Compliance to adjuvant endocrine therapy and survival in breast cancer patients.

BACKGROUND: Data on compliance to adjuvant endocrine treatment (ET) is mainly reported from prospective clinical trials or from smaller retrospective cohorts without correlation to outcome. AIMS: To determine compliance to adjuvant ET and the impact on survival in a population-based series of patients with early breast cancer (BC) advised ET. PATIENTS AND METHODS: 1090 consecutive patients with hormone receptor positive (HR+) stage I-III BC diagnosed from 1 January 1997 to 31 December 2003 from one health care region of Sweden were included. Data on tumour, type of ET, compliance, reason for termination and outcome were collected. Statistical analyses were calculated with patients in three groups. RESULTS: 72 patients were excluded leaving 1018 patients with a HR+ stage I to III BC for analyses. The most common ET was tamoxifen (n = 751, 73.8%). At the last follow up (31 Dec 2019) with a median follow-up of 18 years (interquartile range 16-22) 228 (22.4%) patients had a relapse. 71.1% of the included patients were compliant to endocrine therapy. Older patients ≥74 years had lower compliance, 61% compared with 75% in the other age groups (≤50 years and 51-73 years) (p < 0001), other parameters including type of ET were not associated with compliance. Low compliance remained as an independent risk factor in multivariate analyses for lower relapse-free survival, HR=1.83, 95% Confidence Interval (CI) 1.52-2.19, p < 0.001 and for time to BC death, HR=2.69, 95%CI 1.82-3.98, p < 0.001. CONCLUSIONS: Patients compliant to adjuvant ET have an improved survival.

Discordance of PIK3CA and TP53 mutations between breast cancer brain metastases and matched primary tumors.

There is limited knowledge of the biology of breast cancer (BC) brain metastasis (BM). We primarily aimed to determine the mutations in BCBM and to compare the mutational pattern with the matched primary breast cancer (BC). Secondary aims were to determine mutations in each subgroup (Luminal A-/B-like, HER2+ and TNBC) of BCBM, and to determine survival according to specific mutations. We investigated 57 BCBMs, including 46 cases with matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. Subtype according to immunohistochemistry was re-evaluated. NGS results fulfilling sequencing quality criteria were obtained from 52 BM and 41 PT, out of which 37 were matched pairs. Pathogenic mutations were detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. We show a discordance of PIK3CA and TP53 mutations of roughly 25% indicating the need to develop methods to assess mutational status in brain metastasis where analysis of cell-free DNA from cerebrospinal fluid (CSF) has shown promising results.

Clinical outcome of patients with brain metastases from breast cancer - A population based study over 21 years.

BACKGROUND: Brain metastases (BM) are a feared progression of breast cancer (BC) with impact on quality of life and survival. Despite improved treatments, it is believed patients suffering from BM are increasing. AIMS: To study potential changes in the number of BM, the possible links between BC subgroup and extent of BM with prognosis. To investigate the interval between primary BC/extra cranial recurrence, and diagnosis of BM in the years 1994-2014. PATIENTS AND METHODS: Clinical data from 191 patients with BM diagnosed 1994-2014, was retrieved from charts. Primary tumours where re-evaluated histologically. RESULTS: There was an increase of BM in 5 years cohorts (1994-99 (n = 9); 2000-04 (n = 36); 2005-09 (n = 60); 2010-14 (n = 86)). We found no difference in the time interval from primary BC to BM but an insignificant increase in time from extra cranial relapse to development of BM in the time periods 1994-2004 and 2005-2014 of 15.5 and 25.0 months (p = 0.0612). Survival after BM was 7 months (95% CI 6-10) with a statistically significant difference between HER2 positive and TNBC with an inferior outcome for the latter (p = 0.018) whilst no differences were present when Luminal BC were compared with HER2 positive BC (p = 0.073). CONCLUSIONS: We show an increase of BM over time whilst the time span from primary BC to BM is unchanged supports earlier findings that adjuvant treatments have little preventive function. Time from extra cranial recurrence to BM was prolonged with one year. Patients with TNBC or more advance extent of BM had the shortest survival with BM.