Prevalence of BRCA1 and BRCA2 germ line mutations among women with carcinoma of the fallopian tube

Abstract

Objectives

The purpose of this study is to determine the prevalence of BRCA1 and BRCA2 mutations among a large series of women with carcinoma of the fallopian tube.

Methods

Two series of women diagnosed with carcinoma of the fallopian tube were studied. Women identified from the Ontario Cancer Registry who were diagnosed with fallopian tube cancer between 1990 and 1998 and between 2002 and 2004. A second, hospital-based series was identified at Cedars Sinai Medical Centre, Los Angeles, California. These women were diagnosed between 1991 and 2007. Each subject was approached to provide her family history and ethnic background and to provide a blood sample for genetic testing for mutations in the BRCA1 and BRCA2 genes.

Results

In total, 108 patients with fallopian tube cancer were recruited (70 from Ontario and 38 from Los Angeles). Thirty-three patients (30.6%) were found to have a deleterious mutation; 23 in BRCA1 (21.3%) and 10 in BRCA2 (9.3%). The prevalence of mutations was 55.6% in Jewish women and was 26.4% in non-Jewish women. A family history of ovarian or breast cancer was positive for 24 women (23.3%); of these, 14 had a mutation (58.3%). Fourteen (14.4%) of the patients had a previous history of breast cancer; of these, 10 (71.4%) had a mutation. 40.3% of the women who were diagnosed with fallopian tube cancer before age 60 had a mutation, compared with 17.4% of the women diagnosed at age 60 and above.

Conclusions

Approximately 30% of women with fallopian tube cancer have a mutation in BRCA1 or BRCA2. The highest frequencies of BRCA mutations were seen in women with fallopian tube cancer diagnosed under age 60, in Jewish women, in women with a family history of breast or ovarian cancer, and in women with a personal history of breast cancer. All patients diagnosed with invasive fallopian tube cancer should be considered candidates for genetic testing.

Introduction

Fallopian tube cancer is part of the spectrum of cancers in women with a BRCA1 or BRCA2 mutation. This association is based on the reporting of fallopian tube cancers in families known to carry a deleterious BRCA mutation and more recently, due to the finding in several studies of occult fallopian tube cancers at prophylactic salpingo-oophorectomy in BRCA1 and BRCA2 carriers [1], [2], [3], [4], [5], [6], [7]. In 2001, we tested a series of 44 unselected women with fallopian tube cancer and reported that 16% of these patients carried a BRCA1 or BRCA2 mutation [8]. This rate was higher than the 11.7% we found in women diagnosed with invasive serous ovarian cancer [9]. Since 2001, we have expanded our sample of cases from Ontario from 44 to 70, we have added 38 fallopian cancers from Los Angeles and we have screened the entirety of the BRCA1 and BRCA2 genes for mutations in all cases.