Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship.
BACKGROUND
Predictors for site of distant metastasis and impact on survival in breast cancer are incompletely understood.


METHODS
Clinico-pathological risk factors for site of distant metastasis and survival were analysed in patients with invasive breast cancer treated between 1986 and 2006.


RESULTS
Of 3553 patients, with median follow-up 6.32years, 825 (23%) developed distant metastasis. The site of metastasis was bone in 196/825 (24%), viscera in 540/825 (65%) and unknown in 89 (11%). Larger primary invasive tumour size, higher tumour grade and axillary nodal positivity increased risk of metastasis to all sites. Lobular carcinoma was more likely to first metastasise to bone compared to invasive ductal carcinoma (NST). Oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and/or Human epidermal growth factor (HER2) positive tumours were more likely to metastasise to viscera. A striking relationship between increasing age at diagnosis and a reduction in risk of distant metastasis to bone and viscera was observed. Median time to death from onset of metastatic disease was 1.52 (Interquartile range (IQR) 0.7-2.9)years for patients with bone metastasis and 0.7 (IQR 0.2-1.5)years for visceral metastasis. On multivariate analysis, despite the decrease in risk of distant metastasis with increasing age, there was an elevated hazard for death in patients >50years at diagnosis of metastasis if they developed bone metastasis, with a similar trend observed in the >70years age group if they developed visceral metastasis.


CONCLUSIONS
These findings indicate that there are biological mechanisms underlying the impact of age on the development of distant metastasis and subsequent death. This may have important implications in the treatment of breast cancer.
Division of Cancer Studies, King's College London, UK; Guy's & St Thomas NHS Foundation Trust, London, UK. Electronic address: claire.arnold@kcl.ac.uk.
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Purushotham
Division of Cancer Studies, King's College London, UK.
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E
Shamil
Division of Cancer Studies, King's College London, UK; Guy's & St Thomas NHS Foundation Trust, London, UK.
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M
Cariati
Division of Cancer Studies, King's College London, UK.
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Agbaje
Division of Cancer Studies, King's College London, UK.
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A
Muhidin
Division of Cancer Studies, King's College London, UK.
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Gillett
Division of Cancer Studies, King's College London, UK.
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Mera
Division of Cancer Studies, King's College London, UK.
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Sivanadiyan
Division of Cancer Studies, King's College London, UK; Guy's & St Thomas NHS Foundation Trust, London, UK.
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Harries
Division of Cancer Studies, King's College London, UK.
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Sullivan
Division of Cancer Studies, King's College London, UK; Guy's & St Thomas NHS Foundation Trust, London, UK.
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Pinder
Division of Cancer Studies, King's College London, UK.
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Garmo
Division of Cancer Studies, King's College London, UK.
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Holmberg
D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000737:chemistry / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D001943:Breast Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human; D066246:ErbB Receptors
Age; Breast cancer; Distant metastasis; Relationship