2015
DOI: 10.1038/bjc.2015.247
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Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer

Abstract: Background:The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.Methods:One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated fo… Show more

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Cited by 24 publications
(20 citation statements)
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References 39 publications
(48 reference statements)
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“…Reduced heterogeneity was found after 6 months of AI treatment17. In our data, after much shorter time, we found that the number of mutations and the VAFs were slightly but statistically significantly lower in the surgical samples of treated compared with control patients, possibly indicating a modest treatment effect.…”
Section: Discussionsupporting
confidence: 40%
“…Reduced heterogeneity was found after 6 months of AI treatment17. In our data, after much shorter time, we found that the number of mutations and the VAFs were slightly but statistically significantly lower in the surgical samples of treated compared with control patients, possibly indicating a modest treatment effect.…”
Section: Discussionsupporting
confidence: 40%
“…Results demonstrated no significant difference in tumor response by ultrasonography in the intent-to-treat population (OR, 1.30; 95% CI, 0.64–2.64; P = .47) but higher biological activity for the 500-mg vs the 250-mg doses, consistent with observations in the metastatic setting. Our updated search revealed 1 study 29 that compared neoadjuvant anastrozole with fulvestrant, which showed similar response rates (33 of 56 [58.9%] vs 28 of 52 [53.8%], respectively) and BCS rates (33 of 56 [58.9%] vs 26 of 52 [50.0%], respectively).…”
Section: Resultsmentioning
confidence: 99%
“…We observed FOXA1-CNG and amplification in 20% of the TCGA breast tumors, with a broader FOXA1-CNG distribution in the luminal B subtype. In a recent study reporting genomic profiling of clinical samples, about one-third (7/20) of the ER + residual disease showed CN changes after 6 mo of neoadjuvant anastrozole or Ful treatment (46). Interestingly, compared with the baseline tumors, focal amplicons involving the FOXA1 or ESR1 gene appeared in two separate cases in the anastrozole arm, supporting clonal selection by the treatment in a subgroup of patients as a mechanism to compensate or overcome the inhibition of the clinical target/pathway.…”
Section: Discussionmentioning
confidence: 99%