Use of MRI for breast cancer screening for high risk women

There is no question that breast cancer screening programs have protected the health of thousands of women in the last decade. Various studies recommend that breast cancer screening be undertaken annually, certainly by the age of 50 and even better if women start by the age of 40.

Annual breast cancer screening is generally not necessary for women in their 30’s. There is a general consensus that a majority of breast cancers tend to be linked with hormonal changes associated with menopause.

However, for ‘high risk‘ women, breast cancer screening is recommended annually starting at an earlier age, even beginning around 30. Women at high risk for breast cancer are thought to face a lifetime risk around 20% to 25% for developing breast cancer.

In addition, there is an increasing body of evidence that suggests MRI might be the most useful screening modality for women in these high risk groups. However, the notion is not without some controversy.

I just want to let you all know that this page still has great information but a little outdated, so I have recently decided to create a newer version of this page with more up-to-date information specifically about MRI for high risk women. Although I would still use this page as well.

Women at higher than average risk for breast cancer development

Essentially, there are five basic groups of women who specialists consider at a higher than average risk for developing breast cancer:-

Women who carry the genetic mutations BRCA1 and BRCA2 are certainly at higher risk for breast cancer than the average population.
Also, women who have a first-degree relative or are a carrier for any genetic mutations.
Thirdly, if there is a family history of hereditary breast cancer syndrome, then the risk for breast cancer elevates to around 25%.
Of course, women who already have a high risk marker from a biopsy sample, such as, atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ, will naturally have an increase in the risk for breast cancer.
Finally, women who have had radiation therapy to the chest area prior to the age of thirty and within the last year, have an increase in the risk for developing breast cancer.

(The increase in breast cancer risk from having prior experience with ADH or ALH is not as high as one might think).

There are less well-proven risks factors for breast cancer, such as:-

Obesity
Environmental toxins
Smoking
Taking of menopausal hormones (HRT)
Breast density

but in general, the above are the top five factors which place a woman in a higher risk group for developing breast cancer.

Increased sensitivity for detecting breast cancer using MRI vs. mammography

Within these higher risk populations, studies show that the sensitivity of MRI in detecting breast cancers during screening is between 71% and 100%. In contrast, the sensitivity of mammography alone is between 16% and 40%.

That is quite a difference, but sensitivity does not necessarily lead to the detection of more breast cancers or a reduction in mortality rates. By the way, the sensitivity of ultrasound is approximately that of mammography for women in the high risk group.

However, the same studies invariably show that while the sensitivity is much higher for MRI, the specificity is actually much higher with mammography. This means MRI almost always requires additional studies (recalls and biopsies) to determine the exact nature of a lesion.

The actual detection frequency for breast cancer in high risk women when compared to the overall average population, is still only about 2% higher. There is a difference, but it is relatively small.

One has to weigh both the monetary expense and the psychological toll of MRI screening in high risk women, when the actual rate of breast cancer detection is really not increased significantly.

Prior radiation treatments and existing ADH are the highest risk factors

The decision to use MRI, even in high risk groups, is always a bit of a grey area. On the whole, however, the most justifiable use of MRI for higher risk women is in situations where there is a prior history of radiation treatment in the chest. In addition, in cases where there is a small lesion of

It is the opinion of many experts debating the cost versus the benefit of MRI screening, that the benefits of of MRI outweigh the potential harms of higher recall rates and biopsy rates.

This is particularly the case for women in which a particular ADH-type marker is present before the age of 69. For women with previous radiation treatments, MRI screening is certainly justified beginning as early as age 30, or eight years after the chest irradiation (whichever is later).

Women who have already had radiation treatment to the chest, for example, for Hodgkin disease, really comprise a well-defined high risk group. The risk of secondary breast cancer is particularly high in this situation, and therefore the expert consensus opinion is to use MRI screening for these women.

MRI screening for women with a potential genetic predisposition for breast cancer

Women who have a known genetic abnormality, such as the BRCA1 and BRCA2 variants, have been proven statistically to have a slightly higher risk for breast cancer development.

Breast cancer specialists consider even younger patients with these genetic factors to be ‘high-risk’. So these patients are likely to take part in a breast cancer screening program at a younger age. MRI might be beneficial for women in this situation, but the statistical evidence remains unclear.

In the MRI image below, which is of a women with known genetic variants, one can see a small breast cancer. In certain breast locations, small lesions might be undetectable on mammogram and ultrasound.

The subtraction MRI of the breast confirms an area of contrast enhancement, quite possibly indicative of breast cancer. A biopsy will be necessary for confirmation.

mri-breast-high-risk-women-subtraction

Hook and Wire to guide the surgical excision for evaluation

Sometimes a ‘hook and wire‘ technique is useful to guide the way for a surgeon attempting to excise a very small lesion or one in a difficult location.

