Background

Patients with triple-negative breast cancers (TNBC) are at an increased risk of distant metastasis compared to patients with other subtypes of breast cancer. While TNBCs are aggressive as a group, many are potentially curable, reflecting an underlying heterogeneity. As such, there is an interest in identifying factors that may allow further stratification of patients in relation to the risk of distant metastasis and, ultimately, better tailor treatment plans to individual patients. With the increasing use of neoadjuvant chemotherapy (NAC), past studies have shown that patients who achieve a pathological complete response (pCR) following NAC have a decreased risk of distant metastasis. However, beyond the presence or absence of pCR, other risk factors for distant metastasis have not been well characterized.

Methods

This is a single institution, retrospective study of women with TNBC treated with NAC, surgery, and radiation therapy (RT) between 2000 and 2013. The rate of distant metastasis was estimated and compared between patients who achieved pCR versus those who did not achieve pCR using Kaplan-Meier method. In patients who failed to achieve pCR, patient-specific and treatment-specific factors including age, race, menopause status, family history, smoking history, clinical stage, histology, NAC regimen, whether breast conserving surgery was performed, response to NAC, treatment with adjuvant chemotherapy, and use of RT boost were analyzed using multivariable cox proportional hazards method to evaluate factors associated with distant metastasis.

Results

A total of 153 patients with a median follow up of 48.6 months were included. Of the 153 patients, 108 (70.9%) were identified as not having pCR following NAC. Among those 45 patients that did achieve a pCR, only 1 patient (2.2%) went on to have distant metastasis. In contrast, of the 108 patients that failed to achieve a pCR, 47 (43.5%) went on to have distant metastasis. On univariable analysis, factors associated with distant metastasis in patients that did not achieve a pCR included increasing clinical and pathological T and N stage, positive pathologic lymph node status, multifocality, lymphovascular space invasion (LVSI), extranodal extension, and failure of downstaging after NAC. After controlling for potential confounders in multivariable analysis, higher pathological N stage (HR 2.18, 95% CI 1.12 - 4.22), positive pathologic lymph nodes (HR 2.21, 95% CI 1.02 - 4.80), LVSI (HR 1.87, 95% CI 1.04 - 3.37), and multifocality (HR 2.05, 95% CI 1.05 - 4.03) were found to be independent predictors of distant metastasis.

Conclusions

Approximately 43.5% of patients with TNBC that did not achieve a pCR went on to develop distant metastasis, perhaps reflecting an underlying chemo-resistance of these non-pCR tumors. Here we identify multiple risk factors associated with distant metastasis among patients not achieving a pCR, including positive lymph nodes, LVSI, high pathologic N stage, and multifocality. This data can be used to inform prognoses and treatment decisions in this high-risk cohort of patients and future clinical trials are warranted to lower the risk of distant metastasis in this population.

Citation Format: Tricarico CJ, Gabani P, Weiner AA, Ochoa LL, Thomas MA, Zoberi I. Predictors of distant metastasis in patients with triple negative breast cancer who failed to achieve a pathological complete response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-39.