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Amy Berrington de Gonzalez

Publications and source records attributed to Amy Berrington de Gonzalez.

4 recordsLinked to original sources
PubMed2025

Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma.

BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤3 years, n=42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n=1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.

Journal Article↗
PubMed2003

Cervical cancer and use of hormonal contraceptives: a systematic review.

BACKGROUND: Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women. METHODS: Results from published studies were combined to examine the relationship between invasive and in situ cervical cancer and duration and recency of use of hormonal contraceptives, with particular attention to HPV infection. FINDINGS: 28 eligible studies were identified, together including 12531 women with cervical cancer. Compared with never users of oral contraceptives, the relative risks of cervical cancer increased with increasing duration of use: for durations of approximately less than 5 years, 5-9 years, and 10 or more years, respectively, the summary relative risks were 1.1 (95% CI 1.1-1.2), 1.6 (1.4-1.7), and 2.2 (1.9-2.4) for all women; and 0.9 (0.7-1.2), 1.3 (1.0-1.9), and 2.5 (1.6-3.9) for HPV positive women. The results were broadly similar for invasive and in situ cervical cancers, for squamous cell and adenocarcinoma, and in studies that adjusted for HPV status, number of sexual partners, cervical screening, smoking, or use of barrier contraceptives. The limited available data suggest that the relative risk of cervical cancer may decrease after use of oral contraceptives ceases. However, study designs varied and there was some heterogeneity between study results. INTERPRETATION: Although long duration use of hormonal contraceptives is associated with an increased risk of cervical cancer, the public health implications of these findings depend largely on the extent to which the observed associations remain long after use of hormonal contraceptives has ceased, and this cannot be evaluated properly from published data.

Case-Control Studies↗
PubMed2003

Comparison of documented and recalled histories of exposure to diagnostic x-rays in case-control studies of thyroid cancer.

Most information concerning possible cancer risks attributable to lifetime exposure to diagnostic x-rays comes from studies in which x-ray history was ascertained by interview or questionnaire, but little is known about the accuracy of such information. The authors assessed agreement between medical x-ray histories obtained through interview and by review of medical records from thyroid cancer case-control studies conducted in Sweden (1985-1992; 123 cases and 123 controls) and from members of a prepaid health plan in the United States (1986-1991; 50 cases and 50 controls). In both studies, substantial disagreement was found between the numbers of x-ray examinations reported in the interview and in the medical records. There was an indication of relatively poorer reporting among controls, particularly for certain types of x-ray examinations and for large numbers of such examinations. Estimates of the risk associated with exposure to diagnostic x-rays were similar, regardless of whether interview or medical record data were used, even though ordinal dose classifications based on the two sources differed considerably. In populations with a high frequency of exposure, spurious associations with numbers of x-ray examinations or estimated thyroid dose might arise because of differences in recall. However, in the present data, reporting errors by cases and controls seemed to be largely nondifferential.

Adult↗