Microinvasive Breast Cancer

“Microinvasion” is a term used somewhat informally to describe a borderline difference between completely contained ductal carcinoma in situ (DCIS) (early-stage breast cancer) and a minimally invasive ductal carcinoma.

What it means is that a very small amount of malignant cells (cancer cells) have been found beyond the duct lining and have passed through the basement membrane of the duct and into the surrounding stromal breast tissue or the inside of the breast ducts themselves.

 

 
 

 

The relative size or amount of this infiltrative/invasive carcinoma is not fully agreed upon. Currently ductal carcinoma in situ accounts for about 23% of newly diagnosed breast cancers, while microinvasive ductal carcinoma found in approximately 5–10% of DCIS cases. Microinvasive breast cancer most commonly occurs during the sixth decade of life and in more than half of cases presents as a clinically palpable lesion (though very small).

It is generally agreed that the overall prognosis for microinvasive breast carcinoma is very good.

 
 

Specific criteria for defining microinvasive breast cancer are varied

Microinvasive ductal carcinoma has been referred to by a variety of names, including Microinvasive breast carcinoma (MIC), ductal carcinoma in situ with microinvasion (DCISM or DCIS-MI), Microinvasive carcinoma of the breast (MICB), DCIS with microinvasion or simply microinvasive breast carcinoma (cancer), sometimes identified by the ‘breast cancer staging‘ abbreviation Tmic (which means that a tumor is present, and some microinvasion is also present but with a very small diameter).

Tmic is literally interpreted as an invasive element 1mm in diameter or smaller. However, microinvasive situations often occur with more than one foci, and that complicates the definition. Some studies consider microinvasion breast carcinoma an indication of one or two microscopic foci of possible invasion, but less than 1 mm in greatest dimension. Others state that there either should be a single focus of invasive carcinoma , less than 2 mm in diameter. Another interpretation of microinvasive breast cancer is of up to 3 foci but none can be greater than 1mm in the largest dimension.

Micro-invasion may be considered as a percentage

Another way of interpreting microinvasion of ductal carcinoma is as a percentage, such that the maximal extent of invasive carcinoma comprises less than 10% of the whole tumor, and at least 90% of the tumor still remains as ductal carcinoma in situ (still contained within the breast duct). The size of the tumor is a far more powerful factor in influencing the outcome, than whether or not microinvasion is diagnosed. But for equal-sized tumors, microinvasion will worsen the prognosis.

Improvements in Breast Cancer screening mammography has lead to increased detection of microinvasive DCIS

Improvements in the quality and interpretation of breast cancer screening mammograms, as well as a general increase in the number of women participating in breast cancer screening programs, has lead to an increase in findings of ductal carcinoma in situ, with a corresponding increase in Ductal carcinoma in situ (DCIS) with evidence of microinvasion. DCIS is usually diagnosed by mammography, and usually because of the presence of microcalcifications without a detectable mass. If on mammography there appear to be clusters of microcalcifications in several locations, that would be a clue as to a ‘multi-focal’ presentation of DCIS.

 
 

Ultrasound rarely diagnoses DCIS on its own. Usually mammography occurs before ultrasound, so if there is a suspicious finding on mammography, ultrasound sometimes helps to clarify the situation.

An ultrasound image of a microinvasive breast cancer lesion will likely appear as an irregularly shaped hypoechoic lesion without shadowing.The ultrasound image of microinvasive ductal carcinoma in situ shown below features faintly detectable calcifications.

 
 

Histological analysis of suspected microinvasive DCIS tumors can help clarify the diagnosis

Since treatment for ‘pure’ DCIS (fully contained within the breast ducts) differs or may differ from DCIS with microinvasive status, identifying the smallest focus or foci of any invasive carcinoma is of some significance.

