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DCIS: Individualizing Treatment with the Latest Recommendations about Radiation Therapy, Sentinel Node Biopsy, Tamoxifen, & MRI.

Goodman, Alice

doi: 10.1097/01.COT.0000295130.38667.c0
Special Report

Ductal carcinoma in situ (DCIS) can be called several different names—including Stage 0 breast cancer, pre-cancer, pre-invasive breast cancer—but whatever term is used, the diagnosis should be taken seriously.

“DCIS by itself is not life-threatening, but it is a significant risk factor for invasive breast cancer in the future,” said Marisa Weiss, MD, President and Founder of and Director of Breast Radiation Oncology at Lankenau Hospital in Philadelphia.

Although for many years DCIS was thought to be relatively benign, it is now clear that a proportion of women with DCIS will go on to develop invasive breast cancer, and 3% to 4% of these women will eventually die of metastatic disease.



Surgery is the first approach, with lumpectomy used for small lesions, and mastectomy usually reserved for breasts with larger lesions or with several foci of DCIS. Radiotherapy added to lumpectomy reduces the risk of recurrence by one half to two thirds, and is now considered standard of care.

The course of DCIS is highly variable. Since it is not clear which women with DCIS will go on to develop invasive breast cancer, some experts question whether using radiation and tamoxifen for all women with DCIS represents overtreatment.

OT spoke with several experts to get their perspective on the use of radiation, appropriate use of sentinel node biopsy (SNB), the role of tamoxifen, use of magnetic resonance imaging (MRI), and treatments under study. In general, the consensus was to treat DCIS according to the individual patient's risk profile.

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Risk of Recurrence

>The risk of recurrence after surgical resection of DCIS varies between 5% and 45%, depending on the extent/size, grade, cell type, family history, and genetic abnormalities, Dr. Weiss explained. Half of all recurrences are DCIS, and the other half are invasive breast cancer.

The belief is that if untreated, some DCIS will progress to invasive cancer over time. It is not uncommon to find DCIS at autopsy in women who have died of other causes.

Even though lumpectomy plus radiation is considered standard of care, not all women with DCIS who are candidates for radiotherapy receive it. Reasons include patients' fears, a decision to live with the risk of recurrence rather than the side effects of radiation, logistical problems, difficulty accessing care, and absence of surgical referral.

The surgeon is responsible for recommending radiation, yet studies have shown that surgeons do not always recommend it when it is appropriate, Dr. Weiss said.

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Who Should Have Radiation?

Although radiation is considered standard of care, not all women with DCIS will require it. For example, women with small, low-grade DCIS and large surgical margins are less likely to derive much benefit from radiation, whereas DCIS with larger lesions, s higher grade, and several foci will have greater benefit from radiation, Dr. Weiss said.

“You need to evaluate the relative and absolute risk of recurrence for each individual.”

“Any patient with DCIS who has undergone lumpectomy or segmental mastectomy will benefit from radiotherapy, but whether radiation is appropriate depends on the patient's risk of recurrence after surgery,” said Henry Kuerer, MD, PhD, who is Director of the Breast Surgical Oncology Training Program at the University of Texas M. D. Anderson Cancer Center.

If a patient has a 3% risk of recurrence (i.e., a low grade, small carcinoma with wide margins, is postmenopausal and estrogen receptor positive [ER+]), she might opt to forego radiation and its side effects for an additional. 1.5% reduction in risk.

“I believe patients need to have informed consent and informed refusal—-that is, they should be made aware of their risks based on what studies have shown about factors such as size, grade, margins, ER status, and age,” Dr. Kuerer commented.

In the real world, many women with DCIS do not get radiotherapy. Although radiation reduces local recurrence, it has not been shown to extend overall survival, Dr. Weiss noted. However, radiation increases the chances of preserving the affected breast by reducing the risk of local recurrence and subsequent therapy (mastectomy and lymph node dissection).

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Sentinel Node Biopsy

“DCIS has variable presentation,” Dr. Weiss continued. “In general, DCIS is not life-threatening, but some subtypes are aggressive. Younger women, with diffuse, high-grade, comedo pathology tend to have occult invasive cancers and these women should have mastectomy and sentinel node biopsy.”.



SNB is definitely not the standard for all women with DCIS, stated Monica Morrow, MD, the G. Willing Pepper Chair in Cancer Research and Chair of the Department of Surgical Oncology at Fox Chase Cancer Center. Only 10% to 15% of DCIS diagnosed with large core needle biopsy will turn out to have invasive cancer according to the postsurgical pathology report, she said.

