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.

Comparison of volatile/inhalational and IV anesthesia in long-term survival of patients with breast cancer: a retrospective study.

OBJECTIVE: Breast cancer is a worldwide health concern, and surgical removal has remained the preferred therapeutic option in most patients. Furthermore, the current study was designed to investigate the disease-free survival and overall survival in breast cancer patients, who receive either propofol or isoflurane during operation. METHOD: This retrospective study was conducted on 994 patients (IV group, n = 530; volatile/inhalational group, n = 464) who underwent breast cancer operation from January 2006 to December 2016 at Faghihi Hospital, Shiraz, Iran. All studied patients were followed up till 2020. Patients are classified into two groups, IV and volatile/inhalational, according to the received anesthesia. For statistical analysis, The Cox regression test was conducted to investigate the association between factors affecting the recurrence of the disease and the Log Rank test was utilized to assess the patients' survival. Finally, to reduce the effect of confounding factors, all patients were matched according to age, tumor size and tumor grade. RESULTS: Based on results from the log-rank test, the volatile/inhalational group had a better recurrence-free survival (P = 0.039) compared to the total IV group. However, the overall survival was not considerably different (P = 0.520). CONCLUSION: The current study showed that although 2-year disease-free survival is higher in the volatile/inhalational group, there is no meaningful association between the 5-year overall survival and anesthesia technique.

Expression of Interleukin-21 and Interleukin-21 receptor in lymphocytes derived from tumor-draining lymph nodes of breast cancer.

BACKGROUND: Interleukin-21 (IL-21) is produced by various cell types inducing positive and negative effects in immunity against tumors. OBJECTIVE: To investigate the expression of IL-21 by CD4+T and IL-21 receptor (IL-21R) by B lymphocytes isolated from breast-tumor draining lymph nodes (TDLNs). METHODS: Fresh lymph node samples were obtained from 45 patients with breast cancer. To assess IL-21 expression, mononuclear cells were briefly stimulated whereas IL-21R expression was assessed in unstimulated B cells. Cells were stained with antibodies for CD4, IL-21, CD19 and IL-21R and acquired by flow cytometry. RESULTS: The frequency of IL-21+CD4+T cells did not show significant association with disease parameters. However, the geometric mean fluorescence intensity (gMFI) of IL-21 in CD4+T cells was significantly lower in patients with grade III tumor than grade I + II (P = 0.042). In non-involved LNs, the intensity of IL-21 was significantly higher in patients with stage II compared with stage III (P = 0.038) and correlated negatively with the number of involved LNs. The frequency of IL-21R+CD19+B cells was significantly higher in grade III than grade I + II (P = 0.037). CONCLUSION: The higher intensity of IL-21 in CD4+T cells showed association with good prognosticators in breast cancer and warrants further investigation of the role played by IL-21 in immunity against breast cancer.

Pseudoangiomatous stromal hyperplasia of the breast: A case report.

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign breast entity scarcely reported in the medical literature. Its pathogenesis, etiology, and optimal treatment are still unknown. PASH tumors have a broad spectrum of clinical presentations and might be mistaken for malignancies. The authors present six patients diagnosed with PASH.

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.

Cost-Effectiveness Analysis of Intraoperative Frozen Section in Women with Breast Cancer: Evidence from South of Iran.

Background: Breast cancer is one of the most prevalent malignancies in women worldwide, and the rate of breast cancer is increasing among Iranian women. The purpose of this study is to determine the cost-effectiveness of intraoperative frozen section analysis in women with breast cancer. Methods: This study was a cost-effectiveness analysis, which was implemented as a cross-sectional study from a societal perspective. In this case, total direct and indirect costs were calculated, and the study outcome was involved in preventing reoperation. A data collection form has been used to collect the cost and effectiveness data. The sample size was comprised of all the patients referred to the hospitals of Shiraz University of Medical Sciences for breast cancer surgery in 2019. The patients were studied in two different groups, including individuals who received frozen counseling during surgery, and individuals who did not receive it. A one-way sensitivity analysis was performed for this case. Moreover, the Tree Age and Microsoft Excel Software were employed for analyzing processes. Results: The results demonstrated that the mean costs of frozen and non-frozen patients were 4168$ and 3843$ purchasing power parity (PPP), respectively. In addition, the effectivenesses were 0.996 for the former and 0.8 for the latter. Furthermore, the incremental cost-effectiveness ratio (ICER) was 1658.2 PPP$. This issue revealed that the frozen section procedure during surgery was more cost-effective than the other case. Because, the cost-effectiveness of this option was below the threshold. Besides, the one-way sensitivity analysis confirmed the robustness of the study results. Conclusion: The results showed that performing frozen sections during surgery in women with breast cancer was more cost-effective than ignoring them. Indeed, the frozen section can prevent the costs of subsequent reoperations.