The surgeon inserts a wire with a little hook on the end into the breast and hooks it into a target nodule. The surgeon then follows the wire to find the nodule. Of course for MRI, any wires used must be made of non-magnetic material.

breast-mri-hookwire

The hook and wire X-rays above and below are actually of the same lesion using MRI above. In fact, the biopsy sample reveals no apparent invasive breast cancer, but actually a grade 3 ductal carcinoma in situ. It just goes to show that MRI often leads to recalls and biopsies, but then to unexpected results.

What a pathologist sees under the microscope is sometimes called “the truth”, because the pathological findings are more trustworthy than any other results, generally speaking.

In other words, a pathological evaluation will typically confirm either a ‘true‘ positive, or a ‘false‘ negative. In this particular image, there is no evidence for breast cancer within the suspicious lesion, so doctors may term it a ‘false positive‘.

lesion-hookwire-closeup

Various MRI sub-findings for high risk women in breast cancer screening

New studies have found that a number of additional tissue properties in high risk women may have relevance for breast cancer screening. These include the:-

MRI breast tissue volume
Apparent diffusion coefficient (ADC)
Optical measurements of lipid content.

Additionally, water content and hemoglobin oxygen saturation also show promise for evaluating high-risk populations as these variables are related to breast density.

The psychological impact of MRI screening in high risk women is not trivial

For women who belong to a high risk group, the psychological impact of an increase in the breast cancer risk can be quite profound.

Even in the absence of actual disease, quality of life is often affected due to the increase in anxiety. With the use of MRI screening, the situation is even worse.

On the one hand, these women are at a higher risk for cancer, and on the other hand, the rate of false positive findings because of the MRI is much higher. That is a very difficult combination for a woman to endure on an ongoing basis. While around 90% of women find they can handle the increased stress and return for screening on an ongoing basis, about 4% find breast MRI to be extremely distressing.

Furthermore, just under 50% of high risk women who undergo MRI screening find the process very intrusive and upsetting, though not enough to stop being screened.

However, follow-up studies on the psychological stress of breast cancer screening have uncovered other factors besides the sensitivity and false positive rates associated with breast MRI.

Women who are obsessive ‘self examiners‘ face an increase in anxiety. Also, associated with an increase in anxiety are those closely involved in the care of others with breast cancer, or having relatives with any kind of cancer. And, women who return back for ‘recall’ imaging or biopsy work, always face an increase in anxiety levels.

So, there is a kind of ‘emotional-interplay‘ which occurs for women, and especially for women in high risk groups, between the risks and benefits of MRI breast cancer screening and the potential harm to quality of life while undertaking all of this screening.

When one factors in to this situation:-

a woman’s age
perception of risk
understanding of the issues

it can really have a profound impact in certain cases. With breast cancer MRI screening, it is important to realize that a positive MRI finding is quite likely going to turn out to be false. For high risk women, the high rate of biopsies and further investigations is probably acceptable in terms of anxiety. However, for the general population, it is probably not.

A panel of experts working in MRI breast cancer screening recently concluded that for women in lower risk categories, MRI screening is not advisable and that the harms may well outweigh the benefits.

Not all women with a family history of breast cancer should be offered MRI screening, depending on their age and overall estimated risk

The use of MRI breast cancer screening as an adjunct to mammography for women who are at increased risk for breast cancer development must take into consideration a number of different variables. These include realistic estimates of risk, family history, other clinical factors, and the consensus opinion of experts in those grey areas. MRI will very often lead to false positive findings. Based on current expert consensus, MRI breast cancer screening should probably be offered to women between the ages of 30 and 40 who have a family history of breast cancer with a 10 year risk greater than 8%, and to women in the 40-49 age bracket with a family history and an estimated 10 year risk greater than 20% for developing breast cancer. Women aged 40-49 with a family history who also show a dense breast pattern should also probably be offered MRI screening.

The actual biopsy and breast cancer detection rates for MRI and mammography are over 3 times as high for MRI, but still a very small number

MRI breast cancer screening in high-risk women has demonstrated capability in finding clinically and mammographically occult (hidden/missed) breast cancers. Some studies have found that about 6% of high risk women who show negative mammograms and with negative clinical exams may have occult breast cancer detected by MRI. At the same time, MRI breast cancer screening has been shown to yield about 5% false-positive findings, resulting in benign biopsies. Studies consistently show a biopsy-recommendation rate for MRI in high risk women about four times as high as for mammography (about 8% and 2% respectively) The rate of breast cancer detection shows a similar but smaller ratio between MRI and mammography. MRI tends to diagnose almost 3 times as many breast cancers as mammography in high risk women, although the actual rates of diagnosis are still very small (approximately 0.8% and 0.3% respectively).

MRI screening for women with a history of LCIS is not really required

Women who have been diagnosed with LCIS (lobular carcinoma in situ) are considered to be at increased risk for breast cancer. However, the lifetime risk for women diagnosed with LCIS is only around 20%, and the first 12 years after excision carry a lesser risk than this. In terms of the use of MRI breast cancer screening for higher risk women with a personal history of LCIS, this would need to be determined on a case-by-case basis. There is no pressing need for MRI screening, even though MRI may show a slightly increased ability to identify breast cancer over mammography in this situation. Factors such as age, family history, breast density, the pathological nature of the biopsy sample, and to a certain extent patient preference, play a role in deciding whether or not to use MRI with a history of LCIS.

