Polish Study Shows Inherited PALB2 Mutation Confers Greater Risk and Poorer Outcome of Breast Cancer

Key Points

  • PALB2 mutation was four times more common in women with vs without breast cancer.
  • Among women with breast cancer, 10-year overall survival was significantly lower in those with vs without PALB2 mutation.

In a Polish prospective cohort analysis reported in The Lancet Oncology, Cybulski et al found that PALB2 mutation carriers had increased risk of breast cancer and that those with breast cancer had significantly reduced long-term survival. 

Study Details

In the study, genotyping for two deleterious mutations in PALB2 (509_510delGA and 172_175delTTGT) was conducted in women with invasive breast cancer prospectively recruited from 18 hospitals in Poland between 1996 and 2012. A control group of 4,702 women without cancer were recruited for comparison.

Risk and Survival

Genotyping was successful for 12,529 women from among 17,900 breast cancer patients recruited. A PALB2 mutation was present in 116 patients (0.93%, 95% confidence interval [CI] = 0.76%–1.09%) and in 10 women (0.21%, 95% CI = 0.08%–0.34%) in the control group (odds ratio = 4.39, P < .0001). Ten-year overall survival was 48.0% (95% CI = 36.5%–63.2%) in women with breast cancer and a PALB2 mutation vs 74.7% (95% CI = 73.5%–75.8%) in breast cancer patients without a mutation (adjusted hazard ratio = 2.27, P < .0001).

The investigators concluded: “Women with a PALB2 mutation face an increased risk of breast cancer and might be at a higher risk of death from breast cancer compared with non-carriers. Increased surveillance should be offered to unaffected women who carry a PALB2 mutation.”

Steven A. Narod, MD, of Women’s College Research Institute, Toronto, is the corresponding author for the Lancet Oncology article.

The study was funded by the Polish National Science Centre. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.