Incorporation of TIls in the Residual Cancer Burden Index
NACT followed by surgery is nowadays considered the standard of care for locally advanced/inflammatory BC and is increasingly used in earlier stages with the aim to achieve a tumor down-staging and improve the chance for breast conservation. In addition, it provides the unique opportunity to test in vivo sensitivity to investigational agents, potentially speeding up drug development. pCR, defined as the absence of invasive residual carcinoma in the breast and axillary lymph nodes after NACT, has been proposed as a surrogate endpoint for long-term outcome. However, rates and prognostic impact of pCR are heterogeneous across different BC subtypes. The highly proliferative and more aggressive subtypes such as non-luminal HER2+ BC and TNBC have a higher chance to respond to NACT and the association between failure to achieve pCR and unfavorable prognosis is mostly evident in these subtypes, as compared to luminal BCs. However, some patients without pCR will survive long-term, whereas some patients with pCR will relapse, highlighting the limitations of pCR as a surrogate endpoint for drug efficacy.
For these reasons, the identification of biomarkers to refine risk stratification is urgently needed in order to enable a better identification of high-risk patients eligible for additional systemic treatments. TILs evaluated in RD after NACT have been suggested as a potentially useful and reliable marker for this purpose. A first report by Asano and colleagues suggests that the combination of the residual cancer burden (RCB) and TILs is a significant predictor for breast cancer recurrence after NACT and may be a more sensitive indicator than TILs alone.
The Working Group is launching an international effort to include TILs in the RCB index in order to develop more accurate risk stratification systems after NACT. Join this effort!