Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

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.

Axillary lymph node dissection is not required for breast cancer patients with minimal axillary residual disease after neoadjuvant chemotherapy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is widely used in patients who receive neoadjuvant chemotherapy (NAC). Still, axillary lymph node dissection (ALND) is recommended for patients with any axillary residual disease after NAC. The necessity of ALND in patients with minimal axillary disease is unclear. We aim to investigate regional recurrence rates in patients with limited axillary residual disease after NAC underwent SLNB + image-tailored axillary surgery and adjuvant radiotherapy (RT). METHODS: Patients with clinical stages were T1-3 and N1 at the time of diagnosis, clinically good or complete axillary response after NAC, and limited axillary residue (≤ 3 pathological lymph nodes) with favorable response to NAC in the final pathological examination were included in the study. All patients underwent SLNB + image-tailored axillary surgery. Peripheral lymphatic radiotherapy was applied, and no further surgery was performed in patients with compatible radiology and pathology results. RESULTS: Our study, which evaluated 139 patients with a median age of 47 years, found that the median number of excised lymph nodes was 4. Notably, 46% of patients had between 1 and 3 lymph nodes excised, while 45% had between 4 and 6. Only 9% of patients had ≥ 7 lymph nodes. 83(60%) of the patients underwent breast-conserving surgery (BCS), and 56(40%) underwent mastectomy. The study's median follow-up period was 44 months. During this duration, one breast recurrence (0.7%), one supraclavicular recurrence (0.7%), and six systemic recurrences (4.3%) were observed. No axillary recurrence occurred within the follow-up period. CONCLUSIONS: Patients presenting with pathological-suspicious ≤ 3 lymph nodes on imaging and showing a good response to NAC can be considered suitable candidates for SLNB + image-tailored axillary surgery, followed by adjuvant RT instead of ALND.

Outcomes of reconstructive techniques in breast cancer using BCCT. core software.

BACKGROUND: Surgery remains a priority for breast cancer treatment. This study aimed to compare the cosmetic outcomes of oncoplastic patients who had undergone breast-conserving surgery, mini-LDF (latissimus dorsi flap), and immediate implant reconstruction using both the Japanese scale and the BCCT.core (The Breast Cancer Conservative Treatment cosmetic results software) program and to validate this program. PATIENTS AND METHODS: Patients who underwent surgery for breast cancer between 1997 and 2021 were retrospectively studied. Patients were divided into three groups: 1-those who had undergone breast-conserving surgery (245 patients, 71.3%), 2-those who had undergone mini-LDF after lumpectomy (38 patients, 11.02%), and 3- those who underwent reconstruction with implants after nipple-sparing mastectomy (61 patients, 17.68%). The patients were called for a follow-up examination, and their photos were taken. The photographs were shown to an independent breast surgeon and a plastic surgeon who was not included in the surgeries, and they were asked to evaluate and rate them according to the Japanese cosmetic evaluation scale. The same images were transferred to the computer and scored using BCCT.core. RESULTS: The plastic and breast surgeon evaluation results showed no significant difference between the three cosmetic techniques (p = 0.99, 0.98). The results of BCCT.core software measurements were similar to the results of plastic and breast surgeons (p: 0.43). CONCLUSION: Patients are more knowledgeable about cosmetic outcomes and expect more objective data. In this study, we used 3 different cosmetic evaluation scales. We found that these techniques give results that are compatible with each other in terms of evaluating the work done in a more concrete way. For this reason, we recommend the use of such software, which offers objective results in a subjective field such as aesthetics and is very easy to apply.

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.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

The effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes in patients with breast cancer.

