Genetics
Genetic counseling was upgraded from a footnote to a recommended component of the general work-up, if the patient is at high risk for hereditary breast cancer. The major reason for the emphasis is to make sure physicians perform genetic testing, Dr. Carlson said.
“Doing genetic testing is not really part of breast cancer treatment, but it is so central to what we should be doing that it's important to do and consider early,” he said. “There are also some subtleties, in terms of how you treat the breast locally, that are affected by whether the BRCA1 and BRCA2 mutations are present … and might shift the balance towards mastectomy, as opposed to breast conservation.”
The panel also recommended that the general work-up should include determination of tumor estrogen/progesterone (ER/PR) status and HER2 status. The recommendation is based on two studies utilizing a 21-gene assay (Oncotype DX) in women with hormone receptive–positive, node-negative cancer who receive tamoxifen alone or with chemotherapy.
In the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-14 trial, women with a low recurrence score based on their genetic test had superior survival at 10 years, compared with those with intermediate or high recurrence scores. In the NSABP B-20 trial, only those women with high recurrence scores benefited from tamoxifen plus chemotherapy.
“The recurrence score might be able to stratify women who will benefit from the application of cytotoxic chemotherapy,” Dr. Carlson said.
He went on to note, however, that major use of the assay is limited to ER-positive, HER2-negative, node-negative disease because the assay has been validated only in this setting and in women who were treated with tamoxifen and first-generation chemotherapy, and because most HER2-positive disease has a high recurrence score. There were insufficient data to make a recommendation on the 70-gene Mammoprint assay, he said.
Paclitaxel
Doxorubicin/cyclophosphamide followed by paclitaxel every 3 weeks was removed from the list of recommended adjuvant regimens based on data showing that the thrice-weekly regimen was inferior to paclitaxel every 2 weeks or weekly.
HER2-Targeted Therapy
The panel declined to add either trastuzumab or lapatinib in combination with endocrine therapy to its algorithm as preferred agents for the treatment of ER-positive, HER2-positive, metastatic disease. They cited a lack of evidence demonstrating an overall survival benefit with the agents, and concerns that early use of HER2-targeted therapies in combination with endocrine therapy may negatively impact survival benefit from trastuzumab therapy downstream.
The subject was revisited after the Food and Drug Administration recently added an indication to the lapatinib (Tykerb) package insert for lapatinib in combination with letrozole (Femara) for patients with advanced, ER-positive, HER2-positive cancer in whom hormone therapy is indicated. Overall NCCN panel recommendations regarding HER2 targeted therapy and endocrine therapy will be announced at a later date, Dr. Carlson said.
Disclosures: Dr. Carlson disclosed receiving research support from and being a consultant for AstraZeneca Pharmaceuticals LP, receiving grant support from BiPAR Pharmaceuticals and Genentech Inc., and being a consultant for Pfizer Inc.