Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy

McEwen, Alison; McConnell, Dynes T.; Kenwright, Diane; Gaskell, D. J.; Cherry, A.; Kidd, Alexa

doi:10.1016/j.ygyno.2003.12.003

Cited by 16 publications

(6 citation statements)

References 9 publications

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“…OC resembles the cellular and molecular characteristics of the fallopian tube epithelium, which is embryologically derived from the műllerian duct (20). Furthermore, serous tubal intraepithelial carcinomas (STIC) lesions have been described in carriers of BRCA1 and 2 mutations and proposed to represent precursor cancer lesions (21,22). New data point to the mesothelium-lined peritoneal cavity (15) as a potential origin of a subgroup of ovarian tumors.…”

Section: Ovarian Cancer Biologymentioning

confidence: 99%

New therapeutic targets in ovarian cancer stem cells

Sima¹,

Condello²,

Mate³

2017

Mol.Life

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CANCER STEM CELLS-A PROVOCATIVE CONCEPT Whether classifi ed as "tumor-initiating" cells, "cancer stem-like" cells or simply "cancer stem cells" (CSCs), this small population of highly undiff erentiated and slow cycling cells is implicated in early molecular events linked to cancer development as well as in tumor progression, recurrence, and development of chemotherapy resistance (1). During the last decade an increasing amount of scientifi c reports yielded proof of existence of a subpopulation of cells within tumors bearing the main characteristics of stem cells in normal tissues: quiescence and capacity of self-renewal and diff erentiation (2). Specifi c signaling pathways controlling normal stem cells identity were found to regulate the phenotype of this subset of tumor cells bearing "stemness" features (3). Th e fi rst report documenting a cancer initiating cell phenotype in solid tumors was published in 2003 in a breast cancer model (4). CD44 high /CD24 low cells are characterized by self-renewal properties, tumor initiating capacity in vivo, when injected in small numbers (50-100) in NOD/SCID mice, and ability to diff erentiate into cells with more specifi c phenotypes and functions. Since that report, the fi eld expanded to include most solid tumors, continuously refi ning the cancer stem cell hypothesis. However, the very existence of CSCs remains controversial, as researchers have struggled to defi ne similarities and distinct traits between normal and cancer stem cells (5). Although CSCs were described by Hans Clevers as "malignant equivalents of tissue stem cells" (6), it remains open for debate whether cancer occurs by mutations in normal tissue-specifi c stem cells or whether transformation follows in transit amplifying cells or even in more committed cells driving their dediff erentiation to stem-like cancer cells (7, 8). It is accepted that CSCs represent a rare cell population within tumors, however their precise quantifi cation has been variable. Th e most extreme report comes from the melanoma models, suggesting that CSCs can recapitulate Abstract Ovarian cancer (OC) is the deadliest gynecological malignancy. Characterized by frequent recurrences after standard chemotherapy and a pattern of dissemination in the peritoneal cavity, ovarian tumor development and progression may be driven by cancer stem cells (CSCs). This concept is supported by the identification of a subset of OC cells with stem-like characteristics, including self-renewal, ability to differentiate and to initiate tumors in vivo. It has been proposed that ovarian CSCs are responsible for development of chemotherapy resistance and of disease recurrence, which occur commonly in OC. Several markers are used for the isolation of ovarian CSCs and distinct pathways fuel their survival and proliferation within the tumor microenvironment (TME). Here we aim to review recent advances in the field of ovarian CSCs and to discuss novel therapeutic targets which could be exploited to eliminate this tumor cell sub-population with the goal of pre...

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Section: Ovarian Cancer Biologymentioning

confidence: 99%

New therapeutic targets in ovarian cancer stem cells

Sima¹,

Condello²,

Mate³

2017

Mol.Life

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“…Rebbeck et al (2002) and Kauff et al (2002) both found a significant reduction in both ovarian and breast cancer following a prophylactic salpingo‐oophorectomy and recommended the procedure in patients who screen positive for the BRCA mutation. Recommendations from these studies included a prophylactic salpingo‐oophorectomy as soon as possible after childbearing is complete or by age 35 (McEwen et al, 2004).…”

