| ObjectiveOverall incidence of breast cancer is rising in recent years in our country. It, ranking first among women in urban and rural areas, has been one of the most important malignant tumors endangering life and health. In 1980, Dr. Fisher proposed a new biological opinion that breast cancer is a systemic disease. With the development of the research of breast cancer, Fisher’s view has been accepted by more and more widely. According to the NCCN guidelines in 2015, patients with locally advanced breast cancer are recommended to receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy (NAC), which can improve breast surgery of breast conservation rate and make more and more patients avoid resection of breast, has gradually become conventional diagnosis and treatment. The choice of neoadjuvant chemotherapy regimen is based on pathologic and immunohistochemical assessment of samples from core needle biopsy. In the case that whole tissue can not be obtained, the accuracy of core needle biopsy (CNB) is very important. Although the accuracy of core needle biopsy has been confirmed by some researches, in the process of clinical diagnosis and treatment, there are some difference between core needle biopsy and postoperative pathology, especially in IHC assessment of ER, PR, HER2 and Ki67. The inconsistent proportion of estrogen receptor (ER), progesterone receptor (PR) and humanepidermal growthfactor receptor 2 (HER2) ranged from 3%to 18%. There is little report about whether the changes of biomarker expression can predict neoadjuvant chemotherapy response. We retrospectively studied the effect of CNB and neoadjuvant chemotherapy on pathological types and IHC results by analyzing patients with paired CNB and open excision biopsy (OEB) samples and comparing biomarker status between CNB and OEB. And we research the relationship between changes of biomarker expression and the effect of NAC. Our findings provided some effective guidance for clinical treatment and provide some reference for postoperative adjuvant chemotherapy.MethodsWe retrospectively collected patients with invasive breast cancer diagnosed by CNB from November 2011 to June 2015 in the Affiliated Hospital of Academy of Military Medical Sciences. Patients did not received any anticancer therapy before CNB. According to the patients whether were given neoadjuvant chemotherapy, the patients were divided into two groups: biopsy-operation group and biopsy-chemotherapy-operation group.205 cases were divided into biopsy-operation group contains and 439 cases were divided into Biopsy-operation group.Part 1:Analysis of the pathological consistency of the patients in biopsy-operation group.1. We paired CNB specimen and open excision biopsy (OEB) specimen and collect clinical information which includes ID, name, pathologic type, immunohistochemistry and so on.2 cases were diagnosed of malignant by OEB.5 cases which were diagnosed as atypical hyperplasia and 3 cases which could not be ruled out malignant were recommended open excision biopsy.188 of 205 cases have complete information and were diagnosed of malignant by both CNB and OEB.2. Pathologic type, ER, PR, HER2 and Ki67 expression were reviewed by pathologists. ER, PR, HER2 and Ki67 expression are tested by immunohistochemistry.3.More than 14% Ki67 expression is defined as High expression. The Kappa test for paired data was used to compare biomarker status between CNB and OEB. Concordance rates of biomarkers were calculated and changes of biomarker expression were noted. ER, PR, HER2 and Ki67 expression are tested by immunohistochemistry (IHC). According to the test results, cases are divided into four molecular subtypes:luminal A subtype, Luminal B subtype, triple negative breast cancer and HER2 over-expression breast cancer.Part 2:Analysis of the pathological consistency of the patients in biopsy-chemotherapy-operation group.1. We paired pre-NAC core biopsies and post-NAC specimens and collect clinical information which includes ID, name, menopause or menstruation, pathologic type, immunohistochemistry and so on.205 of 439 cases received NACT comprising docetaxel (75 mg/m2) and doxorubicin (50 mg/m2) or pharmorubicin(75 mg/m2).165 of 205 cases have complete information.28 of 165 cases achieved pathologic complete response.2. Pathologic type, ER, PR, HER2 and Ki67 expression were reviewed by