A comparison of breast cancer guidelines from two of the world’s most prominent oncology organizations, the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), has revealed “substantial concordance,” but also a host of “discrepancies.”

Most of the differences are either in a “gray zone” (and could be resolved by ongoing research) or at the “borders of current indisputable knowledge,” say the authors, led by Flora Zagouri, MD, PhD, from the Alexandra Hospital, University of Athens, Greece.

The authors, all of whom are European, do not judge either guideline or organization.

Instead, they characterize the NCCN as appearing to adopt “new therapeutic strategies in a more straightforward fashion.”

In contrast, “ESMO shows a more conservative approach,” they write in their report, published online March 25 in The Breast.

Some of the guideline differences are well known, such as the NCCN’s promotion of annual screening mammography (at least from age 40 to 70) and ESMO’s stance that it has “no clear recommendation.”

Differences were found in the various breast cancer guidelines for screening, genetic risk evaluation, surgery, systemic therapy, radiotherapy, and follow-up. Most of the NCCN guidelines are from 2014, whereas most of the ESMO guidelines are from 2013.

There is a “fundamental difference in how the ESMO and NCCN guidelines are written,” say Dr Zagouri and her coauthors.

“The ESMO guidelines are written as a review, and the reader is required to interpret the summary of data,” they explain. In contrast, “the NCCN guidelines are written in algorithmic form with a supporting manuscript that provides the data behind the recommendation.”

“I couldn’t say that NCCN guidelines are easier to read. The ESMO guidelines are more concise and are written like a review,” said Dr Zagouri in an email to Medscape Medical News.

Examples of Difference

Some of the “major” discrepancies between the guides are in the area of genetic risk evaluation.

For example, the authors report, ESMO guidelines only recommend testing for BRCA mutations, whereas NCCN guidelines “consider a broad range of different gene mutations.”

According to the NCCN, there is evidence for casting a wider genomic net when doing family testing.
“We have observed over the years, since genetic testing for BRCA1/2 became available, that many families with a compelling history of BRCA-related cancers are negative for mutations in these two genes,” NCCN panel chair Mary Daly, MD, from the Fox Chase Cancer Center in Philadelphia, and vice chair Robert Pilarski, MS, from the Ohio State University Comprehensive Cancer Center in Columbus, said in a joint email to Medscape Medical News.

“Evidence for the role of additional genes, which account for the phenotype of some of these families, has matured to the point where we feel it is important to offer testing for additional genes to family members so that they can pursue risk-reducing options,” they continued.

The pair cited two examples of genes that are tested for, beyond BRCA1/2.

The NCCN recommends testing for the PTEN gene, which confers a significantly increased risk for breast and several other cancers, and the p53 gene, which confers a very high risk for early-onset breast cancer and for several rare cancers.
There are also differences between ESMO and NCCN in the surgical management of breast cancer. Axillary staging is an area of difference that stands out.

The NCCN guide says that staging can be optional in patients with particularly favorable tumors, the elderly, patients with serious comorbidities, and patients for whom adjuvant therapy will not be affected by staging results. The ESMO does not address this issue.

Likewise, ESMO does not define what kind of staging should be undertaken after neoadjuvant systemic therapy. But the NCCN dictates that sentinel lymph node biopsy is used when nodes are negative in an initial ultrasound and fine-needle aspiration/core biopsy. Furthermore, the NCCN indicates that axillary lymph node dissection is indicated when the nodes are positive.

The two organizations have a number of conflicting recommendations on the use of radiotherapy. For example, there is a considerable difference when it comes to the subject of age and accelerated partial breast irradiation (APBI). The NCCN recommends APBI only for certain node-negative women 60 years and older with unifocal disease; the ESMO recommendation is similar but allows for use in women 50 years and older.

In terms of recommendations for follow-up in breast cancer patients, there are “major” differences between the ESMO and NCCN guidelines regarding optimal intervals and proposed laboratory and imaging tests, the authors note.

The NCCN says that intervals for follow-up mammograms should be every 12 months, whereas the ESMO says every 1 to 2 years. Overall, laboratory tests are “not recommended” by the NCCN, but the ESMO says that routine blood tests are indicated for patients on endocrine therapy. The use of hormone replacement therapy is “discouraged” for breast cancer survivors by the ESMO, but is not mentioned by the NCCN, the authors observe. MRI surveillance is recommended by the ESMO for younger patients, especially those with dense breasts or genetic/familial dispositions, but the NCCN does not define MRI use for subpopulations in follow-up.