Predictors of Distant Metastases in Triple-Negative Breast Cancer Without Pathologic Complete Response After Neoadjuvant Chemotherapy

Abstract

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. Methods: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. Results: We identified 153 patients with median follow-up of 4.0 years (range, 0.5–14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54–6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07–3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). Conclusions: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.

Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies

“…The pCR of TNBC post-neoadjuvant chemotherapy (NACT) predicts long-term survival [ 45 , 46 , 47 , 48 , 49 ]. Patients whose tumors exhibit a pathologic incomplete response (pIR) with residual disease post-NACT, are more likely to suffer early recurrence and reduced survival [ 50 , 51 , 52 , 53 ]. Notably, by measuring residual disease after NACT, the risk of developing a future life-threatening distant event can be accurately quantified [ 54 , 55 ] and TNBC patients with high-risk residual disease are now commonly considered for additional adjuvant chemotherapies, including capecitabine, post-operatively [ 7 , 56 , 57 ].…”

Exploitation of sulfated glycosaminoglycan status for precision medicine of platinums in triple-negative breast cancer

“…The major advantage of NACT is the ability to immediately identify patients with chemotherapy-resistant disease who may benefit from second adjuvant therapy following surgery (47). Recent approval of capecitabine, an oral antimetabolite of 5-Flurouracil, resulted from the CREATE-X trial showing a significant improvement in the rate of recurrence-free survival at 5 years (69.8% in the capecitabine group vs 56.1% in the control group) (48).…”

Persistent EGFR/K-RAS/SIAH pathway activation drives chemo-resistance and early tumor relapse in triple-negative breast cancer

“…TNBC is a genetically diverse, highly heterogeneous, and molecularly unstable disease, which challenges our ability to tailor effective individualized treatments for patients [10,18] . TNBC has unique and aggressive tumor biology, and it constitutes a major health threat with the worst prognosis and the highest mortality of all breast cancer subtypes [10,19,20] . Looking more closely, one in three patients with high-risk early-stage TNBC will develop tumor relapse, which typically occurs within the first three years of initial diagnosis; only a third of women with locoregional TNBC will survive their disease; and of those with metastatic TNBC, less than 1 in 9 will survive their disease [5,10,[21][22][23] .…”

“…Standard chemotherapy remains the backbone of systemic therapy in TNBC [20,[24][25][26][27][28] . https://www.cancer.org/cancer/breast-cancer/treatment/treatment-of-triple-negative.html.…”

“…TNBC has unique and aggressive tumor biology, and it constitutes a major health threat with the worst prognosis and the highest mortality of all breast cancer subtypes [ 10 , 19 , 20 ] . Looking more closely, one in three patients with high-risk early-stage TNBC will develop tumor relapse, which typically occurs within the first three years of initial diagnosis; only a third of women with locoregional TNBC will survive their disease; and of those with metastatic TNBC, less than 1 in 9 will survive their disease [ 5 , 10 , 21 - 23 ] . TNBC has a 5-year overall survival (OS) of 78.5%, and the 5-year survival rates for localized, regional, and metastatic diseases are 91.2%, 65.4%, and 12.2%, respectively, which is the worst among the major molecular subtypes in breast cancer ( ).…”