Subtyping of male breast cancer by PAM50 and immunohistochemistry: a pilot study of a consecutive Danish cohort

Abstract

Male breast cancer (MBC) is a rare disease that is still to be fully understood. In female breast cancer, molecular subtyping by gene expression has proven its significance. In this study, we characterize a consecutive cohort of MBC patients surgically treated from 1997 to 2017, identified at our institution (N = 37), and report the association between molecular subtypes found by a surrogate panel of immunohistochemical (IHC) markers, and the PAM50 signature, as well as risk of recurrence score and overall survival for the different subtypes. PAM50 subtypes were determined using the nCounter FLEX system instrument and software. The distribution of molecular subtypes according to the PAM50 signature was as follows: 56% luminal B, 39% luminal A, and 5% basal‐like. None of the tumors were HER2‐enriched. Using IHC surrogate markers, we found 80% luminal B‐like, 15% luminal A‐like, and 5% basal‐like. None were HER2‐positive (non‐luminal). We found a strong statistical association between subtypes found by PAM50 signature and the IHC surrogate markers (p < 0.001). Furthermore, we found luminal A tumors to be smaller in size compared to luminal B tumors (p = 0.04). Patients with luminal A subtype tumors had the lowest ROR scores with a mean of 39, whereas patients with luminal B subtype tumors had a mean ROR score of 69. Significant worse overall survival for luminal B tumors compared to luminal A tumors was seen (p = 0.02). Male breast cancer seems to be a mainly luminal disease, with luminal B being the most frequent subtype. Further studies are needed to ensure correct therapeutic strategies for this select group of patients.

Efficacy of neoadjuvant chemotherapy in male breast cancer compared with female breast cancer

“…The present study showed that, when compared with women with the same subtypes, men had a significantly lower rate of pCR in HR+/HER2+ and a numerically lower rate of pCR in HR–/HER2+ breast cancer. Two prior studies evaluated the distribution of intrinsic subtypes by PAM50 in male breast cancer samples and identified that ≥90% were genomically luminal B or luminal A 10,11 . There was only one HER2+ case among both studies, and therefore the distribution of intrinsic subtypes within HER2+ male breast cancer remains unknown.…”

“…A recent study evaluated 67 MaBC samples by PAM50 and showed that 90% were luminal A or B 10 . Similarly, Christensen et al conducted PAM50 analysis in 37 MaBC samples and reported 95% of cases having luminal A or B subtype 11 . The high prevalence of luminal disease in men may be associated with lower sensitivity to NAC and in turn, lower rates of pCR compared with women.…”

“… 10 Similarly, Christensen et al conducted PAM50 analysis in 37 MaBC samples and reported 95% of cases having luminal A or B subtype. 11 The high prevalence of luminal disease in men may be associated with lower sensitivity to NAC and in turn, lower rates of pCR compared with women. Another possible explanation may be related to differences in the tumor microenvironment between MaBC and FBC.…”

“…Two prior studies evaluated the distribution of intrinsic subtypes by PAM50 in male breast cancer samples and identified that ≥90% were genomically luminal B or luminal A. 10 , 11 There was only one HER2+ case among both studies, and therefore the distribution of intrinsic subtypes within HER2+ male breast cancer remains unknown. Collectively, the data from the previously referenced studies 10 , 11 , 15 , 16 , 17 , 18 and our present analysis suggest that HER2+ breast cancer in men may be more luminal driven and may derive less benefit from anti‐HER2 therapies.…”

“…10,11 There was only one HER2+ case among both studies, and therefore the distribution of intrinsic subtypes within HER2+ male breast cancer remains unknown. Collectively, the data from the previously referenced studies 10,11,[15][16][17][18] and our present analysis suggest that HER2+ breast cancer in men may be more luminal driven and may derive less benefit from anti-HER2 therapies. Further studies on the mechanism of resistance of anti-HER2 therapies in men, as well as whether certain anti-HER2 drugs may be more effective in MaBC, are warranted.…”