Survival Outcomes for Patients With Metastatic Triple-Negative Breast Cancer: Implications for Clinical Practice and Trial Design

Farrah Kassam; Katherine Enright; Rebecca Dent; George Dranitsaris; Jeff Myers; Candi Flynn; Michael Fralick; Ritu Kumar; Mark Clemons


Clin Breast Cancer. 2009;9(1):29-33. 

In This Article

Abstract and Introduction


Background: Clinical experience suggests that many women with triple-negative metastatic breast cancer (MBC) relapse quickly. This has implications for clinical practice and trial design. We evaluated the duration of first-, second-, and third-line chemotherapy as a surrogate for duration of treatment response.
Patients and Methods: We performed a retrospective multicenter chart review of patients with triple-negative MBC receiving palliative chemotherapy. Primary outcome was duration of palliative chemotherapy, and secondary outcome was to identify prognostic variables.
Results: A total of 111 patients were analyzed. Median age at diagnosis was 51 years (range, 26-82 years). Fourteen percent of patients presented with MBC. Twenty-seven percent received neoadjuvant chemotherapy, and 48% received adjuvant chemotherapy. Median distant disease-free interval (DDFI) was 18 months (range, 0-172 months). At presentation of MBC, 68% had visceral and 71% had multiple sites of disease. Median survival with MBC was 13.3 months (range, 0.8-99.8 months). Median duration of first-line palliative therapy was 11.9 weeks (range, 0-73.1 weeks). Eighty-seven patients (78%) went on to receive second-line therapy with a median duration of 9 weeks (range, 0-120.9 weeks), and 55 (49%) received third-line therapy with a median duration of 4 weeks (range, 0-59 weeks). Multivariate analysis revealed that age < 50 years, ALP > 120 U/L, history of previous chemotherapy, DDFI < 12 months, and visceral presentation were all independently associated with a poor prognosis.
Conclusion: Despite the poorer overall prognosis of patients with triple-negative disease, there remains considerable heterogeneity in individual outcomes. Many women with recurrent triple-negative disease will progress quickly on first-, second-, and third-line palliative treatment. Future clinical trials in this population must take into account their shorter time to progression when determining optimal trial design.


Breast cancer is not a homogenous disease but rather consists of many disease subgroups that vary considerably with respect to microscopic appearance, molecular profile, and clinical behavior. In recent years, a molecular classification has been proposed to categorize these subgroups based on gene expression profiling. Four common subgroups have emerged, 2 of which arise predominately from estrogen receptor-positive tumors, and 2 from estrogen receptor-negative tumors (basal-like and HER2-positive).[1,2,3] Basal breast tumors are almost entirely estrogen-, progesterone-, and HER2-negative, making the triple-negative phenotype a sensitive and practical surrogate marker for basal breast cancer.[4]

The 4 molecular subgroups of breast cancer vary importantly with respect to clinical features, natural history, and outcomes. In particular, the basal or triple-negative phenotype appears to have a more aggressive course than other breast cancers, with shorter disease-free survival and overall survival (OS) times.[5,6,7,8,9] Dent et al reported data on a cohort of 1601 patients with breast cancer monitored for a median of 8.1 years. Patients with triple-negative disease (11.2%) had an increased likelihood of distant recurrence (hazard ratio [HR], 2.6) and death (HR, 3.2) within 5 years of diagnosis. Median time to distant recurrence was significantly shorter in the triple-negative group (2.6 years vs. 5 years), as was survival time from diagnosis of distant metastatic disease (9 months vs. 22 months).[8] Basal tumors might also have a predilection for visceral, as opposed to bony, sites of relapse,[10,11] likely contributing to patients' reduced OS.[12]

Because of the relatively poorer prognosis of triple-negative breast cancer, there has been international interest in obtaining improvements in survival in these patients, similar to those efforts seen with their hormone receptor-positive and HER2-positive counterparts. Clinical trials evaluating novel treatment strategies in the metastatic setting are necessary to achieve the desired survival improvements in this poor-risk subgroup. However, clinical experience suggests that many women with triple-negative metastatic disease relapse very quickly when on chemotherapy. This has important implications for both clinical practice and clinical trial design. Because no studies to date have characterized the duration of palliative chemotherapy response in the triple-negative population, we sought to evaluate the duration of first-, second-, and third-line chemotherapy, as a surrogate for duration of treatment response,[13] in a retrospective cohort of patients with triple-negative metastatic breast cancer (MBC).

Finally, despite having an overall poorer prognosis, triple-negative breast cancer is quite heterogeneous with respect to individual patient outcomes. Thus, as a secondary outcome, we sought to identify potential prognostic variables occurring in patients with triple-negative MBC. These variables might be an important source of risk information for the practicing oncologist, potentially leading to enhanced patient care through the proactive optimization of treatment strategies in the poor-prognostic subgroups. The identification of prognostic subgroups might lead to a more accurate comparison and evaluation of investigational therapies.


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