Lacle MM, Moelans CB, Kornegoor R, van der Pol C, Witkamp AJ, van der Wall E, Rueschoff J, Buerger H, van Diest PJ.
Cell Oncol (Dordr). 2015 Jun;38(3):237-45. doi: 10.1007/s13402-015-0227-7. Epub 2015 Apr 24.
Her2, a member of the EGFR family of signaling proteins, is overexpressed in 10-20% of breast cancer in women, and this is associated with more aggressive behavior and the opportunity to use targeted therapy. Her2 status is associated and likely caused by rearrangement and amplification of the neighborhood it is found in on Chromosome 17q.
In small series of male breast cancers it has been found that HER2 amplification is less common, at less than 10%, but a larger study has not yet been reported.
Given Her2’s importance in the biology of breast cancer, knowing more and on the basis of a larger cohort, is valuable. Here Lacle et al took a more in depth look at the region of 17q that is home to HER2, and did so in a larger group of men.
The authors studied a total of 139 cases of male breast cancer from Holland and Germany, which had a fairly typical representation: average age was 67, mostly invasive ductal carcinoma and mostly grade 2 and 3.
The key finding is:
“Overall we found a lower frequency of copy number changes with less complex patterns in [male breast cancer] compared to [female breast cancer].”
Nevertheless 82% of the cases showed some abnormalities on chromosome 17, with 56% showing gain on 17q and 26% loss on 17p.
True amplification of HER2 was seen in only about 6% of cases, in line with prior estimates of below 10%, and lower than the 20% seen commonly for women. When HER2 amplification was seen, it was associated with poorer outcome.
The authors write in their discussion that
“These results suggest a different role of chromosome 17 in male and female breast cancer development.”
This paper is an interesting indication that the biology of Her2 and perhaps other genes on chromosome 17 is different between male and female breast cancer. Given how little we know about differences, it may be an interesting clue, and as always forms the basis of potential future work.
Here we hit a snag though: one logical next step would be to try and model the impact of the changes seen here in chromosome 17 in the laboratory, say in a cell culture or animal model. For example a gene can be overexpressed or eliminated and the impact of tumor behavior measured. Alas, we have no models of male breast cancer that are well described and understood, and in which such an experiment could be done. Such models would need to be created first…