Is Uterine Papillary Serous Adenocarcinoma a Manifestation of the Hereditary Breast–Ovarian Cancer Syndrome?

Goshen, Ran; Chu, William; Elit, Laurie; Pal, Tuya; Hakimi, Jalil; Ackerman, Ida; Fyles, Anthony; Mitchell, Margot; Narod, Steven A.

doi:10.1006/gyno.2000.6003

Cited by 104 publications

(68 citation statements)

References 18 publications

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“…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. Kindelberger et al 21 documented tubal intraepithelial carcinoma in a significant percentage of high-grade serous carcinomas unselected for family history or BRCA mutation status, coexisting with carcinomas designated as of tubal, ovarian, or peritoneal origin, and proposed that tubal intraepithelial carcinoma may be the source of serous carcinoma in many of these tumors.…”

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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“…[7][8][9][10] Several papers suggested that BRCA gene mutations might also be associated with an increased risk of USC among Ashkenazi Jews, 9,11-13 whereas others-including a large prospective study-were unable to confirm such association either among Jews or in an unselected patient population. [14][15][16] Uterine serous carcinoma is the most biologically aggressive variant of endometrial carcinoma, with predilection for deep myometrial and lymphovascular space invasion, as well as peritoneal and distant metastatic spread. 2,17 Although it represents only approximately 10% of endometrial carcinomas, USC has been shown to account for a disproportionate 50% of relapses and 40% of endometrial cancer deaths.…”

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confidence: 99%

HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges

Buza

Roque

Santin

2014

Archives of Pathology &Amp; Laboratory Medicine

126

104

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Context.-In the era of targeted cancer therapy, there is growing interest in developing novel therapeutic strategies against endometrial carcinoma, especially its most biologically aggressive variant, serous adenocarcinoma. Several publications have demonstrated that a significant proportion of uterine serous carcinomas show HER2 overexpression and/or amplification, suggesting that HER2 may be a promising therapeutic target. Case reports have already shown clinical response to trastuzumab, a humanized monoclonal immunoglobulin (Ig) G1 antibody against HER2, and patients are currently being enrolled in a multi-institutional prospective randomized trial to evaluate the therapeutic efficacy of trastuzumab.Objective.-To review current data on HER2 testing and targeted therapy against HER2/neu in endometrial carcinoma. Data Sources.-Review of the literature and personal experience of the authors.Conclusions.-Parallel to the clinical studies, there is a need to develop standardized criteria for HER2 testing in endometrial carcinoma that reflect the unique biological and pathogenetic features of these tumors and correlate with clinical response to therapy. This article presents a comprehensive review of the current state of HER2-based therapy and HER2 testing in endometrial carcinoma.

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“…Early onset EC in carriers without tamoxifen use suggests that further study is required to assess association of modest EC risk with BRCA1/2 mutation status alone. mutation screening, 1-2 exons plus three Jewish founder mutations, in a non-Jewish EC cohort (Goshen et al, 2000). The second and third studies screened Jewish predominantly endometrioid EC patients for common Jewish mutations and identified BRCA1 and BRCA2 mutations at frequencies similar to the baseline frequency of ~2% in the general population (Barak et al, 2010;Levine et al, 2001).…”

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Report of Endometrial Cancer in AustralianBRCA1andBRCA2Mutation-Positive Families

et al. 2011

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There is evidence that tamoxifen treatment ofBRCA1andBRCA2carriers for prior breast cancer increases risk of endometrioid subtype endometrial cancer (EC), and suggestive evidence thatBRCA1andBRCA2mutation carriers may be predisposed to EC in the absence of tamoxifen exposure. We assessed the association of EC withBRCA1orBRCA2mutation status in Australasian breast-ovarian families. Report of at least one case of EC was significantly greater inBRCA1-positive families (35/218 (16%); p = .03) and non-significantly greater inBRCA2-positive families (23/189 (12%); p = .6), compared to high-risk breast cancer families without aBRCA1/2mutation (86/796 (11%)). EC was the first/concurrent cancer for 41% of EC cases with multiple cancer diagnoses fromBRCA1/2families, and early onset for most of these diagnoses. Mutation status was imputed for ungeno-typed individuals from 57BRCA1/2pedigrees reporting EC using BRCAPRO. Effects of genotype on EC diagnosis age, and interaction with tamoxifen therapy, were assessed using Cox proportional hazards regression analysis. EC risk was non-significantly marginally greater forBRCA1carriers (hazard ratio = 1.25, 95%CI = 0.65–2.41), andBRCA2carriers (HR = 1.12, 95%CI = 0.51–2.45), compared to non-carrier family members. Tamoxifen therapy was highly significantly associated with EC (HR = 6.68, 95%CI = 3.12–15.15; p = 1.7 x 10-6) inBRCA1/2families, with no evidence for interaction between tamoxifen therapy andBRCA1/2genotype. Our family-based study supports a 7-fold increase in EC risk with tamoxifen exposure for female family members fromBRCA1/2families. Early onset EC in carriers without tamoxifen use suggests that further study is required to assess association of modest EC risk withBRCA1/2mutation status alone.

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Is Uterine Papillary Serous Adenocarcinoma a Manifestation of the Hereditary Breast–Ovarian Cancer Syndrome?

Cited by 104 publications

References 18 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

HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges

Report of Endometrial Cancer in AustralianBRCA1andBRCA2Mutation-Positive Families

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