Research progress in PARP inhibitors in breast cancer / 国际外科学杂志

Individuals with breast cancer susceptibility genes(BRCA) germline mutations have a significantly increased lifetime risk for breast cancer, BRCA-mutant cancer cells have abnormal homologous recombination repair of DNA.Inhibition of Poly (ADP-ribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency, whether driven by defects in BRCA1, BRCA2, or other pathway components. Currently, under U. S.Food and Drug Administration approval of PARP inhibitor on ovarian cancer, clinical trials for PARP inhibitor are being conducted to assess whether PARP inhibitor as monotherapy or in combination with other drugs could benefit more breast cancer patients. Besides the studies of PARP inhibitor as monotherapy in breast cancer patients, researches in investigating platinum-PARP inhibitor combination in BRCA mutated breast cancer or triple negative breast cancer were conducted. In addition, many studies of immunotherapy combined with PARP inhibitor in breast cancer are ongoing. However, resistance to PARP inhibitors and the toxicity of the drugs remain challenges. This review will discuss the utility and unsolved problems of PARP inhibitor in breast cancer as well as the potential future directions.

Research progress in PARP inhibitors in breast cancer / 国际外科学杂志

Individuals with breast cancer susceptibility genes (BRCA) germline mutations have a significantly increased lifetime risk for breast cancer,BRCA-mutant cancer cells have abnormal homologous recombination repair of DNA.Inhibition of Poly (ADP-ribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency,whether driven by defects in BRCA1,BRCA2,or other pathway components.Currently,under U.S.Food and Drug Administration approval of PARP inhibitor on ovarian cancer,clinical trials for PARP inhibitor are being conducted to assess whether PARP inhibitor as monotherapy or in combination with other drugs could benefit more breast cancer patients.Besides the studies of PARP inhibitor as monotherapy in breast cancer patients,researches in investigating platinum-PARP inhibitor combination in BRCA mutated breast cancer or triple negative breast cancer were conducted.In addition,many studies of immunotherapy combined with PARP inhibitor in breast cancer are ongoing.However,resistance to PARP inhibitors and the toxicity of the drugs remain challenges.This review will discuss the utility and unsolved problems of PARP inhibitor in breast cancer as well as the potential future directions.

Clinical significance and treatment regimen of sentinel lymph node microscopic metastasis in breast cancer / 中华普通外科杂志

Objective To explore the clinical significance and treatment regimen of sentinel lymph node(SLN) micrometastases and isolated tumor cell metastasis in breast cancer.Methods Ninety-seven breast cancer patients with sentinel lymph node micrometastases or isolated tumor cell metastasis from January 2013 to December 2015 were retrospectively studied.The patients were assigned to axillary lymph node dissection group (ALND,41 cases) and non axillary lymph node dissection group(non-ALND,56 cases) according to the final surgery mode to the axilla.Disease-free survival(DFS) and overall survival (OS) were compared between the two groups.Results Neither clinico-pathological factors,such as age,tumor size,grade,ER/PR status,HER-2 gene expression,Ki-67 expression and the size of the SLN metastasis,nor the treatment,such as breast surgery,postoperative adjuvant chemotherapy,radiotherapy and hormone therapy were found statistically different between the two groups (P ＞ 0.05).There were 96 patients evaluable with a median follow up of 24 months.The DFS of the ALND and non-ALND group was 97.5％ and 96.6％ (P ＞ 0.05),and the OS was 100％ and 98.2％ (P ＞ 0.05) respectively with no difference between the two groups.There were 2 ispilateral axillary recurrence in the non-ALND group and non in the ALND group.Conclusion Axillary lymph node dissection may be omitted for the breast cancer patients with sentinel lymph node micrometastases and isolated tumor cell metastases.But the postoperative adjuvant systemic treatment should be emphasized.

Expression of Ki67 and clinicopathological features in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the relationship between the expression level of Ki67 and clinicopathological features in breast cancer.</p><p><b>METHODS</b>Data of 918 female patients with invasive ductal breast carcinoma treated in the Cancer Hospital, Chinese Academy of Medical Sciences from Jan. to Dec. 2010 were analyzed retrospectively. The correlation of Ki67 expression and other clinicopathological features in the breast cancer was analyzed.</p><p><b>RESULTS</b>Among the 918 cases, the Ki67 index was 0.9% to 95% (mean value 27.8%). Taking the Ki67 index 14% as the boundary to divide the patients into two subgroups, 263 cases (28.6%) were ≤ 14%, and 655 cases (71.4%) were >14%. There were significant differences between the Ki67 expression and age, tumor size, axillary lymph nodes status, histological grade and the expressions of C-erbB-2, estrogen receptor (ER) and progesterone receptor (PR) (P < 0.05 for all). All the Ki67 indexes of Ki67 expression in luminal B (30.44%), HER-2 overexpression (36.77%) and triple negative (47.40%) subtypes were significantly higher than that in the luminal A subtype (21.36%)(P < 0.01). The expression level of Ki67 in triple-negative subtype (47.40%) was significantly higher than that in the non-triple-negative subtype (24.79%)(P < 0.001).</p><p><b>CONCLUSIONS</b>Ki67 index is significantly correlated with the age, tumor TNM stage, axillary lymph node status, histological grading, ER status, PR status and HER-2 status. A high expression level of Ki67 is a poor prognostic factor for breast cancer. The expression level of Ki67 should be detected routinely and it may become a useful prognostic marker in the treatment of breast cancer.</p>

