This study investigated the differences in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between breast tumors and nodal metastases in 211 women. Currently, tumor receptors in lymph node metastases are not evaluated after breast cancer surgery and adjuvant therapy is selected based on the characteristics of the primary breast tumor. The authors theorized that differences in receptor expression between primary and nodal breast cancer might contribute to therapeutic resistance, especially in cases where resistance to adjuvant therapy is apparent from the beginning of treatment. In the study, nodal metastases were evaluated for ER, PR and HER2 expression using quantitative immunofluorescence. Differences in expression were also analyzed based on both immunohistochemistry (IHC) and FISH. The quantitative immunofluorescence method found wide variation compared to IHC; many of the disparities in expression between cancer in the breast compared to lymph nodes were large (greater than fivefold). Overall, 46.9% of cases had different breast tumor/nodal metastasis receptor status for at least one receptor. Triple-negative breast cancer was found to change between the breast and the lymph node in 23.1% of the cases. The authors conclude that lymph node receptor status might be a more accurate measurement for guiding adjuvant therapy.

Implications for breast cancer treatment

The study findings confirm those of previous reports that lymph node and other metastases can have different receptor status than the primary tumor in the breast. However, previous studies found a lower percentage of such receptor discordance. This is also the first study in which the authors recommend re-examining the existing practice of relying solely on ER, PR and HER2 of the primary tumor in selecting appropriate adjuvant treatment.

Treatment for what amounts to the wrong receptor status is a possible reason for failure of adjuvant therapy to prevent breast cancer metastases. For example, a woman with nodal metastases having (untested) HER2 overexpressing cells might benefit from treatment with Herceptin but will not be given this treatment if the primary tumor in the breast is not Her2 overexpressing. The assumption that it would be best to tailor treatment based on the nodal receptor status appears reasonable since breast cancer cells that have already demonstrated the ability to metastasize to lymph nodes presumably are capable of forming metastases in other parts of the body. The implication is that patients require repeat biopsy and evaluation of receptors upon disease recurrence to optimize treatment planning.