Aim: This study investigated the effect of neoadjuvant chemotherapy (NAC) on stromal tumor-infiltrating lymphocytes (sTILs) and their treatment response. Materials & methods: 115 patients with pre-NAC core biopsies and post-NAC surgical resection specimens were reviewed. Results: There was no significant change between pre- and post-treatment sTILs. Both pre- and post-NAC sTILs were significantly lower in patients with luminal A subtype. An increase in sTILs was observed in 21 (25.9%) patients after NAC, a decrease in 29 (35.8%) and no change in 31 (38.3%; p = 0.07). Pretreatment sTIL density was independent predictor of pathological complete response in multivariate analyses (odds ratio: 1.025, 95% CI: 1.003-1.047; p = 0.023). Conclusion: High sTIL density in core biopsies was independently related to pathological complete response. In addition, ER appears to be the most crucial factor determining the rate of sTIL.

New studies have shown that the tumor microenvironment is critical in tumor behavior. Immune cells surrounding tumor cells are the main components of the tumor microenvironment. Our study aimed to investigate the change in immune cells before and after chemotherapy in breast cancer patients. Our study included 115 patients. All patients underwent chemotherapy before surgery to shrink the tumor. Tru-cut biopsy pieces and the breast tissue obtained after surgery were examined. The presence of estrogen or progesterone receptors on tumor cells decreased the number of immune cells surrounding the tumor cells. The number of immune cells did not decrease after chemotherapy. Another finding was that the greater the number of immune cells around the tumor, the more likely that the tumor would disappear after chemotherapy.

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.

LONG-TERM SURVIVAL EFFECTS OF PREOPERATIVE BREAST MRI IN PATIENTS WITH BREAST-CONSERVING SURGERY.

The benefit of breast magnetic resonance imaging (MRI) in breast-conserving surgery (BCS) is unclear. Our study compared breast cancer patients with and without preoperative breast MRI and their long-term oncologic outcomes are reported. A total of 1378 BCS cases with early breast cancer between 1996 and 2017 were reviewed. Patients with carcinoma in situ or neoadjuvant treatment or having breast MRI after tumor excision were excluded. Of 1378 patients, 270 (19.5%) had preoperative MRI. There were no significant differences regarding T and N stage and molecular subtypes between the groups. Surgical margins were significantly wider in the breast MRI group. Five-year overall survival (OS) was 96.9% in the MRI group and 94.3% in the control group, and this difference was not significant (p=0.11). Five-year local-regional recurrence-free survival (LRFS) was not significantly different either (98.8% and 96.5%, respectively, p=0.41). When analyses were repeated only for patients with hormone receptor-negative or triple-negative breast cancer, there was still no significant difference in OS, LRFS, or disease-free survival. In conclusion, MRI does not seem necessary in all patients undergoing BCS. New prospective randomized controlled trials are needed to determine appropriate use of preoperative MRI and its effects on oncologic outcomes in early breast cancer patients.

TIM3 expression on TILs is associated with poor response to neoadjuvant chemotherapy in patients with locally advanced triple-negative breast cancer.

BACKGROUND: The expression of immune checkpoint receptors (ICRs) on tumor-infiltrating lymphocytes (TILs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). METHODS: Expressions of ICRs were examined immunohistochemically in surgical specimens (n = 61) using monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, and CTLA-4. Positivity was defined as staining > 1% on TILs. RESULTS: The median age was 49 (24-76) years. The majority of patients were clinically T3-4 (n = 31, 50.8%) and clinically N1-3 (n = 58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas PD1, PDL-1, LAG3, and TIM-3 expressions on TILs were 62.3, 50.9, 26.2, and 68.9%. A high expression of CTLA-4 was found to be associated with a better chemotherapy response (OR = 7.94, 95% CI: 0.9-70.12, p = 0.06), whereas TIM-3 positivity was contrarily associated with a worse chemotherapy response (OR = 0.253, 95% CI: 0.066-0.974, p = 0.047) as measured by the MDACC Residual Cancer Burden Index. At a 47-month follow-up, ypN0 (DFS; HR = 0.31, 95% CI: 0.12-0.83, p = 0.02 and DSS; HR = 0.21, 95% CI: 0.07-0.62, p = 0.005) and CTLA-4 high expression on TILs (DFS; HR = 0.38, 95% CI: 0.17-0.85, p = 0.019 and DSS; HR = 0.34, 95% CI: 0.15-0.78, p = 0.01) were found to be associated with improved survival. CONCLUSIONS: These findings demonstrate that CTLA-4, PD-1, PDL-1, and TIM-3 were highly expressed in TNBC. Based on these high expression patterns, further studies directed towards combined therapies are warranted in advanced TNBC in future.

