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.