The relationship between tumour size, nodal status and distant metastases: on the origins of breast cancer

Abstract

Background: In patients with breast cancer, increasing tumour size at diagnosis is associated with an increased likelihood of axillary lymph node involvement and increased breast cancer-specific mortality. However, this relation is based on studies which combine all tumours smaller than 1.0 cm in a single category and all tumours larger than 5.0 cm in another category. This coarse classification may obscure a nuanced description of the effects of tumour size across the full range of possible sizes.

Methods: We examined the relationship between primary tumour size, lymph node status and distant metastases in a cohort of 819,647 women diagnosed with first primary invasive breast cancer from 1990 to 2014 in the Surveillance, Epidemiology and End Results (SEER) registries database. All patients in the cohort had a known primary tumour size between 1 and 150 mm in greatest dimension. Primary tumour size was examined as a continuous (1-150 mm) and categorical variable (15 size groups; 10-mm intervals). For each 1- or 10-mm size group, we determined the proportion of patients with positive lymph nodes at diagnosis, the proportion of patients with distant metastases at diagnosis and the actuarial cumulative risk of breast cancer-specific mortality at 15 years from diagnosis.

Results: Among 819,647 patients with invasive breast tumours between 1 and 150 mm in size, there was a non-linear correlation between increasing tumour size and the prevalence of lymph node metastases at diagnosis (% node-positive), the prevalence of distant metastases at diagnosis (% stage IV) and the 15-year rate of breast cancer-specific mortality across the entire size spectrum. For very small tumours (under 10 mm) and for very large tumours (larger than 60-90 mm) there was little correlation between tumour size and metastasis risk.

Conclusions: The relationship between tumour size, lymph node status and distant metastases in patients with invasive breast cancer is not linear. This calls into question the conventional model that the capacity for a primary breast tumour to metastasize increases as the tumour enlarges.

Keywords: Breast cancer; Distant metastases; Lymph node metastases; Mortality; Tumour size.

Fig. 1

a Prevalence of lymph node metastases at diagnosis among all breast cancer patients in the cohort stratified according to the size of the primary tumour, by 10-mm intervals (N = 792,123). b Prevalence of lymph node metastases at diagnosis among all patients with invasive breast cancer between 1 and 10 mm in size, stratified according to tumour size by 1-mm intervals (N = 199,455). c Prevalence of lymph node metastases at diagnosis among patients with invasive breast cancer 11–50 mm in size, stratified according to tumour size by 5-mm intervals (N = 538,641). d Prevalence of lymph node metastases at diagnosis among all patients with invasive breast cancer 51–150 mm in size, stratified according to tumour size by 10-mm intervals (N = 54,027)

Fig. 2

Increase in the prevalence of metastases to the lymph nodes per 20-mm increase in primary tumour size, according to categorical tumour size (size groups in Fig. 1a), all patients (N = 792,123)

Fig. 3

Relationship between lymph node-positivity and primary tumour volume among all breast cancer patients in the cohort, stratified according to tumour diameter by 1-mm intervals (N = 792,123)

Fig. 4

Relationship between lymph node-positivity and primary tumour volume (logarithmic scale) among all patients with invasive breast cancer up to 20 mm in diameter (1-mm intervals) (N = 488,086)

Fig. 5

Actuarial 15-year rates of breast cancer-specific mortality among all breast cancer patients in the cohort stratified according to the size of the primary tumour by 10-mm intervals (N = 768,947)