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1197 Carcinogenesis mammary signaling pathways avenues for research translational & personalized medicine
  1. Mohamed Abdellahi El Moctar1,
  2. Kawtar Laaouini,
  3. MB Idrissi,
  4. K Saoud,
  5. N Mamoun,
  6. S Errarhay,
  7. C Bouchikhi and
  8. A Banani2
  1. 1Obstetrics Gynecology I Department of the CHU Hassan II, Faculty of Medicine, Sidi Mohamed Ben Abdellah University, Fès, Morocco
  2. 2Obstetrics Gynecology I Department of the CHU Hassan II, Faculty of Medicine, Sidi Mohamed Ben Abdellah University, Fès, Maroc


Introduction/Background Study of genetic alterations practical interests

  • Understanding the molecular mechanisms of carcinogenesis

  • Genetic risks (hereditary)

  • Inherited mutations: BRCA1, BRCA2, PALB2...

  • Biomarkers in clinical oncology

  • screening

  • diagnostic assistance

  • prognosis

  • prediction of response to treatment

  • Development of new therapeutic approaches (targeted therapies)

Methodology Biomarkers :

Ability of the test to measure the biomarker with reliability and reproducibility

Clinical utility

Treatment decision can be based on test result (prospective study with test/objective)

Clinical validity

Ability of test to correlate with prognosis and/or response prediction (statistical significance)

Molecule (protein or gene (DNA or RNA)) that influences tumor cell behavior and can predict prognosis and/or sensitivity/resistance to a specific treatment.

Results PERSONALIZED MEDICINE PREVENTIVE STRATEGY personalized screening (example: predisposition to cancer)

Prognostic criterion: -Which patient will do well without further treatment

(natural history) example: chemo in breast cancer if risk of relapse

Predictive criterion: -Which patient will do well with which type of treatment (example: hormone receptor positive and hormone therapy )

Therapeutic target: What molecular abnormality of the tumor can be targeted (example: HER2 overexpression and anti-HER2)?

Biomarkers: genomic signatures -early breast cancer RH+/HER2-

  • Prognostic value demonstrated

  • Clinical validity: confirmed in large retrospective cohorts:

  • Clinical utility: prospective evaluation of prognostic value and impact on therapeutic decisions (indication for adjuvant chemotherapy):

Predictive criteria

Predictive of what?

Predictive of treatment efficacy

Assumes that the treatment ’works’ in certain subgroups and not in others: ’interaction’ between the predictive factor and the treatment effect.

Examples: Hormone receptors and hormone therapy

HER2 and anti-HER2

Conclusion biomarkers Thanks to the development of molecular biology and high-throughput analysis, more and more markers are available to predict treatment efficacy.

The ’mapping’ of gene anomalies (overexpression, gene mutations) to predict efficacy or resistance to a given targeted therapy is the basis of personalized medicine in oncology.

A large number of targeted therapies are thus inseparable from their ’companion’ test, a predictor of their possible effect...

The measurement of certain predictive ’biomarkers’ can be repeated over time (iterative biopsies and/or ’liquid’ biopsies)

Disclosures The authors declare no conflict of interest.

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