Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer - the SONIA study: study protocol for a randomized controlled trial

BACKGROUND: Combining cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors with endocrine therapy is an effective strategy to improve progression-free survival in hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. There is a lack of comparative data to help clinicians decide if CDK4/6 inhibitors can best be added to first- or second-line endocrine therapy. Improvement in median progression-free survival in first-line studies is larger than in second-line studies, but CDK4/6 inhibitors have not consistently shown to improve overall survival or quality of life. They do come with added toxicity and costs, and many patients have lasting disease remission on endocrine therapy alone. No subgroup has been identifie

Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer

Background: Improved breast cancer (BC) survival and evidence showing beneficial effects of internal mammary chain (IMC) irradiation underscore the importance of studying late cardiovascular effects of BC treatment. Methods: We assessed cardiovascular disease (CVD) incidence in 14,645 Dutch BC patients aged <62 years, treated during 1970–2009. Analyses included proportional hazards models and general population comparisons. Results: CVD rate-ratio for left-versus-right breast irradiation without IMC was 1.11 (95% CI 0.93–1.32). Compared to right-sided breast irradiation only, IMC irradiation (interquartile range mean heart doses 9–17 Gy) was associated with increases in CVD rate overall, ischaemic heart disease (IHD), heart failure (HF) and valvular heart disease (hazard ratios (HRs): 1.6–2.4). IHD risk remained increased until at least 20 years after treatment. Anthracycline-based chemotherapy was associated with an increased HF rate (HR = 4.18, 95% CI 3.07–5.69), emerging <5 years and remaining increased at least 10–15 years after treatment. IMC irradiation combined with anthracycline-based chemotherapy was associated with substantially increased HF rate (HR = 9.23 95% CI 6.01–14.18), compared to neither IMC irradiation nor anthracycline-based chemotherapy. Conclusions: Women treated with anthracycline-based chemotherapy and IMC irradiation (in an older era) with considerable mean heart dose exposure have substantially increased incidence of several CVDs. Screening may be appropriate for some BC patient groups

Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

Purpose: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted. Methods: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40–50%) and severe cardiotoxicity (LVEF 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity. Conclusions: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment

Long-term prognosis of young breast cancer patients (<= 40 years) who did not receive adjuvant systemic treatment

__Introduction__ Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient’s prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative. Our aim is to reduce overtreatment of women diagnosed with breast cancer aged ≤40 years. __Methods and analysis__ All young, adjuvant systemic treatment naive breast cancer patients, who had no prior malignancy and were diagnosed between 1989 and 2000, were identified using the population based Netherlands Cancer Registry (n=3525). Archival tumour tissues were retrieved through linkage with the Dutch nationwide pathology registry. Tissue slides will be digitalised and placed on an online i

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

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