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.

Determination of Oncologic Outcomes, Satisfaction, and Psychosocial Well-being in Patients with Breast Cancer after Oncoplastic and Conventional Breast Conserving Surgery.

Background: Breast cancer is the most common cancer in women and surgery is necessary for its treatment. We aimed to determine the oncologic outcomes, satisfaction with breasts, and psychosocial well-being in the patients with breast cancer, after oncoplastic and conventional breast conserving surgery (BCS). Method: The patients with breast cancer from Shahid Motahari Clinic affiliated to Shiraz University of Medical Sciences, Shiraz, Iran from December 2020 to December 2021 were allocated to two groups, one who had undergone BCS alone and the patients who had undergone oncoplastic BCS. For all the patients, demographic data, data about surgery, oncologic outcomes, wound complications, and BREAST-Q© questionnaire score were collected and compared between two groups. Result: The mean age of the patients in the oncoplastic BCS and BCS group was 48.13±9.73 (median=48), and 50.01±8.47 (median=50) years, respectively. The mean score of psychosocial well-being was higher in the oncoplastic BCS group in comparison with BCS alone. (P-value< 0.0001). Also, the mean score of satisfaction with breast was higher among the oncoplastic BCS group in comparison with the BCS group (P-value< 0.0001). Conclusion: Replacing traditional BCS with oncoplastic BCS does not adversely affect the oncologic results of surgery but improves the consequent psychosocial well-being and satisfaction in the patients.

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.

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.

Regulatory T cells express Tumor Necrosis Factor Receptor 2 with the highest intensity among CD4+ T cells in the draining lymph nodes of breast cancer.

Tumor Necrosis Factor Receptor 2 (TNFR2) is one of the receptors of TNF-α, which is expressed on various cell types. TNFR2 signaling has a balancing role between regulatory and effector functions of T cells. Herein, we investigated the expression of TNFR2 on regulatory T cells (Tregs) and non-Tregs in breast tumor-draining lymph nodes. Mononuclear cells were isolated from 16 axillary lymph nodes, and the expressions of TNFR2, Foxp3 and CD25 were assessed in CD4+ T cells by flow cytometry. Our results showed that the majority of TNFR2+CD4+ T cells were Foxp3-CD25-. However, the percentage of TNFR2+ cells was significantly higher in Foxp3+CD25+CD4+ Tregs compared to Foxp3-CD25-CD4+, Foxp3+CD25-CD4+, and Foxp3-CD25+CD4+ T cell subsets. Among these subsets, Foxp3+CD25+TNFR2+CD4+ T cells were found to have the highest intensity of TNFR2 expression. The intensity of Foxp3 expression in Foxp3+CD25+TNFR2+CD4+ Treg cells was significantly higher than in their TNFR2- counterpart. Collectively, we showed that most of TNFR2+CD4+ T lymphocytes were Foxp3-CD25-, while the majority of Foxp3+CD25+CD4+ Tregs were TNFR2+, and they expressed TNFR2 with the highest intensity. This report highlights the importance of TNFR2 expression on Tregs and paves the way for further investigation of the effects of TNF-α on the suppressive activity of Tregs in the tumor microenvironment.

Determinants of Prognosis in Triple-Negative Breast Cancer: Report from a Large Breast Cancer Registry.

