Individual approach to the planning of neoadjuvant chemotherapy (NAC) in patients with luminal B breast cancer

Background

Breast cancer is a leading cause of death in women worldwide. Neoadjuvant chemotherapy (NAC) is one of the treatment options for locally advanced breast cancer patients. Currently, there are no clinically useful predictive markers of response to NAC. We previously identified the chromosome regions in which copy number variations (CNVs) were correlated with response to NAC. Several studies have shown associations between drug effects and gene expression levels and specific mutations.

Methods

The criteria for inclusion in the study were as follows: luminal B breast cancer and clinical stage II or III disease. The study group consisted of 36 patients and the control group comprised 71 patients. The tissue samples were obtained with a biopsy prior to NAC. CNVs in biopsy specimens were tested using the high-density microarray platform. The expression levels of TYMS and Top2a were determined by PCR. Depending on the molecular and genetic characteristics of the tumor, patients began treatment with NAC: docetaxel or FAC (fluorouracil, adriamycin, сyclophosphamide) or CAX (сyclophosphamide, adriamycin, capecitabine) or CP (сyclophosphamide, cisplatin) or AD (adriamycin, docetaxel) or surgery. All patients in the control group received NAC followed by surgery. Response to NAC was assessed by means of International Union Against Cancer criteria.

Results

Based on the findings of previous studies and literature data, we had developed an algorithm of personalized treatment with NAC for breast cancer patients. Patients having CNV markers of response to NAC (deletions in АВСВ1, АВСB3, ABCC1, ABCG2, АВСС5, АВСВ7, deletions in 18р11.1 – 32; 11q21 – 25 and amplification in1q21.3-44) began treatment with NAC. The choice of the NAC regimen depended on the Тор2а amplification, deletions in BRCA1 and TUBB3, expression level of Top2a and TYMS. Of the 36 patients, 26 had markers of response to NAC and began treatment with NAC. Partial and complete response rate was 88.5 % in the study group and 53.8% in the control group (p = 0.002).

Conclusions

The CNVs mentioned above could be considered as new markers of NAC response. The developed algorithm can be used for personalized treatment of breast cancer patients.

Clinical trial identification

Legal entity responsible for the study

P. Kazantseva

Funding

Tomsk Cancer Research Institute, Tomsk, Russian Federation

Disclosure

All authors have declared no conflicts of interest.