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The DCIS Dilemma

Ductal carcinoma in situ is the fourth most common cancer diagnosis in women. Some say it's not "really" cancer. But you wouldn't know that based on how it is treated. By Sue Rochman

For Melissa Resnick, Valentine’s Day 2012 holds a particular significance: It is the day she had a mammogram that led to a biopsy showing she did—yet did not—have breast cancer.


And Then There's LCIS
A lobular carcinoma in situ diagnosis increases risk, but experts aren't sure to what extent.

But Is It Really DCIS?
It may be worth it to get a second opinion from a pathologist.
The biopsy showed that Resnick had DCIS—ductal carcinoma in situ. Breast cancer is staged according to a system that takes into account how large the tumor is and how far it has spread. DCIS is stage 0: It has not spread outside a breast duct (where virtually all breast cancer begins) into the surrounding breast tissue. For this reason, DCIS is often referred to as a precancer.

If left untreated, some DCIS lesions go on to become invasive cancers, while others remain a harmless precancer and never leave the duct. But despite decades of effort, doctors can’t yet tell a woman which type she has. As a result, breast specialists recommend that all DCIS be treated with surgery, often followed by radiation and hormone therapy. Yet many of the women treated for DCIS are likely to have not needed treatment at all.

The In Situ Impasse
The American Cancer Society estimates that this year slightly more than 60,000 women in the U.S. will be diagnosed with an in situ breast cancer. About 83 percent of these women will have DCIS; most of the others will have lobular carcinoma in situ (LCIS), also called lobular neoplasia. (See “And Then There’s LCIS.")

Without mammography, DCIS would be a rare diagnosis. Unless it turns into a lump, which isn’t often the case, DCIS is detected only when a radiologist observes microcalcifications—clusters of white specks of calcium—on a mammogram. (See “But Is It Really DCIS?”) With mammography’s introduction as a screening tool in the late 1970s and early 1980s, DCIS diagnoses began to increase rapidly. Today, DCIS is the fourth most common cancer diagnosed in women.

Laurel Habel, an epidemiologist at Kaiser Permanente Northern California Division of Research in Oakland, has spent most of her career trying to determine the appropriate treatment for women with DCIS. “I have been doing research on DCIS since the 1990s, and it was a dilemma then and it still continues to be a dilemma today,” says Habel.

This leaves women with DCIS and their doctors in a quandary. Cancer treatments are generally given to reduce a patient’s risk of dying. Women can die when an invasive breast cancer spreads to and affects other organs in the body. But women don’t die from DCIS, because the cells can’t wreak havoc when they are inside the duct.

“We know we are overtreating DCIS,” says Eileen Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre’s Odette Cancer Centre in Toronto. “In most women, it will not become an invasive breast cancer and it will not be life-threatening. But for some, DCIS is the first step to invasive cancer—and we don’t know who these women are.”

A nurse-midwife, Resnick, now 51, says she understood right away that having DCIS meant her disease was at a very early stage. “I was like, take a breath, it’s all right, it is not going to kill you,” she recalls. “It gave me some peace of mind in a way. I knew I was not going to die, and that is what you need to hear.”

But that didn’t make treatment decisions easy. “I remember crying and [telling the breast surgeon] just spare my breast,” Resnick says. The breast surgeon said that was possible, but that Resnick would not end up with a good cosmetic result. So, she had a bilateral mastectomy, followed by reconstruction. “I understand that is drastic,” she says. “But I didn’t do it because I was concerned I was going to die. I did it because I wanted to have a good aesthetic result.” And as someone who had often been called back for a repeat mammogram because of calcifications, and then had to have a mammogram every six months, she says, “I didn’t want to have to worry about continuing to have mammograms and having to go through this again.”

Radiation Recommendations
Sixty-nine percent of the women diagnosed with DCIS between 2007 and 2011 were treated with breast-conserving surgery, such as lumpectomy. Of these, 68 percent also had radiation. Seemingly, one of the easiest ways to reduce overtreatment would be to determine which of these women needed radiation to prevent a recurrence. But as a recent study suggests, the problem is not only identifying cancers that are “good risk”—those that likely don’t need radiation—but also explaining risk to patients.

The study, published in the March 1, 2015, Journal of Clinical Oncology, randomly assigned several hundred women with what might be described as “good risk” DCIS to either radiation or observation after breast-conserving surgery. A “good risk” cancer was defined as DCIS that occurred in only one place in the breast, had a low or intermediate nuclear grade (determined by the size and shape of the cell’s nucleus), was less than 2.5 centimeters and had been removed with a clear margin around it that was at least 3 millimeters wide. After a median follow-up of seven years, two of the 287 women who received radiation had a recurrence compared with 19 of the 298 women who did not have radiation. Of those who had radiation and a recurrence, one had DCIS and one had an invasive cancer; of those who didn’t have radiation, eight had invasive cancer and 11 had a recurrence of DCIS.

On the one hand, the overall rate of recurrence was low whether the women had radiation or not—suggesting that the study’s definition of “good risk” can be used to identify many women with DCIS who probably don’t need radiation. On the other hand, the study results also suggest that radiation can significantly reduce the risk of recurrence. And different patients will interpret their own risk of recurrence in different ways.

“What I start with and then circle back to with patients is that … your decision to have radiation or not” is not going to influence survival, says Beryl McCormick, a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York City, who led the study. “[Ten-year] survival rates are 99 percent. You will be fine no matter what you decide to do—and that helps women feel confident about their decision.
 
“I have patients who have had several benign biopsies before being diagnosed with DCIS, and they are so fed up with mammography that they want to have a mastectomy,” she continues. “There are others who have breast conservation and choose radiation because they want to minimize their chance of needing future biopsies. And there are others who say it’s not going to impact my survival and the chance of it coming back is low, and only half of those that do come back are invasive, and since I can only have radiation once, I’ll wait and do it if it comes back.”

Molecular Markers
The radiation study also illustrates the extent to which attempts to identify a “good risk” DCIS based on the tumor’s pathological characteristics—such as its grade and size—fall short, and why researchers are trying to find molecular markers that would provide more personalized information. Genomic Health makes OncotypeDX, a 21-gene test that provides women who have hormone-sensitive invasive breast cancer with information about their risk of recurrence. The test has allowed many women to opt for hormone therapy alone and avoid chemotherapy. That success led Genomic Health, in 2014, to begin marketing a similar test that uses a subset of OncotypeDX’s 21 genes to give women who have DCIS information about their risk of recurrence.

Rakovitch recently collaborated with Genomic Health to see how well the subset of genes predicted recurrence in a large group of women with DCIS she has followed for about a decade. At the time of their diagnoses, the women had had their DCIS removed with clear margins. None had radiation. Over the next 10 years, about 18 percent had a recurrence.

Genomic Health’s DCIS test was performed on preserved tumor tissue from these women, allowing the study team to see how well the test score—which can be a number from 0 to 100—would have predicted how these women fared. Findings that Rakovitch presented in December 2014 at the San Antonio Breast Cancer Symposium showed that the DCIS score helped differentiate those with a low risk of recurrence from those with a higher risk.
 

06/26/2015
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