BACKGROUND: The outcome of patients with triple-negative breast cancer (TNBC) is highly dependent on demographic factors and ethnicity. We aimed to evaluate the clinicopathological determinants of prognosis among women with TNBC using data from one of the largest breast cancer (BC) registries. METHODS: A total of 6145 patients with BC from our referral center were evaluated from 1995 to 2018, among whom 523 had TNBC. The baseline, menstrual and reproductive, treatment and pathology related characteristics were evaluated. RESULTS: Among TNBC patients, the rate of stage 3 and 4 BC (29.9% vs. 14.4% and 7.8% vs. 0% for stage 3 and 4, respectively; P<0.001), invasive ductal carcinoma (90.7% vs. 75.6%; P=0.004), nodal involvement (46.7% vs. 33.4%; P=0.026), mastectomy (57.3% vs. 37.8%; P=0.001) and axillary node dissection (76.7% vs. 59.8%; P=0.019) was significantly higher in the group that developed recurrence. Disease-free-survival was 80.6% (157.76 ± 9.48 months) and overall-survival was 90.1% (182.73 ± 3.28 months). For death, stage 3 BC (compared to stages 0 and 1 as base) showed a higher risk of earlier death (adjusted HR: 4.191, 95% CI=1.392-12.621; P=0.011). For recurrence, stage 3 BC (adjusted HR: 1.044, 95% CI=1.209-6.673; P=0.017) (compared to stages 0 and 1 as base) showed significantly higher risk for developing earlier recurrence. Moreover, those who had invasive ductal carcinoma (compared to other types of BCs) had a higher risk for developing earlier recurrence (adjusted HR: 3.307, 95% CI=1.191-0.724; P=0.012). CONCLUSION: BC stage plays a significant role in both earlier recurrence and earlier mortality among patients with TNBC.

Tumor infiltrating NK cell (TINK) subsets and functional molecules in patients with breast cancer.

INTRODUCTION: NK cells have been introduced as the main innate arm of immunity against malignancies. Recent advances introduced new subsets of, and new effector molecules on NK cells suggesting new paradigms for NK cell functions in tumor immunity. Considering these new paradigms, in the current research we investigated the frequency of tumor infiltrating NK cell (TINK) subsets and their functional molecules in breast tumor tissues by flowcytometry method. METHODS: Breast tumor tissues were obtained from 32 untreated patients with breast cancer. The tissues were then minced mechanically to acquire a single cell suspension and surface-stained with monoclonal antibodies against CD3, CD56, CD11b, CD27, NKG2A, NKG2D and CXCR3. For intracellular staining (ICS), the surface-stained cells were then fixed, permeabilized and stained with anti-Perforin and anti-Granzyme B antibodies. The samples were run and the data were acquired on a four-color flowcytometer. RESULTS: The cell suspension derived from tumor tissue encompassed 3.10 ± 0.52 % CD3-CD56+(bright/dim) total NK cells. Based on the conventional classification the percentages of cytotoxic (CD3- CD56dim) and regulatory (CD3- CD56bright) NK cells were respectively 1.74 ± 0.24 % and 1.36 ± 0.48 %. According to the new classification the percentages of cytotoxic (CD3- CD56+ CD11b+ CD27-), regulatory (CD3-CD56+ CD11b+/- CD27+) and tolerant (CD3-CD56+ CD27- CD11b-) NK cells were respectively 0.48 ± 0.07, 1.55 ± 0.34 and 1.15 ± 0.51. A significant higher frequency of total NK cells (CD3-CD56+ (bright/dim)) in the breast tumor tissues of the patients whose tumor draining lymph nodes (TDLNs) has not been yet involved by tumor cells (LN- patients) compared with the ones with lymph nodes involvement (LN+) (5.91 ± 1.79 % Vs. 2.20 ± 0.20 %, P < 0.004). Furthermore, NK cells with overexpressed activating receptor; NKGD2 (CD3- CD56+(bright/dim) NKG2D+ NK cells) was observed to be elevated in LN- patients compared with the LN+ ones (70.01 ± 7.96 Vs. 42.5 ± 4.81, P < 0.011). Correlation analysis revealed the percentages of conventional regulatory NK cells (CD3- CD56bright) in breast tumor tissue to be in positive correlation with the tumor size (R = 0.380, P < 0.04). The mean percentage of this cell subset was also observed to be higher in patients with T3 tumor size compared with smaller T1 tumor size (1.61 ± 0.20 % vs. 0.75 ± 0.15 %, P < 0.023. CONCLUSION: Our observations suggest that accumulation of NK cells as well as the expression of activating NKG2D receptor by TINKs may play roles in breast tumor regression especially in the LN- patients. As the tumor growths and the size of tumor increases the accumulation of regulatory NK cells may facilitate the tumor improvement. These observations may have implications in cancer NK cell-based immunotherapy.

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.

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.

Significance of TIM-3 expression by CD4+ and CD8+ T lymphocytes in tumor-draining lymph nodes from patients with breast cancer.

