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    • HER genotype was determined in breast cancer tissue

    2022-01-14

    HER2 genotype was determined in breast cancer tissue of 73 breast cancer patients. As previously reported, Ile655Val and Ala1170Pro genotypes measured in breast cancer tissues were available for 71 and 69 breast cancer patients, respectively. Briefly, 77.5% (55/71) of patients were homozygous for the Ile/Ile genotype, 7.0% (5/71) were heterozygous for the Ile/Val genotype, and 15.5% (11/71) were homozygous for the Val/Val genotype. Regarding the Ala1170Pro polymorphism, 52.2% (36/69) of patients were homozygous for the Ala/Ala genotype, 13.0% (9/69) were heterozygous for the Ala/Pro genotype, and 34.8% (24/69) were homozygous for the Pro/Pro genotype. Association between Ile655Val polymorphism and DFS is presented in Table 5. Compared to patients with the Ile/Ile genotype, those with the Val/Ile or Val/Val genotypes showed worse DFS after adjustment for potential confounders (HR, 4.96, 95% CI, 1.45-17.02, P = .01). Regarding the Ala1170Pro polymorphism, compared to patients with the Ala/Ala genotype, those with the Ala/Pro or the Pro/Pro genotypes showed nonsignificant better DFS even after adjustment for confounding factors (HR, 0.70, 95% CI, 0.23-2.09, P = .77).
    Discussion In a cohort of nonmetastatic HER2-positive breast cancer patients, we observed that tobacco use before breast cancer diagnosis or during trastuzumab treatment was associated with breast cancer recurrence. Moreover, our results suggest that heavy tobacco exposure, in amount and duration, before breast cancer diagnosis increases the risk of recurrence. To our knowledge, only one other study has investigated the association between tobacco consumption and trastuzumab response. In T-5224 to our results, Santini et al reported that tobacco exposure before breast cancer diagnosis was not associated with targeted treatment response among 248 metastatic trastuzumab-treated HER2-positive breast cancer patients. Furthermore, they reported that the number of cigarettes smoked before breast cancer diagnosis was not associated with patient outcome. This inconsistency in results could be explained by the differences in study population (early HER2-positive vs. metastatic HER2-positive breast cancer patients) and in the analyses performed (multivariate vs. univariate). Moreover, Santini et al did not consider the numbers of years spent smoking before breast cancer diagnosis; nor did they perform stratified analysis according to ER status. MAPK signaling is reportedly significantly hyperactivated in ER-negative tumors overexpressing HER2. In agreement with these preclinical observations, we observed that tobacco exposure before diagnosis and during trastuzumab treatment was not only associated with worse DFS but also had a stronger effect in the ER-negative subgroup. In addition, a recent study observed that the effect of tobacco consumption before breast cancer diagnosis differed according to molecular tumor subtype. Similar to our results, the authors reported that breast cancer recurrence risk was significantly higher in breast cancer patients harboring the HER2 tumor subtype (therefore HER2 positive and ER negative). In our study, alcohol consumption before breast cancer diagnosis was associated with better treatment response. However, we did not observe an association between alcohol consumption during trastuzumab treatment and breast cancer recurrence. To date, no other study has evaluated the association between alcohol intake and response to trastuzumab. Given that our results contrasted with our initial hypothesis that alcohol exposure augmented the risk of relapse in trastuzumab-treated HER2-positive breast cancer patients, we evaluated the effect of alcohol type on DFS. Although our sample size was small, our results suggest that not all types of alcohol but only wine consumption before breast cancer diagnosis may reduce the risk of recurrence. Some preclinical data suggest that resveratrol, a polyphenol contained in the skin of grapes and in red wine, may be protective against some types of cancers, including breast cancer.31, 32, 33 These results are in line with another recent preclinical study that showed that the addition of resveratrol to HER2-positive breast cancer cell lines treated with trastuzumab increased the cytotoxicity of the anti-HER2 agent compared to HER2-positive breast cancer cell lines treated with trastuzumab alone.