Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

Turmeric Inhibits MDA-MB-231 Cancer Cell Proliferation, Altering miR-638-5p and Its Potential Targets.

Objective: Recent research suggests curcumin extracted from the turmeric plant may inhibit the proliferation of cancer cells by controlling the expression of microRNAs (miRNAs). The effect of phenolic curcumin on miR-638-5p and potential target gene expressions in the triple negative breast cancer (TNBC) cell line MDA-MB-231 was investigated in this study. Materials and Methods: GSE154255 and GSE40525 datasets were downloaded and analyzed using GEO2R to identify dysregulated miRNAs in TNBC. To find differently expressed genes in breast cancer (BRCA), The Cancer Genome Atlas Program data was examined. Utilizing in silico tools, KEGG, GO, and other enrichment analyses were performed. The databases miRNet, miRTarBase v8.0, and TarBase v.8 were used for miRNA and mRNA matching. Real-time quantitative reverse transcription polymerase chain reaction was used to examine the levels of miRNA and its targets in miRNA mimic transfected/curcumin-treated MDA-MB-231 cultures and controls. The cell viability detection kit-8 method was used to assess cell viability, and the scratch assay was used to conduct migration assessment. Results: Bioinformatics analysis showed that miR-638-5p was significantly reduced in TNBC patients. Experimental results showed that miR-638-5p was upregulated in MDA-MB-231 treated with curcumin, while the potential target genes of miR-638-5p, CFL1, SIX4, MAZ, and CDH1 were downregulated. Mimic miR-638-5p transfection inhibited MDA-MB-231 cell proliferation and reduced migration and expression of CFL1, SIX4, and MAZ genes was decreased in mimic miR-638-5p transfected cells. Conclusion: These findings suggest that curcumin exerts its anticancer effects on MDA-MB-231 cells by modulating the expression of miR-638-5p and its possible target genes.

A Novel Surgical Technique for Gynecomastia: Air-Assisted Minimally Invasive Surgery With Single Axillary Incision.

BACKGROUND: Gynecomastia is a benign condition that develops due to the proliferation of breast tissue in men. Surgical excision is the most effective treatment method. Minimally invasive techniques can be used to avoid visible scarring. We evaluated the efficacy and safety of air-assisted subcutaneous mastectomy in the treatment of gynecomastia. PATIENT AND METHODS: 10 patients with gynecomastia underwent air-assisted subcutaneous mastectomy and liposuction through a single axillary incision, between June 2022 and February 2023. Demographic and clinical data of the patients, duration of surgery, and complications were recorded. The satisfaction levels of the patients regarding physical appearance, mental status, and social environment were measured. The body Q questionnaire was performed preoperatively and in the postoperative third month. RESULTS: The median age was 26 (range, 18-54). Surgical excision was measured as a median of 69 gr (range, 41-177), and liposuction volume was measured as a median of 210 ccs (range, 63-400). The median operation time was 50 minutes (range, 21-60) for excision and 21 minutes (range, 20-75) for liposuction. Body, chest, and nipples related appearance satisfaction levels were measured preoperatively as a median of 44 (range, 36.5-52), 31 (range, 27.5-39), and 51.5 (range, 21-69.8) points vs postoperatively as 92 (range, 92-100), 93 (range, 93-94.8) and 90 (range, 90-100) points, respectively. The patients had a median follow-up of 6 months (range, 3-11). No complications were observed during the follow-up period. CONCLUSION: Air-assisted subcutaneous mastectomy and liposuction is a feasible technique that may provide good cosmetic outcomes by avoiding anterior chest wall scarring.

Local steroid injection in severe idiopathic granulomatous mastitis as a new first-line treatment modality with promising therapeutic efficacy.