T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which is expressed by immune and nonimmune cells, has been shown to play immunoregulatory roles in the tumor microenvironment. In this study we assessed the expression of TIM-3 by T cells from tumor draining lymph nodes (TDLNs) of patients with breast cancer and its association with disease progression. Lymphocytes were isolated from 41 TDLNs, and flow cytometry was used to determine the expression of TIM-3 on CD4+ and CD8+ T cells, along with the simultaneous expression of CD25, Foxp3 and TIM-3 in CD4+ T cells. The results showed that the frequency of TIM-3+CD8+ T cells was associated with higher tumor grade, and the geometric mean fluorescence intensity (gMFI) of TIM-3 in CD4+ and CD8+ T cells was significantly higher in patients with more than 9 involved lymph nodes than those with fewer involved nodes. The gMFI of TIM3 in CD4+ T cells also showed a direct correlation with the number of metastatic lymph nodes. Phenotypic characterization of TIM-3+CD4+ T cells showed that the majority of CD4+TIM3+ lymphocytes were Foxp3 ̶ CD25 ̶, and the majority of Foxp3+CD25+ regulatory T cells were TIM-3-. Our findings showed that TIM-3 was expressed by CD4+, CD8+ and regulatory T cells in breast TDLNs, and that expression on CD4+ and CD8+ T cells was mostly associated with poor prognosticators such as a higher number of involved lymph nodes or higher tumor grade. More studies are required to confirm TIM-3 as a prognostic marker and a target for immunotherapy in breast cancer.

The Effects of Low HER2/neu Expression on the Clinicopathological Characteristics of Triple-Negative Breast Cancer Patients.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer (BC), and its diagnosis is associated with negative expression of hormone receptors and HER2/neu. It consists of 10-20% of all BCs diagnosed. METHODS AND MATERIALS: This study focuses on three groups with different pathology: group one showed complete triple-negative HER2 expression with IHC of BC; groups two and three included patients with ER-, PR-, and HER21+, and ER-, PR-, and HER22+ with a negative FISH test. These three groups were compared from the point of prognosis, which consisted of tumor size, patients' age, lymphatic, vascular and perineural invasion, organ metastasis, number of lymph nodes involvement, and the survival rate. RESULTS: A total of 459 TNBC patients were enrolled, of which 268 were placed in the HER20 group, 146 in the HER21+ group, and 45 in the HER22+ group. Distant metastasis and recurrence rate were more common in HER20 patients, but bone metastasis was more common in patients with low HER2 expression. All patients with HER20 had a smaller tumor size at the time of BC diagnosis in comparison to patients in the low HER2 expression group. Patients with HER22+ had less lymphatic and vascular invasion as well as axillary lymph nodes involvement, but larger tumor size at presentation, resulting in a lower rate of recurrence and higher overall survival. CONCLUSION: The findings revealed that patients with HER22+ had better outcome in comparison to the patients with HER20 and HER21+. Furthermore, the results showed that many patients with HER22+ expression were not basal-like and had good prognosis amongst TNBC patients.

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.

The balance of regulatory and stimulatory B cell subsets in breast cancer draining lymph nodes correlates with tumor prognostic factors.

AIMS: B cells can promote or inhibit immune responses against breast cancer. We investigated changes in the frequency of B cells with stimulatory or regulatory capacity in breast tumor draining lymph nodes during cancer progression. MAIN METHODS: We isolated mononuclear cells from fresh axillary lymph nodes (LNs) of 44 patients with breast cancer and stained lymphocytes with antibodies against CD19, CD80, CD86, CD39 and CD73. To assess programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) expression, lymphocytes were briefly stimulated, stained for CD19, PD-1 and PD-L1, and examined with flow cytometry. KEY FINDINGS: The frequency of CD80+ B cells was higher in nonmetastatic lymph nodes, while the percentage of CD86+ B cells showed a positive relationship with higher tumor grade and higher numbers of involved LNs. A small proportion of unstimulated B cells expressed PD-1 or PD-L1 but these molecules were rapidly upregulated on B cells following activation. The frequency of stimulated PD-L1+ B cells showed an inverse association with estrogen and progesterone receptor expression and a nonsignificant positive association with tumor grade. In addition, the percentage of unstimulated PD-1+ B cells was higher in patients with higher-grade tumors. CD73 expression on B cells was associated with lower numbers of involved LNs, and the frequency of CD39+ B cells was higher in patients with larger tumors. SIGNIFICANCE: CD86+, CD39+, PD-1+ and PD-L1+ B cells showed associations with poor prognostic factors, therefore their potential role in the suppression of the immune responses against breast cancer should be evaluated in greater detail.