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Poster display session

5429 - Limited value of currently used germline brca mutations predictive tools in prostate cancer

Date

10 Sep 2017

Session

Poster display session

Presenters

Lucia Oliva Fernández

Citation

Annals of Oncology (2017) 28 (suppl_5): v269-v294. 10.1093/annonc/mdx370

Authors

L. Oliva Fernández1, M.A. Márquez-Aragonés2, N. Romero-Laorden3, B.I. Pajares Hachero4, I. Moreno2, M. Ruiz Vico1, G. Duran Ogaya4, C. Muriel2, J. Pascual1, C. Fernández de Souza2, M.E. Dominguez Recio1, G. Grau5, M.I. Sáez5, A. Montesa6, R. Correa5, D. Olmos Hidalgo7

Author affiliations

  • 1 Medical Oncology, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, 29010 - Malaga/ES
  • 2 Familial Cancer Unit, Medical Oncology, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, 20010 - Málaga/ES
  • 3 Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, 28029 - Madrid/ES
  • 4 Familial Cancer Unit, Medical Oncology, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, 29010 - Malaga/ES
  • 5 Cnio-ibima Genitourinary Cancer Research Unit, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga/ES
  • 6 Cnio-ibima Genitourinary Research Unit, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga., Málaga/ES
  • 7 Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre, 028029 - Madrid/ES
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Resources

Abstract 5429

Background

Germline BRCA1 and BRCA2 mutations have been associated to poor prostate cancer (PrCa) outcomes and may have implications for cancer treatment. Identification of these carriers would also serve for the early identification of other family members at increased risk of breast and ovarian cancer. Several tools have been developed to estimate the probability of a gBRCA mutations in the context of a family history of breast and/or ovarian cancer but its performance has not been evaluated in PrCa patients.

Methods

This is single-centre study aimed to: 1) compare the contribution of PrCa to identify families known to harbour a germline BRCA1 or BRCA2 mutation; and 2) estimate the ability of predicting a BRCA mutation in these families based on the cancer history at the time of PrCa diagnosis. A comprehensive reassessment of families attending our Familial Cancer screening program at Málaga Univ. Hospitals between 2012-16 identified 104 families known to harbour a gBRCA mutations. gBRCA mutation risk estimations were calculated with 2 commonly used risk assessment models: BRCAPRO 6.0 and Manchester Score (MS).

Results

Finally, a total of 98 families (42 BRCA1, 56 BRCA2) were included in the study, after exclusion for further analyses of families with PrCa cases in non-carriers (phenocopies). As expected, PrCa was more common in BRCA2 carriers (2 vs 19, p = 0.002). Median age of PrCa diagnosis was 70 yrs (48-83). Male breast cancer was more common in families with PrCa (24% vs 4% p = 0.003), particularly in BRCA2 families (26.3% vs 5.4%, p = 0.023), but no other differences in family history of cancer were observed between families with or without PrCa cases and therefore their scores using BRACAPRO and MS did not differ. A ≥ 10% probability of finding a BRCA2 mutation was identified in 47% of families using BRCAPRO, decreasing to 21% when the proband was the PrCa patient (p = 0.002). Similar results were observed when the probability was calculated using MS (42% vs 21%, p = 0.011)

Conclusions

The currently available predictive tools underestimate the probability of a BRCA mutation when the proband is a prostate cancer patient and should not be used as unique tools to decide which PrCa patients should undergo genetic testing.

Clinical trial identification

Legal entity responsible for the study

Institutod e Investigación Biomédica en Málaga (IBIMA)

Funding

Asociación para el apoyod e la Investigación O

Disclosure

All authors have declared no conflicts of interest.

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