, or heterogeneously epithelial (adenocarcinoma) and mesenchymal (matrix, spindle cell and sarcomatous). In common practice now, all breast carcinomas with obvious carcinomatous and sarcomatous features will tend to be referred to as ' biphasic metaplastic sarcomatoid carcinoma' of the breast.


carcinosarcoma of the breast, cells


Treatment, management, and prognosis for metaplastic breast cancer

In most cases, metaplastic breast cancers are treated by mastectomy, with or without axillary node dissection. Metaplastic breast carcinoma tends to be treated with adjuvant chemotherapy in a vast majority of cases, and radiation treatment is less common, tending to be used in about 50%-60% of cases. The rate of local recurrence is variable of course, but might be estimated at around 30%. The five year disease free rate can be estimated around 40%, and the overall survival rate for metaplastic breast cancer tends to be around 50%-65%. (though some studies place it as high as 71%) There tends to be a signiciant drop off in survival rates if the cancer has reached stage three or higher, at just over 50%, but survival rates for stage I and II metaplastic breast cancers are very good. Metaplastic breast tumors tend to be of medium size, on average about 4-5 cm, but curiously, size of tumor has little bearing on prognosis. The same holds true for nodal status, menopausal status, histologic subtype, and a womans age. The extent of surgery and the use of adjuvant therapy likewise tends to have no generalizeable impact on recurrence and survival, though there is some suggestion that patients receiving a complete surgical resection, where available, tend to do better.

Metaplastic breast cancers may have a carcinosarcoma-like aspect

If the metaplastic breast carcinoma tends to have a carcinosarcoma-like differentiation, the treament and prognosis may be different. Sarcomas tend to have different metastatic pathways than carcinoma, and chemotherapy will tend to be oriented towards the sarcomatous component. Axillary lymph node involvment is actually quite rare with carcinosarcoma, whereas the rate of lymph node involvment in metplastic breast carcinomas ranges up to 30%. The overall 5-year survival rate for breast carcinosarcoma is estimated at around 40%, and most likely influenced by the tumor size, histologic type, grade, and possibly on the type and grade of the mesenchymal component in particular.

The survival rate for metaplastic breast cancers is about the same as for other NOS breast cancers of similar stage and grade

So, generally speaking, metaplastic carcinoma of the breast has poor prognostic indicators, but the survival rate is thought to be no different from other breast cancers of a similar stage and given the same aggressive multi-modal treatments. One brighter spot for metaplastic breast carcinoma is that some tumors do show an increased EGFR (HER1) expression, which does provide for some specifically targeted chemical interventions. Although molecular analyses for possible genetic alterations in the EGFR might be required, there is a good possibility that women fighting metaplastic breast cancer might benefit from treatment with protein kinase inhibitors, such as gefitinib (ZD1839, Iressa) and cetuximab (Erbitux).



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