The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patients: protocol MF07-01Q.

BACKGROUND/OBJECTIVE: Since more solid evidence has emerged supporting the effectiveness of loco-regional treatment (LRT), clinicians consider LRT a treatment option for selected de novo stage IV breast cancer (BC) patients. This is the first report on long-term quality of life (QoL) in a cohort of patients who were randomized to receive either LRT and then systemic treatment (ST) or ST alone in the protocol MF07-01. We aimed to evaluate QoL in patients living at least 3 years since randomization using scores from the SF-12 health survey. METHODS: SF-12 (V2) forms were completed during visits of patients who were living 36 months after the randomization. We first calculated PCS-12 (Physical Health Composite Scale) and MCS-12 (Mental Health Composite Scale) scores from de novo stage IV BC patients and compared them with the scores of patients diagnosed with stage I-III BC who lived more than 3 years. Further, PCS-12 and MCS-12 scores were compared between the LRT and ST groups with de novo stage IV BC. Additionally, general health, physical functioning, role functioning, bodily pain, vitality, mental health, and social functioning were evaluated and compared between the groups. Considering age-related changes in QoL, we also compared PCS-12 and MCS-12 scores of patients below or above 55 and 65 years of age. Responses to four additional questions (compare your physical health, mental health, daily activities, and energy currently vs. at diagnosis of BC) were recorded, considering cultural differences. RESULTS: There were 81 patients in this analysis; 68% of patients (n = 55) had LRT, and 32% (n = 26) received ST. General health was good or very good in 62% (n = 34) in the LRT group and 66% (n = 17) in the ST-only group (p = 0.63). Mean PCS-12 score was 40.8 + 1.6, and mean MCS-12 score was 43.4 + 2.0 (p = 0.34 and p = 0.54, respectively). PCS-12 and MCS-12 score difference was lower than that of the general Turkish population (PCS-12 = 49.3 + 12.8 and MCS-12 = 46.8 + 13.0) and stage I-III BC patients (PCS-12 = 51.1 ± 0.5, MCS-12 = 45.7 ± 0.6). PCS-12 and MCS-12 scores were similar between the LRT and ST-only groups in patients younger and older than 55 and 65, but QoL scores were much better in stage I-III BC patients younger than 65 when compared to the scores of those with de novo stage IV BC. Although treatment with or without LRT did not affect physical health, mental health, daily activities, and energy at 3 years vs. at diagnosis of BC in de novo stage IV BC patients (p > 0.05), these variables were significantly better in stage I-III BC patients (p < 0.001). CONCLUSION: The current MF07-01Q study demonstrates that patient who had LRT has similar physical and mental health outcomes compared to ST only in a cohort of patients who lived longer than 3 years. Trial registration This study is registered on clinicaltrials.gov with identifier number NCT00557986.

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.

Clinical impact of PD-L1 expression in triple-negative breast cancer patients with residual tumor burden after neoadjuvant chemotherapy.

BACKGROUND: Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival. METHODS: PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC). RESULTS: Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by "MD Anderson Cancer Center Residual Cancer Burden Index" (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS. CONCLUSIONS: Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.

Usefulness of imaging findings in predicting tumor-infiltrating lymphocytes in patients with breast cancer.

