Sir,

Preoperative systemic therapy in locally advanced breast cancer (LABC) has many benefits and has become widely used in the present times. The study by Bansal et al. [1] was a welcome addition to our knowledge. A wide range of factors predicting response to neoadjuvant chemotherapy (NACT) in LABC have been identified, but the quest remains inconclusive. In this regard, we would like to emphasize some important aspects.

Breast carcinoma as an entity is comprised of molecularly distinct diseases. It is natural that these entities would have different predictors of resistance to chemotherapy. A recently published study, de Ronde et al. [2] analyzed this and found that for human epidermal receptor (HER) +ve, estrogen receptor − ve breast cancer, subtype specific predictor based on clinical features outperformed the generic, nonspecific predictor. They advocated that both specific and generic predictors should be evaluated when attempting to predict treatment response in breast cancer. It primarily would depend on the specific type of predictor being evaluated.

The molecular predictors evaluated by Bansal et al. [1] that is, carcinoembryonic antigen related cell adhesion molecules, carcinoembryonic antigen-related cell adhesion molecule 5, 6 (CEACAM 5, 6) and SLC7A5 have been used as predictors of therapy in breast cancer earlier. CEACAM 6 has also been used to predict breast cancer recurrence to endocrine therapy. In a study, Maraqa et al. [3] retrospectively tested whether significantly up-regulated CEACAM 6 on immunohistochemistry specimens was predictive of breast cancer resistance to tamoxifen therapy on long term follow-up. The results were indicative of significantly more CEACAM 6 expression in the relapsed group of patients as compared to nonrelapsed control, supporting an important role of CEACAM 6 in endocrine resistant breast cancers. Similarly, SLC7A5 has also been implicated in endocrine resistance in breast cancers. Mihαly et al. [4] in a meta-analysis to validate predictors to tamoxifen resistance identified SLC7A5 as one of the most promising genes along with two other genes.

Tsang et al. [5] evaluated CEACAM 6 expression in two independent cohorts of invasive breast cancer patients, and CEACAM 6 expression was found in 37.1% of invasive cancers. It was significantly positively correlated with HER two expression especially the HER overexpressed subtype. In this subtype, it was associated with high nodal stage patient outcome.

Thus, it needs to be prioritized that expression of these three molecular predictors be correlated with receptor/molecular subtypes of breast cancer to know their exact significance as a predictor of response to neoadjuvant therapy in carcinoma breast. It would have been highly appreciable to know the correlations of the molecular markers with breast cancer subtypes in the study done by Bansal et al. [1] The molecular markers CEACAM 6 and SLC7A5 have been proven as markers of endocrine resistance in various studies and need to be studied in that context.

To sum up, there is a dire need of clinically evaluable markers of response to NACT, and if markers such as CEACAM 6 and SLC7A5 are evaluated in the right perspective, they may help to fill the gap.