Background: Intralesional steroid injection has recently evolved as a novel treatment modality for localized idiopathic granulomatous mastitis (= IGM). We aimed to explore the therapeutic efficacy of local steroid injections (LSI) in patients with severe IGM. Methods: Fifty-one patients diagnosed with severe IGM were included in the study and treated with either local steroid injection (LSI) alone (n = 25) or combined LSI with systemic oral steroid treatment (OST) (n = 26). The local steroid injection protocol included an intralesional triamcinolone acetonide injection into the palpable granulomas every 4-week, and topical administration of steroid-containing pomades twice a day on the affected surface of the breast. Patients with a combined LSI and OST received low-dose oral methylprednisolone (<16 mg). Results: Patients with LSI alone required more LSI applications than those in the combined LSI with OST group (LSI: 5 ± 2.9; vs. LSI/OST: 3.5 ± 2.5; p = 0.080) to obtain an effective optimum therapeutic response. At a median of 12 months (range, 4-42), no difference was found in complete response rates between patients in the LSI group and the combined LSI group with OST (52 vs. 53.9%, p = 0.999). However, steroid-related systemic side effects were lower in the LSI alone group (p < 0.008). Conclusion: Local steroid injection could be considered as the first-line treatment in patients with severe IGM until a therapeutic response has been obtained either as the sole treatment modality or combined with oral steroids. Compared with systemic oral steroid therapy, local steroid administration can be considered a new treatment modality with fewer side effects.

Long-term outcomes and predictors of recurrence in node-negative early stage breast cancer patients.

BACKGROUND: We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study. METHOD: Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient's demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test. RESULTS: A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65 years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45 cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence. CONCLUSIONS: Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

Ozone therapy as a novel complementary therapeutic approach in refractory idiopathic granulomatous mastitis.

Background: Autoimmunity may play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). The therapeutic potential of ozone therapy has recently been shown in rheumatological diseases, and this study aimed to assess the clinical efficacy of ozone therapy (OT) in refractory IGM. Methods: Patients with biopsy-verified IGM and incomplete response after steroid therapy (n = 47) between 2018 and 2021 were enrolled. Of these, 23 cases in cohort A had standard treatment with further steroid therapy (ST), and 24 were treated with systemic OT via autohemotherapy (AHT) in addition to steroid therapy (cohort B). Results: The median age was 33 years (range, 24-45). Patients in cohort B had a higher complete response rate after completion of a four-month ozone therapy than those in the ST-group (OT-group, 37.5% vs. ST-group, 0%; p = 0.002). At a median follow-up of 12 months (range, 12-35), the patients treated with OT had a lower one-year recurrence in the affected breast than cases in cohort A treated with ST (OT-group, 21% vs. ST-group, 70%; p = 0.001). No significant side effects were observed in patients in cohort B related to AHT. Furthermore, OT significantly decreased the total steroid treatment duration (median week of steroid use; 26 weeks in cohort A vs. 12 weeks in cohort B; p = 0.001). Conclusion: Systemic OT increases the complete response rate and decreases the duration of steroid treatment in patients with refractory IGM. Therefore, ozone therapy is an effective, well-tolerated, and safe novel complementary therapeutic modality.

Diverging prognostic effects of CD155 and CD73 expressions in locally advanced triple-negative breast cancer.

