Is low-grade serous ovarian cancer part of the tumor spectrum of Hereditary Breast and Ovarian Cancer?
ABSTRACT To determine whether women with low-grade serous ovarian cancer (LGSOC) have personal and family histories of breast and ovarian cancer that are less suggestive of Hereditary Breast and Ovarian Cancer (HBOC), as compared to women with high-grade serous ovarian cancer (HGSOC).
A single institution, case-control retrospective review of medical records was conducted. Personal demographics, personal cancer history, and family history of breast and ovarian cancer of women with LGSOC were collected and compared to controls with HGSOC, which is known to be associated with HBOC.
195 cases of LGSOC and 386 controls with HGSOC were included in the analysis. Women with LGSOC were significantly less likely to have a first- or second-degree relative with breast or ovarian cancer (p=0.0016). Additionally, when the personal and family histories were quantified using the AMyriad BRC mutation prevalence tables, women with LGSOC had lower scores indicative of a less suggestive family history for HBOC (p=0.027).
In this study, women with LGSOC had family histories that were less suggestive of HBOC compared to women with HGSOC, especially when the degree of relatedness of affected relatives was taken into account. By beginning to determine if LGSOC is part of the tumor spectrum seen in HBOC, this study is an important step towards refining hereditary cancer risk assessment for women with ovarian cancer.
SourceAvailable from: Adam H Buchanan[Show abstract] [Hide abstract]
ABSTRACT: Identification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer. BRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy. One hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P < .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02). Patients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history.Journal of Clinical Oncology 03/2014; 32(12). DOI:10.1200/JCO.2013.50.6055 · 17.88 Impact Factor
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ABSTRACT: For the past several years, all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance leading to separate clinical trials for patients with this subtype originating from the Gynecologic Oncology Group's Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20-40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare-about 5%. Primary treatment of low-grade serous carcinoma includes surgery+platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonger overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormonal therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations.Gynecologic Oncology 05/2013; 130(3). DOI:10.1016/j.ygyno.2013.05.021 · 3.69 Impact Factor
Article: Genetic Risk and Gynecologic Cancers[Show abstract] [Hide abstract]
ABSTRACT: Although most gynecologic malignancies are sporadic, hereditary cancer syndromes cause a substantial portion of these cancers. Given that the diagnosis of these syndromes has prognostic and therapeutic implications for the patient, as well as preventive implications for her family members, genetic testing is now an accepted part of the management of the patient who has gynecologic cancer.Hematology/oncology clinics of North America 02/2012; 26(1):13-29. DOI:10.1016/j.hoc.2011.11.003 · 2.07 Impact Factor