A population-based study on trajectories of HER2 status during neoadjuvant chemotherapy for early breast cancer and metastatic progression.

BACKGROUND: This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications. METHODS: This is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007-2020 in the Stockholm-Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification. RESULTS: In total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status. CONCLUSION: HER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.

Women with short survival after diagnosis of metastatic breast cancer: a population-based registry study.

PURPOSE: Despite therapeutic advances, overall survival of metastatic breast cancer (MBC) at the population level has seen little improvement over the past decades. Aggressive tumor biology or delay in access to cancer care might be contributing factors. With this retrospective population-based study we aimed to quantify and characterize patients with very short survival time following MBC diagnosis. METHODS: Women diagnosed with MBC between Jan 1st, 2005 and Dec 31st, 2016 were identified using the population-based Stockholm-Gotland breast cancer registry. Data regarding demographic and clinicopathological characteristics, survival, and treatment were extracted retrospectively from the registry and from patient charts. Patients who died within 90 days following diagnosis of MBC were identified and their characteristics were compared with all other patients diagnosed with MBC during the same period. RESULTS: Between 2005 and 2016, 3124 patients were diagnosed with MBC, of whom 498 (16.2%) died within 90 days of diagnosis. Nearly half (N = 233) did not receive any antitumoral treatment. Patients with short survival were older (p < 0.001), had higher primary tumor grade (p < 0.001), higher clinical stage at primary diagnosis (p = 0.002), and more often estrogen receptor (ER)-negative breast cancer (p < 0.001). Visceral metastases were more frequent (p < 0.001) and patients with short survival received adjuvant chemotherapy (p < 0.001) to a lesser extent compared to patients with a better prognosis. In multivariable analysis older age, time period of diagnosis, metastasis site, adjuvant chemotherapy, and primary tumor grade were independent predictors for short survival, whereas ER status was not. CONCLUSION: Nearly one out of six patients with MBC survive less than 3 months after diagnosis. Our findings demonstrate a different spectrum of MBC at population level and can potentially inform on individualized follow-up strategies and treatment algorithms.

Discordance of PD-L1 status between primary and metastatic breast cancer: A systematic review and meta-analysis.

INTRODUCTION: Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility. METHODS: Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance. RESULTS: Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001). CONCLUSION: The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.