One of the histological ‘hallmarks‘ of microinvasive breast carcinoma is the presence of a dense lymphocytic infiltrate. Evidence of an inflammatory reaction is often part of the overall diagnosis of an aggressive, invasive situation, but the pathologist must be careful not to dismiss the finding as simply an inflammatory reaction possibly due to infection or other illness.

The microinvasive carcinoma element which has caused the inflammatory response might be very small, almost undetectable. However, invasive tumor cells are readily distinguished from inflammatory cells by cytokeratin AE1/3 immunostaining. In the microscopic (low magnification) image of microinvasive ductal carcinoma below, inflammatory cells ‘mask’ the focus of invasive ductal carcinoma. Recent studies which highlight myoepithelial cells using antibodies to cytoskeletal proteins, or to the nuclear protein p63, (a member of the p53 gene family), has also proven to be a useful histological tool in distinguishing invasive carcinoma from similar-appearing, benign breast diseases. False-positive diagnosis of microinvasive breast carcinomas often turn out later to be radial sclerosing lesions or sclerosing adenosis.

Microvinvasive breast carcinoma cells are often ‘comedo’type.

Microinvasive ductal carcinoma are frequently associated with a higher nuclear grade ‘comedo’ type ductal carcinoma in situ. Other histologic subtypes of DCIS such as cribriform, papillary and solid, are thought to invade less frequently than comedo DCIS. If the microinvasive DCIS element comprises cells of either the solid, papillary, or cribriform pattern, the changes of lymph node metastasis (already very low) are reduced even further.

The status of hormone receptors in micro-invasive breast tumors is highly variable

The hormone receptive status of microinvasive breast carcinomas is variable, but generally speaking less than 50% of these tumors are positive for the most common receptors, (estrogen receptor and progesterone receptor) and either negative or unclear in the other half. HER-2 is over-expressed in about 1/3 of postive HR status patients. The hormone-receptive status of microinvasive breast cancer tumors will have to be identified in each individual case, will possible chemical and endocrine-based treatments tailored by the cancer-treatment team.

Staging and treatment of microinvasive breast cancer : Is Axillary lymph node investigation necessary?

Staging of microinvasive ductal carcinoma in situ is somewhat of a controversial topic. The general consensus surrounding ‘pure’ ductal carcinoma in situ is that axillary lymph node metastasis is so very improbable that lymph node staging or sentinel lymph node biopsy are not necessary. (There are some still some cancer physicians who disagree, and some women ‘pressure’ their doctors to investigate the lymph nodes to appease their anxiety, but studies on routine axillary dissection for DCIS have demonstrated a rate of lymph node metastasis at less than 1%.)

The overall estimated rate of lymph node metastases in patients with microinvasive breast carcinoma is low, but not negligible. The statistics also tend to be quite inconsistent, adding to the dilemma. Some studies on lymph node metastasis of microinvasive DCIS place the rate from 0 to just over 5%. Other studies suggest a rate of lymph node metastasis as high as 10%-11%, while others place it as high as 28%.

Risk of lymph node metastasis is extremely low in micro-invasive dcis breast tumors

So, there is agreement that the risk of lymph node metastasis is very low, but the debate then turns to analyzing the various presenting factors in the microinvasive breast cancer tumor which might positively or negatively influence the incidence rate. Some studies have considered the difference in frequency of axillary node metastasis between tumors with ‘measurable’ invasion, versus those of ‘microfocal’ invasion. (‘Measurable’ invasion would generally refer to a ‘T1’ status, which is the first staging category above Tmic, and refers to tumors up to 2cm in diameter.) The rate of axillary lymph node metastasis for microinvasive tumors is estimated at around 4%, and about 8%-9% for measurable tumors. Whether or not the statistical difference is significant is still a matter of interpretation. However, the ‘T1’ threshold seems to be significant among physicians, and these larger tumors, even if 90% of the tumor is still DCIS, are thought to be more worrisome.

