Optimal adjuvant endocrine treatment of ER+/HER2+ breast cancer patients by age at diagnosis: A population-based cohort study

Background Prior randomised controlled trials on adjuvant hormonal therapy included HER2any patients; however, a differential effect of aromatase inhibitors (AIs) versus tamoxifen (TAM) may have been missed in ER+/HER2+ patients that comprise 7–15% of all breast cancer patients. In addition, a woman's hormonal microenvironment may influence sensitivity to TAM and AIs in the adjuvant setting, which changes during menopausal transition, a process that takes years. We studied the efficacy of AIs versus TAM in ER+/HER2+ breast cancer patients grouped by age at diagnosis as a proxy for menopausal status using treatment and outcome data from the nationwide population-based Netherlands Cancer Registry (NCR). Patients and methods All women diagnosed between 2005 and 2007 with endocrine-treated, TanyNanyM0, ER+/HER2+ breast cancer were identified through the NCR (n = 1155). Patients were divided by age at diagnosis: premenopausal (≤45 years; n = 326), perimenopausal (4555 years; n = 525). A time-dependent variable, indicating whether AI or TAM was received for >50% of endocrine treatment duration, was applied to subdivide groups by predominant treatment received. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier survival estimation and Cox regression. Hazard ratios (HRs) were adjusted for chemotherapy, trastuzumab, age at diagnosis, N-status, grade, pT-stage and ovarian ablation. Results During follow-up, 237 recurrences and 182 deaths occurred. Perimenopausal women derived significant RFS and OS benefit from AI compared with TAM, HR 0.47 (95% CI 0.25–0.91; P = 0.03) and HR 0.37 (95% CI 0.18–0.79; P = 0.01), respectively, whereas premenopausal women derived no benefit from AI compared with TAM. Treatment effects differed significantly between these age groups (interaction P = 0.03 and P = 0.02, respectively). Among postmenopausal women a small but non-significant AI benefit was observed. Conclusion AI treatment, preferably without any TAM treatment, was associated with the best RFS and OS outcome in ER+/HER2+ perimenopausal breast cancer patients

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