Core needle biopsy for the diagnosis of breast tumor / 中华普通外科杂志

Objective To evaluate the accuracy of core needle biopsy (CNB) in diagnosing breast masses and its coherence with immunohistochemical (IHC) examination results of estrogen receptor (ER), progesterone receptor (PR) and Her2 protein between pre-and post-chemotherapy in invasive breast cancer. Methods The results of 516 CNB cases from June, 2005 to April, 2008 were analyzed retrospectively. The pathological examination was performed by two pathologists independently. Results 484 cases of malignant tumor, carcinoma in situ and phyllodes tumor were found in this group with the sensitivity of 96.7%. Sixteen cases of false negative (3. 3% ) were demonstrated by surgical biopsy. The accurate rate of CNB was not influenced by the maximum diameter of masses ( P = O. 423 ). The agreement rate of IHC results of ER, PgR and Her2 between pre- and post-chemotherapy were 90. 3%, 76. 8% and 82.5%, respectively. Conclusion CNB is a useful diagnostic method with a satisfactory accuracy in any size of breast masses. Given the histological heterogeneity of invasive breast cancer and the influence of ehemotherapy, the coherence of prechemotherapy IHC for ER, PgR and Her2 is not optimal with that of post-chemotherapy.

Localized Biopsy of Nonpalpable Breast Lesions and It’s Role in Early Diagnosis and Treatment of Breast Cancer / 中国普外基础与临床杂志

Objective To evaluate the localized biopsy of nonpalpable breast lesions (NPBLs) and its role in the early diagnosis and treatment of breast cancer. Methods One hundred and fifty-eight NPBLs from a series of 141 women detected by mammography were resected with wire localization technique. Results Forty-two lesions (26.6%, 42/158) in 42 patients were diagnosed with malignant result, including 12(28.6%) patients with stage 0 breast cancer, 24(57.1%) with stageⅠ, 2(4.8%) with stage Ⅱ and 4(9.5%) with stage Ⅲ disease according to American Joint Committee on Cancer (AJCC) staging system(the 6th edition). The contralateral axillary lymph nodes metastasis were found in only one (2.4%) patient with stage Ⅲ disease and the other forty-one patients remained free of recurrent disease at a median follow-up of 31 months.Conclusion The results showed that the most nonpalpable breast cancers detected by mammography were early-stage breast cancers and had good prognosis. The NPBLs should get a localized biopsy in order to facilitate the early diagnosis and treatment of nonpalpable breast cancers.

Expression of extracellular signal-regulated kinase and its relationship with clinicopathological characteristics of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of extracellular signal-regulated kinase (ERK) and its relationship with clinicopathological characteristics of breast cancer as well as the effect of preoperative chemotherapy on ERK expression.</p><p><b>METHODS</b>Expression of ERK-1 and ERK-2 protein was examined by Western blot in the breast cancer and normal breast (control) tissue of 48 patients, of whom 8 had received preoperative chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), with distribution of ERKs protein detected by immunohistochemical method.</p><p><b>RESULTS</b>Expression of ERK-1 and ERK-2 protein was increased in tumor specimen as compared with control tissue (P < 0.01). A positive correlation was observed between ERK-1 and ERK-2 (r = 0.457, P < 0.01). Protein level of ERK-1 and ERK-2 was higher in stage III patients than in stage I and stage II patients (P < 0.05). Expression of both ERK-1 and ERK-2 in the carcinoma tissue was decreased in patients who had received preoperative chemotherapy of 5'-DFUR. ERK-1 and ERK-2 proteins were mainly located in the cytoplasm.</p><p><b>CONCLUSION</b>The hyperexpression of ERK may play an important role in the initiation and development of human breast cancer. Preoperative chemotherapy of 5'-DFUR is able to partially inhibit ERK expression.</p>

Nonpalpable breast lesions categorization by breast imaging reporting and data system (BI-RADS) / 中国普通外科杂志

Objective To evaluate breast imaging reporting and data system (BI-RADS) in categorization and biopsy of nonpalpable breast lesions (NPBLs). MethodsOne hundred and sixty-two NPBLs from 144 female patients detected by mammography were retrospectively categorized according to BI-RADS. All the lesions finally got histopathological diagnosis by wire-localization biopsy. Results There were 46 malignant lesions, with the positive predictive value for cancer of 28.4% (46/162). The cases of BI-RADS 2-5 lesions were 11, 55, 77, and 19 after categorization according to the BI-RADS, and the positive predictive value of each category for cancer was 0% (0/11),3.6% (2/55),37.7% (29/77),78.9% (15/19) respectively. ConclusionBI-RADS categorization improves the diagnostic specificity of nonpalpable breast lesions and helps decision-making for biopsy. It is suggested that NPBLs on category of BI-RADS 4 or 5 should undergo biopsy.

Experiences of sentinel lymph node biopsy in breast cancer / 中国普通外科杂志

Objective To evaluate the feasibility of sentinel lymph node biopsy(SLNB)during surgery of breast cancer. MethodsRadioactive colloid and blue dye were injected intradermally around the tumor seperately before the operation and the SLN were detected first by lymph scintigraphy. SLN was detected and located using ?-finder and the blue dye. Axillary lymph node dissection(ALND)was performed routinely after the SLNB. Results Among 116 breast cancer patients,this procedure was successful in 98.3% of cases. The sensitivity, accuracy and false negative rate were 93.6%, 97.4% and 6.4%, respectively. Conclusions SLNB is a simple, safe and reliable technique.Routine ALND could be raplaced by SLNB in breast cancer patients undergoing surgery.