Abstract: Background and purpose: Breast cancer can be divided into several molecular subtypes according to its biomarkers. The pattern of distant metastasis has a great clinic significance but was rarely investigated. This study investigated the impact of molecular subtype of breast cancer on initial sites of metastasis. . Methods: All the patients with operable invasive breast cancer diagnosed in Zhongshan People’s Hospital between 1998 and 2004 were recruited. Subtypes were defined as Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple negative (TN) according to the expression of estrogen receptor (ER), progestogen receptor (PR) and HER-2 status. The first distant metastatic sites and the time of their appearances were recorded. Survival curves were constructed using the Kaplan- Meier technique. Results: Among 390 eligible patients, there were 215(55.1%) with Luminal A, 43 (11.0%) with Luminal B, 52 (13.3%) with HER-2 enriched, and 80 (20.5%) with TN. The median follow-up time was 118 months (11-163 months). Seventy-two (18.5%) distant metastases occurred during follow-up: 37 metastases in Luminal A, 8 in Luminal B, 10 in HER-2, 17 in TN. Bone was the most common site of the first distant metastasis (39/72, 54.2%) followed by lung (25/72, 34.7%), liver (22/72, 30.6%), and brain (7/72, 9.7%). Among all the metastases, tumors of Luminal type (Luminal A 70.2%, Luminal B 50.0%) had a higher chance of bone involvement than that of HER-2 enriched (30.0%) and TN (35.3%, P=0.03). Both Luminal B (37.5%) and TN (17.6%) subtypes had a higher percentage of brain involvement than Luminal A and HER-2 enriched (P=0.01). The survival analysis showed no significant difference among the four subtypes in 9-year distant metastasis-free survival. However, distant metastasis appeared earlier in HER-2 enriched and TN breast cancer than in Luminal type. Conclusion: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Bone metastasis occurs more in luminal type than in other types. Luminal B and TN types of tumors had more chance of brain metastasis than Luminal A and HER-2 enriched type of tumors.

Key words: Breast cancer, Molecular subtype, Metastasis pattern