Primary Tumor FDG Avidity and Hormone Receptor Status Influence the Site of First Distant Metastasis in Breast Cancer Patients

Objectives The site of metastasis, which occurs through compatibilities between cancer cell and distant organ, is highly relevant to the clinical course and outcome of patients. Identification of primary tumor-specific features that affect metastatic pattern may improve our understanding of the mechanisms for cancer dissemination. We thus investigated how primary breast cancer FDG avidity and hormone receptor status influence the site of metastasis.

Methods Subjects were 264 patients with advanced breast cancer who underwent FDG PET/CT at diagnosis and had metastatic disease at presentation (n = 193) or had metastatic relapse during follow-up after curative resection (n = 71). Distant metastatic sites included lung, liver, brain, bone, lymph node (L/N) and pleura or peritoneum. Primary tumors were categorized as FDG avid if SUVmax exceeded 10.0. Tumors with estrogen and progesterone receptor expression were categorized as hormone positive.

Results In patients with metastasis at presentation, the bone was the most common site of first metastasis (63.7%) followed by lung (30.1%) and liver (25.4%). In this group, patients with FDG-avid primary tumor had significantly greater frequency of lung metastasis (37.8% vs. 22.1%; P = 0.018), while those with hormone positive primary tumor had significantly greater frequency of metastasis to the bone (68.7% vs. 53.9%; P = 0.036) and less to LNs (13.0% vs. 26.9%; P = 0.015). In patients with metastatic relapse, the bone, lung, and LN were the site of first metastasis in similar frequencies (35 to 38%). In this group, patients with FDG-avid primary tumor had significantly greater frequency of metastasis to the lung (48.4% vs. 25.0%; P = 0.041) and liver (29.0% vs. 5.0%; P = 0.008), while those with hormone positive primary tumor had significantly greater frequency of bone metastasis (55.6% vs.27.3%; P = 0.017). Furthermore, in patients with metastasis at presentation, lung metastasis was substantially increased when primary tumors were FDG avid and hormone receptor-negative (57.9%) compared to the remaining subjects (26.9%).

Conclusions Primary tumor FDG avidity, as well as hormone status, significantly influences the site of breast cancer metastasis. This may represent greater aggressiveness of breast cancer cells with heightened glycolytic activity that are more apt for survival in more harsh conditions such as the lung and liver, compared to the bone.