Section: What Are Women's Concerns?mentioning

confidence: 99%

Breast and Ovarian Cancer: A New Model For Educating Women

Mangerich

Stichler

2008

Nursing for Women's Health

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“…Primary peritoneal cancer may occur either owing to an occult ovarian cancer focus or from carcinoma arising de novo in peritoneal mesothelium. Occult ovarian and fallopian tube carcinomas have been found at the time of PO in 2-10% of BRCA1/2 mutation carriers (Salazar et al, 1996;Lu et al, 2000;Colgan et al, 2001;McEwen et al, 2004;Powell et al, 2005). The role of peritoneal washings at this time is unclear (Colgan et al, 2002;Powell et al, 2005).…”

Section: Primary Peritoneal Cancer and Fallopian Tube Carcinomamentioning

confidence: 99%

Clinical management of BRCA1 and BRCA2 mutation carriers

Domchek

Weber

2006

Oncogene

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The cancer susceptibility genes BRCA1 and BRCA2 appear to be responsible for virtually all hereditary breast ovarian families, and a smaller subset of hereditary sitespecific breast cancer families. Fortunately, effective strategies have been developed to reduce the risk for the development of breast and ovarian cancer in women with BRCA1/2 mutations, making genetic testing for these mutations an important part of the management at women with a strong family history of these diseases. Here, we review the current evidence for risk reduction strategies and outline future research directions. Oncogene (2006) 25, 5825-5831. doi:10.1038/sj.onc.1209881Keywords: BRCA1; BRCA2; oophorectomy; breast cancer; ovarian cancer; management Management of ovarian cancer risk Prophylactic oophorectomyThe lifetime risk of ovarian cancer for women with BRCA1 mutations is estimated at 40-50% (Ford et al., 1994;Antoniou et al., 2003;King et al., 2003) and in those with BRCA2 mutations, at 10-20% (1999;Antoniou et al., 2003;King et al., 2003). We and others have shown conclusively that prophylactic oophorectomy (PO) in women with BRCA1/2 mutations reduces the risk of ovarian cancer by approximately 90% (Kauff et al., 2002;Rebbeck et al., 2002;Rutter et al., 2003;Domchek et al., 2006). Data with short-term follow-up also suggests that oophorectomy is associated with an improvement in breast cancer-specific survival, ovarian cancer-specific survival and overall survival (Domchek et al., 2006) (Figure 1). Table 1 reports the details of studies examining PO in BRCA1/2 mutation carriers. Rebbeck et al. (2002) examined 551 women from 11 centers in North America and Europe who either did (n ¼ 259) or did not (n ¼ 292) undergo PO, with a mean follow-up of over 8 years in each group. Eight PO subjects (3.1%) were diagnosed with ovarian cancer or primary peritoneal cancer at or following PO compared with 58 controls (19.9%). Six of the eight PO subjects diagnosed with ovarian cancer were diagnosed at the time of PO, all of which were stage I. After excluding these six cases, only two women (both with BRCA1 mutations) who underwent PO subsequently developed primary peritoneal cancer. Compared with women who did not undergo PO, the occurrence of post-PO ovarian cancer corresponded to a hazard ratio (HR) of 0.04 (95% confidence interval (CI): 0.01-0.16). In addition to this striking reduction in the risk of ovarian cancer, an approximately 50% breast cancer risk reduction after PO was also observed (HR ¼ 0.47; 95% CI: 0.29-0.77). In an another study with similar results, Kauff et al. (2002) identified 170 women with BRCA1/2 mutations who had not previously undergone PO, who then chose to either undergo ovarian cancer surveillance or undergo PO. During a mean follow-up of 24.2 months, ovarian cancer or primary peritoneal carcinoma was diagnosed in one of 98 women who chose to undergo PO compared to five ovarian or peritoneal cancers in the 72 women who chose surveillance. This risk reduction corresponded to a HR of 0.15 (95% CI: 0.02-1.31).Finally, ...

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Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy

Cited by 16 publications

References 9 publications

New therapeutic targets in ovarian cancer stem cells

New therapeutic targets in ovarian cancer stem cells

Breast and Ovarian Cancer: A New Model For Educating Women

Clinical management of BRCA1 and BRCA2 mutation carriers

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