Atypical memory B cells increase in the peripheral blood of patients with breast cancer regardless of lymph node involvement.

BACKGROUND: Breast cancer is the most common cancer in females. The immune system has a crucial role in the fight against cancer. B and T cells, the two main components of the adaptive immunity, are critical players that specifically target tumor cells. However, B cells, in contrast to T cells, and their role in cancer inhibition or progression is less investigated. Accordingly, in this study, we assessed and compared the frequency of naïve and different subsets of memory B cells in the peripheral blood of patients with breast cancer and healthy women. RESULTS: We found no significant differences in the frequencies of peripheral CD19+ B cells between the patients and controls. However, there was a significant decrease in the frequency of CD19+IgM+ B cells in patients compared to the control group (P=0.030). Moreover, the patients exhibited higher percentages of atypical memory B cells (CD19+CD27‒IgM‒, P=0.006) and a non-significant increasing trend in switched memory B cells (CD19+CD27+IgM‒, P=0.074). Further analysis revealed a higher frequency of atypical memory B cells (aMBCs) in the peripheral blood of patients without lymph node involvement as well as those with a tumor size greater than 2cm or with estrogen receptor (ER) negative/progesterone receptor (PR) negative tumors, compared with controls (P=0.030, P=0.040, P=0.031 and P=0.054, respectively). CONCLUSION: Atypical memory B cells (CD19+CD27‒IgM‒) showed a significant increase in the peripheral blood of patients with breast cancer compared to the control group. This increase seems to be associated with tumor characteristics. Nevertheless, additional research is necessary to determine the precise role of these cells during breast cancer progression.

The expression pattern of membranous TNF-α is distinct from its intracellular form in breast cancer-draining lymph nodes.

Tumor necrosis factor-alpha (TNF-α) is mostly known as a soluble cytokine. This study, however, focused on its membranous form whose significance is rarely investigated in antitumor immunity. Herein, we assessed the expression of both membranous and intracellular forms of TNF-α (m/icTNF-α) in the lymphocytes derived from breast cancer-draining lymph nodes. CD4+T cells were the main subset expressing mTNF-α with the highest intensity, whereas icTNF-α expression was most intense in CD8+T cells. An inverse correlation was seen between the frequency of mTNF-α and the expression intensity of this cytokine in B cells. In the clinical context, the higher intensity of mTNF-α expression in CD19+ cells correlated with poor prognosticators, while the frequency of mTNF-α+CD19+ cells showed a reverse correlation with the number of involved lymph nodes. The two forms of TNF-α did not show similar associations with cancer parameters, which highlights the complex role of this cytokine in breast cancer immunity.

Intraoperative radiation therapy for early stage breast cancer.

BACKGROUND AND OBJECTIVE: We report our experiences with Intraoperative radiation therapy (IORT) among breast cancer (BC) patients in our region. METHODS: All patients who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria included: Age equal or older than 45 years old; All cases of invasive carcinomas (in cases of lobular carcinomas only with MRI and confirmation); Patients who were 45-50 years old with a tumor size of 0-2 cm, 50-55 years old with a tumor size of < 2.5 cm, and those who were ≥ 55 years old with a tumor size of < 3 cm; Invasive tumors only with a negative margin; Negative nodal status (exception in patients with micrometastasis); A positive estrogen receptor status. Primary endpoints included death and recurrence which were assessed using the Kaplan-Meier method. RESULTS: Overall, 252 patients entered the study. Mean (SD) age of patients was 56.43 ± 7.79 years. In total, 32.9% of patients had a family history of BC. Mean (SD) tumor size was 1.56 ± 0.55 cm. Mean (IQR) follow-up of patients was 36.3 ± 18.7 months. Overall, 8 patients (3.1%) experienced recurrence in follow-up visits (disease-free-survival of 96.1%), among which four (1.5%) were local recurrence, two (0.8%) were regional recurrence and two patients (0.8%) had metastasis. Median (IQR) time to recurrence was 46 (22, 53.7) months among the eight patient who had recurrence. Overall, one patient died due to metastasis in our series. Eleven patients (4.3%) with DCIS in our study received IORT. All these patients had free margins in histopathology examination and none experienced recurrence. CONCLUSION: Inhere we reported our experience with the use of IORT in a region where facilities for IORT are limited using our modified criteria for patient selection.