Background: Immune checkpoint inhibition, combined with novel biomarkers, may provide alternative pathways for treating chemotherapy-resistant triple-negative breast cancer (TNBC). This study investigates the expression of new immune checkpoint receptors, including CD155 and CD73, which play a role in T and natural killer (NK) cell activities, in patients with residual TNBC after neoadjuvant chemotherapy (NAC). Methods: The expression of biomarkers was immunohistochemically examined by staining archival tissue from surgical specimens (n = 53) using specific monoclonal antibodies for PD-L1, CD155, and CD73. Results: Of those, 59.2% (29/49) were found to be positive (>1%) for PD-L1 on the tumour and tumour-infiltrating lymphocytes (TILs), while CD155 (30/53, 56.6%) and CD73 (24/53, 45.3%) were detected on tumours. Tumour expressions of CD155 and CD73 significantly correlated with PD-L1 expression on the tumour (p = 0.004 for CD155, p = 0.001 for CD73). Patients with CD155 positivity ≥10% were more likely to have a poor chemotherapy response, as evidenced by higher MDACC Residual Cancer Burden Index scores and Class II/III than those without CD155 expression (100% vs 82.6%, p = 0.03). At a median follow-up time of 80 months (range, 24-239), patients with high CD73 expression showed improved 10-year disease-free survival (DFS) and disease-specific survival (DSS) rates compared to those with low CD73 expression. In contrast, patients with CD155 (≥10%) expression exhibited a decreasing trend in 10-year DFS and DSS compared to cases with lower expression, although statistical significance was not reached. However, patients with coexpression of CD155 (≥10%) and low CD73 were significantly more likely to have decreased 10-year DFS and DSS rates compared to others (p = 0.005). Conclusion: These results demonstrate high expression of CD73 and CD155 in patients with residual tumours following NAC. CD155 expression was associated with a poor response to NAC and poor prognosis in this chemotherapy-resistant TNBC cohort, supporting the use of additional immune checkpoint receptor inhibitor therapy. Interestingly, the interaction between CD155 and CD73 at lower levels resulted in a worse outcome than either marker alone, which calls for further investigation in future studies.

Evaluation of Benign Breast Diseases With or Without Atypical Epithelial Hyperplasia Accompanying Radial Scars.

Objective: A radial scar (RS) is a benign breast lesion (BBL) that has an obscure etiology. RS is easily confused with breast carcinoma and therefore correct identification radiologically and pathologically is important. The aim of this study was to determine the incidence of atypical lesions by evaluating RS detected with BBL and to investigate whether atypia and RS are related to their characteristics. Materials and Methods: A total of 1.370 patients with a diagnosis of BBL postoperatively in a single department were analyzed retrospectively. Forty-six confirmed RS/complex sclerosing lesion (CSL) cases were selected. The demographic and clinical characteristics of the patients and the relationship between RS and other BBL were evaluated. In addition, the relationship between RS/CSL and the presence of atypia was interpreted. Results: The mean age was 45.17±8.72 years. Spiculated lesion (34.8%) on mammography and microcalcification (37%) on histopathological examination were the most common features. The most common BBL accompanying RS/CSL was adenosis. Atypical epithelial hyperplasia (AEH) was presented in 15 (32.6%) of those diagnosed with RS. Although all patients were benign, the frequency of AEH accompanying RS was found to be significantly higher. The mean size of RS was 10.8±8.4 mm (2-30 mm). The size of RS/CSL was not significantly associated with atypia. Conclusion: RS/CSLs usually present as suspicious lesions that must be distinguished radiologically from malignancy. However RS, which can be present with malign breast lesions, can be also seen with all BBL. Therefore, core biopsy and/or excisional biopsy continue to be important for definitive histopathological diagnosis.

Pure Tubular Breast Carcinoma: Clinicopathological Characteristics and Clinical Outcomes.

Objective: Tubular breast carcinoma (TBC) is a rare subtype of breast carcinoma (BC) with a good prognosis. In this study, we aimed to assess the clinicopathological characteristics of pure TBC (PTBC), analyze factors that may influence long-term prognosis, examine the frequency of axillary lymph node metastasis (ALNM), and discuss the need for axillary surgery in PTBC. Materials and Methods: Fifty-four Patients diagnosed with PTBC between January 2003 and December 2020 at Istanbul Faculty of Medicine were included. Clinicopathological, surgical, treatment, and overall survival (OS) data were analyzed. Results: A total of 54 patients with a mean age of 52.2 years were assessed. The mean size of the tumor was 10.6 mm. Four (7.4%) patients had not undergone axillary surgery, while thirty-eight (70.4%) had undergone sentinel lymph node biopsy and twelve (22.2%) had undergone axillary lymph node dissection (ALND). Significantly, four (33.3%) of those who had undergone ALND had tumor grade 2 (p = 0.020) and eight of them (66.7%) had ALNM. Fifty percent (50%) of patients who were treated with chemotherapy had grade 2 and multifocal tumors and ALNM. Moreover, the frequency of ALNM was higher in patients with tumor diameters greater than 10 mm. Median follow-up time was 80 months (12-220). None of the patients had locoregional recurrence, but one patient had systemic metastasis. Furthermore, five-year OS was 97.9%, while ten-year OS was 93.6%. Conclusion: PTBC is associated with favorable prognosis, good clinical outcomes and high survival rate, with rare recurrences and metastases.