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Two Basic Approaches

Dr. Morrow outlined two basic approaches to sentinel node biopsy. The first is to use it in all women with DCIS, avoiding the need for a second surgical procedure. The second approach is to reserve SNB for women at higher risk for invasive cancer (i.e., women slated for mastectomy for DCIS [large tumor]; and those with clinically evident DCIS [palpable, which is about 1% to 2% of women]).

SNB is not necessary for high-grade DCIS, Dr. Morrow noted, pointing out that most small Grade 3 DCIS does not have invasion.



Dr. Kuerer agreed, saying that SNB should be offered to patients who need a mastectomy, because the risk of invasive cancer in these women can approach 20%. “But in the general patient with DCIS, where the risk of invasive cancer is much lower, SNB should not be routine,” he said.

Sentinel node biopsy carries small but important risks, which include some degree of lymphedema, nerve injury, and an allergic reaction to the dye. “I prefer to do as little [surgery] as possible in the general patient with DCIS,” Dr. Kuerer said.

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Dr. Weiss noted that only recently has the role of hormone receptors in DCIS been understood. A major advance is the finding that DCIS that is ER positive is most likely to benefit from tamoxifen.

Radiation reduces the risk of recurrence by one half to two thirds, and the addition of tamoxifen can reduce risk by an additional 50%. The decision to use tamoxifen rests on a number of factors—mainly a woman's predicted risk of recurrence.

For example, if the risk of recurrence was 15% and radiation reduced this risk to between 5% and 7%, tamoxifen would further reduce the risk to between 2.5% and 3.5%.

“Tamoxifen is powerful. It can reduce the risk of breast cancer in high-risk women and in women with DCIS,” Dr. Weiss stated.

Tamoxifen should be offered only to women with ER+ DCIS who have undergone breast-conserving surgery, Dr. Kuerer said. Over 10 years, tamoxifen can provide a further 2% to 3% risk reduction. A woman with DCIS and an ER+ tumor with clear margins who has undergone radiotherapy has a 6% chance of recurrence over 10 years.

“In this woman, the risk of local recurrence is quite small,” Dr. Kuerer said. “And tamoxifen has real risks, so you have to weigh the risks and benefits. A low risk for local recurrence would suggest a small benefit with tamoxifen, which might not be worth the risks of this drug.”

He noted that a 2004 survey by his group found that physicians discussed tamoxifen with breast cancer patients about 50% of the time and about 50% of patients chose to take it (Yen TW et al: Cancer 2004;100:942–945). “This suggests that not every oncologist would offer it, nor would every patient take it.”

Tamoxifen is an option for women with ER+ DCIS, but it is not mandatory, Dr. Morrow agreed. The risk/benefit ratio of tamoxifen depends on whether one or two breasts are at risk and the woman's age.

“Tamoxifen is not a ‘one size fits all’ approach,” Dr. Morrow said. “One needs to consider other factors, such as age, the presence of a uterus, the presence of other risk factors for deep vein thrombosis, and the patient's attitude, all of which are very important. The choice is partly dependent on what the patient is most afraid of—recurrence or the side effects of tamoxifen. Remember, tamoxifen is for prevention—not for treatment.”

Tamoxifen has not been shown to increase survival in DCIS, but it has been shown to reduce recurrence. Recurrence carries a great deal of psychological morbidity, usually results in mastectomy, and may also require chemotherapy and additional treatments that compromise quality of life, so reducing the risk of recurrence is important, Dr. Morrow commented.

There are no published data on the use of aromatase inhibitors (AIs) in DCIS. Trials of AIs are now ongoing, and these studies should provide more data. “If a clinician were following guidelines, he or she would not offer an AI to women with DCIS as a routine practice,” Dr. Morrow stated.

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She said she strongly advises against using MRI for DCIS and invasive breast cancer: “The test is very sensitive and picks up many false positives, resulting in treatment delays and multiple biopsies. It also results in mastectomies that otherwise wouldn't be done. There is not a shred of evidence showing that preoperative MRI reduces the risk of breast cancer recurrence.”

About 60% of women with DCIS who appear to have cancer confined to a single area will have multiple foci evident on a detailed microscopic exam, which is the rationale for the addition of radiation, Dr. Morrow explained.

“When we see multiple foci on a mammogram or clinically, we perform a mastectomy. But most women with DCIS too small to identify with these modalities are adequately treated with surgery and radiation. Whether the additional DCIS found with MRI needs to be surgically removed is unclear, but that is what is happening.”

