BackgroundDetection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse.MethodsThis monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment. Circulating ESR1 mutations (D538G, Y537S/N/C) were assessed by droplet digital PCR in plasma samples taken at the end of adjuvant treatment, at time of relapse and at time of progression under first line metastatic treatment.ResultsA total of 42 patients were included, with a median adjuvant AI exposure of 60 months (range 41–85). No circulating ESR1 mutation was detectable at the end of AI adjuvant therapy. At first relapse, 5.3% of the patients (2/38) had a detectable circulating ESR1 mutation. At time of progression on first-line metastatic treatment, 33% of the patients (7/21) under AI had a detectable circulating ESR1 mutation compared to none of the patients under chemotherapy (0/10). The two patients with a detectable ESR1 mutation at relapse were treated by AI and had an increase of their variant allele fraction at time of progression on first-line metastatic treatment.ConclusionsCirculating ESR1 mutation detection at the end of AI-based adjuvant treatment is not clinically useful. Circulating ESR1 mutation could be assessed as soon as first relapse to guide interventional studies.
Inflammatory breast cancer (IBC) is an aggressive BC subtype with poor outcomes. A targetable somatic PIK3CA mutation is reported in 30% of IBC, allowing for treatment by PI3Kα-specific inhibitors, such as alpelisib. The aim of this study was to evaluate the detection rate of circulating PIK3CA mutation in locally-advanced IBC (LAIBC) patients harbouring a PIK3CA mutation on initial biopsy. This monocentric retrospective study was based on available stored plasma samples and tumour biopsies at diagnosis from all LAIBC patients treated with neo-adjuvant chemotherapy (NCT) between 2008 and 2018 at the Centre Henri Becquerel. PIK3CA mutations (E542K, E545K, H1047R/L) were assessed by droplet digital PCR (ddPCR) in plasma samples and tumoral tissue at diagnosis. A total of 55 patients were included. Overall, 14/55 patients (25%) had a PIK3CA mutation identified on baseline biopsy (H1047R = 8; H1047L = 3; E545K = 2; E542K = 1). Among them, 11 (79%) patients had enough DNA for circulating DNA analyses, and corresponding circulating PIK3CA mutations were found in 6/11 (55%). Among the 41 patients without PIK3CA mutations on biopsy, 32 (78%) had enough DNA for circulating DNA analysis, and no circulating PIK3CA mutation was identified. Our results revealed no prognostic or predictive value of PIK3CA mutations at the diagnosis of non-metastatic IBC but highlighted the prognostic value of the cfDNA rate at diagnosis. Our study showed that a corresponding circulating PIK3CA mutation was identified in 55% of LAIBC patients with PIK3CA-mutated tumours, while no circulating mutation was found among patients with PI3KCA wild-type tumours.
We retrospectively analysed data from patients with recurrent breast cancer (BC) treated at two Bulgarian centres -National Hospital of Oncology and Lozenets University Hospital. Data from primary BCs and recurrences were compared. The level of adherence to MS was assessed by a selection of the quality indicators (QIs) that are adopted by European Society of Breast Cancer Specialists (EUSOMA).Results: We included 263 patients treated for local recurrence of BC between January 2012 and March 2020. Median age at the time of first diagnosis was 45,2 years old. The time interval between the primary tumour (PT) and recurrence was between 1 month to 36 years. Most PTs were in T1 stage -68.8% (T1a -1,5%, T1b e 49%, T1c e 18,3%), and only 0.8% of them were T3. The lymph nodes status was N0 in 52% of patients. Regional lymph nodes could not be assessed (Nx) in 11,4% of patients, leading to decrease levels of adherence to MS. 67,3% of relapsing patients had high oestrogen receptor (ER+) titres (!50%). We reported HER2 À in 79,8% of patients with PT and in 85,2% of relapsing patients. ER+/PR+ and HER2À patients have higher risk of recurrence after 5 years, especially in patients with high ER titre. We assessed the level of adherence to MS using main QIs: 4a, 10a, 10b, 10c, 11a, 11c, 12, 13a and 13b. The results showed significant differences in the level of adherence to MS according to the patients' age, biological characteristics and clinical treatment.Conclusions: Despite many efforts that are being made to improve the quality of BC care, it would be greatly improved if we could reduce recurrences. Knowledge of the characteristics, prognostic factors and the monitoring of level of adherence to MS for BC recurrence can aid in the development of treatment strategies and follow-up in these patients at risk of recurrence.
Si la présence de cellules tumorales circulantes (CTC) et d’ADN tumoral circulant (ADNtc) est connue de longue date, seuls les progrès technologiques récents ont permis d’évaluer l’intérêt de cette approche dans le cancer du sein. La détection de CTC, tant pour les cancers du sein localisés que métastatiques, est un facteur de mauvais pronostic établi, mais qui ne permet pas de proposer de prise en charge spécifique. L’usage de l’ADNtc nécessite des validations prospectives, mais semble particulièrement prometteur pour la recherche demaladie résiduelle ou l’identification de clones tumoraux porteurs de mutations (PI3KCA, ESR1) permettant de prédire l’efficacité ou la résistance thérapeutique.
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