No Excess Mortality up to 10 Years in Early Stages of Breast Cancer in Women Adherent to Oral Endocrine Therapy: A Probabilistic Graphical Modeling Approach

Abstract

Breast cancer (BC) is globally the most frequent cancer in women. Adherence to endocrine therapy (ET) in hormone-receptor-positive BC patients is active and voluntary for the first five years after diagnosis. This study examines the impact of adherence to ET on 10-year excess mortality (EM) in patients diagnosed with Stages I to III BC (N = 2297). Since sample size is an issue for estimating age- and stage-specific survival indicators, we developed a method, ComSynSurData, for generating a large synthetic dataset (SynD) through probabilistic graphical modeling of the original cohort. We derived population-based survival indicators using a Bayesian relative survival model fitted to the SynD. Our modeling showed that hormone-receptor-positive BC patients diagnosed beyond 49 years of age at Stage I or beyond 59 years at Stage II do not have 10-year EM if they follow the prescribed ET regimen. This result calls for developing interventions to promote adherence to ET in patients with hormone receptor-positive BC and in turn improving cancer survival. The presented methodology here demonstrates the potential use of probabilistic graphical modeling for generating reliable synthetic datasets for validating population-based survival indicators when sample size is an issue.

Ten-Year Probabilities of Death Due to Cancer and Cardiovascular Disease among Breast Cancer Patients Diagnosed in North-Eastern Spain

“…The cohort did not show a significantly higher risk of death from colon cancer, the second cause of cancer death, compared to the general population, but the increasing risks of developing this cancer in Spanish women aged 65 and older [52] (second tumour in the ranking of cancer incidence in Catalonia in women aged 74 and older), together with the good survival prospects of BC [15], are factors suggestive of an elevated future risk of colorectal incidence in our cohort. In contrast, the downward trend for risk of death due to leukaemia and haematological malignancies detected in our previous study [12] is consistent with our current results, since these tumours showed a non-significant risk relative to the general population.…”

“…Treatment for HER2+ BCs includes chemotherapy plus HER2-targeted antibodies or small-molecule inhibitor therapy, whereas triple-negative tumours receive chemotherapy alone [6,7]. In this line, in a previous study, we found no excess mortality in HR+ patients diagnosed beyond 49 years of age at Stage I or beyond 59 years at Stage II if they followed the prescribed endocrine treatment regimen [15]. As survival of BC improves, there is an increased interest in the long-term outcomes in these patients, including their cause-specific probabilities of death [15,16].…”

“…Stage data, however, usually cannot be used when comparing BC mortality between populations since not all population-based cancer registries collect it [3]. In the literature, BC is commonly divided into luminal A, luminal B, HER2 (human epidermal growth factor receptor 2)-enriched, and triple negative tumours [6,7,14,15]. Given that few population-based cancer registries worldwide routinely collect data on Ki-67, epidermal growth factor receptor, and cytokeratin testing [6,7,12,14,15], the BC subtypes are generally categorized as hormone receptor positive (HR+), based on expression of oestrogen and/or progesterone receptor; HER2-positive (HER2+), regardless of hormone receptor status; and triple-negative, lacking expression of HER2 and oestrogen or progesterone receptors [6,7].…”

“…In the literature, BC is commonly divided into luminal A, luminal B, HER2 (human epidermal growth factor receptor 2)-enriched, and triple negative tumours [6,7,14,15]. Given that few population-based cancer registries worldwide routinely collect data on Ki-67, epidermal growth factor receptor, and cytokeratin testing [6,7,12,14,15], the BC subtypes are generally categorized as hormone receptor positive (HR+), based on expression of oestrogen and/or progesterone receptor; HER2-positive (HER2+), regardless of hormone receptor status; and triple-negative, lacking expression of HER2 and oestrogen or progesterone receptors [6,7]. Those BC subtypes each have distinct biological and clinical characteristics, including differences in risk factors, disease management, recurrence rates, and survival outcomes [6,7].…”

“…During the first 10 years of follow-up, BC remains the most common cause of death following a diagnosis of this cancer, followed by heart and cerebrovascular diseases [9][10][11][12][13][14][15][16]. Studies about mortality in BC cohorts with follow-up longer than 10 years have shown that the largest proportion of deaths may occur within 1 to 10 years after diagnosis, and the number of deaths decrease as more years pass after cancer diagnosis [9][10][11][12][13].…”