Hyman Muss, MD
Professor of Medicine, University of Vermont Director of Hematology Oncology, Fletcher Allen Healthcare

Edited comments by Dr Muss

Defining ER positivity

We are in an era when every pathology laboratory should report the percentage of cells staining positive for estrogen receptors, rather than just reporting “positive” or “negative.” Negative should be defined as tumors with virtually no cells staining positively — truly “stone cold zero.” Data from women whose tumors have just a few percent of cells expressing estrogen receptors show that these women derive benefit from endocrine therapy. A common standard in the United States is for laboratories to report less than 10 percent of cells staining as negative. When invasive breast cancer is reported to be ER-negative, you should call your pathologist and verify the numbers. It's not just academic anymore, it's very important in treating patients.

Estrogen receptor status and DCIS

Craig Allred reported very provocative data from the NSABP-B-24 trial on estrogen receptor assays in women with DCIS at the 2002 San Antonio Breast Cancer Symposium. In this trial, women with DCIS received lumpectomy and breast radiation and then were randomized to receive five years of tamoxifen or not.

A central slide review in the NSABP laboratories found that only women with ER- or PR-positive DCIS derived benefit from tamoxifen in preventing ipsilateral breast tumor recurrence and new contralateral primary tumors. They also found a great deal of disparity in reporting the estrogen receptor data, especially in community centers.

Based on this data and Dr Allred’s recommendations, it is appropriate to test for estrogen and progesterone receptors in patients with DCIS. Fifteen to 20 percent of patients in B-24 had ER-negative DCIS, therefore, the actual benefit from tamoxifen may be even greater than was reported in that trial, and more careful selection of patients for tamoxifen will probably result in a higher benefit-to-risk ratio for the drug.

Updated results of the ATAC trial

The ATAC trial is a superb study of more than 9,000 patients. An update of the data was presented by Dr Aman Buzdar in San Antonio and showed that at four years follow-up, anastrozole was superior to tamoxifen with respect to disease-free survival and event rates. In addition, anastrozole is a less toxic drug, without the risks of endometrial cancer or thromboembolic disease. Anastrozole was associated with an increased risk of fractures, which is important because fractures are a cause of mortality in the United States; we need a lot more information with regard to bone. This statistically powerful trial gives us another option for adjuvant therapy in estrogen receptor-positive postmenopausal patients, and I discuss both tamoxifen and anastrozole with patients.

Communication with oncologists about axillary status

There are two goals of axillary surgery: one is to decrease the risk of local recurrence; the other is for prognosis. Axillary dissection is performed to help the medical oncologist make treatment decisions. Axillary nodal status remains the best prognostic indicator we have for predicting recurrence.

Radiation and medical oncologists should be involved early to help determine whether or not axillary surgery should be performed. I like multidisciplinary clinics because the surgeon can ask the radiation or medical oncologist whether knowing the axillary status will help guide treatment decisions. For most patients, this information will help, but not always — especially in women with coexisting illnesses in whom we may not want to use chemotherapy. In some cases, knowing the precise number of positive lymph nodes will not change treatment decisions. It’s much easier to decide on adjuvant endocrine therapy, which is probably less toxic than aspirin.

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