Effect of Cold Therapy on Managing Postoperative Pain Following Breast Conserving Surgery.

BACKGROUND: Cold therapy is an important non-pharmacologic method used for pain relief. AIM: In the present study, we aimed to evaluate the therapeutic effect of cold therapy on managing postoperative pain following breast-conserving surgery (BCS) and assess its effect on recovering quality. METHOD: The study was planned and implemented as a randomized controlled clinical study. Sixty patients with breast cancer were included in this study. All patients underwent BCS at Istanbul Faculty of Medicine. There were 30 patients in both the cold therapy and control groups. In the cold therapy group, a cold pack was placed around the incision line for 15 minutes every hour from the first hour after the operation until the 24th hour. To all the patients in both groups, pain levels were measured by visual analog scale (VAS) at the postoperative 1st, 6th, 12th, and 24th hours, respectively, and the quality of recovery was evaluated by a Quality of Recovery-40 questionnaire at the postoperative 24th hour. RESULTS: The patients' median age was 53 (range: 24-71). All patients were T1-2 clinically and had no lymph node metastasis. Interestingly, the mean of pain level in the cold therapy group was statistically significantly lower in the first 24 hours (1st, 6th, 12th, and 24th hours) of the postoperative period (p = .001). Notably, the cold therapy group had higher recovering quality than the control group. In the first 24 hours, only 4 (12.5%) patients in the cold therapy group received additional analgesics, whereas all patients (100%) in the control group received additional analgesics (p = .001). CONCLUSIONS: Cold therapy is an easy and effective non-pharmacologic method for pain relief after BCS in patients with breast cancer. Cold therapy reduces the acute pain of the breast and contributes to the quality of recovery of those patients.

Is Breast Conserving Surgery Efficacious in Breast Cancer Patients with BRCA1 or BRCA2 Germline Mutation?

Background: The optimal surgical therapy for newly diagnosed breast cancer with germline mutations in susceptibility genes is still uncertain for many physicians. In this study, we aimed to determine the efficacy of breast conserving surgery (BCS) in breast cancer patients with BRCA1 or BRCA2 mutation by assessing its outcomes and locoregional recurrence (LR) rates. Materials and Methods: Seventy-five patients operated with BCS or mastectomy for breast cancer between 2006 and 2017 and had BRCA1 or BRCA2 mutation were included in the study. Effects of the performed breast surgery and clinicopathological characteristics on surgical outcomes, LR rates and survival were analyzed with showing the distribution of BRCA1 and BRCA2 germline mutations. Results: The median age of the patients was 42 years (20-77). BRCA1 mutations were found in 46 (61.3%) patients and BRCA2 mutations in 29 (38.7%) patients. Compared to BRCA2 carriers, BRCA1 carriers were more likely to have higher tumor grade (84.8% vs 44.8%; p = 0.001) and non-luminal subtype tumors (67.4% vs 13.8%; p = 0.001). A total of 44 (58.7%) patients underwent unilateral mastectomy and 31 (41.3%) patients underwent BCS. At a median follow-up time of 60 (12-240) months, LR was observed in 6 patients equally divided in both BCS and mastectomy groups. LR rates were slightly higher after BCS versus mastectomy (9.7% and 6.8%, respectively). Additionally, there were no statistically significant differences in disease-free survival (DFS) and disease-specific survival (DSS) rates after 10 years in the BCS group versus the mastectomy group (p = 0.117 and 0.109, respectively), but in fact, the rates were better in the BCS group. Conclusion: Our findings indicate that BCS may serve as an efficacious alternative to mastectomy for breast cancer patients with BRCA1 or BRCA2 mutation. Additionally, tumor size, lymph node positivity, and TNM stage should be taken into consideration for a better surgical decision-making.

