BREAST DENSITY: PART ONE

According to a new law in California, radiologists who read mammograms will soon need to inform patients if their breasts are dense as seen with the mammograms.  The reason is that breast cancer occurs more often in women with dense breasts than in women with low-density or fatty breasts.  What should you do if you get a letter like this? First, please don’t panic!

Dense breasts are the normal starting point.

Virtually all breasts start out dense.  We don’t usually do mammograms on young women, but when we do, they are invariably dense.  It is how breasts grow during adolescence.  For this reason, breast density is better understood as persistence of how breasts grew in the first place than as a change.   The reason is that, as women age, the gland tissue is often replaced with fat, even though the breasts can stay the same size.  Fat is less dense on mammograms, so breasts often become less dense after breastfeeding, after menopause, or after stopping hormone replacement therapy at menopause.  Whatever the cause, it is the low-density, fatty breast that has changed, not the other way around. Persistent breast density is literally the lack of change.

Cancer starts more easily where there is more gland tissue.

Density of breast tissue does not make the tissue bad – it’s just that dense breasts have more tissue that can go bad because of other factors.  When breast tissue is examined, there are some types of fibrocystic change that predict cancer, and some types of fibrocystic change that indicate no increase in risk. Years ago, we did a study to see if dense breasts had more of the kind of fibrocystic change that predicted cancer.  We found that dense breasts do not have more high-risk fibrocystic change.

So, you might ask, why is breast density related to breast cancer risk?  The answer is that breast cancer has to start in gland tissue, and when there is more gland tissue – for example, when gland tissue persists and makes the breast dense – there is more tissue where cancer can begin. We’ve actually known for a long time that cancer occurs where there is more breast gland tissue:  if a woman is lying down, there is much more tissue in the part of her breast toward her armpit, and that part toward the armpit is also where the most cancers occur.  So it is pretty logical that cancer would be more likely if breast gland tissue persists.  And similarly, there will be less cancer if there is less gland tissue in which cancer can begin, like in a fatty replaced breast. 

The risk is real, but it often decreases over time.

What is the risk that a woman with no family history of breast cancer and no history of any breast biopsy – two factors that independently predict higher risk of breast cancer – will develop breast cancer in the next five years?  This table shows the percent of women who develop breast cancer in the next five years, for women without a family history and who have not had a breast biopsy*.  Women with family history of breast cancer, or who have had a biopsy, have an increased risk even if they do not have dense breasts.  The most important thing to remember when looking at this table is that breast density tends to decrease over time, so a woman who has dense breasts at age 45 can have less dense breasts, and thus less risk, when she reaches age 65.

Understanding the risk with dense breasts.

To understand the effect of density from this table, compare the percent of women with fatty breasts who get breast cancer to the percent of women with very dense breasts who get cancer.

For example, the women who are age 60 to 64 with fatty breasts get cancer 0.7% of the time over five years, but the women age 60 to 64 with very dense breasts get cancer 2.7% over the same time.  This can be summarized two ways, and both are correct:  1. women with fatty breasts have about one-quarter the risk of women with very dense breasts (0.7 ÷ 2.7 = 0.26); or 2. women with dense breasts have about four times the risk of women with fatty breasts (2.7 ÷ 0.7 = 3.9). It all depends on which perspective you want to take. 

The table is also useful to compare relative risk and absolute risk.  If you look at the same women who are age 60 to 64, the absolute difference in risk is 2 percent (2.7 – 0.7 = 2 percent).  This is the largest difference for any age group in the table.  Thus, it is correct to say that the risk of cancer is “four times higher” with dense breasts, but the absolute difference is only 2 percent. This is a real difference – especially for the women who are affected – but emphasizing the “four times higher” relative risk description may cause more anxiety than fits the facts.

An important additional observation is that many women lose density over time so that a person who is at higher risk now, will tend to lose gland tissue (it gets replaced by fat) and thus experience reduced risk over time. 

Fatty (low-density) breasts are not risk free.

Breast cancer is more likely in dense breasts, but fatty, low-density breasts are not guaranteed to stay cancer free.  As the table shows, we still find cancer in fatty breasts, and it is important for everyone to be vigilant.  The best advice is to be careful, get your mammograms, and hopefully there will be improved ways to screen for cancer in women whose breasts remain dense.

* These percentages were published in 2008 in an article by Tice et al, “Using Clinical Factors and Mammograpic Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model.”  Annals of Internal Medicine, 2008; 148: 337-347, Table 5.  Percentages apply only to women who do not have the risk factors of family history and/ or a previous breast biopsy.

