Outcome for triple negative breast cancer in a retrospective cohort with an emphasis on response to platinum-based neoadjuvant therapy

Abstract

PurposeThe rate of pathological complete response (pCR) for patients with triple negative breast cancer (TNBC) is increased when carboplatin is added to neo-adjuvant chemotherapy (NACT). However, while phase III trial data showing a survival benefit are awaited, carboplatin is not yet standard-of-care for TNBC. The aim of this study was to examine the rate of pCR and the outcome for those treated with carboplatin and to examine the predictors of response to therapy.MethodsThe retrospective series comprised 333 consecutive patients with TNBC (median follow-up time, 43 months). Adjuvant chemotherapy was given to 51% (n = 168) of patients and 29% (n = 97) received anthracycline–taxane NACT with carboplatin given to 9% (n = 31) of patients.ResultsOverall, 25% (n = 78) of patients experienced a breast cancer recurrence and 22% (n = 68) died from disease. A pCR breast and pCR breast/axilla was more common in those who received carboplatin (n = 18, 58% and n = 17, 55%, respectively) compared those who did not (n = 23, 36% and n = 18, 28%, respectively) (p = 0.041 and p = 0.011, respectively). By multivariable analysis, carboplatin and high tumor grade were independent predictors of pCR breast/axilla (ORnon-pCR = 0.17; 95% CI 0.06–0.54; p = 0.002; and ORnon-pCR = 0.05, 95% CI 0.01–0.27; p < 0.001, respectively). pCR breast/axilla was an independent predictor of DFS (HRnon-pCR=6.23; 95% CI 1.36–28.50; p = 0.018), metastasis-free survival (HRnon-pCR = 5.08; 95% CI 1.09–23.65; p = 0.038) and BCSS (HRnon-pCR = 8.52; 95% CI 1.09–66.64; p = 0.041).ConclusionCarboplatin therapy and high tumor grade are associated with a significant increase in the rate of pCR, which is an independent predictor of outcome. These data support the use of carboplatin in NACT for TNBC, while results from phase III studies are awaited.Electronic supplementary materialThe online version of this article (10.1007/s10549-018-5066-6) contains supplementary material, which is available to authorized users.

Chromosome 12p Amplification in Triple-Negative/BRCA1-Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity

“…In a retrospective study patients with TNBC who received carboplatin with anthracycline/taxane-based neoadjuvant therapy have significantly higher rate of complete regression compared with those who received anthracycline/taxane alone (48), which substantiate the efficacy of docetaxel and carboplatin combinations in the clinical setting (49,50).…”

Expression and clinical significance of MAPK and EGFR in triple‑negative breast cancer

“…Correlation analysis determined that MAPK was significantly associated with EGFR expression, suggesting that MAPK and EGFR may act synergistically to promote TNBC progression. Lymph node metastasis and TNM staging are important for evaluating clinical prognosis in patients with TNBC (21), and can provide a basis for the selection of treatment options (22). The present study determined that in patients with TNBC, both MAPK and EGFR expression were significantly associated with both lymph node metastasis and clinical stage.…”

Tumor suppressor PLK2 may serve as a biomarker in triple-negative breast cancer for improved response to PLK1 therapeutics

“…The previous combination of biochemical, genetic, and bioinformatic studies suggests that inhibiting PLK1 in a setting with low PLK2 expression, such as TNBC, may provide a targeted approach for a disease in which chemotherapy is still the only systematic treatment (44). Therefore, we tested the effects of a PLK1 inhibitor both as a single agent and in combination with chemotherapy in both novel p53 -/- GEM and PDX preclinical models with low vs. high PLK2 expression.…”