Single axillary incision endoscopic surgery and liposuction for gynecomastia.

Gynecomastia is a common type of breast tissue hypertrophy in men. Surgical excision is the most effective treatment for this condition. Minimally invasive surgical techniques can be used to avoid visible chest scarring. In this study, we evaluated the efficacy and safety of single-axillary-incision endoscopic mastectomy and liposuction for the treatment of gynecomastia. Nipple-sparing mastectomy via a single-port axillary incision was successfully performed in all patients. Twenty-four bilateral procedures were performed in total. Twenty patients underwent liposuction concomitantly. The median weight of the mastectomy pieces was 88.5 g (range: 42.5-440 g), and the median amount of liposuction was 262.5 cc (range: 25-350 cc). The median duration of surgery was 120 minutes (range, 73-195 minutes). Two patients developed a seroma, and 1 patient developed a hematoma in the early postoperative period. The mean satisfaction levels related to physical appearance, mental status, and social environment were 8.75 (standard deviation [SD]: 1.19), 9.17 (SD: 1.44), and 9.33 (SD: 0.76) points, respectively, on a 10-point visual analog scale. Endoscopic single-port nipple-sparing mastectomy combined with liposuction is a technically feasible method to avoid anterior chest wall scarring with good cosmetic results. Between June 2021 and June 2022, 30 patients underwent endoscopic single-port nipple-sparing mastectomy through a small axillary incision, while 20 underwent concomitant liposuction. The demographic information of the patients, duration of surgery, amount of tissue removed, and complications were recorded. Patients' levels of satisfaction with their physical appearance, mental status, and social environment were measured.

Surgery for phyllodes tumour of the breast. What should be surgical margins?

BACKGROUNDS: Optimal and tailored surgical treatment of phyllodes tumour(PT) of the breast is controversial. This study aims to determine the appropriate surgical margin in the treatment of PT. METHODOLOGY: The data of 132 patients who underwent breast surgery with the diagnosis of PT at the Breast Unit of Istanbul Faculty of Medicine from 2000 to 2022 were retrospectively reviewed. RESULTS: Median age was 38 and patients with benign PT were younger than others(median age was 34, 44, and 43 for benign, borderline, and malignant, respectively) (P = 0.001). Local recurrence was observed in 7 (5.3%) patients, systemic recurrence was observed in 3 (2.3%) patients, and disease-related death was observed in 2 (1.5%) patients. Local recurrence occurred in 1.4% (n = 1) of benign tumours, 8.3% (n = 2) of borderline tumours, and 10.3% (n = 4) of malignant tumours. All of the systemic recurrences and deaths were seen in the malignant group. The local recurrence rate was found to be higher in borderline and malignant tumours with surgical margins less than 10 mm (44.4% versus 3.7%, P = 0.003), and tumours larger than 5 cm (11.8% versus 1.3%, P = 0.015). In comparison, there was no correlation between the surgical margin proximity, tumour diameter, and local recurrence rates in benign PT (P > 0.05). CONCLUSION: According to our findings, negative surgical margins seem to be sufficient in the treatment of benign phyllodes tumours. Furthermore at least 1 cm negative surgical margins must be achieved for malignant and borderline phyllodes tumours to avoid local recurrence.

Ozone therapy restores immune dysfunction in refractory idiopathic granulomatous mastitis as a novel potential therapeutic approach.

