Estrogen receptor-negative progesterone receptor-positive breast cancer - “Nobody's land“ or just an artifact?

The estrogen receptor α (ER) and the progesterone receptor (PgR) are one of the most important prognostic and predictive immunohistochemical markers in breast cancer. Breast cancers may express various profiles of hormone receptors: ER(+)/PgR(+), ER(−)/PgR(−), ER(+)/PgR(−) and ER(−)/PgR(+). The existence of the latter profile is a matter of controversy since PgR expressions is induced by ER-dependent pathways in breast cancer cells. One of the most extensively propagated hypotheses trying to explain the origin of ER(−)/PgR(+) breast cancers claims that they are technical artifacts dependent on the immunohistochemical procedure. On the other hand, in recent years there is a growing body of evidence, suggesting that such cancers create a unique group with distinct molecular and clinical features. In the following review, we present background theories on the ER(−)/PgR(+) breast cancer origin and their epidemiological and clinicopathological characteristics, including the predictive and prognostic significance of these rare tumors.