Breast cancer: certain medications prescribed before diagnosis have a major prognostic influence

Breast cancer: certain medications prescribed before diagnosis have a major prognostic influence
Breast cancer: certain medications prescribed before diagnosis have a major prognostic influence

Because the incidence of breast cancer increases with age, the existence of comorbidities and treatments at the time of diagnosis of the tumor disease is common (30 and 70% of women). Various studies have already described links between taking certain molecules and the prognosis of the disease. Researchers involved in the FRESH study (French Early Breast Cancer Cohort), set up by the National Cancer Institute (INCa) wanted to continue exploring these interactions by studying the influence of current treatments delivered before the diagnosis of breast cancer on the progression of the disease.

Analysis of the journey of more than 230,000 French women

The FRESH cohort included all women diagnosed with non-metastatic breast cancer between 2011 and 2017 and enrolled in the general scheme. The treatments delivered were analyzed, a treatment being qualified as chronic when it had been prescribed for at least 3 months at the recommended dosage during the 6 months preceding diagnosis. At the same time, 52 comorbidities were searched for and grouped into 12 categories for analysis.

From these data, a causal inference analysis was conducted to establish causal relationships between comorbidities, their treatment and prognosis. This work is based on a process to adjust the data according to patient characteristics and then explore the effects of treatment on the Kaplan-Meier survival curves. The authors calculated the hazard ratio (Cox HR) for each of the molecules, a value less than 1 indicating a lower risk.

The analysis was able to include 235,368 patients (mean age 60 years). In this cohort, 65.1% of cancers were luminal and 81.2% had no lymph node involvement. 47% of them had at least one comorbidity and three-quarters had concomitant treatment before diagnosis. The most frequent pathologies were cardiovascular (25.6%) or endocrine and metabolic (21.9%). After an average follow-up of 54 months, 12.1% of patients relapsed or died.

Towards affordable adjuvant drugs?

The molecules having a favorable influence on overall survival were rabeprazole (HR 0.77), alverine (HR 0.78), atenolol (HR 0.77), estriol (vaginal or transmucosal HR 0, 58). Hypromellose had a favorable influence on PFS (HR 0.77). Finally, three molecules favorably influenced both parameters: simvastatin (HR SG 0.73 and PFS 0.76), rosuvastatin (HR SG 0.64 and PFS 0.72) and nomegestrol (HR SG 0.39 and PFS 0.39). 0.74) (all were statistically significant).

Conversely, ferrous fumarate (HR SSP 1.74), carbimazole (HR SSP 1.42), alprazolam (HR SSP 1.12), hydroxyzine (HR SSP 1.16), and mianserin (HR PFS 1.36) were associated with shorter overall or progression-free survival. Finally, three molecules simultaneously influenced the two parameters in an unfavorable manner: prednisolone (HR SG 1.78 and PFS 1.58), pristinamycin (HR SG 1.88 and PFS 1.64) and oxazepam (HR SG 1.64). .27 and PFS 1.20) (all were statistically significant).

The potential mechanisms of some of these associations have already been mentioned elsewhere, such as that of rabeprazole or atenolol. Nevertheless, the impact of hormonal treatments on the prognosis of overall survival and progression-free survival could be linked to their influence on tumor biology. On the other hand, certain molecules were identified for the first time in this work and will require investigations: this is particularly the case of prednisolone, the use of which is not uncommon in the management of the disease. The authors suggest that work be carried out quickly on the subject.

Concerning molecules having a favorable impact, researchers see a “ prospect of improving disease prognosis with affordable drugs » provided that the effects are confirmed. All data can be consulted online.



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