NCCN Breast Cancer Updates

At the National Comprehensive Cancer Network (NCCN) 15th Annual Meeting, Robert W. Carlson, MD, chair of the NCCN Breast Cancer Panel Members and professor of medicine in the Division of Oncology at Stanford Comprehensive Cancer Center, reviewed changes to the NCCN Breast Cancer Guidelines for invasive breast cancer. Major changes were made to protocols regarding the initial workup and evaluation of patients, and the administration of local therapy, adjuvant systemic therapy, and systemic therapy for metastatic disease.

Initial Workup

NCCN's updated guidelines now recommend offering genetic counseling to patients at high risk for hereditary breast cancer during their initial evaluation. In addition, PET/CT scanning, which combines the molecular/functional imaging of FDG-PET with the anatomical imaging of CT scanning, was added as optional study to supplement bone and CT scanning; this is a category 2B recommendation. Carlson noted that FDG PET/CT is most useful in cases where standard staging studies yield suspicious or unequivocal findings, especially in the setting of locally advanced or metastatic disease, noting it may identify unsuspected regional or distant metastasis, though biopsy in these cases may ultimately prove more useful. He also cautioned that "the use of PET or PET/CT scanning is not indicated in the staging of clinical stage I, II, or operable stage III disease."

Local Therapy

The updated guidelines call for limiting the staging of clinically negative axilla to sentinel lymph node (SNL) biopsy, which according to the literature identifies more than 95% of SNLs accurately and has a less than 10% false-negative rate. In addition, it has a high prognostic value and low rate of complications, with less than 1% of women with negative SNLs experiencing axillary recurrence and only 7% experiencing lymph edema. One drawback to this recommendation is that SNL biopsy may not readily be available in certain parts of the United States or in some of the countries that are seeking to adopt the NCCN guidelines.

Adjuvant Systemic Therapy

The updated guidelines divide women into biologically meaningful subsets, including hormone receptor status or HER2 status and applies an algorithm using OncotypeDX technology to determine recurrence score (RS), which is then used to determine whether adjuvant endocrine therapy is offered in combination with chemotherapy. Women with an RS below 18 are considered low risk, 18 to 30 intermediate risk, and 31 or greater are high risk. The update was reflective of several studies, including one that found that only those women who started with high recurrence scores appeared to benefit from cytotoxic chemotherapy. Further, Carlson noted that the 21-Gene RT-PCR test should be used only in patients with ER-positive, node negative disease, as most patients with HER2-positive disease have a high RS; this finding, however, was validated only in tamoxifen-treated patients who received first-generation chemotherapy. Another significant change is that the use of AC chemotherapy followed by a course of paclitaxel every 3 weeks was removed from the adjuvant regimen options, as the regimen was found to be inferior.

Systemic Therapy for Metastatic Disease

The updated guidelines revisit the use of endocrine therapy recommendations in HER2-positive disease. In the first-line therapy setting of postmenopausal HR-positive metastatic disease, the addition of lapatinib to letrozole endocrine therapy yielded no benefit in women with HER-2 negative disease, and the US FDA recently updated the lapatinib label to indicate it should only be used in women with HER2-positive disease. In addition, regarding HER2-targeted therapy, Carlson noted that chemotherapy plus trastuzumab increases progression-free survival (PFS) and overall survival, that endocrine therapy plus either trastuzumab or lapatinib increases PFS, that endocrine therapy plus trastuzumab does not increase survival, and that use of lapatinib has not improved overall survival in any situation. He noted that we do not yet know whether using HER2 targeted therapy early in combination with endocrine therapy may impact the survival benefit of trastuzumab.

Future Direction

The NCCN Breast Cancer Guidelines will continue to evolve based upon scientific evidence. “My expectation is that the next version for the breast cancer guideline will have substantial changes, hopefully in particular more clarity,” said Carlson. In addition, the NCCN will continue to collaborations to develop international versions of the guidelines, which aim to remain respectful of

resources available and specific to the populations and social settings in which they are used.