I have previously posted the following and hope that everyone with a strong family history of her2+ breast cancer chimes in so that, if it is the case, we can interest some up and coming geneticist to take an interest and clarify the situation so oncologists have more data to reveal whether or not there may be a hereditary/familial subtype of her2+ breast cancer. It comes from a thread that I will try to provide a link for from June of 2010:
CELL
Volume 129, Issue 7, 29 June 2007, Pages 1275-1286
doi:10.1016/j.cell.2007.04.034
Article
FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene
Tao Zuo2, Lizhong Wang1, Carl Morrison3, Xing Chang1, Huiming Zhang1, Weiquan Li1, Yan Liu1, Yin Wang1, Xingluo Liu3, Michael W.Y. Chan2, Jin-Qing Liu3, Richard Love4, Chang-gong Liu2, Virginia Godfrey5, Rulong Shen3, Tim H.-M. Huang2, Tianyu Yang3, Bae Keun Park6, Cun-Yu Wang6, Pan Zheng1, , and Yang Liu1, ,
1Division of Immunotherapy, Section of General Surgery, Department of Surgery, Comprehensive Cancer Center, and Program of Molecular Mechanisms of Disease, University of Michigan, Ann Arbor, MI 48109, USA
2Program in Molecular, Cellular, and Developmental Biology and Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA
3Department of Pathology, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA
4Department of Internal Medicine, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA
5Department of Pathology, University of North Carolina, Chapel Hill, NC 27599, USA
6Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA Received 6 July 2006; revised 12 September 2006; accepted 10 April 2007. Published online: June 14, 2007. Available online 14 June 2007.
SUMMARY
The X-linked Foxp3 is a member of the forkhead/ winged helix transcription factor family. Germ- line mutations cause lethal autoimmune dis- eases in males. Serendipitously, we observed that female mice heterozygous for the ‘‘scurfin’’ mutation of the Foxp3 gene (Foxp3sf/+) devel- oped cancer at a high rate. The majority of the cancers were mammary carcinomas in which the wild-type Foxp3 allele was inactivated and HER-2/ErbB2 was overexpressed. Foxp3 bound and repressed the HER-2/ErbB2 promoter. Dele- tion, functionally significant somatic mutations, and downregulation of the FOXP3 gene were commonly found in human breast cancer sam- ples and correlated significantly with HER-2/ ErbB2 overexpression, regardless of the status of HER-2 amplification. Our data demonstrate that FOXP3 is an X-linked breast cancer sup- pressor gene and an important regulator of the HER-2/ErbB2 oncogene.
My comment at the time:
When a male inherits an X chromosome affected by this FOX-P3 mutation, they can die in utero or be born with severe immunodeficiency with a named syndrome, IPEX., so I doubt this is what caused your father's prostate cancer. Interestingly they contrast her2 overexpression and her2 amplification perhaps part of the problem as to why your sister's her2 status results were inconsistant. By the way, one of the ways ER+her2- tumors excape antihormonal treatment is by becoming her2+ which also might be what happened to your sister. There are so many possibilities.
http://her2support.org/vbulletin/sho...ITED+HER2+Lani
http://her2support.org/vbulletin/sho...R2+Lani&page=2