Breast density is more and more considered to be a true risk factor, but MRI breast cancer screening shows no clear benefit

Women with dense breasts are a little bit more difficult to screen using mammography, simply because the dense tissue blocks the transmission or light to a certain extent. There are different pattern classifications for breast density, and for women with a much greater percentage of fibrous tissue vs. fat tissue, the risk for breast cancer is certainly higher than for the average women. However, at the present time there is no clear indication that screening women with dense breasts using MRI instead of mammography will catch any developing breast cancer at an earlier stage and lead to a reduction in deaths due to breast cancer.

The Cost Effectiveness of MRI breast cancer screening in high risk women

If you really weigh all the variables involved in breast cancer screening with MRI, one would have to take into account the cost of the equipment, the cost of the technicians and radiologists’ time, the materials, and the time and people and expense involved in taking and evaluating biopsy samples. It adds up. Some recent studies have actually come up with relative dollar numbers for MRI breast cancer screening in high-risk women. It is expensive, but the cost-effectiveness is improved where breast cancer is actually detected. So, it becomes much more justifiable to do MRI screening for women in which the elevated breast cancer risk is truly significant. Sometimes these figures are calculated in ‘quality of life years‘ (QALY), so the hospital boards can calculate how much it would cost to ‘add‘ MRI breast cancer screening, relative to the number of high quality of life years the patient would likely benefit from such a procedure.

For example, the cost of adding MRI screening for women who have a 50% risk of carrying a BRCA gene mutation is approximately $50000. If we look at this from an annual point of view, the cost will be adjusted according to different age groups. Adding MRI screening to a high-risk women, for example who carries or very likely carries a BRCA gene variant, is about $14000 for women between 40 and 49, and about $25000 for women between 30 and 39. Add to this the subjective measure of overall estimated risk (usually a 10 year risk) based on a subjective assessment of many different and unique aspects of a particular patient. When the 10 year risk of breast cancer is over 30%, the overall added cost of adding MRI screening to mammography might be about $14000, while for a women with a 12% estimated 10 year risk of breast cancer, that cost soars to around $53000. And, for a women with an estimated 10 year risk of breast cancer at only around 6%, the estimated cost of adding MRI screening is a staggering $96000.

So, one gets a sense that in order to really consider using MRI breast cancer screening for women thought to be at higher risk for breast cancer, the physicians will probably only make that recommendation if they truly believe the patient is indeed at an increased risk for breast cancer. If MRI breast cancer screening is not thought to be essential, then it probably should not be done.

Overall recommendation for MRI breast cancer screening in women with increased risk of breast cancer

Many studies have now demonstrated the ability of MRI to detect earlier-stage tumors, and also in finding certain types of breast cancer that can quite often be cured, and so MRI use is usually associated with better outcomes where cancer is actually found. And it follows that women thought to be at a higher risk of developing any kind of breast cancer would benefit the most from this type of screening intensity. But, when one carefully weighs the monetary and psychological costs of MRI screening, a blanket approach to its use cannot be recommended.

Overall, MRI breast cancer screening is recommended for women in which there is an apporximately 20-25% or greater lifetime risk for breast cancer. Certainly, this would include women with a strong family history of breast or ovarian cancer, and women already treated for Hodgkin disease. For the other subgroups often linked with high risk, such as women with a personal history of breast cancer, women with dense breasts, and women with DCIS, LCIS, or atypical hyperplasia, the available data is insufficient to recommend either for or against breast cancer screening based on statistics alone. It would have to be determined on a case-by-case basis.

Below are a couple Q&A …

Who will be considered at high risk of breast cancer? Women aged 30-69 will be considered high risk if they have any of the following risk factors:

1) Genetic testing confirming that they have a mutation (BRCA1, BRCA2 or TP53) that increases their risk for breast cancer.

2) A parent, sibling or child with genetic testing confirming a mutation that increases their risk for breast cancer.

3) A family history that indicates a hereditary breast cancer syndrome and a 25% or greater lifetime risk of breast cancer confirmed through a genetic assessment.

4) Radiation therapy to the chest before 30 years of age and more than eight years ago as treatment for another cancer or condition.
Why is it important to screen women who are at high risk of developing breast cancer? The risk of developing breast cancer is two to five times higher for women at high risk than in the general population. Women at a high risk develop breast cancer at a younger age than the general population. And breast cancer is more aggressive in younger women who are a high risk, so it’s important that it is identified early.

References

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Warner, E., Messersmith, H., Causer, P. Eisen, A., Shumak, R., Plewes, D., Magnetic Resonance Imaging Screening of Women at High Risk for Breast Cancer. Report for the Quality Initiative of the Program in Evidence-based Care (PEBC), Cancer Care Ontario (CCO) April 12, 2007.
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