Varying outcomes of triple-negative breast cancer in different age groups–prognostic value of clinical features and proliferation

Abstract

Purpose Triple-negative breast cancer (TNBC) is an aggressive disease lacking specific biomarkers to guide treatment decisions. We evaluated the combined prognostic impact of clinical features and novel biomarkers of cell cycle-progression in age-dependent subgroups of TNBC patients. Methods One hundred forty seven TNBC patients with complete clinical data and up to 18 year follow-up were collected from Turku University Hospital, Finland. Eight biomarkers for cell division were immunohistochemically detected to evaluate their clinical applicability in relation to patient and tumor characteristics. Results Age at diagnosis was the decisive factor predicting disease-specific mortality in TNBC (p = 0.002). The established prognostic features, nodal status and Ki-67, predicted survival only when combined with age. The outcome and prognostic features differed significantly between age groups, middle-aged patients showing the most favorable outcome. Among young patients, only lack of basal differentiation predicted disease outcome, indicating 4.5-fold mortality risk (p = 0.03). Among patients aged > 57, the established prognostic features predicted disease outcome with up to 3.0-fold mortality risk for tumor size ≥ 2 cm (p = 0.001). Concerning cell proliferation, Ki-67 alone was a significant prognosticator among patients aged > 57 years (p = 0.009). Among the studied cell cycle-specific biomarkers, only geminin predicted disease outcome, indicating up to 6.2-fold increased risk of mortality for tumor size < 2 cm (p = 0.03). Conclusion Traditional clinical features do not provide optimal prognostic characterization for all TNBC patients. Young age should be considered as an additional adverse prognostic feature in therapeutic considerations. Increased proliferation, as evaluated using Ki-67 or geminin immunohistochemistry, showed potential in detecting survival differences in subgroups of TNBC.

Single‐cell combined with bulk‐RNA data reveal a pattern related to angiogenesis in breast cancer patients: Individualized medicine

“…TNBC accounts for 15%–20% of subtypes of breast cancer and shows specific biological behavior changes and clinical pathological features. It has higher risk of distant metastases and chance of visceral and brain metastases, which is not sensitive to conventional endocrine and targeted therapy, showing poorer prognostic value than other types 22–24 . Sequential chemotherapy is still the standard of care for TNBC patients, but it has a low response rate, a short PFS period, and is prone to drug resistance 25,26 .…”

“…It has higher risk of distant metastases and chance of visceral and brain metastases, which is not sensitive to conventional endocrine and targeted therapy, showing poorer prognostic value than other types. [22][23][24] Sequential chemotherapy is still the standard of care for TNBC patients, but it has a low response rate, a short PFS period, and is prone to drug resistance. 25,26 The advent of tumor immunotherapy and antibody-drug conjugate (ADC) modalities has ushered in promising prospects for TNBC's clinical management.…”

Precision unveiled: Synergistic genomic landscapes in breast cancer—Integrating single‐cell analysis and decoding drug toxicity for elite prognostication and tailored therapeutics

“…6 And these traditional prognostic predictors of tumor and lymph node status are only more applicable to older patients. 7 This underscores an imperative need for innovative markers to refine prognostic accuracy.…”

“…Concurrently, the molecular heterogeneity inherent to breast cancer challenges the precision of conventional prognostic indices, including histological and TNM gradations, in forecasting patient survival 6 . And these traditional prognostic predictors of tumor and lymph node status are only more applicable to older patients 7 . This underscores an imperative need for innovative markers to refine prognostic accuracy.…”

The chromatin architectural regulator SND1 mediates metastasis in triple-negative breast cancer by promoting CDH1 gene methylation

“…Triple-negative breast cancers (TNBC) is one of the most malignant and aggressive breast cancer [ 3 , 4 ]. TNBC is highly invasive, and approximately 46% of TNBCs undergo distant metastasis, which is also the main factor for the mortality of patients [ 5 , 6 ]. Due to the relationship between metastasis and TNBC prognosis, further investigation of the detail mechanism regulating TNBC metastasis is absolutely imperative.…”