Extended Abstract

Introduction
Breast cancer is the most common type of cancer in women. Although the 5-year survival rate for this cancer has increased to 85% in developed countries, approximately half a million of the 7.6 million cancer-related deaths in 2012 were due to breast cancer. In Iran, the incidence rate is reported to be 22 per 100,000 people, and the prevalence is determined to be 120 per 100,000 people, with the highest prevalence occurring between the ages of 40 and 49. Breast cancer has both genetic and non-genetic backgrounds, and some genetic mutations have been reported, with these mutations playing a role in 20-25% of breast cancers. Alcohol use and mutations in the CASP8 gene have been linked to this cancer. Some risk factors such as race, diet, smoking, alcohol, age, obesity, physical activity, increased breast density, ionizing radiation, age at childbirth, gland function, history of breast disease, and hormone therapy have been implicated in the development of breast cancer. Breast cancer is diagnosed through clinical examination, imaging practices, and ultimately biopsy.
Treatment for this cancer varies based on the extent of the disease, the characteristics of its spread, and the type of tissue, and primarily includes surgery, chemotherapy, radiation therapy, and hormone therapy. The type and extent of surgery are also determined based on the patient’s condition. Although some studies have not reported an increase in overall survival in early-stage breast cancer with neoadjuvant chemotherapy (NAC), better overall survival has been achieved in patients with locally advanced breast cancer in case of a pathologic complete response (PCR). NAC was first introduced in 1970 for patients with locally advanced breast cancer who were inoperable, increasing the chance of breast conservation and, more importantly, increasing overall survival. It also helps in treating micrometastases. Although approximately 36% of patients show a therapeutic response in clinical examination and imaging, only 3-30% of them have a PCR, which is helpful in determining prognosis. Tumors with high proliferation and no expression of hormone receptors have a higher probability of PCR. In contrast, well-differentiated tumors with low proliferation rates and hormone receptor expression have a lower probability of PCR. However, what is certain is that a PCR is a very good prognostic factor for long-term benefits of NAC, particularly when breast cancer is triple-negative or human epidermal growth factor receptor 2 (Her2)-positive.
This study aimed to determine the response rate to NAC in patients with locally advanced breast cancer based on common molecular receptors.
Methods
This descriptive-analytical study was conducted on 100 patients with breast cancer aged between 26 and 68 years.
After diagnostic procedures and confirmation of tumor type and staging, the type of treatment was determined. Patients with locally advanced tumors were candidates for NAC. After completion of the chemotherapy protocol, modified mastectomy or lumpectomy and axillary lymph node dissection were performed.
Patients with metastases and concomitant cancer in another area, pregnant patients, and patients with incomplete records were excluded from the study.
Information regarding clinical, paraclinical, and pathological indicators, including biomarkers, tumor subtypes, and the extent of lymph node involvement, was entered into a checklist. Patients with no residual invasive tumor in the tissue sample were placed in the PCR group, and those with residual tumor in the breast and axillary tissue were placed in the partial or no PCR group. The AC-T and TAC drug regimens were used in two groups of 50 patients as follows:
AC-T regimen: Adriamycin 60 mg/m² and cyclophosphamide 600 mg/m² every two weeks for 4 cycles, followed by paclitaxel 175mg/m² every two weeks for 4 cycles, for a total of 8 cycles.
TAC regimen: Taxotere 75 mg/m², adriamycin 50 mg/m², and cyclophosphamide 500 mg/m² every 3 weeks for 6 cycles.
Patients in the PCR and partial PCR groups were compared in terms of age, family history of breast cancer, tumor size, histology, grade, estrogen and progesterone receptor status, Her2-neu and Ki-67, axillary lymph nodes, and type of NAC regimen.
Results
The mean tumor size before NAC was 3.01±2.47 cm (range= 0-8, median= 2), with 16% grade one, 52% as grade 2, and 32% as grade 3. Thirty-six percent of patients had a positive family history.
Common molecular receptors showed 46% estrogen receptor (ER) positive, 40% progesterone receptor (PR) positive, 22% Her-2 positive, 12 patients with weak Her-2 positivity, and 66% Her-2 negative.
Ki-67 index was over 30% in 36%, 10-30% in 20%, 5-10% in 16%, and less than 5% (negative) in 28% of patients.
After NAC and pathologic surgery and evaluation, PCR was achieved in 18% and incomplete or no response to treatment in 82% of patients. Tumor size in the no PCR group was 67.23±3.2 mm and zero in the PCR group (P<0.001). The mean and standard deviation of age in the no PCR group was 45.41±40.9 years and 44.12±27.41 years in the PCR group.
The rate of PCR to NAC in patients with locally advanced breast cancer was significantly associated with a positive family history (P<0.012), no involvement of axillary lymph nodes (P<0.001), high histological tumor grade (P<0.002), negative ER (P<0.001), negative PR (P<0.003), Her2 positivity (P<0.001), and high Ki-67 levels (P<0.001). The type of chemotherapy protocol did not have a statistically significant effect on PCR.
Conclusion
Based on the results of this study, a PCR was achieved in 18% of patients with locally advanced breast cancer following NAC and surgery. Other studies have reported PCR rates ranging from 12.6% to 27%.
Ethical Statement
This study was approved by the Research Ethics Committees of Golestan University of Medical Sciences (IR.GOUMS.REC.1397.056).
Funding
This article has been extracted from a thesis by Dr. Farzad Bagherian, submitted for a fellowship degree in General Surgery (No. 235) at the Faculty of Medicine, Golestan University of Medical Sciences.
Conflicts of Interest
No conflict of interest.
Acknowledgment
The authors would like to thank all colleagues in the field of General Surgery and Oncology, the technicians of the surgery ward, and the esteemed staff of the Fifth Azar Educational and Therapeutic Center in Gorgan.

Key message: PCR to NAC in patients with locally advanced breast cancer was significantly associated with a positive family history, negative axillary lymph node involvement, high-grade histology, negative ER and PR, Her2 positivity, and high Ki-67 levels.