Male versus female breast cancer: differences hidden behind similarities

M.M. Lacle

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

Abstract

Breast cancer in males is a rare disease. Due to its rarity, little research has been conducted on male breast cancer (MBC), especially when compared to its female counterpart. Knowledge on MBC is therefore based on small single institutional studies, as large series are lacking. The optimal clinical management of MBC may not be known and most treatment algorithms are yet derived from studies on its female counterpart. In our institution we collaborated with different institutes to collect a large group of MBC cases. Our aim was to better identify differences between male and female breast cancer (FBC), find better prognosticators, novel targets for therapy and thereby a better understanding of the MBC carcinogenesis. Based on our findings we conclude that although MBC and FBC are similar in many ways, behind these similarities clear differences are hidden. We therefore support the notion that MBC should be considered separately when in search for novel prognosticators and targets for therapy. Our findings on protein level Other than in FBC, Bcl2 expression has no significant associations with clinicopathologic features in MBC. In addition, the Bcl2/mitotic index combination did not predict survival in MBC, as opposed to FBC. In view of the important role of the microenvironment in cancer progression, stromal CTGF is an interesting target for novel therapies and molecular imaging in MBC. In the light of our findings it would be interesting to further explore and unravel the interactions of CTGF with other members of the CCN family and with other pathway effectors. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied. Prognostic models, originally developed and validated for FBC, also perform quite well for MBC. These models may therefore help in MBC prognostication and decisions on adjuvant systemic therapy. Our findings on the molecular level Copy number loss on the long arm of chromosome 16 in combined with gain of the short arm identified a group of MBC with low propensity to develop lymph node metastasis, and copy number increase of NEUROD2 emerged as an independent prognostic factor. It would be interesting to verify these findings on a larger group of MBC and using more extensive techniques to shed a light on the possible mechanisms behind these observations. Having said that, work continues on the massive parallel sequencing of our MBC cases using a next generation sequencing platform. This will enable us to thoroughly study many known and interesting oncogenes moving forward in unraveling the carcinogenesis in MBC and finding novel possible targets for therapy. We propose a role for chromosome X in male carcinogenesis. Further studies are needed to clarify this role and its possible clinical value in terms of therapy. The predictive and prognostic value of BRCA2-like profile in MBC also deserves further study in light of uncovering better regimens to treat men with breast cancer. This urges a prospective clinical trial stratifying MBC patients for PARP inhibitors/platinum-based or conventional chemotherapy according to aCGH profile.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University Medical Center (UMC) Utrecht
Supervisors/Advisors
  • van Diest, Paul, Primary supervisor
  • Moelans, CB, Co-supervisor
Award date14 Oct 2014
Publisher
Print ISBNs978-90-393-6189-4
Publication statusPublished - 14 Oct 2014

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