Dr. Weiss said that digital mammography is the best method for diagnosing DCIS in women under age 50, and she believes that MRI is not the most sensitive way to find DCIS. However, MRI has an important role in selected women with DCIS.

“In women with a family history of breast cancer and DCIS, I believe that mammography plus MRI scan is the best approach for finding invasive cancers early,” she said.

Dr. Kuerer pointed out that MRI is costly and also carries the incentive of high reimbursement, which may encourage its use. However, MRI has several problems.

First, as Dr. Morrow also said, MRI is sensitive and picks up many irrelevant lesions, which leads to mastectomy in cases where lumpectomy and radiation would be sufficient treatment. Also, there are no protocols for MRI and no standardization. In some centers, a specialist may not be the person who reads the scan.

“In general, the problems of MRI outweigh the benefits,” Dr. Kuerer said. “We need standardized methods and very specific guidelines.”

Like Dr. Weiss, he believes that MRI is useful in certain situations, such as when more information is needed following mammography or ultrasound.

“MRI is useful in a patient with palpable nodes under the axilla where we can't identify the primary cancer. It is also helpful to identify leaks from silicone implants. And MRI can be used in patients with a family history and BRCA gene mutations to detect invasive breast cancer earlier than standard mammography,” he explained.

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DCIS & Family History

In the past, much of the focus in DCIS was on a family history of invasive breast cancer. However, a family history of DCIS is also very important, Dr. Weiss said, since it carries the same significance as a family history of invasive breast cancer in identifying women at increased risk for invasive breast cancer.

“DCIS in family history is more commonly seen in women with the BRCA1 and BRCA2 genetic abnormalities, and it needs to be taken seriously,” she stated.

Some doctors and patients may want to minimize the importance of DCIS, Dr. Weiss said. The doctor wants to reassure the patient, and the patient wants to believe that surgical removal represents a “cure.”

But oncologists should not downplay the importance of DCIS in a woman with a family history of DCIS or breast cancer, Dr. Weiss emphasized, recommending continued vigilance and monitoring.

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Future Approaches

Henry Kuerer, MD, PhD, Director of the Breast Surgical Oncology Training Program at M. D. Anderson Cancer Center, said that DCIS is not life-threatening, and that in his opinion it is currently overtreated.

“I am working to change the perception of DCIS and to consider our treatments as prevention,” he said. “My colleagues and I are studying therapies other than surgery and radiation and trying to define benefits in a preventive setting.”

Two recently proposed trials are designed to evaluate the ability of trastuzumab to downstage the disease and prevent the transition to invasive cancer in HER-2/neu-overexpressing DCIS.

M. D. Anderson has begun accruing patients to a feasibility trial of neoadjuvant DCIS. Because trastuzumab has been associated with cardiac toxicity, patients are excluded if they have a history of cardiac disease or have received previous anthracyclines.

In addition, an NSABP Phase III randomized trial will enroll patients with DCIS treated with breast-conservation surgery who have negative margins and HER-2/neu-overexpressing disease. Patients will be randomized to receive six weeks of whole-breast irradiation with or without concurrent trastuzumab. The trial has a planned enrollment of 1,000 patients.

Also, Dr. Kuerer and his colleagues at M. D. Anderson are looking at different schedules of radiation in DCIS treated with breast conservation in an attempt to determine whether a five-day schedule of radiation therapy is as effective as the standard six-week schedule.

The investigators are also evaluating partial breast irradiation delivered with the MammoSite balloon brachytherapy applicator, which permits shorter treatment duration and more consistent delivery of radiotherapy to the lumpectomy area. (Jeruss JS et al: Ann Surg Oncol 2006;13:967–976).

“I am working to change the perception of DCIS and to consider our treatments as prevention,” he said. “My colleagues and I are studying therapies other than surgery and radiation and trying to define benefits in a preventive setting.”

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Badge of Courage?

Are women with DCIS entitled to the same “badge of courage” as women with more aggressive, life-threatening breast cancers?

Dr. Marissa Weiss, President and Founder of and Director of Breast Radiation Oncology at Lankenau Hospital in Philadelphia, noted that she finds that in chat rooms on the Internet, women separate themselves according to cancer type.

“People with inflammatory breast cancer want to talk to other people with inflammatory breast cancer. In fact, they want to share experiences with women of the same cancer type, same age, same number of children, and same ages of children.”

Looking at trends on the Internet, it appears that women may perceive DCIS as a “different animal” compared with other invasive cancers, she said.

© 2006 Lippincott Williams & Wilkins, Inc.
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