All about Metaplastic Breast Cancer
Metaplastic breast carcinoma (MpBC) is a rare form of breast cancer in which there is a mixture of malignant mesenchymal and epithelial elements.
This type of breast cancer is 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.
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What types of Cells make up Metaplastic Breast Cancer
Within the normal breast, epithelial cells make up the duct lining. Unfortunately, it is these epithelial cells that are the 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 ‘stromal’ breast tissues.
Breast stromal tumors are rare and the cells tend to have a ‘spindle’ appearance. So, essentially with metaplastic breast cancer, cancerous cells of an ‘epithelial’ origin are found in combination with non-specific malignant spindle cells of mesenchymal origin.
Interestingly, the mesenchymal component can also include other types of developments, such as:-
- Osteogenic sarcoma
What actually happens is that immature breast glandular epithelial cells ‘differentiate’ into non-glandular 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.
Metaplasia and Dysplasia: What is the Difference?
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 occurrence, but the cause is likely to be 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 instead of the growth into a normal, mature cell. Dysplasia, however, 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 environment. For example the cells normally proliferating in any given area, are no longer thriving in that location.
Metaplastic Breast Cancer Features on Imaging
On mammographic imaging, most metaplastic breast cancer tumors will either be ‘fatty’ or heterogeneously 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.
On ultrasound, metaplastic breast cancer masses often show microlobulation or sometimes discrete well-circumscribed oval contours. Some metaplastic breast carcinoma tumors show heterogeneous echogenicity, which might indicate the presence of both cystic and solid components. At other times the echogenicity might be homogeneous, 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 fibroadenoma ).
However, other factors such as age and family history, might suggest the possibility of metaplastic breast cancer. If this is the case histological tests should follow as soon as possible.
Histological considerations for metaplastic breast carcinoma
So, histologically, most metaplastic breast tumors tend 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 carcinom sarcomatoid cells.(Carcinom sarcomatoid cells include both epithelial and mesenchymal features).
Sometimes metaplastic breast cancer tumors will feature predominantly spindle cells or a mixture of spindle cells with matrix-producing cells. If the mass appears to show ‘heterogeneous 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 is an acceptable diagnostic approach with metaplastic breast tumors. This is because 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 if they suspect metaplastic breast cancer. This is especially true in cases where there is a possibility of necrosis or hemorrhage.
Hormone receptor status of metaplastic breast cancers
The majority of all breast cancers have positive status for certain hormone receptors. Indeed, estrogen receptors are present in about 75% of breast cancers and progesterone receptors in about 55%.
The over expression of the HER2 receptor is less commonly present in approximately 25% of all breast carcinomas. Hormone receptors can have quite a bearing on prognosis and treatment strategies. So, generally speaking a higher level of hormone receptor positivity leads to a more favorable outcome. Indeed, adjuvant hormonal therapy and chemotherapy is largely based upon the receptor status of the primary tumor.
Metaplastic breast 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.
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 negative for ER and PR receptors as well. So, medics call cancers that are either lacking or very low in all three types of receptors ‘triple negative’.
‘Triple-negative’ cancers in general form a potential subtype of breast carcinoma as the cancer cells behave in an aggressive fashion with a somewhat distinctive patterns of metastasis (including to the brain).
Sadly, 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 survival rates amongst patients with 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.
In addition, there is often a rapid decline following recurrence, in opposition to a more consistent recurrence course for breast cancers that are not triple negative.
Triple negative metaplastic breast carcinomas tend to have a higher-than-expected prognosis
However, what is interesting about metaplastic breast cancer 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 in comparison with the triple-negative metaplastic breast carcinoma.
Carcinosarcoma of the breast: A 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. Indeed, it occurs in only about 0.1% of all cases.
The term carcinosarcoma describes a malignant
Specialists do not fully agree on the cells of origin for breast carcinosarcoma. However, 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, medics will tend to refer to all breast carcinomas with obvious carcinomatous and sarcomatous features, as ‘biphasic metaplastic sarcomatoid carcinoma’ of the breast.
Treatment, management and Prognosis for Metaplastic Breast Cancer
In the vast majority of cases, doctors will also use adjuvant chemotherapy in the treatment of metaplastic breast carcinoma. In addition, doctors may prescribe radiation therapy, but this is less common, (in around 50% to 60% of cases).
Prognosis and Recurrence Rates
The rate of local recurrence is variable of course, but researchers estimate it to be around 30%. Studies also estimate the five year disease free rate to be around 40%. Furthermore, estimates for the overall five year survival for metaplastic breast tends to at around 50% to 65%, (although some studies place it as high as 71%).
The stage of the cancer also has a bearing on survival rates. So if the cancer is at Stage III or above the survival rate is just over 50%.
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 to 5 cm. Curiously, unlike other tumors, the size of tumor has little bearing on prognosis.
The same holds true for nodal status, menopausal status, histologic subtype and a woman’s age. The extent of surgery and the use of adjuvant therapy likewise tends to have no generalizable impact on recurrence and survival. However, 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 treatment 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
The overall 5-year survival rate for breast carcinosarcoma is estimated at around 40%, and most likely influenced by:-
- the tumor size
- histologic type
- 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 researchers think that the survival rate is no different from other breast cancers of a similar stage with the same aggressive multi-modal treatments.
One brighter spot for metaplastic breast carcinoma is that some tumors do show an increase in EGFR (HER1) expression, which does provide for some specifically targeted chemical interventions.
Molecular analysis for possible genetic alterations in the EGFR may be necessary. So there is a good chance that women fighting metaplastic breast cancer might benefit from treatment with protein kinase inhibitors. These include Gefitinib (ZD1839, Iressa) and Cetuximab (Erbitux).
Let’s summarize with a few Q&A’s …
What are the Symptoms of Metaplastic Breast Cancer?
- A lump or lumps in the breast or under the arm
- Thickening of the skin of the breast
- nipple tenderness
- nipple discharge or physical changes such as nipple turned inward or a persistent sore
- a change in the size or shape of the breast
- Skin irritation or changes, such as puckers, dimples, scaliness, or new creases
- Redness or a rash resembling the skin of an orange (may be called peau d’orange)
- Swelling of the breast
- Pain in the breast (not usually a symptom of breast cancer)
- Warmth of the breastor pain in the breast
How is Metaplastic Breast Cancer diagnosed?
- Biopsy (fine needle, image-guided, or surgical)
- blood tests
What is the treatment for Metaplastic Breast Carcinoma?
- lymph node removal and analysis, sentinel lymph node biopsy
- axillary lymph node dissection
- reconstructive (plastic) surgery
- radiation therapy
- partial breast irradiation
- intensity-modulated radiation therapy
What kind of drugs are involved?
- Pegylated liposomal doxorubicin
- Protein bound paclitaxel
What are the side effects associated with these drugs?
It all depends on the individual and the dosage of the drug. However side effects can include:-
- risk of infection
- nausea and vomiting
- hair loss
- loss of appetite
These side effects usually go away when treatment is complete.
- Beatty JD, Atwood M, Tickman R, Reiner M. (2006) Metaplastic breast cancer: clinical significance. Am J Surg. 2006 May;191(5):657-64 https://www.ncbi.nlm.nih.gov/pubmed/16647355
- Gibson GR, Qian D, Ku JK, Lai LL. (2005) Metaplastic breast cancer: clinical features and outcomes. Am Surg. 2005 Sep;71(9):725-30. https://www.ncbi.nlm.nih.gov/pubmed/16468506
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