Addition of carboplatin-gemcitabine as second-line neoadjuvant chemotherapy in non-responsive locally advanced breast cancer patients to standard neoadjuvant chemotherapy and evaluation of factors affecting response: a randomized controlled trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is the prime approach to the management of locally advanced breast cancer (LABC). Influenced by different factors such as pathologic tumor characteristics, hormone receptor status, HER2 and proliferation marker expressions, response to therapy cannot be easily predicted. Pathologic complete response (pCR) has been considered as an endpoint to NACT; however, pCR rates have been unsatisfactory in such patients. In this randomized trial, we studied the efficacy of carboplatin/gemcitabine as second-line NACT while evaluating the impact of different factors affecting response. METHODS: In this randomized controlled trial, 52 clinically non-responsive (confirmed by palpation and/or ultrasonography) LABC patients to 4 cycles of doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel ± trastuzumab were randomly allocated to two groups. "Control" group underwent breast surgery and were further evaluated for pCR (ypT0/is ypN0). "Intervention" group received 2 cycles of carboplatin/gemcitabine and patients were further evaluated for pCR following surgery. RESULTS: In a total of 52 patients, pCR rate was 30.7%. pCR and response rate in lymph nodes were higher in carboplatin/gemcitabine recipients (32% vs 29.7 and 44% vs 40.7% respectively), however differences were insignificant. In both the "intervention" group and total study population, most pCR cases were of the hormone receptor (HR)+/HER2+ subtype (87.5% and 75% respectively). HER2 positivity, ki67 expression, lower extent of ER positivity, higher tumor grade and tumor-infiltrating lymphocyte (TIL) lead to higher pCR rates. Adverse events following addition of carboplatin/gemcitabine were mostly hematologic and none required hospitalization. Anemia was the most common grade 3 adverse event observed. No grade 4 toxicity was evident. CONCLUSION: Although the proposed carboplatin/gemcitabine combination could not improve pCR rates as expected, probability of immune activation following use of carboplatin in achieving response to NACT may be considered. Accounting for the highest number of pCR cases in the "intervention" group, the HR+/HER2+ subtype with high TILs may be considered as most responsive to the proposed regimen in this study. It is noteworthy that the proposed combination imposed minimal toxicity. TRIAL REGISTRATION: This trial was prospectively registered in IRCT.ir ( IRCT2017100136491N1 ). Date of registration: 19 November 2017.

Occurrence of residual disease in specimens of re-excision surgery in patients with positive margins of primary quadrantectomy.

Performing a re-intervention following a positive margin after primary lumpectomy in patients with breast cancer entails several disadvantages such as additional costs and postponing the follow-up treatments. In the present study, we sought to measure the incidence rate of residual disease in specimens taken from breast cancer patients who had positive margins after quadrantectomy and also compare the clinical and pathological factors between patients with and without a residual disease after the secondary surgery. All of the medical records of patients undergoing quadrantectomy from December 1994 to December 2019 were collected from Shiraz Breast Cancer Registry (SBCR). Patients were divided into two subgroups of patients with and without residual disease from the secondary surgery and also with and without positive margin from the first operation. Two groups were compared in terms of all clinicopathological factors. The records of 4843 patients undergoing quadrantectomy were reviewed, of which 132 (2.3%) had involved margins. Of these, 112 patients underwent a secondary surgery and 28 had residual disease (25%). No clinicopathological factor was correlated with presence of residual cancer. Also, bigger tumor size (p < 0.001) and the presence of in situ component (p < 0.001) were associated with positive margin and hence the need for a re-excision surgery. These results revealed that the significant rate of residual disease in the specimens of the secondary surgery indicates that a re-operation (either re-excision or simple mastectomy) cannot be omitted after obtaining a positive margin from the primary quadrantectomy.

How accurate is frozen section pathology compared to permanent pathology in detecting involved margins and lymph nodes in breast cancer?

