Newly Discovered Gene Mutations Strongly Linked To Breast Cancer

Dr Marc Tischkowitz MD PhD University Lecturer (Associate Professor) and Honorary Consultant  Physician in Medical Genetics Department of Medical Genetics, University of Interview with:
Dr Marc Tischkowitz MD PhD
University Lecturer (Associate Professor) and
Honorary Consultant  Physician in Medical Genetics
Department of Medical Genetics, University of Cambridge

Medical Research: What are the main findings of the study?

Dr. Tischkowitz: The PALB2 gene was first identified in 2006 and linked to breast cancer in 2007 but until now we have not had good breast cancer risk estimates for women who have inherited PALB2 mutations. This study was started in 2009 by an group of research institutions (The PALB2 Interest Group) in Canada, US, Europe (UK, Belgium, Greece, Italy, Finland) and Australia. We studied 362 individuals with PALB2 mutations from 154 families. We found that awomen with a PALB2 mutation will on average have a 35% risk of developing breast cancer by the age of 70, rising to 58% if there is a strong family history. Our study will help clinicians to better advise and manage such women.

There are several new aspects.

  • It is by far the largest study to date and provides the most accurate risk estimates for PALB2 mutation carriers.
  • It shows that the breast cancer risk is modified by the family history.

Medical Research: Were any of the findings unexpected?

Dr. Tischkowitz: We found that the breast cancer risk is higher in younger women (those born after 1960) with PALB2 mutations, even when allowing for general increase in breast cancer rates seen over the last few decades. The reason for this is unclear, but a similar phenomenon is seen in BRCA1 and BRCA2 mutation carriers.

Medical Research: What should clinicians and patients take away from your report?

Dr. Tischkowitz: Our study will allow physicians to provide more accurate advice to women with inherited PALB2 mutations. They may for example recommend increased breast cancer surveillance to these women. It also means that genetic testing can be offered to their relatives to see whether or not they have inherited the mutation. PALB2 mutations are much less common than BRCA1 or BRCA2, but as this gene is now routinely tested for as part of the breast cancer gene panels it is likely that we are going to see an increase in the number of women who are found to be carriers for PALB2 mutations.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Tischkowitz:  This is another piece of the puzzle in inherited breast cancers, and it puts PALB2 firmly on the map as an important breast cancer gene after BRCA1 and BRCA2. A large proportion of hereditary breast cancer still remains unexplained, but with ever more powerful gene sequencing techniques and ever larger international collaborations we expect that further significant advances will be made in this field in the coming years.


Breast-Cancer Risk in Families with Mutations in PALB2

Antonis C. Antoniou, Ph.D., Silvia Casadei, Ph.D., Tuomas Heikkinen, Ph.D., Daniel Barrowdale, B.Sc., Katri Pylkäs, Ph.D., Jonathan Roberts, B.Sc., Andrew Lee, Ph.D., Deepak Subramanian, M.B., B.Chir., Kim De Leeneer, Ph.D., Florentia Fostira, Ph.D., Eva Tomiak, M.D., Susan L. Neuhausen, Ph.D., Zhi L. Teo, Ph.D., Sofia Khan, Ph.D., Kristiina Aittomäki, M.D., Ph.D., Jukka S. Moilanen, M.D., Ph.D., Clare Turnbull, M.D., Ph.D., Sheila Seal, M.I.Biol., Arto Mannermaa, Ph.D., Anne Kallioniemi, M.D., Ph.D., Geoffrey J. Lindeman, F.R.A.C.P., Ph.D., Saundra S. Buys, M.D., Irene L. Andrulis, Ph.D., Paolo Radice, Ph.D., Carlo Tondini, M.D., Siranoush Manoukian, M.D., Amanda E. Toland, Ph.D., Penelope Miron, Ph.D., Jeffrey N. Weitzel, M.D., Susan M. Domchek, M.D., Bruce Poppe, M.D., Ph.D., Kathleen B.M. Claes, Ph.D., Drakoulis Yannoukakos, Ph.D., Patrick Concannon, Ph.D., Jonine L. Bernstein, Ph.D., Paul A. James, M.B., Ch.B., Ph.D., Douglas F. Easton, Ph.D., David E. Goldgar, Ph.D., John L. Hopper, Ph.D., Nazneen Rahman, M.D., Ph.D., Paolo Peterlongo, Ph.D., Heli Nevanlinna, Ph.D., Mary-Claire King, Ph.D., Fergus J. Couch, Ph.D., Melissa C. Southey, Ph.D., Robert Winqvist, Ph.D., William D. Foulkes, M.B., B.S., Ph.D., and Marc Tischkowitz, M.D., Ph.D.

N Engl J Med 2014; 371:497-506August 7, 2014DOI: 10.1056/NEJMoa1400382


Last Updated on August 7, 2014 by Marie Benz MD FAAD