DeCure for Triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor, and HER2 expression. In a 2008 immunohistochemical study of 116 breast cancer samples, 22 (19%) were triple-negative. That phenotype correlated significantly with larger tumour size, higher histological grade, positive lymph node status, p53 expression, and EGFR expression, but not with age, menopausal status, or VEGF protein. After a median follow-up of 96 months, 12 of the 22 TNBC patients had distant relapse compared with 20 of the 94 non-TNBC patients (p < 0.05). Triple-negative phenotype was inversely associated with overall survival (p < 0.05) but not significantly with disease-free survival (p = 0.2877). Tumour size, lymph node status, histological grade, and triple-negative phenotype each provided independent predictive power in a multivariate Cox model.

The same 2008 review noted that TNBC carries a poor prognosis and is insensitive to most available hormonal or targeted agents. Gene expression profiling had classified breast cancers into five subtypes, and the authors stated that limited understanding of TNBC biology presented a challenge for developing novel therapies. A 2013 review reiterated that TNBC is heterogeneous, that recurrence after resection is common, that survival is low, and that available treatment options after recurrence are few. Chemotherapy was described as the main treatment strategy, and the authors called for new molecular predictive markers and drug targets.

A 2014 paper reported results for 128 patients with operable TNBC who received surgery, adjuvant or neoadjuvant chemotherapy, and pre- or postoperative radiotherapy. The authors concluded that the combination treatment procedures were highly effective, and they traced five-year relapse-free and overall survival rates. A 2018 paper on metastatic TNBC similarly concluded that the combination treatments used were highly effective, and noted that the risk of relapse for TNBC is much higher for the first 3–5 years but then drops sharply and substantially below that of hormone-positive breast cancers. A 2019 review stated that TNBC is very responsive to neoadjuvant chemotherapy and that patients are more likely to achieve pathologic complete remission, which is associated with improved survival. The same review noted that TNBC lacks the molecular therapeutic targets expressed by other breast cancer subtypes.

What remains missing is prospective validation of molecular predictive signatures that could characterise TNBC subtypes and guide treatment selection. No targeted therapy has been shown in these abstracts to improve outcomes specifically for TNBC beyond standard chemotherapy. The evidence base consists of retrospective series and reviews; no randomised controlled trial data comparing a novel agent against standard care in a well-stratified TNBC population are presented. Funding for such trials and for the identification of actionable molecular targets is still needed.