BACKGROUND: Frozen section (FS) pathology has multiple limitations, and different institutions report variable experiences with the use of FS for diagnosis of tumor involvement. We aimed to compare the FS accuracy with that of permanent pathology (gold standard) regarding marginal involvement and lymph node status using data from the largest breast cancer registry in Iran. METHODS: In this retrospective study, women who had both FS and permanent pathology reports were included. The two pathology reports were cross compared with regard to the involvement of tumor margins and sentinel lymph nodes. RESULTS: Overall, 2786 patients entered the study. Mean age of patients was 48.96±11.44 years. A total of 1742 margins were analyzed. Accordingly, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FS pathology for detection of involvement of involved margins were 78.49%, 97.63%, 65.1%, and 98.7%, respectively. The accuracy and area under the curve (AUC) for FS pathology were 96.61% and 0.73 (95% CI: 0.64-0.831), respectively. A total of 1702 sentinel lymph node biopsies were assessed. Sensitivity, specificity, PPV, and NPV, of FS pathology for detection of lymph node involvement, were 87.1%, 98%, 95.5%, and 93.3%, respectively. Accuracy and AUC of FS for diagnosis of involved lymph nodes were 94.1% and 0.926 (95% CI: 0.909-0.942), respectively. CONCLUSION: Frozen pathology is a suitable method for identifying involved sentinel lymph nodes in patients with breast cancer, but this method has a less than optimum efficacy for detecting and confirming marginal involvement.

Diversity of KIRs in invasive breast cancer patients and healthy controls along with the clinical significance in ER/PR/HER2+ patients.

Killer cell immunoglobulin-like receptors (KIR) consists of activating and inhibitory genes are essential for natural killer cell education. To determine the association of KIRs with susceptibility to invasive Breast cancer (BC), genotyping of 16 KIRs was performed by sequence-specific primers-polymerase chain reaction in 226 confirmed cases of BC with defined estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status and 226 healthy controls (CNs). We observed a lower frequency of 2DL1 and 2DS4del along with increased frequency of 2DS4fl in cases compared to CNs. Further analysis revealed a higher frequency of KIR2DL2, 2DS1, 2DS2,3DS1 in ER+ cases, 2DL2, 2DL5 in PR+ and 2DL1 in HER2+ cases compared to CNs. The detrimental role of KIR2DS4fl was observed in ER+ and PR+ cases whereas 2DS4del confers protection against ER+, PR+, and HER2+ cases. We noted the predisposing role of Bx genotype, KIR2DS1, 2DS2, 2DS5, 2DL2, 2DL5 for lymphatic invasion in ER+ cases along with a higher rate of lymph node metastasis (LNM) in carriers of Bx genotype and KIR2DS1 in ER+ cases. We suggest a link between B haplotype associated genes with the increased risk of lymphatic invasion and LNM, particularly in ER+ cases of BC.

Intraoperative radiation therapy in non-breast cancer patients: A report of 26 cases from Shiraz, south of Iran.

Background: Intraoperative radiation therapy (IORT) is the delivery of radiation at the time of surgery. Whereas the dose delivered by external beam radiation therapy (EBRT) is limited by the tolerance of the surrounding normal tissues, IORT allows exclusion of a part or all of the dose-limiting sensitive structures by operative mobilization and/or direct shielding of these structures. The aim of the present study was to report the non-breast cancer patients' outcomes after receiving IORT in Shiraz, Iran. Methods: In this retrospective study, all cases who had received IORT and had non-breast malignancies were selected. Diagnosis was confirmed by biopsy. Additional imaging was done by sonography, magnetic resonance imaging (MRI) and computed tomography (CT). IORT was applied by self-shielded, LIAC 6-12 MeV Sordina mobile linear accelerator. Typically, a single dose of 10-21 Gy was given for maximally resected tumors. The statistical analyses were carried out using SPSS (version 21). Results: Twenty-six patients were treated with IORT alone or combined with EBRT. Different tumors were treated, including colorectal adenocarcinoma (10 cases, 38.4 %), Soft Tissue Sarcomas (STS, 11 cases, 42.3 %), head and neck cancers (3 cases, 11.5 %), one cervix malignancy case and one paravertebral fibromatosis case. Mean ± SD overall survival was 15±14.89 (0-38) and 34.3±15.72 (14-53) months for colorectal cancer and STS, respectively. Conclusion: IORT is mostly useful for pelvic and abdominal malignancies where normal bowel limits the dose that can be delivered with EBRT. However, the dose delivered in a single fraction with IORT is rarely sufficient for tumor control; therefore, IORT is usually preceded or followed by additional EBRT which should be further evaluated preferably in prospective randomized trials.

Chronological changes and trend of breast cancer clinics and pathology among Iranian women during 22 years from the largest breast cancer registry in Iran.

