Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Diagnostic capabilities of artificial intelligence as an additional reader in a breast cancer screening program.

OBJECTIVES: We aimed to evaluate the early-detection capabilities of AI in a screening program over its duration, with a specific focus on the detection of interval cancers, the early detection of cancers with the assistance of AI from prior visits, and its impact on workload for various reading scenarios. MATERIALS AND METHODS: The study included 22,621 mammograms of 8825 women within a 10-year biennial two-reader screening program. The statistical analysis focused on 5136 mammograms from 4282 women due to data retrieval issues, among whom 105 were diagnosed with breast cancer. The AI software assigned scores from 1 to 100. Histopathology results determined the ground truth, and Youden's index was used to establish a threshold. Tumor characteristics were analyzed with ANOVA and chi-squared test, and different workflow scenarios were evaluated using bootstrapping. RESULTS: The AI software achieved an AUC of 89.6% (86.1-93.2%, 95% CI). The optimal threshold was 30.44, yielding 72.38% sensitivity and 92.86% specificity. Initially, AI identified 57 screening-detected cancers (83.82%), 15 interval cancers (51.72%), and 4 missed cancers (50%). AI as a second reader could have led to earlier diagnosis in 24 patients (average 29.92 ± 19.67 months earlier). No significant differences were found in cancer-characteristics groups. A hybrid triage workflow scenario showed a potential 69.5% reduction in workload and a 30.5% increase in accuracy. CONCLUSION: This AI system exhibits high sensitivity and specificity in screening mammograms, effectively identifying interval and missed cancers and identifying 23% of cancers earlier in prior mammograms. Adopting AI as a triage mechanism has the potential to reduce workload by nearly 70%. CLINICAL RELEVANCE STATEMENT: The study proposes a more efficient method for screening programs, both in terms of workload and accuracy. KEY POINTS: • Incorporating AI as a triage tool in screening workflow improves sensitivity (72.38%) and specificity (92.86%), enhancing detection rates for interval and missed cancers. • AI-assisted triaging is effective in differentiating low and high-risk cases, reduces radiologist workload, and potentially enables broader screening coverage. • AI has the potential to facilitate early diagnosis compared to human reading.

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.

Evaluation of immune density, PD-L1, and CXCR4 expressions in metaplastic breast carcinoma to predict potential immunotherapy benefit.

Metaplastic breast carcinoma (MBC) -rare but fatal subtype of invasive breast carcinomas- provides limited benefit from conventional triple-negative breast carcinoma chemotherapy. We aimed to determine the immune density of this tumor and to evaluate of programmed death-ligand 1 (PD-L1) and chemokine receptor type 4 (CXCR4) expressions to determine whether it would benefit from immunotherapy. Clinicopathological characteristics of 85 patients diagnosed as MBC between 1997 and 2017 were retrospectively assessed. We evaluated the immunohistochemical expression of PD-L1 and CXCR4, and the extent of tumour infiltrating lymphocytes (TILs), with survival data. TILs groups were statistically significantly associated with lymph node status, histological subtype, squamous component, local recurrence and/or systemic metastasis, and disease-related deaths (p < 0.05). PD-L1 positivity in immune cells (ICs) has a statistically significant relationship with the presence of squamous component (p = 0.011) and HER2 positivity (p = 0.031). PD-L1 positivity in tumor cells (TCs) was found to be significantly more frequent in high-TILs density (p = 0.003). PD-L1 combined positive score was significantly associated with the tumors containing high-TILs density (p = 0.012) and squamous component (p = 0.035). Disease-free and disease-specific survival rates were found to be longer for the cases displaying PD-L1 positivity in ICs; and also PD-L1 positivity in ICs was found to be an independent prognostic factor. When the expression of CXCR4 was compared with clinicopathological and survival parameters, no statistically significant association was found (p > 0.05). Based on the results of this retrospective study, PD-L1 and TILs appear to be prognostic. This study provides rationale for further studies to determine whether a subset of patients with metaplastic breast cancer could derive a meaningful benefit from immune-targeting therapies.

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.

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.

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.

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.

Localization Techniques for Non-Palpable Breast Lesions: Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411).

BACKGROUND: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. METHODS: We performed a systematic review on localization techniques for non-palpable breast cancer. RESULTS: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons' and radiologists' attitudes towards these techniques. CONCLUSIONS: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

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.

Favorable locoregional control in clinically node-negative hormone-receptor positive breast cancer with low 21-gene recurrence scores: a single-institution study with 10-year follow-up.

BACKGROUND: Recent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up. METHODS: The study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed. RESULTS: The median age was 48 years (range, 29-72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age < 40 years, age < 50 years, high histological or nuclear grade, high Ki-67-scores (≥ 15%, ≥ 20%, ≥ 25%, ≥ 30%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS ≥ 18, and RS > 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS < 16 (75% vs. 100%, respectively; p = 0.039). CONCLUSIONS: The results suggest that patients with clinically node-negative disease and RS ≥ 16 are more likely to benefit from adjuvant chemotherapies. However, those with RS < 16 have an excellent outcome and local control in long-term follow-up with endocrine treatment alone.

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.

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.