BRCA germline mutations in Jewish women with uterine serous papillary carcinoma

Lavie, Ofer; Hornreich, Gila; Ben-Arie, Alon; Rennert, Gad; Cohen, Yoram; Keidar, Rehuven; Sagi, Shlomi; Levy-Lahad, Ephrat; Auslander, Ron; Beller, U.

doi:10.1016/j.ygyno.2003.11.009

Cited by 120 publications

(98 citation statements)

References 19 publications

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“…Hysterectomy may be considered in women treated with tamoxifen, to eliminate the risk of tamoxifen-associated uterine malignancies, and other benefits include the option of hormone replacement without progesterone. 22 Some reports 23,24 suggest that mutation carriers may be at increased risk of uterine serous carcinoma, although two independent studies failed to show an increased risk in BRCA mutation carriers. [25][26][27] Tubal intraepithelial carcinoma is not confined to BRCA mutation carriers.…”

Section: Discussionmentioning

confidence: 99%

Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers

et al. 2009

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Occult invasive and intraepithelial carcinomas have been identified in the tubal fimbria of BRCA mutation carriers undergoing prophylactic surgery, and recently described lesions overexpressing p53 in the distal tubes of mutation carriers, and non-carriers, have been proposed as histological precursors of high-grade serous carcinoma. The aim of this study was to confirm these findings in a larger, independent case set, to further characterize the cancer precursor lesions, and to determine their frequency in BRCA mutation-positive (n ¼ 176) and control groups (n ¼ 64). For the purposes of this study, we excluded cases without documentation of a germline mutation of BRCA1/2, and without histological examination of the entire tube, and cases with a diagnosis of invasive carcinoma. Controls included salpingectomies from women undergoing surgery for reasons other than ovarian malignancy. Diagnostic categories were assigned based on combined histological review and immunostaining results. Histological abnormalities were identified in 23% of the BRCA group and in 25% of the control group, and included localized p53 overexpression in 20% of the BRCA group and 25% of the control group. Tubal intramucosal carcinoma was identified in 8% of the BRCA cases and in 3% of the control group. Four cases of intraepithelial carcinoma (21%) did not overexpress p53. There was no significant difference in the median age, frequency of histological abnormalities, p53 signatures, or tubal intraepithelial carcinoma between the BRCA mutation-positive and control groups. This large, blinded review of tubes from BRCA mutation carriers confirms previous reports of putative cancer precursors in distal tubal mucosa, and that p53 signatures occur with similar frequency in women at low and high genetic risk of tubal/ovarian carcinoma. Tubal intraepithelial carcinoma, which, like invasive serous cancer, usually but not always overexpresses p53 protein, is more frequent in BRCA mutation carriers.

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Section: Discussionmentioning

confidence: 99%

Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers

et al. 2009

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“…Genetic analysis showed loss of the wild-type allele, suggesting a link between germline BRCA1 mutation and serous cancer. A following study of Ashkenazi Jewish patients with endometrial serous carcinoma confirmed a high incidence of BRCA1 mutation and LOH (75% of tumor samples) (Lavie, Hornreich et al 2004). A contradictory result was found in a study by the same group on a population of germline-BRCA mutation carriers, showing no relationship to increased risk of endometrial cancer.…”

Section: Brca Mutationsmentioning

confidence: 92%

“…A subset of relatively younger women with hereditary breast cancers are also at increased risk for the development of subsequent ovarian/tubal serous malignancies as a manifestation of hereditary breast-ovarian syndrome (Hall, Jamison et al 2001;Arai, Utsunomiya et al 2004), and in patients with BRCA mutations (Lavie, Hornreich et al 2004). An earlier paper by Curtis et al in 1973, had described other malignancies that may follow breast cancer, including endometrial cancer (Inskip and Curtis 2007).…”

Section: Brca Mutationsmentioning

confidence: 99%

Endometrial Intraepithelial Neoplasia

Shahin¹,

Pang²,

Li³

et al. 2012

Intraepithelial Neoplasia

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“…Occult cancers are detected at a frequency of 1-4% in cases in which RRSO is performed; thus, both the ovaries and Fallopian tubes should be removed (27,28). In HBOC, the risk for developing endometrial cancer in BRCA1 mutation carriers is 2.6-fold higher compared to that in non-carriers (29) and the relative risk for endometrial cancer is 11.6 following tamoxifen treatment in BRCA1/2 mutation carriers (30). Since the uterus is non-functional following BSO, a hysterectomy should be performed at the same time as BSO (31).…”

Section: Techniques Of Rrsmentioning

confidence: 99%

Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer

Adachi

Banno

Yanokura

et al. 2014

Molecular and Clinical Oncology

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Abstract. Risk-reducing surgery (RRS) is defined as a prophylactic approach with removal of organs at high risk of developing cancer, which is performed in cases without lesions or absence of clinically significant lesions. Hereditary gynecological cancers for which RRS is performed include hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. For HBOC, RRS in the United States (US) is recommended for women with mutations in the breast cancer susceptibility (BRCA)1 and BRCA2 genes and bilateral salpingo-oophorectomy (BSO) is generally performed. This procedure may reduce the risk of breast, ovarian, Fallopian tube and primary peritoneal cancer, although ovarian deficiency symptoms occur postoperatively. For Lynch syndrome, RRS in the US is considered for postmenopausal women or for women who do not desire to bear children and BSO and hysterectomy are usually performed. This approach may reduce the risk of endometrial and ovarian cancer, although ovarian deficiency symptoms also occur. For RRS, there are several issues that must be addressed to reduce the risk of cancer development in patients with HBOC or Lynch syndrome. To the best of our knowledge, this is the first review to discuss RRS with a focus on hereditary gynecological cancer. IntroductionHereditary gynecological cancers include ovarian cancer associated with hereditary breast and ovarian cancer (HBOC); endometrial and ovarian cancer associated with Lynch syndrome; endometrial, cervical and ovarian cancer associated with Peutz-Jeghers syndrome; and ovarian cancer associated with Cowden disease. HBOC is an autosomal dominant hereditary disease that may cause breast, ovarian, Fallopian tube and peritoneal cancer.Mutations of the breast cancer susceptibility (BRCA)1 and BRCA2 genes have been identified in ~8-13% of patients with ovarian cancer (1,2). By the age of 70 years, the estimated risks of developing ovarian cancer are 35-60 and 10-27% in BRCA1 and BRCA2 mutation carriers, respectively (2). The mean ages at diagnosis of ovarian cancer are 54, 62 and 63 years for BRCA1 and BRCA2 mutation carriers and non-carriers, respectively, indicating that BRCA1 mutation carriers are more likely to be affected by ovarian cancer at a younger age (3). Clinicopathologically, the majority of ovarian cancers that are BRCA1/2 mutation-positive are of serous histology and are poorly differentiated (grade 3) stage III-IV tumors, according to the International Federation of Gynecology and Obstetrics (FIGO) staging criteria, as defined in 1988 (4,5). In BRCA1/2 mutation-positive and -negative cases, the rates of serous adenocarcinoma are 63-86 and 57-58%, those of poorly differentiated tumors 68-87 and 48-58% and those of stage III-IV tumors 72-88 and 62-70%, respectively.Lynch syndrome, also referred to as hereditary non-polyposis colorectal cancer, is an autosomal dominant hereditary disease that may lead to colorectal, endometrial, gastric and ovarian cancer. Lynch syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes, which include mu...

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BRCA germline mutations in Jewish women with uterine serous papillary carcinoma

Cited by 120 publications

References 19 publications

Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers

Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers

Endometrial Intraepithelial Neoplasia

Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer

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