How Much Can Women Trust That Breast Cancer Biopsy?

By Nancy Shute

Published March 18, 2015 at 3:11 PM CDT

Pathologists use slides like this one to look for signs of cancer in breast tissue.

When a woman is diagnosed with breast cancer, the person who does the diagnosing is a doctor she never sees — the pathologist.

But though pathologists do a great job of identifying invasive cancer, they aren't as good at spotting two less clear-cut diagnoses that bring women a lot of uncertainty and worry, a study finds.

The doctors correctly identified invasive breast cancer 96 percent of the time compared with an expert panel, according to a study published Tuesday in JAMA, the journal of the American Medical Association, and correctly identified normal tissue 87 percent of the time.

But they misdiagnosed ductal carcinoma in situ, or DCIS, 16 percent of the time, and atypia, or atypical hyperplasia, 52 percent of the time. That's troubling, because both conditions can go on to become invasive cancer.

With atypia, 17 percent of the readings were false positives, meaning that a woman might undergo surgery and other treatment she doesn't need, and 32 percent were false negatives, meaning women wouldn't know they are at increased risk of cancer.

"The first thing for women to remember is that making a diagnosis from tissue is part science and part art," says Dr. Jean Simpson, president of in Nashville, Tenn., who was not involved in the study.

The science involves putting thin slices of biopsy samples onto glass slides, so a pathologist can look at them under a microscope.

Invasive cancer is easy to spot, according to Dr. David Rimm, a pathology researcher at Yale School of Medicine. "Here are criteria I can write down: This cluster of cells has enlarged and irregularly shaped nuclei and architecturally irregularly shaped clusters and high nuclear to cytoplasmic ratio."

But what if the sample has just some of those things? "And what if it has some suggestion of enlargement or some suggestion of arch irregularity?" Rimm asks. "Then we get into that gray area. That's what happens. That's the real world."

And as the JAMAstudy shows, it's not hard to fall into the gray area with DCIS, and especially atypia.

The study had three expert pathologists classify samples from 240 women, then gave them to 115 doctors to identify. It was a clever way to design a study, but it doesn't reflect how pathologists work, which includes reviewing the woman's medical record and often asking a colleague for advice on a confusing or complex slide. "Frequently it might be seen by more than one other person," Rimm says.

Experience matters, too, Rimm says. "When you've looked at breast cancer for 20 or 30 years you develop an eye where you can see something that you can't really define."

And the doctors will confer and try to make their best interpretation. But we should be able to do better than that, says Rimm, who was coauthor of an editorial accompanying the study. "There's a need for more scientific approaches to these borderline cases. Unfortunately, there's relatively little focused research in this area."

But for women who are wondering what do to with a diagnosis of DCIS or atypia, it's important to know that the diagnosis isn't infallible, both Simpson and Rimm say.

"It's a question of uncertainty and how you want to deal with it," Rimm says. His own mother went through this with a breast biopsy, he says. "She had the ability to call her son and say, 'David, what should I do?' I said, 'Let's see what happens; let's watch it.' "

But of course he did also say, "Mom, how about we look at it here at Yale — send it to us." He agreed with the first diagnosis.

Those of us without a pathologist in the family are more than justified in getting a second opinion, Simpson says. "I will tell patients that a second opinion is a fairly inexpensive process," and insurance often pays for it. "And what value can you put on peace of mind?"