Abstract
Metastatic breast cancer (MBC) patients with bone only metastasis (BOM) are a unique population with limited characterization. We identified patients followed at MD Anderson Cancer Center from 01/01/1997 to 12/31/2015 for at least 6 months with a BOM diagnosis as first site of metastasis. Tumor subtype (TS) was assessed by initial breast biopsy immunohistochemistry using hormonal receptor (HR) and HER2 status, with four subtypes identified: HR+/HER2−, HR+/HER2+, HR−/HER2−, HR−/HER2+. HR+ was defined as estrogen receptor or progesterone receptor ≥1%. We identified 1445 patients with BOM, 1048 with TS data available. Among these patients, the majority were HR+/HER2− (78%). Median time from breast cancer diagnosis to first bone metastasis was 2.3 years (95% CI 2.1, 2.5) and varied significantly by TS, with longer time to distant disease in HR+/HER2− patients relative to all other TS (p < .0001). Median overall survival (OS) from breast cancer diagnosis was 8.7 years (95% CI 8.0, 9.7) and varied significantly by TS with poorer OS for HR−/HER2− and HR-/HER2+ patients relative to HR+/HER2− TS (p < .0001). The 442 patients with de novo BOM disease, defined as bone metastasis diagnosis within 4 months of breast cancer diagnosis, had significantly shorter OS (p < .0001). Overall, several higher risk BOM subsets were identified in this analysis, most notably HR−/HER2+ and HR−/HER2− TS and de novo BOM patients.
Highlights
Development of metastases in breast cancer patients constitutes the single largest risk factor for increased morbidity and mortality, with approximately 90% of deaths during treatment attributed to metastasis.[1,2] Despite advances in breast cancer treatment, 13–30% of early breast cancer patients will develop distant metastases.[1,3] Bone is the most frequent site of breast cancer metastasis, with bone metastases noted in 60–80% of metastatic breast cancer (MBC) patients, and is the first site of metastatic disease in 25–40% of MBC patients.[4,5]Patients with bone only metastasis (BOM) are a unique MBC subpopulation, representing up to 51% of patients with bone relapse.[2]
Unique clinical characteristics were seen in this BOM patient group, with the majority of patients at time of BOM diagnosis having multiple bone metastasis, most often lytic in nature and located in both the axial and appendicular skeleton, typically associated with pain
With respect to Tumor subtype (TS) classification, distinct clinical characteristics associated with TS grouping included a higher percentage of hormonal receptor (HR) +/HER2− TS seen in non-Hispanic, white patients and significantly younger patients with HR+/HER2+ TS tumors as compared with HR+/HER2− and HR−/HER2− TS tumors
Summary
Patients with bone only metastasis (BOM) are a unique MBC subpopulation, representing up to 51% of patients with bone relapse.[2] Despite representing a significant number of MBC patients, these patients have routinely been excluded from clinical trials given bone only metastases have been defined as nonmeasurable per Response Evaluation Criteria in Solid Tumors (RESIST) criteria. The updated RECIST 1.1 criteria include bone metastases with soft tissue masses greater than 10 mm as measurable disease, this still excludes most patients with BOM. Despite representing a significant number of MBC patients, BOM patients are still inadequately characterized, limiting therapeutic strategies including clinical trial involvement. There has been limited evaluation of BOM patients with regards to breast cancer subtype, which is known to have prognostic significance and association with development of BOM.[6,7] To further characterize this distinct
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