Triple-negative breast cancer that progressed as estrogen receptor-positive skin metastases

The mechanisms responsible for changes in biomarker expression between primary and recurrent breast cancer are not clearly understood, but several possibilities have been proposed, including methodological and technical errors, intratumoral heterogeneity, clonal selection caused by previous treatment, anda switch in tumor biology during progression [1,2]. In our case, we initially confirmed the negativity of the tumor for ER, PR, and HER2 and skin invasion combined with tumor emboli within dermal lymphatic channels in the primary breast cancer obtained from a surgical specimen. Considering that skin metastases occurred in the operation bed and that dermal lymphatic invasion was observed in both primary and recurrent tumor tissues, it is likely that the remaining tumor cells in the lymphatic system had progressed and spread out along the skin. This suggests a change in tumor biology during disease progression or intratumoral heterogeneity in ER expression in the primary breast tumor. Subpopulations of cancer cells in the same patient may exist across different geographical regions of a tumor or evolve over time, which is known as intratumoral heterogeneity. Another lesson from our case is that these biomarkers can change even with a short time to progression. Further study is needed to identify the mechanisms responsible for receptor gain in TNBC, the prognostic impact of a change in tumor phenotype, and the optimal therapeutic strategies.