pathologists. ER, PR, HER2 and Ki67 expression are tested by immunohistochemistry.3. More than 14% Ki67 expression is defined as High expression. The Kappa test for paired data was used to compare biomarker changes after NAC. Concordance rates of biomarkers were calculated and changes of biomarker expression were noted.Part 3:Whether the changes of biomarker expression can predict neoadjuvant chemotherapy response?1. In the basis of the changes of biomarker expression caused by NAC, we divided the patients into consistency group and difference group.2. Clinical response rate(cRR) of every patient is calculated. cRR=[(Maximum diameter before treatment-Maximum diameter after treatment)/Maximum diameter before treatment]3. The Chi-square test was used to assess the difference of cRR between the two groups. All data were analyzed with SAS statistics software (Version 9.1) and P-value<0.05 was considered statistically significant.ResultsBiopsy-operation group is made up of 188 cases of patients of breast cancer. The pathological types of CNB and OEB were basically consistent. P=0.9955 indicates the difference was not statistically significant. Concordance rate of Molecular subtypes is 72.34%, k=0.6064. Concordance rate of ER, PR and HER receptor were 94.68%, k=0.862,93.62%, k=0.8658 and 94.68%, k=0.8539.Good consistency is showed by high concordance rate and k value. Ki67 expression in OEB samples is higher than in CNB samples (25.90% vs 21.65%, P< 0.001).Kappa test of Ki67,which Concordance rate is 73.40% and k value is 0.1492, suggests poor consistency. The Ki67 value of the two groups were paired with the signed rank sum test of quantitative data. S=617, P=0.0013 testify the differences were statistically significant.Biopsy-chemotherapy-operation group consist of 137 patients who received NACT comprising one to eight cycles of docetaxel (75 mg/m2) and doxorubicin (50 mg/m2) or pharmorubicin(75 mg/m2).There was no significant difference in ER, PR and HER2 expression before and after NAC treatment in all subtypes. Concordance rate of Molecular subtypes of pre-NAC biopsies and post-NAC specimens is 56.64%, k=0.3778. Concordance rate of ER, PR and HER receptor were 87.61%, k=0.6678、80.53%, k=0.5959 and 93.81%, k=0.4305.K,ranging from 0.45 to 0.75,means general consistency. Compared with the result of biopsy-operation group, the neoadjuvant chemotherapy can affect ER, PR, and HER2 receptor to some extent. It has little effect on expression of ER and HER2.was no significant difference in ER and HER2.However, NAC is more likely to make expression of PR decrease. Consistency of HR receptor, avoiding the effect of NAC, is good. There was a significant decrease in expression of Ki67 (P= 0.000) in post-NAC specimens compared to pre-NAC core biopsies. Ki67 mean value dropped from 35.75% to 19.12% after NAC.44 of 137 patients, accounting for 32.11% of the group, have a change in the receptor status either of ER, PR, and Her2. According to the number of cycles of neoadjuvant chemotherapy, the cases were divided into 4-cycle groups,6-cycle group and 8-cycle group. Change rates of biomarkers of three groups respectively were 27.00%,39.22% and 38.46%.In the light of change the status of biomarker expression, we divided the patients into consistency group and difference group. Clinical response rate of every patient is calculated. The mean clinical remission rate(cRR) of two groups is 48.51% and 48.20% respectively. T test show the difference was not statistically significant.Conclusion1. CNB can accurately define the status of ER, PR and HER2 and Ki67 value in breast cancer. Preoperative core needle biopsy is accurate in determining non-Luminal molecular subtypes of breast cancer. The Ki67 value of hormone receptors (HR)+/HER2-specimens will probably rise after CNB. When making neoadjuvant therapy decisions, the underrated Ki67 value of CNB should be considered.2. NAC does not affect ER, PR and HER2 receptor status, but can lead to a decrease in Ki67 values. The difference of ER, PR and HER2 was not statistically significant, and HR receptor was not affected.3. The change rate is proportional to the number of cycles of chemotherapy.4. Changes in receptor status does not lead to the different efficacy of neoadjuvant therapy. The initial CNB may be as a prognostic indicator. |
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