Breast Cancers Diagnosed Between Mammograms are More Aggressive

Guidelines on when to undergo mammography to detect breast cancer may need to be revised for women who are at high risk of having a particularly poor prognosis if cancer develops, according to a study published May 3, 2018 in the journal JAMA Oncology. The study explored cases of what’s known as “interval cancers” — cancers that are diagnosed after a negative mammography screening but before the next recommended screening exam.

Interval breast cancers include situations where a tumor was present when the mammography was performed but the cancer was missed, as well as tumors that arise during the interval between mammograms. These fast-growing tumors tend to be more aggressive and associated with a poorer prognosis.

Interval cancers are among the most frustrating problems associated with breast cancer screening. But studying how and why these cases occur may help researchers identify subgroups of women who need mammography more frequently, at younger ages or who would benefit from a more rigorous type of screening, such as screening with ultrasound or magnetic resonance imaging (MRI) technology.

“We know that mammography screening works, but we know it’s imperfect,” says Anne Marie McCarthy, PhD, lead investigator of the study and an assistant in epidemiology at Massachusetts General Hospital and an instructor at Harvard Medical School in Boston. “We estimate about 15 percent of breast cancers are diagnosed during a reasonable interval after a negative mammogram. It’s rare for women to get cancer within a year of mammography, but it does happen, and it’s very upsetting.”

Interval Breast Cancers: Fast Growing and Deadlier

“When we think about creating screening guidelines, we’re thinking about what works for the whole population,” she says. “We have this blanket recommendation. But are there specific groups of women who are at higher risk and may need more frequent screening or other types of screening? Our idea is we might want to focus on risk factors and prevention strategies for the cancers with the poorest prognosis.”

Dr. McCarthy and her colleagues analyzed data from 306,028 women age 40 and older who had no earlier diagnosis of breast cancer and underwent mammography screening. Cases of cancer found after a negative mammography screening were more likely to be linked to a poor prognosis (cases in which the cancer had already spread or the cancer was a more aggressive type). About 43 percent of interval cancer cases were defined as having a poor prognosis compared with almost 27 percent of cases of cancer found during routine mammography screening.

Higher breast density, with tissue that consists of more supportive material rather than fat, was linked to a higher chance of having an interval cancer. Women with dense breast tissue had twice the odds of having an interval cancer diagnosis compared with women with nondense breasts. Those women did not tend to have a worse prognosis, but women with interval cancers who were younger did have a poorer prognosis.

“While density predicts diagnosis of cancer after a negative mammogram, it doesn’t predict poor prognosis,” McCarthy says. “This is important because there has been a lot of push to identify women with dense breasts, because these women are more likely to have interval cancer. But it’s not predicting the poorer prognosis. So perhaps density isn’t the whole story.”

RELATED: Fewer Call Backs From Mammography Screening Centers Linked With More Missed Cases of Breast Cancer

Who Needs More Frequent or Aggressive Screening?

“Perhaps women with dense breast are getting cancers missed, but they may be more slow growing and have a better prognosis. Whereas younger women are more likely to have more aggressive cancers,” McCarthy says. “If we’re going to move the dial on breast cancer mortality we have to focus on what can we do about the cancers that are more likely to kill women. It’s important to dial in on poor prognosis cancers and what can we do about that.”

Currently, the U.S. Preventive Services Task Force (USPTF) recommends most women begin regular breast cancer screening at age 50 unless an individual has a family history of the disease or has tested positive for genetic markers that increase risk, such as the BRCA genes. In the future, research may suggest guidelines for specific groups of women, such as those most at risk for cancer with a poor prognosis.

There are several types of breast cancer, McCarthy notes, and they differ in treatment options and prognosis. For example, a type called triple negative breast cancer has fewer treatments and is linked to worse outcomes.

“Very few women are going to get diagnosed with breast cancer before 50, but for those who do, the cancer tends to be of poorer prognosis,” McCarthy says. “It’s this trade-off of the risks and benefits of screening. I think the recommendations of the USPSTF are good. They are evidence-based and make sense. But I think that we need to be able to identify women who are at higher risk who need screening in a different way.”

Reproductive health history, genetic markers, and other information may be useful to eventually suggest which women should be screened earlier in life and more frequently, she says.

Women Who’ve Had Interval Cancer May Need Careful Screening Going Forward

In the meantime, women who experience the shock of having an interval cancer may need to review screening options after treatment, McCarthy says.

“Once you’re diagnosed with breast cancer, your oncologist and care team will work on your treatment plan based on the profile of your cancer,” she says. “But further down the line, it might be a discussion about whether mammography is sufficient or whether ultrasound or MRI may be used in screening as well.”

Breast cancer screening is highly successful, overall, at preventing cancer deaths. But guidelines for who to screen and when may need to evolve. Women who have had a negative mammogram but who have concerns about their breasts should seek evaluation and not wait for the next routine mammography, she says.

“For women experiencing interval cancer, it can be particularly frustrating because they are doing things right and seeking preventative care, and in their cases, it didn’t help them,” McCarthy says. “We did such a good job at rightfully pointing out the benefits of mammography, but we forget that no screening test is perfect and there will always be false positives and false negatives.”

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