Metastasis for micro-invasive breast cancer is slightly more common in younger women

Patients with axillary metastasis tend to be younger (but not much younger, on average in their early 50s as opposed to the late 50s). The presence of comedonecrosis, multifocal DCIS, multifocal invasion, or the development of a palpable mass have not actually been convincingly linked to higher risk of axillary metastasis. Positive progesterone and estrogen receptor status, which tends to be the case in a minority of cases, also does not correspond with higher risk for axillary nodal involvement.

The decision to proceed with exploratory lymph node dissection is a subject of debate with microinvasive breast tumors

With microinvasive breast cancer, we find a curious situation where physicians can look at the same set of statistics, and yet come to different conclusions; some say that axillary lymph node dissection is warranted, other feel that it is completely unnecessary, also pointing to the cost, discomfort and stress involved. They are many ‘grey area’ decisions in breast cancer treatment, and an experienced physician will tend to have a ‘feel’ for the subtleties in all of the diagnostic presentations and risk factors associated with the patient, and make an appropriate decision.

The prognosis for microinvasive carcinoma of the breast is very good.

There is universal agreement that the prognosis for ductal carcinoma discovered and intervened at a ‘microinvasive’ stage, is very good. Patients with microinvasive breast cancer can typically expect a cure rate very close to 100%, with local treatment alone. Most microinvasive breast cancers will be treated by breast conserving surgery (just over 50%) or by radical mastectomy (just under 50%). Adjuvant treatment is still a bit controversial, but radiotherapy is very common (employed in over 80% of cases), while chemical and endocrine treatments are much common and will likely depend on the hormone receptor status of individual patients.

Local recurrence may happen, but does not affect the overall outcome

Local recurrence is rare with microinvasive ductal carcinoma and factors associated with recurrence tend to be close surgical margins, breast conservation versus mastectomy, and a younger age. Local recurrence tends not to be a serious issue with microinvasive breast carcinoma, and tends to be treated and cured locally.

Lymph node metastasis may be slightly more likely when infiltration is in clusters

In the unlikely event of lymph node metastasis following the presentation of microinvasive ductal carcinoma, the prognosis for the patient tends to be mostly influenced by the number of metastatic nodes, irrespective of the absolute quantity of invasive carcinoma in the breast area. Some studies also suggest that lymph node metastasis, which is highly unlikely, is slightly more probable for microinvasive tumors in which the infiltration of the periductal stroma occurs by ‘clusters’ of cells, rather than by ‘single’ cells. But even with these ‘clustered’ microinvasive formations, the risk of metastasis is at most about 10%.

For microinvasive DCIS, breast conserving surgery with radiation is usually considered the most reasonable approach.

Because of the high rates of survival and freedom from distant metastases and because of the ability to salvage patients with local recurrence, breast-conserving surgery and definitive irradiation should continue to be considered as an alternative to mastectomy for appropriately selected and staged patients with microinvasive ductal carcinoma of the breast. However, virtually all microinvasive ductal carcinoma tumors which eventually metastasize are shown to be tumors with a ‘T1’ invasive status. (which is not really microinvasive breast carcinoma. )

The overall survival rate for micro-invasive breast cancer is extremely high.

In terms of management and follow up, it is felt that microinvasive breast carcinoma behaves in a manner more like DCIS than invasive ductal carcinoma. The rate of local recurrence is generally 17% or less, and distant metastasis is extremely rare. The overall 5 year survival rate for women with microinvasive carcinoma of the breast can be estimated at around 95% or higher.

Here are a few Q&A’s…

If I do have an abnormal mammogram, what happens next? If there is anything suspicious on mammogram you will have a breast biopsy so that a breast tissue sample can be analysed to give a definitive diagnosis. You may have a needle biopsy such a a fine-needle biopsy whereby a small sample of cells are taken or a core needle biopsy which can take larger cell samples. Sometimes an incisional or excisional biopsy will be requested. The cells are then examined under a microscope so that a diagnosis can be made.

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