BACKGROUND AND OBJECTIVE: We evaluated clinicopathological changes of breast cancer (BC) during a 22-year time period among the Iranian population. METHODS: This study is part of the largest BC registry in Iran. Patients were categorized as those diagnosed with BC during 1993-2005, 2006-2011, and 2012-2017 and compared regarding baseline characteristics and socioeconomical determinants, and obstetrical/gynecological and BC characteristics. RESULTS: Overall, 688, 1871, and 3020 patients entered the 1993-2005, 2006-2012, and 2012-2017 year groups, respectively. Mean (SD) age at first presentation of BC increased throughout the year groups (47.40 ± 10.34, 49.12 ± 11.70, and 49.43 ± 12.07 years, respectively; p < 0.001). Mean (SD) tumor size increased from 1993-2005 to 2006-2011 and decreased onto 2012-2017 (2.82 ± 1.69, 2.91 ± 1.49, and 2.66 ± 1.52 cm, respectively; p < 0.001). Number of individuals with stage 4 and grade 3 BC also showed an increasing pattern (p < 0.001). Tumor necrosis rates showed an increase onto 2011-2017 (43%, 47.3%, and 56%, respectively; p < 0.001). ER positive (62.4%, 73.4%, and 77.1%, respectively; p < 0.001) and PR positive individuals (59.5%, 64.3%, 72.6%, respectively; p < 0.001) showed an increasing trend. HER2 positive expression rates increased from 1993-2005 to 2005-2011 (24.5% and 31.5%, respectively) and decreased onto 2012-2017 (31.5% and 26.8%, respectively, p < 0.001). Number of involved lymph nodes increased (5.70 ± 6.56, 5.65 ± 6.00, and 5.95 ± 6.99, respectively; p < 0.001). Pattern of BC invasion and recurrence showed significant change (p < 0.001). CONCLUSION: Clinical and pathological characteristics may be showing a changing pattern among the Iranian population.

Mesenchymal stem cells induced anti-inflammatory features in B cells from breast tumor draining lymph nodes.

The immune-modulatory effect of adipose-derived stem cells (ASCs) on B cells in cancer has not been well elucidated. Herein, the interaction between B cells and ASCs isolated from the breast fat of either normal (nASCs) or breast cancer women (cASCs) was investigated. B cells derived from breast tumor draining lymph nodes were co-cultured with nASCs or cASCs and B cells proliferation was assessed in direct and transwell assays. Moreover, B cells were co-cultured with cASCs, nASCs or mesenchymal stromal cells of the tumor tissue (TSCs) and B cell cytokine production was assessed using flow cytometery. cASCs or TSCs were co-cultured with either intact or B cell depleted lymphocytes and frequencies of CD25+ FoxP3+ Tregs, IL-10+ or IFN-γ+ CD4+ T cells were assessed. Results showed that co-culture of B cells with ASCs in transwell chambers did not affect B cell proliferation. nASCs, however, was able to significantly reduce B cell proliferation in direct co-culture experiments (P = 0.004). The frequencies of IL-10+ , TNF-α+ , IL-2+ , and IFN-γ+ B cells were not significantly different in the co-cultures of B cells with ASCs or TSCs. But the TNF-α+ / IL-10+ B cells ratio decreased in all co-cultures, a reduction merely significant in B cell-cASCs co-culture (P = 0.01). The frequencies of CD4+ T cells subsets in either intact or B cell depleted lymphocytes did not undergo significant changes following co-culture with ASCs or TSCs. Therefore, ASCs is capable of inhibiting B cell proliferation in a contact dependent manner and shifting the cytokine profile of B cells toward an anti-inflammatory profile.

Cancer and normal adipose-derived mesenchymal stem cells (ASCs): Do they have differential effects on tumor and immune cells?

Adipose-derived mesenchymal stem cells (ASCs) are known to have immunomodulatory properties through soluble factors or by direct cell-to-cell contact. This study aimed to assess the expression of HLA-G and IDO activity in breast cancer and normal ASCs and to see whether ASC is capable of modulating both tumor cells and immune system cells in vitro. ASCs were enzymatically isolated from 15 breast cancer patients and 10 normal individuals. Then they were cultured, and the impact of their conditioned media on the movement of the MDA-MB-231 breast cancer cell line was studied in wound healing scratch assay. Next, PBLs from the peripheral blood of normal individuals were separated and co-cultured with breast cancer and normal ASCs. PBLs proliferation and apoptosis were assessed using CFSE labeling dye and annexin V/7AAD staining, respectively. IDO activity and HLA-G protein expression in ASCs were examined using kynurenine assay and Western blotting, respectively. Tumor-derived ASCs, especially those from higher stages of breast cancer, have stronger effects on the proliferation and movement of MDA-MB-231 cells than normal ASCs (P-value < 0.05). Apoptosis in PBLs increased in the presence of ASCs compared to PBLs cultured alone (P-value < 0.05). In contrast, necrosis of PBLs decreased in the presence of ASCs compared to apoptosis in these cells (P-value < 0.001). Collectively, ASCs may have strategic effects on both tumor cells and cells of the immune system in the tumor microenvironment, resulting in tumor development, growth, and metastasis.

