Predominance of Brain and Lung Metastases in Triple-Negative Breast Cancer Patients.

Abstract Background: Patients with triple-negative breast cancer have an increased likelihood of recurrence compared to other types of breast cancer, however, little is known about their pattern of metastatic spread. Our object was to evaluate the metastatic patterns of women diagnosed with triple-negative breast cancer compared to other subtypes. Methods: We studied a cohort of 572 white patients diagnosed with invasive breast cancer at West Virginia University Hospital between 1999 and 2004. Hospital registry, charts, and pathology records provided clinical data including tumor receptor status and biopsy-proven metastatic spread to bone, brain, liver and lung. Breast cancers that were negative for estrogen, progesterone, and HER2neu, otherwise known as triple-negative were compared with HER2neu-postive and HER2neu-negative (endocrine receptor positive) disease. Body mass index was calculated and a value of ≥30 considered indicative of obesity. Specimens of primary carcinoma were available for analysis of Ki67 mitotic index and expression of p53. Results: 134/572 (23.4%) had triple-negative breast cancer, while the frequencies were 108/572 (18.9%) and 330/572 (57.7%) in HER2neu-positive and HER2neu-negative (endocrine receptor positive) groups. Women with triple-negative disease were more likely to have brain-metastasizing breast cancer; 10.5% versus 4.6% for HER2neu-positive and 3.3% for HER2neu-negative (P<0.05). They were also more likely to have metastasis to the lung; 10.5% versus 2.8% for HER2neu-positive and 7.0% for HER2neu-negative (P<0.05). Triple-negative breast cancer patients who developed brain and lung metastases were younger <50 years and significantly more obese (P=0.0236). High Ki67 labeling index and p53 expression were associated with more advanced disease indicating an aggressive phenotype for this group.Patterns of metastasis in breast cancer subtypesSite of metastasisTriple-negativeHER2-positiveHER2-negativeP valueBone20/134 (14.9)7/108 (6.5)38/330 (11.5)0.1037Brain14/134 (10.5)5/108 (4.6)11/330 (3.3)0.0136*Liver11/134 (8.2)4/108 (3.7)22/330 (6.7)0.3261Lung14/134 (10.5)3/108 (2.8)23/330 (6.9)0.0507*Other5/134 (3.7)3/108 (2.8)3/330 (0.91)0.1093 Conclusion: The excess risk of brain and lung metastasis in women with triple-negative breast cancers versus other subtypes needs further validation. The unique biology of triple-negative tumors may explain this pattern of metastatic spread. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6159.