Immunological dysfunction has been suggested to play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). We recently showed that ozone therapy was effective in patients with steroid-resistant IGM. This study assessed alterations in intracellular cytokine expression patterns in different T-lymphocyte subsets after ozone therapy in refractory IGM. Peripheral blood T lymphocyte subsets (CD8+ , CD4+ , CD4+ CD25+ CD127- ) were analyzed via flow-cytometry for intracellular cytokine expressions IFN-γ, TNF-α, IL-10, and TGF-ß before and after completion of 4-month systemic ozone therapy. Ozone therapy significantly increased the CD4+ IFN-γ+ (p = 0.032), CD4+ TNF-α+ (p = 0.028), and the CD8+ TNF-α+ (p = 0.012) T cells. In contrast, significant decreases in CD4+ IL-10+ (p = 0.047) and CD8+ IL-10+ T cells (p = 0.022) and CD4+ CD25+ CD127-//low Treg cells secreting TGF-ß (p = 0.005) were found after ozone therapy. When patients were analyzed according to the response to ozone therapy, patients with a complete remission were more likely to have increased CD3- CD16+ CD56+ natural killer cells (p = 0.0027) and decreased CD19+ B lymphocytes (p = 0.046) following ozone therapy. Our results suggest that ozone therapy stimulated a T-helper-1 response associated with IFN-γ production and downregulation of TGF-ß expression in CD4+ CD25+ CD127- Treg cells. These alterations in the immune system following ozone therapy can improve wound healing and restore immune dysfunction in patients with refractory IGM.

Pure Mucinous Breast Carcinoma With a Favorable Tumor Biology and Clinical Outcomes.

Objective: A few studies suggest that mucinous breast carcinoma (MBC) is a rare breast carcinoma with good prognostic features. Therefore, the aim of this study was to evaluate biological features and clinicopathological characteristics of pure mucinous breast carcinoma (PMBC) to determine clinical outcome in PMBC. Materials and Methods: The data of 87 patients diagnosed with PMBC between November 2004 and February 2022 were retrospectively analyzed in terms of clinicopathological and demographic characteristics, management, and outcome. Results: The majority of the patients in this study were female, with a median (range) age of 63 (28-90) years. Out of 87 patients, 60 had breast conserving surgery, 27 had a mastectomy, 58 had sentinel lymph node biopsy (SLNB), and 24 had axillary dissection due to a positive SLNB or clinical axilla. Due to age and comorbidities, five patients were not suitable for axillary surgery. The median largest tumor diameter was 23 (5-100) mm. Only 23 patients (26.4%) received adjuvant chemotherapy, whereas almost all patients received hormone therapy. The median duration of follow-up was 53 (6-207) months. There was no local or systemic recurrence in any of the patients. Only 10 patients (11.5%) died from non-cancer causes during the follow-up and treatment period. In this study, tumor diameter was significantly higher in grade II/III tumors (p = 0.039) and in patients under the age of 50 (p = 0.027). Furthermore, lymph node metastasis was statistically significantly more likely in patients under the age of 50 (60% versus 40%, p = 0.013). Patients who had not received chemotherapy or radiotherapy tended to be older than 50 years (p = 0.002). Conclusion: In this study, the majority of patients were in the luminal subgroups with excellent prognosis and low incidences of lymph node metastasis. As a result, PMBC has favorable tumor biology. We believe that minimal axillary surgery would be the most appropriate approach during patient treatment, due to the low rate of lymph node involvement and favorable prognosis in PMBC patients.

High co-expression of immune checkpoint receptors PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT on tumor-infiltrating lymphocytes in early-stage breast cancer.

