Long-term tumour dormancy in a<i>BRCA1</i>heterozygote

Amuzu, Setor; Fu, Lili; Demko, Nadine; Rivera, Bárbara; Domecq, Céline; Kock, Leanne de; Hamel, Nancy; Gilbert, Lucy; Polak, Paz; Ragoussis, Jiannis; Foulkes, William D.

doi:10.1136/jmedgenet-2021-108269

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…Note in Proof: A recent publication by Amuzu, et al describes a case of a 0.8 mm HGSC in the setting of STIC identified at preventive surgery in a woman with a germ-line BRCA1 mutation, that metastasized and lay dormant in the peritoneum for 15 years. The secondary HGSC differed from the original by whole genome doubling, inferring a single "catastrophic" genomic event in the genesis of the recurrent tumor [50]…”

Section: Hypothesis and Preventionmentioning

confidence: 99%

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention

Yoon

Chapel

Goebel

et al. 2022

The Journal of Pathology

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The current theory of carcinogenesis for the deadliest of ‘ovarian’ cancers—high‐grade serous carcinoma (HGSC)—holds that the malignancy develops first in the fallopian tube and spreads to the ovaries, peritoneum, and/or regional lymph nodes. This is based primarily on the observation of early forms of serous neoplasia (serous tubal intraepithelial lesions [STILs], and serous tubal intraepithelial carcinomas [STICS]) in the fimbria of women undergoing risk reduction surgery. However, these lesions are uncommon in the general population, confer a low risk (5%) of HGSC following their removal in at‐risk women with germ‐line BRCA1/2 mutations, and require 4 or more years to recur as intraperitoneal HGSC. These features suggest that isolated STILs and STICs behave as precursors, with uncertain cancer risk rather than carcinomas. Their evolution to HGSC within, or after, escape from the tube could proceed stepwise with multiple biologic events; however, it is unclear whether tubal or ovarian HGSCs encountered in the setting of advanced disease evolved in the same fashion. The latter scenario could also be explained by a ‘catastrophic’ model in which STICs suddenly develop with invasive and metastatic potential, overwhelming or obscuring the site of origin. Moreover, a similar model might explain the sudden emergence of HGSC in the peritoneal cavity following escape of precursor cells years before. Long‐term follow‐up data from opportunistic or prophylactic salpingectomy should shed light on where malignant transformation occurs, as well as the timeline from precursor to metastatic HGSC. © 2022 The Pathological Society of Great Britain and Ireland.

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Section: Hypothesis and Preventionmentioning

confidence: 99%

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention

Yoon

Chapel

Goebel

et al. 2022

The Journal of Pathology

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Incidence of peritoneal cancer after oophorectomy among BRCA1 and BRCA2 mutation carriers

Narod,

Gronwald,

Karlan

et al. 2024

JNCI: Journal of the National Cancer Institute

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Background To estimate the incidence of primary peritoneal cancer following preventive bilateral oophorectomy in women with a BRCA1 or BRCA2 mutation. Methods A total of 6,310 women with a BRCA1 or BRCA2 mutation who underwent a preventive bilateral oophorectomy were followed for a mean of 7.8 years from oophorectomy. The 20-year cumulative incidence of peritoneal cancer post-oophorectomy was estimated using the Kaplan-Meier method. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CI) associated with the age at oophorectomy, year of oophorectomy, and family history of ovarian cancer as well as hormonal and reproductive risk factors. Results Fifty-five women developed primary peritoneal cancer (n = 45 in BRCA1, 8 in BRCA2, and 2 in women with a mutation in both genes). Their mean age at oophorectomy was 48.9 years. The annual risk of peritoneal cancer was 0.14% for women with a BRCA1 mutation and was 0.06% for women with a BRCA2 mutation. The 20-year cumulative risk of peritoneal cancer from the date of oophorectomy was 2.7% for BRCA1 carriers and was 0.9% for BRCA2 mutation carriers. There were no peritoneal cancers in BRCA1 carriers who had the operation before age 35 or in BRCA2 carriers who had the operation before age 45. Conclusions For BRCA1 mutation carriers, the annual risk of peritoneal cancer for 20 years post-oophorectomy is 0.14% per year. The risk is lower for BRCA2 carriers (0.06% per year).

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Long-term tumour dormancy in aBRCA1heterozygote

Cited by 2 publications

References 15 publications

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention

Incidence of peritoneal cancer after oophorectomy among BRCA1 and BRCA2 mutation carriers

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