**2.9 Is there a triple-negative paradox?**

Higher Ki-67 predicts a higher response to chemotherapy and a higher pCR rate, which generally means a good prognosis [21]. However, high Ki-67in TNBC is

*Inter-Relationship of Ki-67 and Triple-Negative Breast Cancer DOI: http://dx.doi.org/10.5772/intechopen.109586*

associated with poor recurrence-free or overall survival. This was termed as a "triple negative paradox." However, this paradox can be explained by a higher likelihood of relapse in patients whose pCR was not achieved. In a study by Keam et al., only 18.2% of TNBC patients achieved pCR, and patients with high Ki-67 residual disease had statistically significant poor prognoses than patients with residual disease and low Ki-67 or patients with pCR with high Ki-67 [28]. Similarly, in a study by Carey et al., only 27% of patients with basal subtype achieved pCR [32]. Therefore, in patients with TNBC, the higher number of non-pCR patients tilt the results toward poor prognoses resulting in the so-called "triple negative paradox."

Only 20–30% of patients with TNBC achieved pCR on neoadjuvant chemotherapy [21, 32], and pCR was strongly associated with prolonged overall survival [15, 33, 34]. Moreover, patients with TNBC who achieve pCR have the same prognosis as patients with non-TNBC [33]. However, among patients who did not achieve pCR, patients with TNBC have a significantly poorer outcome than patients with non-TNBC [33].

#### **3. Conclusions**

Although marred by intratumoral heterogeneity and inter-observer variability, true to the highly proliferative nature of TNBCs, higher baseline Ki-67 levels are seen as compared to luminal tumors. A higher Ki-67 is associated with a higher pCR rate in TNBC. However, the best cutoff point of this marker as a prognostic and predictive factor in TNBC remains to be seen even after many researchers have explored this idea. Moreover, the "triple negative paradox" concept is more of a myth arising from more non-pCR patients in the TNBC group.

#### **Acknowledgements**

Thanks to Dr. Biswajit Dubashi , Professor, Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India, for reviewing the manuscript and suggesting improvements.

#### **Conflict of interest**

The authors declare no conflict of interest.

#### **Acronyms and abbreviations**