High expression of immune checkpoint receptors (ICRs) in the tumor microenvironment regulates the anti-tumor response. In this study, the differential expressions of ICRs on tumor-infiltrating lymphocytes (TILs) in patients with early-stage breast cancer were investigated.The study included 32 patients who underwent surgery with a diagnosis of early-stage breast cancer between September 2018 and March 2020. TIL isolation was performed using a MACS tumor separation device and tumor separation kit. PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT expression of cytotoxic T and natural killer (NK) cells on TILs and peripheral blood lymphocytes (PBLs) were determined by flow cytometry.Patients with a high Ki-67 index, high TIL density, and HER-2 positivity were more likely to have increased CD16+CD56dim NK cells on TILs. Patients with T2 tumors were more likely to have increased expression of PD-1, LAG-3, and TIGIT on tumor-infiltrating CD8+ cytotoxic T cells than those with T1 tumors. PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 expression of CD8+ T and CD16-CD56bright NK cells in TILs showed significant positive correlations with each other. PD1+CD8+, TIGIT+CD16+, and CTLA-4+CD56+ cells in PBLs and TILs were found to be negatively correlated, whereas only TIM-3+ expression of CD8+ T and CD16+CD56dim cells in PBLs and TILs showed positive correlations.Our results suggest that CD16+CD56dim NK cells on TILs may play a major role in the immune response against HER2-positive or highly proliferating breast tumors in patients with early-stage breast cancer. Furthermore, various ICRs were found to be highly co-expressed with each other on TILs, including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT. These receptors may synergistically suppress the response to the tumor, which may trigger immune escape mechanisms in the early stage of carcinogenesis. However, ICR expressions other than TIM3 on PBLs were not found to accompany their counterparts on TILs.

SPECT/CT Lymphoscintigraphy Guidance Simplifies and Improves Targeted Axillary Dissection of the Clipped Nodes After Neoadjuvant Chemotherapy in Initially Node-Positive Breast Cancer.

PURPOSE: We assessed the feasibility of SPECT/CT lymphoscintigraphy ( 99m Tc-nanocolloid) method to simplify and improve targeted axillary dissection of clipped axillary lymph node (axLN) after neoadjuvant chemotherapy (NAC) in initially node-positive breast cancer. PATIENTS AND METHODS: Fifteen patients who had clip placement to biopsy-confirmed axLN metastasis due to clinically node-positive breast cancer before NAC and underwent SPECT/CT lymphoscintigraphy for surgery after NAC were included into the study. SPECT/CT lymphoscintigraphy was performed to localize the clipped node and to assess if the clipped lymph node (LN) had 99m Tc-nanocolloid uptake or not. In case the clipped node had no uptake on SPECT/CT, the patient was referred to wire-guided localization procedure. Blue dye was also injected for dual mapping of sentinel LN biopsy. RESULTS: All patients had only ipsilateral axLN metastasis. SPECT/CT lymphoscintigraphy showed that clipped LNs were radioavid in 12 of 15 patients (80%). Clipped LNs were not blue-stained in 5 patients (33.3%), and in 2 of them, clipped LNs were radioavid in SPECT/CT. Wire-guided localization was required in only 3 patients (20%) for nonradioavid/blue-stained clipped LNs. Removal of the clipped nodes was confirmed in all cases with a success rate of 100% by specimen graphy. CONCLUSION: SPECT/CT lymphoscintigraphy seems feasible to determine the clipped LNs intraoperatively without requiring additional invasive methods in most of the patients. This technique simplifies and improves targeted axillary dissection of the clipped axLNs after NAC in initially node-positive breast cancer and can be adapted to clinical practice with further investigations.

Abbreviated and Standard Breast MRI in Neoadjuvant Chemotherapy Response Evaluation: A Comparative Study.

OBJECTIVES: This study aims to investigate the efficacy of abbreviated breast magnetic resonance imaging (MRI) in neoadjuvant chemotherapy (NAC) response evaluation. METHODS: MR images of 50 locally advanced breast cancer patients who underwent standard protocol (SP) breast MRI before and after NAC were re-evaluated retrospectively. Abbreviated protocol (AP) was obtained by extracting images from SP and then evaluating them in a separate session. Protocols were compared with the histological findings after surgery as the reference standard. RESULTS: A statistically significant difference was found between the two protocols in response evaluation by the McNemar test (p=0.018). However, the Kappa value was 0.62 (p<0.001), which indicates substantial agreement. No statistically significant differences were found between the two protocols (AP and SP) and pathological results in the McNemar test (p=0.12, p=0.60, respectively). Kappa values were 0.48 (p<0.001) and 0.60 (p<0.001), respectively, which indicates moderate agreement for both protocols with higher values by SP evaluation. The residual maximum median diameters were smaller than the pathology, with both protocols (p<0.001). CONCLUSION: Despite the statistical differences, there was a significant correlation in response evaluation between the two protocols. The pathological results were moderately correlated with both protocols, with SP slightly higher. However, the residual maximum median diameters were smaller than the pathology with both protocols. These results may limit the use of AP in evaluating the local extent of the tumor, especially in patients who will undergo breast-conserving surgery.

