Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes

Abstract

Telomeres are nucleoprotein structures that protect chromosome ends from degradation and recombination. Cancers often have critically shortened telomeres, contributing to genomic instability. Many of these tumors activate telomerase to stabilize telomeric ends and achieve a capacity for unlimited replication. Telomere shortening has been reported in in situ and invasive carcinomas, including breast, and has been associated with disease recurrence after surgical resection. However, previous studies have not evaluated breast cancer subtypes. The objective of this study was to evaluate telomere lengths in different subtypes of breast cancer. Breast carcinomas (n = 103) identified between 2001 and 2010 from patients seen at the Johns Hopkins Hospital were categorized into luminal A (n = 18), luminal B (n = 28), HER-2-positive (n = 20) and triple-negative carcinomas (n = 37) based on tumor characteristics. Telomere lengths were assessed directly at the single cell level by fluorescence in situ hybridization, and patient groups were compared using Fisher’s exact tests. ER-negative status (P = 0.022), PR-negative status (P = 0.008), HER-2-positive status (P = 0.023) and p53-positive status (P = 0.022) were associated with shorter telomere length. A larger proportion of luminal A cancers had normal or long telomere lengths as compared with luminal B cases (P = 0.002), HER-2-positive cases (P = 0.011) or triple-negative cases (P = 0.0003). Luminal B, HER-2-positive and triple-negative cases did not differ significantly. Telomere length was shorter in more aggressive subtypes, such as luminal B, HER-2-positive and triple-negative tumors, suggesting that tumor telomere length may have utility as a prognostic and/or risk marker for breast cancer.

Mindfulness‐based cancer recovery and supportive‐expressive therapy maintain telomere length relative to controls in distressed breast cancer survivors

“…There have also been reports that TL varies with breast cancer subtype, such that women with more aggressive types, including luminal B, human epidermal growth factor receptor 2 (HER2)-positive, and triple-negative tumors, had shorter TL. 49 Unfortunately we did not have subtyping data available. TL also may be affected by chemotherapy among patients with breast cancer, but effects varied across participants in previous research.…”

Telomere length alterations unique to invasive lobular carcinoma

“…As previously described [18], telomere lengths were qualitatively scored by direct visual assessment of the stained slides, comparing the intensity of telomere signals from cancer cells to the intensity of telomere signals from normal or benign cells (normal myoepithelial cells and/or benign stromal cells) from the same case. In all cases, signals from normal or benign cells were considered 3+.…”

“…Telomere lengths were assessed by fluorescence staining for telomeric DNA as previously described [14,18,22], with the following modifications. Briefly, deparaffinized slides were hydrated through a graded ethanol series and placed in deionized water, followed by deionized water plus 0.1% Tween-20.…”

“…We have previously shown that short telomere lengths are associated with human epidermal growth factor receptor (Her2)-positive carcinoma and triplenegative (TNBC; ER−/PR−/Her2−) ductal carcinomas [18]. Recently, Martinez-Delgado and colleagues [19] demonstrated that short telomeres correlated with ER negativity in sporadic breast carcinomas, but not in familial breast carcinoma cases.…”

Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer

“…It is believed that the shortening of telomeres in cancer cells is also associated with characteristics and prognosis of cancer. Recently, telomere length has been reported to be associated with tumor size, lymph node metastasis, histological grade and specific breast tumor subtypes (12,13 ) and triple-negative tumors (14). Although it is not yet fully understood, these processes may also be reflected in telomere length alteration in peripheral blood leukocytes (15).…”