Imaging Vigilance for Patients at High Risk for Breast Cancer

Elizabeth A. Morris, MD

As part of our coverage of the 34th Annual Miami Breast Cancer Conference, held March 9–12 in Miami Beach, Florida, we spoke with breast imaging radiologist Elizabeth A. Morris, MD, Chief, Breast Imaging Service and Larry Norton Chair at the Memorial Sloan Kettering Cancer Center in New York, New York, who presented at the meeting on imaging vigilance for women at high risk of developing breast cancer.

Cancer Network:How has imaging for breast cancer screening changed in recent years?

Dr. Morris: I think what has been happening in the last few years is we’ve gone from treating every woman as the same, screening them the same, to seeing that women at increased risk of breast cancer-those with family history, a high-risk lesion on prior biopsy, BRCA mutations-warrant more vigilant screening. Clearly, not all women have the same risk of developing breast cancer.

Many guidelines are one for all. Currently, we recommend that women who are age 40 years and older get screened by mammography every year, for everyone.

But the American Cancer Society is putting together a panel to investigate whether or not we should have stratification for screening recommendations based on patient risk.

Mammography is a good test, but not a perfect test. There is new technology coming along that is very much embraced in the United States, called breast tomosynthesis. It is also called “3D mammography” or “DBT.” It is just a much better mammogram. In the United States, as older mammograms become old, they’re being replaced with these 3D mammograms. That is going to take over current practice for mammography.

It provides a 3D look inside the breast and can pick up more cancers. It has an increased detection rate and a decreased recall rate because it addresses pitfalls and problems with regular mammography, which has false-positives and misses some tumors.

Tomosynthesis offers a better look at the breast, so there are fewer false-positives. Instead of one image with superposition of tissue, it provides 20 to 50 images to look at. You can feel more confident that there is nothing going on-or that there really is actually a mass.

Because you have an improved ability to look at mass margins, you can see, and be much more confident, that the mass you are looking at is a probable cancer. If it has smooth margins, it might be a cyst or another benign mass. So you can actually go straight from DBT to ultrasound instead of, as in the past, ordering additional views. It has really streamlined the work flow.

It has been a really big improvement in imaging.

Cancer Network:How does breast density affect mammography and imaging decisions?

Dr. Morris: About 10% of the population has extremely dense breasts and what we call heterogeneously dense, or level 3, breasts are seen in 40% of the population. So, women with dense breasts make up 50% of the population. That’s a large number of women!

Over the past several years, many states have passed breast density notification legislation. The problem with traditional mammograms is that with dense breasts, there’s a double whammy: dense breast tissue masks tumors so it’s much harder to pick up cancer in those breasts, and dense breasts have a small but real increase in cancer risk. So it is obvious that mammography isn’t doing the job for women with dense breasts. So many states enacted laws saying radiologists must tell women if they have dense breasts or not, because if they are dense, they have a lower chance of being picked up on mammography and are at increased risk for cancer. Those women might want to talk with a clinician about alternatives like ultrasound or MRI.

So that’s addressing risk based on breast tissue density.

Cancer Network:What is the gold standard imaging modality for women deemed to be at high risk for breast cancer?

Dr. Morris: So, there is risk based on breast tissue density. But then there is family history and genetic abnormalities. If women have a really strong history of breast cancer-more than a 20% lifetime risk, then they really should be getting annual contrast injection MRI exams for screening. It is the best test we have for picking up early breast cancer.

But it is expensive and cannot accommodate all women; It is for women at high risk. The injection and expense are problems and we sometimes have to fight insurers to get it covered. It is not widely used. Of women eligible to receive breast MRI, with high family risk, only 2% actually get the test.

There has to be better communication between the people recommending these screening tests, society guidelines, and patients and providers. A lot of women do not know they’re at high risk. And a lot of women who are at high risk don’t know they should be receiving breast MRI.

MRI has very high sensitivity, approaching 99%. There are false-positives, though. But there are also false-positives on mammography. Any time you add another screening test you’ll get false-positives, and that is a problem.

Cancer Network:Are there other imaging techniques gaining favor for breast cancer screening?

Dr. Morris: There are new kids on the block that are not widely used. We do quite a bit of screening with contrast mammography. It involves injection of an iodine-based contrast agent. We inject and then wait a few minutes and do a mammogram, a special acquisition image with contrast. It is the poor person’s MRI, sort of. It gives you vascular information about the breast, including small, very vascularized masses that will enhance.

For women with dense breast tissue who are at moderate, not at super high risk, we use contrast mammography. We think it is better than ultrasound. More people are looking at it because it’s cheap and easy to implement, to put into the clinic. The work flows are not that difficult. Compared to MRI, it’s super cheap.

MRI is still the standard. It’s the best we have, so there haven’t been a lot of studies comparing contrast mammography to MRI-so we don’t know if it can replace it yet. Those studies are under way.

Cancer Network: Are there gene variants other than BRCA that can identify which women are at high risk? Are there genomic assays to help with stratification for screening with imaging?

Dr. Morris:BRCA patients definitely need MRI screening from the minute they test positive.

There are a lot of different groups developing panels with single nucleotide polymorphisms (SNPs). We think it’s interesting data. We are looking to do a research project to see about stratification with SNPs. That is still in the research phase.

It’s very promising because SNP testing can be very cheap. You can do a cheek swab for $20 and stratify a patient based on risk. That’s very appealing. So, there might be in the future SNP tests, if they are validated and proven to show correlation with outcome, that can stratify patients. We could even possibly screen patients less and screen other patients with more sensitive modalities. I think that could be the future.

Competing with that, there is a lot of interest in circulating tumor DNA in the blood. Quite a few companies are working in that space. GRAIL is starting a big screening trial to pick up cancer before the mammogram, in the blood.

Will screening go that route? That will depend on the sensitivity of the blood tests. Can a blood test pick up a 1-mm tumor of the breast? Will there be enough circulating tumor DNA?

The future is interesting for screening. If we could have screening tests like a cholesterol test every year at your doctor’s visit, and there’s a potential abnormality or red flag, then patients could receive a high-end MRI or other screening test. That might be the future.

But it is early days. GRAIL is enrolling patients. Their ultimate goal, I think, is a multi-cancer panel that could pick up different types of cancer.