Introducing novel and comprehensive models for predicting recurrence in breast cancer using the group LASSO approach: are estimates of early and late recurrence different?

BACKGROUND: In here, we constructed personalized models for predicting breast cancer (BC) recurrence according to timing of recurrence (as early and late recurrence). METHODS: An efficient algorithm called group LASSO was used for simultaneous variable selection and risk factor prediction in a logistic regression model. RESULTS: For recurrence < 5 years, age (OR 0.96, 95% CI = 0.95-0.97), number of pregnancies (OR 0.94, 95% CI = 0.89-0.99), family history of other cancers (OR 0.73, 95% CI = 0.60-0.89), hormone therapy (OR 0.76, 95% CI = 0.61-0.96), dissected lymph nodes (OR 0.98, 95% CI = 0.97-0.99), right-sided BC (OR 0.87, 95% CI = 0.77-0.99), diabetes (OR 0.77, 95% CI = 0.60-0.98), history of breast operations (OR 0.38, 95% CI = 0.17-0.88), smoking (OR 5.72, 95% CI = 2.11-15.55), history of breast disease (OR 3.32, 95% CI = 1.92-5.76), in situ component (OR 1.58, 95% CI = 1.35-1.84), tumor necrosis (OR 1.87, 95% CI = 1.57-2.22), sentinel lymph node biopsy (SLNB) (OR 2.90, 95% CI = 2.05-4.11) and SLNB+axillary node dissection (OR 3.50, 95% CI = 2.26-5.42), grade 3 (OR 1.79, 95% CI = 1.46-2.21), stage 2 (OR 2.71, 95% CI = 2.18-3.35), stages 3 and 4 (OR 5.01, 95% CI = 3.52-7.13), and mastectomy+radiotherapy (OR 2.97, 95% CI = 2.39-3.68) were predictors of recurrence < 5 years. Moreover, relative to mastectomy without radiotherapy (as reference for comparison), quadrantectomy without radiotherapy had a noticeably higher odds ratio compared to quadranectomy with radiotherapy for recurrence < 5 years. (OR 17.58, 95% CI = 6.70-46.10 vs. OR: 2.50, 95% CI = 2-3.12). Accuracy, sensitivity, and specificity of the model were 82%, 75.6%, and 74.9%, respectively. For recurrence > 5 years, stage 2 cancer (OR 1.67, 95% CI = 1.31-2.14) and radiotherapy+mastectomy (OR 2.45, 95% CI = 1.81-3.32) were significant predictors; furthermore, relative to mastectomy without radiotherapy (as reference for comparison), quadranectomy without radiotherapy had a noticeably higher odds ratio compared to quadranectomy with radiotherapy for recurrence > 5 years (OR 7.62, 95% CI = 1.52-38.15 vs. OR 1.75, 95% CI = 1.32-2.32). Accuracy, sensitivity, and specificity of the model were 71%, 78.8%, and 55.8%, respectively. CONCLUSION: For the first time, we constructed models for estimating recurrence based on timing of recurrence which are among the most applicable models with excellent accuracy (> 80%).

Do site and type of metastasis in breast cancer show a changing pattern with increased age? A cross comparison of clinicopathological characteristics between age groups.

