Letter to editor/comment

I read with a great interest a recently published clinical study of Takala et al 1 on metaplastic carcinoma of the breast. The authors explored 78 patients with the diagnosis of metaplastic carcinoma in the period 2002‐2016. In line with previous studies, the authors confirmed predominantly triple‐negative phenotype of metaplastic carcinomas (85%) exhibiting a poor therapeutic response with an ag‐ gressive clinical course and poor outcome. Two things are worthy of further discussion: First, 12% of the pa‐ tients were estrogen receptor (ER)‐positive, eight of which received adjuvant endocrine therapy. I would appreciate more information from the authors regarding the percentage of ER positivity in these metaplastic carcinomas and a potential response to endocrine treat‐ ment. It is well known that most metaplastic carcinomas are ER‐neg‐ ative and if ER‐positive, the percentage of positive cancer cells is usually low (range, 1%‐10%). This fact may substantially affect the response to endocrine therapy, as the patients with lower ER posi‐ tivity in their breast cancers are less responsive to anti‐ER treatment modalities. Another important issue is a targeted therapy of metaplastic carcinomas that has recently come into focus. Multiple molecular studies have revealed potentially targetable biomarkers in met‐ aplastic carcinomas of the breast. These include PI3K (PIK3CA, PTEN, PIK3R1), MAPK (NF1, KRAS, NRAS), RB1, and Wnt path‐ ways.2‐9 Of these, PI3K pathway alterations are of particular im‐ portance in metaplastic carcinoma given that several studies have shown their relevance in predicting the response to mTOR/PIK3CA inhibitors.6,10‐13 In addition, programmed death‐ligand 1 (PD‐L1) expression in cancer and/or inflammatory cells, as a predictor of response to immune checkpoint inhibitors, has also been described in a substantial proportion of metaplastic carcinomas.3,14‐16 A pecu‐ liar case report of Adams et al revealed an impressive therapeutic response of the PD‐L1‐positive metaplastic carcinoma to the com‐ bined treatment with pembrolizumab (anti‐PD‐1 drug) and nab‐ paclitaxel therapy.16 Of note, the Food and Drug Administration (FDA) has recently approved atezolizumab, an anti‐PD‐L1 drug, for the treatment of PD‐L1‐positive triple‐negative breast cancers.17,18 Given the period of your cohort, I was wondering if any of the pa‐ tients were profiled for the aforementioned targetable biomarkers and treated accordingly? Semir Vranic MD, PhD