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Triple-negative breast cancer is considered to be the most aggressive subtype of breast cancer. Due to its lack of expression of estrogen receptor (ER) , progesterone receptor (PR) and HER-2, there is still a lack of clear prognostic judgments and biomarkers that guide treatment. With the development of tumor immunology, the relationship between tumor immune microenvironment and tumor occurrence and development has gradually gained attention. More and more evidence suggests that the higher the level of tumor-infiltrating lymphocytes (TIL) infiltration in triple-negative breast cancer lesions, the better the prognosis of patients. However, TIL is not a single type of cell, and its different lymphocyte subpopulations have different prognostic effects in patients with triple-negative breast cancer. This article summarizes the relationship between different immune cell subgroups in the tumor immune microenvironment and the prognosis of TNBC patients.
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The pathological subtypes of breast cancer can be further divided into different molecular subtypes based on their immunohistochemical staining, such as estrogen receptor (ER) , progesterone receptor (PR) , human epidermal growth factor receptor2 (HER2) and Ki67 expression, including luminal subtype, HER2 overexpression subtype and triple negative subtype. The luminal subtype is defined as ER and/or PR positive. In molecular mechanism, the expression activity of ER can regulate the expression of PR, so the expression of ER and PR is usually consistent. However, in the process of detection, some breast cancers with inconsistent ER/PR expression often appear, especially those with ER (-) /PR (+) . There is still controversy about whether such cases are true. Patients with this type of breast cancer should be subjected to ER and PR immunohistochemical staining again, and then reclassified according to HER2 status. The expression of ER/PR is closely related to the efficacy of endocrine therapy for breast cancer, so its test results will directly affect the treatment options of clinician. This article will review and discuss the research progress of the causes and mechanisms of ER (-) /PR (+) breast cancer.
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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.
ABSTRACT
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.
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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.
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Objective To explore the risk factors and metastasis of non-sentinel lymph node (NSLN) in breast cancer patients with sentinel lymph node metastasis≤2. Methods 88 cases of breast cancer with sentinel lymph node metastasis≤2 were retrospectively analyzed. Factors influencing the status of NSLN were studied. Results 8 cases (9.09%) had NSLN metastasis. Variance analysis showed that tumor stage(P=0.014), histolog-ical grade(P=0.014) and ER statuts(P=0.009) were correlated with NSLN metastasis. Logistic analysis showed that only histological grade was the independent predictor for NSLN metastasis (P=0.016,OR=1.150,95%CI=0.598~7.740).18 cases had micro-metastasis of sentinel lymph node and 70 cases had macro-metastasis of sentinel lymph node. The ratio of false negative SLN was 10.23%. The mean follow-up time was 11 months. There was no case of recurrence, metastasis or death. Conclusions The metastasis rate of NSLN is relatively low in breast cancer patients with small number of positive SLNs. NSLN metastasis is related to tumor stage, histological grade, and ER expression.
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Spindle cell carcinoma of the breast (SpCC) is a very rare variant of breast cancer characterized as large tumor size,high histological grade and high negative expression of hormone receptors and HER2/neu protein.It has a high tendency for local recurrence and distant metastasis,while the axillary lymph node metastasis is less common occured,which leads to poor outcomes.Given the relatively low incidence,our knowledge about SpCC is limited.The main unsolved obstacles are the early dection and diagnosis,and the improvement in treatments.Herein,this article reviewed the clinicopathologic characteristic,diagnosis,treatment and prognosis of the spindle cell carcinoma of breast.
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<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>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Age Factors , Breast Neoplasms , Metabolism , Pathology , Carcinoma, Ductal, Breast , Metabolism , Pathology , Ki-67 Antigen , Metabolism , Lymphatic Metastasis , Neoplasm Grading , Neoplasm Staging , Prognosis , Receptor, ErbB-2 , Metabolism , Receptors, Estrogen , Metabolism , Receptors, Progesterone , Metabolism , Retrospective StudiesABSTRACT
ObjectiveTo assess the value of intraoperative radiotherapy (IORT) combined with postoperative concurrent chemoradiotherapy for locally advanced pancreatic cancer. MethodsFrom May 2008 to May 2011, 85 cases of locally advanced pancreatic cancer patients in our hospital were analyzed retrospectively.The treatment group included 40 cases treated by IORT plus drainage combined with postoperative concurrent chemoradiotherapy ( group A), and the control group included 45 undergoing IORT plus drainage ( group B).The clinical manifestation, operation plan etc.were summed up and all cases were followed up regularly to evaluate the survival time.ResultsThe follow-up time was from 6 to 15 months and the follow-up rate is 90％ (77/85).For group A and group B, the mean survival time was 10.17 ±0.58 months VS 8.05 ±0.48 months and the median survival time was 11.40 months VS 8.30 months.The survival analysis showed that group A had a significant survival advantage than group B (P =0.027 ).10 patients died in group A and 12 patients died in group B.The difference had no statistical significance (P =0.805 ).ConclusionIORT plus postoperative concurrent chemoradiotherapy can improve the survival rate of patients with locally advanced pancreatic cancer.
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Objective To investigate the safety and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors.Methods From May 2008 to August 2009, 52 patients with abdominal tumors were treated with intraoperative electron radiotherapy,including 14 patients with breast cancer,19 with pancreatic cancer,3 with cervical cancer, 4 with ovarian cancer, 6 with sarcoma, and 6 with other tumors.Fifteen patients were with recurrent tumors.The intraoperative radiotherapy was performed using Mobetron mobile electron accelerator, with total dose of 9 - 18 Gy.In all, 29, 4 and 19 patients received complete resection, palliative resection and surgical exploration, respectively.The complications during the operations and within 6 months after operations were graded according to Common Terminology Criteria for Adverse Events v3.0 (CTC 3.0).Results The median duration of surgery was 190 minutes.Intraoperative complications were observed in 5 patients, including 3 with hemorrhage, 1 with hypotension,and 1 with hypoxemia, all of which were treated conservatively.The median hospitalization time and time to take out stitches was 12 and 13 days, respectively.And the in-hospital mortality was 4% (2/52).Twentyfour patients suffered post-operative adverse events, including 3 postoperative infections.With a median follow-up time of 183 days, 20% of patients sufferred from grade 3 to 5 adverse events, with hematological toxicities being the most common complication, followed by bellyache.Grade 1 and 2 toxicities which were definitely associated with intraoperative radiotherapy was 28% and 4%, respectively.None of grade 3 to 5 complications were proved to be caused by intraoperative radiotherapy.Conclusions Intraoperative electron radiotherapy is well tolerable and could be widely used for patients with abdominal tumors, with a little longer time to take out stitches but without more morbidities and toxicities compared surgery alone.
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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.