BACKGROUND: In here, we evaluated pattern of metastasis and cross-compared clinicopathological features between different age groups with breast cancer (BC). METHODS: This study was conducted in the Shiraz Breast Cancer Registry (largest BC registry in Iran). Patients were classified as < 30 years old (group 1), 30-60 years old (group 2), and > 60 years old (group 3). The three age groups were compared regarding clinical and baseline characteristics. RESULTS: Overall, 564 individuals entered group 1, 4519 group 2, and 670 group 3. Group 1 had lower rates of tumor necrosis (p < 0.001), higher lymphatic or vascular invasion (p = 0.002), estrogen receptor-negative individuals, and HER2-positive individuals (p ≤ 0.001). Younger groups had more stage 3 BC (31.1, 25.6, and 19.7% for groups 1, 2, and 3, respectively) (p = 0.016), grade 3 BC (27.4, 20.6, and 16.5% for groups 1, 2, and 3, respectively) (p = 0.001), and grade 3 nucleus (43.1, 34.5, and 27.6% for groups 1, 2, and 3, respectively) (p < 0.001). Group 1 had higher rates of regional metastasis (4.7 vs. 1.5 and 2.1% for groups 2 and 3, respectively). Younger individuals had higher rates of brain metastasis (13.3, 5.4, and 1.1% for groups 1, 2, and 3, respectively). Moreover, those > 60 years old had more lung metastasis (33 vs. 12.6 and 6.7% for groups 2 and 1, respectively) (p < 0.001). Younger groups had more < 5-year recurrence (16.3, 11.7, and 8.9%, for groups 1, 2, and 3, respectively) (p = 0.023). CONCLUSION: Pattern and site of recurrence changes according to age in BC. This brings up the question whether age is an independent predictor of organ of metastasis or is site of metastasis the result of other clinicopathological determinants which differ between age groups.

Medullary Breast Carcinoma and Invasive Ductal Carcinoma: A Review Study.

BACKGROUND: Medullary breast carcinoma (MBC) is a unique histological subtype of breast cancer. The present study aimed to evaluate the classic and non-classic characteristics of MBC and its differences with IDC. The present review study incorporates 22 years of practical experience from a breast disease research center-based series of cases. METHODS: Retrospectively, the medical records of 3,246 patients were reviewed in the Breast Disease Research Center, Shiraz University of Medical Science (Shiraz, Iran), from December 1993 to December 2015. The tumor size, lymph node metastasis, pathologic stage, nuclear and histological grade, hormonal receptor status, recurrence, disease-free, and overall survival were reviewed. Differences between medullary breast carcinoma and invasive ductal carcinoma were analyzed statistically using the Chi-square, Fischer, independent-sample t test, and Kaplan-Meier analysis (SPSS version 19.0). P<0.05 were considered statistically significant. RESULTS: A total of 179 patients were identified with MBC and 3,067 patients were identified with IDC. The MBC group had a significant association with a higher histological grade (P<0.001) as well as negative estrogen receptor (P<0.001), progesterone receptor (P<0.001), and HER-2 (P=0.004) status. The MBC patients predominantly had triple-negative breast cancer (TNBC) according to the molecular subtype (P<0.001). In local invasion, MBC was less invasive compared to IDC (P<0.001). The disease-free survival (DFS) and overall survival (OS) differed significantly between the MBC and IDC groups (5-year DFS: 94.2% vs. 86.3%, P=0.008; 5-year OS: 98.1% vs. 92.8%, P=0.004). CONCLUSION: Despite the poor and aggressive pathological features of MBC, its clinical outcome is more favorable compared to IDC. Our findings can be useful in improvement of diagnosis and treatment of less known breast cancer subtypes, such as MBC.

The Evaluation of Cancer Testis Gene PIWIL2 Expression Levels as a New Prognostic Biomarker for Breast Cancer.

BACKGROUND: Breast cancer is the most prevalent cancer and foremost reason of death resulting from malignancy among women worldwide. In recent years, it has been reported that a group of genes named cancer testis genes (CTg) express in adult immune privileged sites and some embryonic tissues. Likewise, it has been demonstrated that CTgs express aberrantly in various tumors and play essential roles in both initiation and development of cancers. In this study, PIWIL2, one member of CTgs, which has an indispensable role in spermatogenesis and tumorigenesis, was examined as an efficient prognostic and diagnostic biomarker in breast cancer. It is worth mentioning that the expression study of PIWIL2 by qPCR on breast cancer samples was performed for the first time, since this approach is much more sensitive than western blot, RT-PCR, and immunohistochemistry. METHODS: To investigate the expression status of PIWIL2 in breast cancer, 72 fresh cancerous and normal adjacent specimens from 44 patients who had undergone surgery in Shahid Faghihi Hospital were used. None of the patients had received chemotherapy. The relationships between the PIWIL2 status and the clinicopathological parameters were ultimately determined. RESULTS: It was ascertained that the expression rates of PIWIL2 in cancerous breast tissues were related to patients' age, tumor stage, tumor size, tumor grade, and lymph node involvement (p < 0.05). CONCLUSIONS: The PIWIL2 gene could be considered as an efficient prognostic biomarker in breast cancer.

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.