Introduction:

The most common metastatic sites in breast cancer (BC) are bone, lung and liver, but metastases to CNS, other visceral organs, skin and lymph nodes are often seen. Depending on the BC subtypes there are data on different patterns of the metastatic sites. However, little is known about the risk for development of new metastatic sites during the course of the disease. Possibly, the development of new sites of the disease is signs of novel intrinsic capabilities of the metastases that might be explained by new mutations. Primary aim of this study was to examine the metastatic pattern and development of new metastatic sites in different BC subgroups.

Materials and Methods:

This is a population based cohort study covering patients in the Uppsala County treated for metastatic BC (MBC) from 2009 to 2014. The information was collected from the real-time treatment registry and medical records. The distant sites were classified as bone, lung/pleura, soft tissue, other visceral and CNS and the timing was defined in steps starting with M1 when patient first was defined as having MBC. The BC subtypes were defined as luminal A, luminal B, HER2-positive (HER2) and triple negative (TN) based on immunohistochemical analyses. The metastatic patterns at death were compared with the patterns at M1.

Results:

Totally 391 patients with MBC with a median age of 65 years were included. Median disease-free survival was 51 months. The development of metastases in new sites occurred in up to three distinguished steps, with median lag times of 22, 13 and 14 months, respectively. The median survival from M1 was 69, 37, 64 and 17 months for the luminal A, luminal B, HER2 and TN subtypes.

The frequencies of metastases in in first (M1) and subsequent sites (next) in each subtype

M1%/next% Bone Lung/pleura Soft tissue Liver Other visceral CNS 
Luminal A 74/4 31/21 22/10 20/28 16/15 1/4 
Luminal B 66/11 44/14 38/3 27/32 16/5 4/10 
HER2 46/15 36/20 42/17 19/28 10/13 19/31 
TN 27/7 46/17 51/6 29/0 17/11 17/17 
M1%/next% Bone Lung/pleura Soft tissue Liver Other visceral CNS 
Luminal A 74/4 31/21 22/10 20/28 16/15 1/4 
Luminal B 66/11 44/14 38/3 27/32 16/5 4/10 
HER2 46/15 36/20 42/17 19/28 10/13 19/31 
TN 27/7 46/17 51/6 29/0 17/11 17/17 

The sums of the figures represent the risk for metastases in a certain site at death.

Conclusion:

The pattern of metastatic sites at M1 in different BC subtypes does not represent the pattern for development of new metastatic sites during the course of the disease. We observed a significantly different risk for developing new metastatic sites depending on subtypes, most obvious regarding liver metastases. TNBC seemed to have less ability to develop new metastatic sites.

Citation Format: Lindman H, Haji A. The development of the metastatic site pattern during time in different subtypes of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-04.