Metaplastic Breast Cancer: Mesenchymal Subtype Has Worse Survival Outcomes.

Background: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer that accounts for 0.2-1% of all breast cancers. To date, there are only few institutional studies comparing survival rates between different subtypes. In this retrospective cohort study, we aim to evaluate factors effecting survival rates of different subtypes of MBC. Methods: This retrospective cohort study observed 118 nonmetastatic MBC patient records extracted from 15,244 breast cancer cases between December 2000 and December 2020. In order to analyze factors effecting survival rates of mesenchymal subtype of MBC, all cases are classified as mesenchymal (n = 45) and other (n = 48). Twenty-five cases could not be sub-classified due to the missing data. Univariate and multivariate logistic regression analyses were performed to define factors associated with survival rates. Results: Of the 15,244 cases, 118 (0.8%) were nonmetastatic MBC. 105 were triple negative and 12 were nonluminal HER2. There was no significant difference between mesenchymal and other subgroups for age, median tumor size, AJCC staging, and type of surgery. Of the five local recurrences with known subgroup, four of them had mesenchymal subtype. It is demonstrated that mesenchymal subtype was significantly associated with worse 5-year disease-free survival and disease-specific survival (HR: 2.35 [1.01-5.48], p = 0.049, and HR: 3.16 [1.06-9.47], p = 0.040 with 95% CI, respectively). Conclusion: This study is one of the few studies presenting the survival outcomes of subtypes of MBCs. Nonetheless, it is the only study demonstrating that mesenchymal subtype had worse survival outcomes. Further studies are needed to determine the outcome of different subtypes of MBCs.

Differential Expression of Novel Immune Checkpoint Receptors on Tumor Infiltrating Lymphocytes in Patients with Locally Advanced Breast Cancer after Neoadjuvant Chemotherapy.

Immune checkpoint receptors (ICRs) were recently found to modulate the anti-tumoral immune response. This study aimed to determine the clinical and pathological associations of ICRs expression on tumor-infiltrating lymphocytes (TILs) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NAC). Expressions of ICRs including PD-1, LAG-3, TIM-3, TIGIT, and CTLA-4 on CD8+ T lymphocytes and Natural Killer (NK) cells on TILs were analyzed by flow cytometry. Patients <50 years were more likely to express CTLA-4 on CD8+ T lymphocytes compared to those ≥50 years (p=0.004). In addition, patients with ypT3-4 tumors were more likely to have increased LAG-3 expression on CD16-CD56bright NK cells (p=0.042) and PD-1 (p=0.014) and CTLA-4 (p=0.018) expressions on CD8+ T cells in regard to those with ypT1-T2, respectively. Contrarily, PD-1 expression on CD16-CD56bright NK cells was found to be decreased in patients with ypN+ compared to those with ypN- (p=0.022). Furthermore, patients with HER2+ tumors were more likely to have increased TIM-3 expression on CD8+ T cells (p=0.043), whereas patients with a better response to NAC were more likely to express TIGIT on CD8+ T (p=0.014) and CD16-CD56bright NK cells (p=0.003), respectively. The new generation ICRs, TIM-3, LAG-3, and TIGIT are highly expressed in LABC following NAC in patients with poor prognostic factors. Therefore, new evolving therapies using inhibitory mAbs directed to TIM-3, LAG-3, and TIGIT could be also be considered in locally advanced breast cancers expressing these ICRs.