Male breast cancer precursor lesions: analysis of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.
Doebar SC, Slaets L, Cardoso F, Giordano SH, Bartlett JM, Tryfonidis K, Dijkstra NH, Schröder CP, van Asperen CJ, Linderholm B, Benstead K, Dinjens WN, van Marion R, van Diest PJ, Martens JW, van Deurzen CH
Mod Pathol. 2017 Jan 13. doi: 10.1038/modpathol.2016.229. [Epub ahead of print]
Understanding where a tumor comes from, in terms of the precursor lesions and the genetic mutations that drive them, is important for the development of early detection strategies and ultimately for prevention. In the case of male breast cancer, it also has the potential to identify similarities or differences with the female disease.
This study leverages the work of the International Male Breast Cancer Program which is a European-American collaboration involving many centers, including MD Anderson Cancer Center, where I work and receive my cancer care. Dr. Giordano represents MD Anderson in this work and is an author – she is also my doctor. This group has come together to make studies possible that require more samples than are available at any single center. One part of the program has collected male breast cancer cases treated between 1990 and 2010 across the network, a total of 1822 cases from 23 centers. Disclosure: I am involved as the patient advocate in a clinical trial led by this team.
The authors identified 1328 cases from the total of 1822 that had the required tissue available for study and met other standard study criteria, and these represented the typical population of male breast cancers well in terms of type and grade and also how they were treated. Of these just under half – 613 – had a precursor lesion adjacent to the tumor and so available for study. Almost all of them (97.9%) were ductal carcinoma in situ (DCIS), as would be expected from men where almost all the tumors that present are invasive ductal carcinomas and where the breast tissue has ducts but only rudimentary lobules.Analysis of the DCIS and aggressive tumors next to them for various characteristics, including hormone receptor (ER/PR) and Her2 status and for a handful of cases the presence of known mutations in female breast cancer (PIK3CA, GATA3, TP53 and MAP2K4) showed that these were almost always shared, which suggests the more advanced and aggressive components were derived from the DCIS lesions. This is consistent with studies of the female disease.
The same was also true of the very rare lobular cancers, where lobular DCIS was found adjacent to lobular invasive cancers.
The authors also looked at whether the presence of DCIS adjacent to the invasive tumor was associated with differential survival, and found this to be true for Luminal B Her2+ subgroup, which is a relatively small minority of male breast cancers.
The authors conclude that DCIS is commonly found next to invasive tumors in males with breast cancer, and is likely the precursor lesion.
This study provides solid evidence that invasive male breast cancers derive from DCIS lesions, as is the case for female breast cancers that are like them, i.e. invasive ductal carcinomas. Furthermore, the fact that the DCIS lesions share the ER/PR status and Her2 status with their adjacent aggressive descendants suggests that these characteristics are acquired early and may be driving early stages of tumor evolution. The same may be true of the gene mutations studied, but the numbers of samples where sequencing could be performed was small and the number of genes analyzed was also very small, and so a large study perhaps with better tissue collected prospectively needs to be done.
Overall then this study supports that male and female breast cancers evolve in similar ways, at least in terms of how they look and act and the hormone receptor changes that drive them. Whether the detailed molecular changes accumulate in the same way remains to be seen.