A comparison between young and old patients with triple-negative breast cancer: biology, survival and metastatic patterns

Tzikas, Anna-Karin; Nemes, Szilárd; Linderholm, Barbro

doi:10.1007/s10549-020-05727-x

Cited by 58 publications

(74 citation statements)

References 29 publications

(40 reference statements)

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“…Moreover, we also found that breast cancers of post-menopausal patients tended to have high densities of nerves, suggestive of poorer prognosis of these patients. Indeed, older breast cancer patients commonly have worse survival than those diagnosed at younger ages [50,51]. Nevertheless, we did not identify differences in breast cancer innervation among different age groups.…”

Section: Discussioncontrasting

confidence: 56%

High nerve density in breast cancer is associated with poor patient outcome

et al. 2021

Preprint

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Background: Active crosstalk between the nervous system and breast cancer cells as well as other cell types within the tumour microenvironment has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to better define the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features.Methods: Immunohistochemical staining was conducted in formalin-fixed paraffin-embedded breast cancer tissue sections using antibodies against the pan-neuronal markers protein gene product 9.5 (PGP9.5) and growth-associated protein 43 (GAP-43), and the sympathetic nerve-specific marker tyrosine hydroxylase (TH). Nerve trunks (comprised of many nerve fibres/axons) and isolated nerve fibres (positively stained cells with or without typical morphology of axons outside definable nerve trunks) were quantitated. The chi-squared test was used to determine the associations between nerve trunk or isolated nerve fibre counts and clinicopathological parameters. The Log-rank test was used to compare differences in patient progression-free survival (PFS) and overall survival (OS). A multivariate analysis was performed according to the Cox Proportional Hazards Model to assess independent prognostic factors.Results: Nerve trunks and isolated nerve fibres were detected in 75% and 77% of breast cancers, respectively. The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin (positive for TH). While high density of nerve trunks or isolated nerve fibres was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Conclusions: Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.

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Section: Discussioncontrasting

confidence: 56%

High nerve density in breast cancer is associated with poor patient outcome

et al. 2021

Preprint

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“…Indeed, older breast cancer patients commonly have worse survival than those diagnosed at younger ages. 46,47 Nevertheless, we did not identify differences in breast cancer innervation among different age groups. What causes these paradoxes is unknown, but our results suggest that the innervation status be considered in stratifying patients in future studies.…”

Section: High Nerve Trunk Density In Breast Cancer May Predict Poorer...contrasting

confidence: 55%

High nerve density in breast cancer is associated with poor patient outcome

Liu

Zheng

et al. 2022

FASEB BioAdvances

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Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to clarify the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features. Immunohistochemical staining was conducted in formalin‐fixed paraffin‐embedded breast cancer tissue sections using antibodies against the pan‐neuronal markers protein gene product 9.5 and growth‐associated protein 43, and the sympathetic nerve‐specific marker tyrosine hydroxylase. Nerve trunks and isolated nerve fibers were quantitated. The chi‐squared test was used to determine the associations between nerve counts and clinicopathological parameters. The log‐rank test was used to compare differences in patient progression‐free survival (PFS) and overall survival (OS). The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin. While high density of nerve trunks or isolated nerve fibers was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.

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“…This may reflect the poor prognosis for young adults with cancers, such as breast cancer [23] and colorectal cancer [24]. Breast cancers in young adults have a higher incidence of the more aggressive triple-negative form and are less hormonesensitive than those in older adults [25]. As to colorectal cancers, they have a more mucinous histology and greater frequency of signet ring cells in young adults than in older adults, resulting in a markedly poor prognosis [26].…”

Section: Discussionmentioning

confidence: 99%

Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retrospective study

et al. 2021

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Background The situation of patients developing multiple primary cancers is becoming more frequent and graver. This study investigated the risks of developing second primary cancers that are related to first primary cancers, and the interval times of synchronous and metachronous multiple primary cancers. Patients and methods Retrospective data were retrieved from 109,054 patients aged ≥18 who were diagnosed with a first solid cancer and registered at Siriraj Cancer Center between 1991 and 2015. A two-month period between first- and second- primary cancers was used to differentiate metachronous and synchronous multiple primary cancers. The combinations of subsequent cancers and relative risks (RRs) of having multiple primary cancers versus having single primary cancer for the top-ten first and second primary cancers were examined. The RR was adjusted for age of the first primary cancer. A survival analysis of the time to second-primary-cancer development was performed. Results Multiple primary cancers were found in 1785 (1.63%) patients. Most (70.87%) second primary cancers occurred after 2 months of first breast, skin, colorectal, lung, head and neck, liver, male genital cancer–prostate, thyroid, and female genital cancer–non-uterine cancers, resulting in those cancers being classified as metachronous multiple primary cancer. After adjustment for age at first diagnosis, head and neck cancers had the highest metachronous association with second esophageal cancers (RR, 25.06; 95% CI, 13.41–50.77). Prostate cancer and second colorectal cancer also demonstrated a high metachronous association (RR, 2.00; 95% CI, 1.25–3.05). A strong synchronous association was found between uterine and ovarian cancers (RR, 27.77; 95% CI, 17.97–43.63). The median time from the first uterine cancer to second-cancer development was 55 days. Conclusions The top-ten most frequent multiple primary cancers were the following: breast; liver; head and neck; colorectal; male genital cancer–prostate; skin; female genital cancer–uterine; thyroid; lung; and female genital cancer–non-uterine. Second primary cancers showed specific associations that depended on the first primary cancer. Physicians should be cognizant of the most common combinations and the interval times of metachronous and synchronous multiple primary cancers.

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A comparison between young and old patients with triple-negative breast cancer: biology, survival and metastatic patterns

Cited by 58 publications

References 29 publications

High nerve density in breast cancer is associated with poor patient outcome

High nerve density in breast cancer is associated with poor patient outcome

High nerve density in breast cancer is associated with poor patient outcome

Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retrospective study

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