NIH examines DCIS data; issues new recommendations

NIH recommended better risk stratification strategies, elimination of the term ‘carcinoma’ and examination of imaging technology.

The National Institutes of Health has issued a new state-of-the-science statement on the diagnosis and management of ductal carcinoma in situ.

The statement contains recommendations regarding DCIS and discusses relevant issues including incidence, risk factors, screening, prognostic factors and treatment of the disease.

It was based on available data on the diagnosis and management of DCIS presented by 22 experts from relevant fields at the NIH State-of-the-Science Conference in Bethesda, Md. These data were then reviewed by a 14-member panel representing various medical fields.

Ultimately, the panel made several recommendations focusing on future research as a key to improving outcomes in DCIS. Particularly challenging concerns included: a lack of data related to the natural history of DCIS; a change in the precise classification of DCIS over time, as methods of detection and pathological examination have become more advanced; and finally, very few randomized, clinical trials have been conducted to examine therapeutic interventions.

The panel was asked to address five key questions to develop recommendations for future research, which would help improve procedures for the diagnosis and management of DCIS:

• What are the incidence and prevalence of DCIS and its specific pathologic subtypes, and how are incidence and prevalence influenced by mode of detection, population characteristics and other risk factors?
• How does the use of MRI or sentinel lymph node biopsy affect important outcomes in patients diagnosed with DCIS?
• How do local control and systemic outcomes vary in DCIS based on tumor and patient characteristics?
• In patients with DCIS, what is the effect of surgery, radiation and systemic treatment on outcomes?
• What are the most critical research questions for the diagnosis and management of DCIS?

Incidence increased; imaging efficacy unclear

From 1973 to the late 1990s, the incidence of DCIS increased more than sevenfold, but levels have recently leveled off. Women aged 50 years or older had the highest incidence. For example, the age-adjusted incidence rate is 32.5 per 100,000 vs. 88 per 100,000 among women aged 50 to 64 years. Incidence rates were also higher among white women compared with other ethnicities.

Much of the increased incidence of DCIS can be attributed to the development of more advanced diagnostic techniques, such as mammography and MRI. MRI is considered more sensitive than mammography for detection. However, data on MRI’s specificity is limited. Even if MRI is an improvement on mammography, the modality may both underestimate and overestimate the size of DCIS lesions compared with pathological examination, according to Carmen J. Allegra, MD, and other panel members.

Allegra is panel and conference chairperson, as well as professor and chief in the division of hematology/oncology in the department of medicine at the University of Florida Shands Cancer Center, Gainesville, Fla. He is also the associate director for clinical and translational research.

Allegra and the panel explained that although sentinel lymph node biopsy — a less invasive diagnostic method — may be reasonable in women undergoing mastectomy for DCIS, its use in all women with DCIS is less clear.

“The clinical significant of positive sentinel lymph node metastases in patients who have DCIS is indeterminate, given that the majority of them are micrometastases or isolated tumors cells,” the panel wrote. Findings from previous studies were reported only in “highly selected patient populations that may not represent of the general population of women with DCIS.”

Panel recommendations for future research included determining the effectiveness of MRI for managing DCIS, specifically surgical management after diagnostic biopsy; improving breast MRI techniques to distinguish between the need for intervention or surveillance; and determining the prognostic significance of sentinel lymph node micrometastases.

Also, to learn more about the incidence and pathology of DCIS, the panel recommended research with a focus on conducting epidemiological studies by pathological subtypes, using consistent criteria, and adopting national standardized reporting of DCIS by the U.S. pathology community.

Path to progression uncertain

Researchers are still struggling to identify which patients with DCIS will be more likely to progress to invasive breast cancer. Therefore, it is important that diagnostic accuracy and reproducibility of DCIS classification and grading be improved moving forward.

In addition, the panel suggested that future research focus on molecular events, as well as pathological and radiographic features on DCIS, to better understand DCIS clinical outcomes.

Consistency in choice of treatment options is yet another problematic aspect of DCIS. The disease typically has high rates of long-term DFS, ranging from 96% to 98% when treated with available therapies, according to the panel. It is uncertain, however, if all patients with DCIS respond similarly to these therapies.

“Given the lack of clarity and the incomplete data surrounding the natural history, prognostic factors and biology of DCIS, important therapeutic questions remain unanswered,” the panel said.

It suggested that stratification models be developed and validated. Strategies to determine which patients are at high risk for DCIS recurrence or invasive carcinoma, comparative effectiveness analysis to define the role of current therapies, and the integration of patient-reported outcomes and data on patient perceptions of risk and treatment preference are also considered crucial.

Further efforts are key

Overall, efforts toward improvement in major areas are necessary for the advancement of understanding DCIS and include using standardized reporting methods and terminology across disciplines; collecting consistent and detailed data on various characteristics of DCIS; validating various factors to improve risk stratification, allowing optimal therapy; researching patient–provider communication; examining diagnosis and treatment and how it relates to quality of life; and investigating comparative effectiveness of the methods of treatment.

Additionally, of note is the panel’s recommendation to remove the term “carcinoma” from the description of DCIS, as it produces anxiety, even though the disease is noninvasive and typically has a favorable prognosis.

“The primary question for future research must focus on the accurate identification of patient subsets diagnosed with DCIS, including those [people] who may be managed with less therapeutic intervention without sacrificing the excellent outcomes presently achieved,” the panel said.

For more information:

• Allegra CJ. J Natl Cancer Inst. 2009;doi:10.1093/jnci/djp485.
• Virnig BA. J Natl Cancer Inst. 2010;102:doi:10.1093/jnci/djp482.