WHO SHOULD HAVE A SCREENING BREAST MRI?

MRI is the most sensitive technology currently available to detect breast cancer.  However, in a situation akin to the proverbial million-dollar “hammer” where everything starts to look like a nail, there is a temptation to think of MRI as the solution to all breast diagnostic situations.  The result is an epidemic of radiology reports that suggest a breast MRI “if clinically indicated” without reference to specific clinical guidelines.

Screening MRI works for high-risk women

Breast MRI has a defined role in the evaluation of high-risk women.  When compared to mammograms and clinical breast exam, it can identify cancers that would otherwise be missed.  In a sample of recent screening studies, MRI identified additional cancers after a negative mammogram in the contralateral breast (the breast without cancer on the other side) of 2.9 to 5.4% of women with primary breast cancer at the time of diagnosis.  In studies where patients were followed with repeat MRIs over time, MRI detected breast cancer for 4% of women with history of chest radiation for treatment of other cancers (such as Hodgkin’s Disease), for 5.4% of women diagnosed with lobular carcinoma in situ, and for 1.1 to 1.4% of women with a genetic predisposition to breast cancer.  In a separate study of high-risk women, mammograms found as many cancers as MRI, but the MRI found the cancers at a smaller size and earlier stage.  [It is important to note that mammograms and MRI are complementary.  In each of these studies, mammograms found cancers that were missed by MRI.]

Groups of women at high-risk

Based on these observations, several organizations* have published guidelines for use of screening breast MRI for high-risk women.  The agreed high-risk groups for routine screening breast MRI include:

1.  Women predisposed to breast cancer because they carry a deleterious mutation in the “breast cancer gene” BRCA 1 or 2

2.  Women predisposed to breast cancer because they carry a deleterious mutation in another gene associated with several different types of cancer such as PTEN (Cowden’s Syndrome) or p53 (Li-Fraumeni Syndrome)

3.  Women with an estimated lifetime risk of breast cancer of 20 % or more by a standard risk model based on family history such as the Gail Model, etc. 

4.  Women with previous radiation exposure of the breasts as with treatment of Hodgkin’s disease or monitoring tuberculosis or scoliosis (particularly if multiple x-rays were done during adolescence).

Some organizations also include:

5. Women with a previous biopsy showing lobular carcinoma in situ or atypical ductal or lobular hyperplasia, but this is often redundant since these conditions are frequently associated with a 20% lifetime risk in the Gail model above.

Screening breast MRI can be falsely positive and falsely negative

MRI has not been recommended for general screening because of the high false positive rate.  Even in recent studies published in 2010 through 2012, MRI was reported as abnormal about five times more often than women actually had breast cancer.  MRI also misses cancer: in the screening studies that reported all cancers – including those found between screening tests – about five percent of cancers were diagnosed in the interval after a negative MRI.

Should women with dense breasts have MRIs?

Recently, California Governor Jerry Brown signed a bill requiring radiologists, “…to include in the summary of the written [mammogram] report that is sent to the patient a prescribed notice on breast density.”  The bill also states, “Nothing in this section shall be deemed to create a duty of care or other legal obligation beyond the duty to provide notice as set forth in this section.”  This creates the uncertain situation where women will receive this information, but as yet, there is no good way to advise women on what to do about it.

One possibility is to do screening breast MRIs for these women because they have dense breasts on mammograms, but this is an untested option.  In fact, I have found only one study reporting MRI in women with dense breasts, but in that study, all women had an additional factor – in addition to dense breasts on mammograms – that increased their risk, such as family history, etc.  Even in the 612 women in this study who had factors in addition to dense breasts that increased their risk, 43 biopsies based on MRI alone were needed to find 9 cancers.  If the other factors were not present, it is likely even more biopsies would have been needed to find this number of cancers which means that even more women would have had negative biopsies that did not help them. There is study underway in the Netherlands using breast density as a criteria for MRI screening, but there is no information from that study yet.  Given the significant false-positive rate of screening breast MRI – and the real possibility of unreliable reassurance from a falsely negative study – this is an untested option. 

This is a field with much active research, and we all hope for better answers as soon as possible.  For the present, screening MRI should be used in accordance with guidelines offered by various professional organizations.   All these guidelines are essentially the same and suggest screening MRI for women at high-risk.  There is no consensus whether mammographically dense breasts meet this criteria for women who do not have other risk factors.

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*  Guidelines for screening breast MRI from various organizations:

American Cancer Society

American College of Radiology

American Society of Breast Surgeons

National Comprehensive Cancer Network You will need to create a log in for the NCCN Guidelines.