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have been determined as a new prognostic indicator of immunotherapy response in breast cancer (BC). The aim of this study is to investigate the effectiveness of imaging features in predicting the TIL levels in invasive BC patients. METHODS: A total of 158 patients with invasive BC were included in our study. All lesions were evaluated based on the BIRADS lexicon. US was performed for all the patients and 89 of them underwent MRI. The histologic stromal TIL (sTIL) levels were assessed and associations between the sTIL levels and imaging features were evaluated. RESULTS: Tumors with high sTIL levels had more circumscribed margins, round shape, heterogeneous echogenicity, and larger size on ultrasonography (p < 0.005). There was a statistically significant positive correlation between the sTIL levels and ADC value (p < 0.001). Tumors with high sTIL levels had significantly more homogeneous enhancement than the tumors with low sTIL levels (p = 0.001). Logistic regression analysis showed that the ADC was the most statistically significant parameter in predicting the sTIL levels (the odds ratio was 90.952; p = 0.002). The optimal cutoff value for ADC in predicting low and high sTIL levels was found to be 0.87 × 10-3 mm2 s-1 (AUC = 0.726, 73% specificity, and 60% sensitivity). CONCLUSIONS: Imaging findings, especially the ADC, may play an important role as an adjunct tool in cases of uncertain situations and may improve the accuracy of biopsy results. The prediction of sTIL levels using imaging findings may give an opportunity to predict prognosis. KEY POINTS: • Preoperative assessment of TILs is an important biomarker of prognosis and treatment efficacy. • ADC value can be a useful tool in distinguishing high and low sTIL levels as a non-invasive method. • The prediction of sTIL levels using imaging findings may give an opportunity to predict prognosis and an optimal treatment for the BC patients.

Comparison of breast cancer patients who underwent partial mastectomy (PM) with mini latissimus dorsi flap (MLDF) and subcutaneous mastectomy with implant (M + I) regarding quality of life (QOL), cosmetic outcome and survival rates.

PURPOSE: The latissimus dorsi muscle has long been used in breast cancer (BC) patients for reconstruction. This study aimed to compare early stage BC patients who had partial mastectomy (PM) with mini latissimus dorsi flap (MLDF) and subcutaneous mastectomy with implant (MI) with respect to quality of life (QoL), cosmetic outcome (CO), and survival rates. PATIENTS AND METHODS: The data of patients who underwent PM + MLDF (Group 1) and M + I (Group 2) between January 2010 and January 2018 were evaluated. Both groups were compared in terms of demographics, clinical and pathological characteristics, surgical morbidity, survival, quality of life, and cosmetic results. The EORTC-QLQ C30 and EORTC-QLO BR23 questionnaires and the Japanese Breast Cancer Society (JBCS) Cosmetic Evaluation Scale were used to assess the quality of life and the cosmetic outcome, respectively. RESULTS: A total of 317 patients were included in the study, 242 (76.3%) of them in group 1 and 75 (23.6%) of them in group 2. Median follow-up time was 56 (14-116) months. There were no differences identified between the groups in terms of tumor histology, hormonal receptors and HER-2 positivity, surgical morbidity, and 5-year overall and disease-free survival. Group 2 patients were significantly younger than group 1 (p = 0.003). The multifocality/multicentricity rate was higher in group 2 (p ≤ 0.001), whereas tumor size (p = 0.009), body mass index (BMI, p = 0.006), histological grade (p ≤ 0.001), lymph node positivity (p = 0.002), axillary lymph node dissection (ALND) rate (p = 0.005), and presence of lympho-vascular invasion (LVI, p = 0.013) were significantly higher in group 1. When the quality of life was assessed by using the EORTC QLQ C30 and BR23 questionnaires, it was seen that the body image perception (p < 0.001) and nausea/vomiting score (p = 0.024) were significantly better in PM + MLDF group whereas physical function score was significantly better in M + I group (p = 0.012). When both groups were examined in terms of cosmesis with JBCS Cosmetic Evaluation Scale, good cosmetic evaluation score was significantly higher in patients in MLDF group (p = 0.01). DISCUSSION: The results of this study indicate that in comparison to M + I procedure, the PM + MLDF procedure provides significantly superior results in terms of body image and cosmetic result with similar morbidity and oncologic outcomes. In selected patients with small breasts and a high tumor/breast ratio, PM + MLDF may be an alternative to subcutaneous mastectomy and implant.

Evaluation of the eating habits of breast cancer patients.

OBJECTIVE: To determine the relationship between the dietary characteristics of breast cancer patients. METHODS: Patients with breast cancer whose treatments have finished and are in remission formed the study group and healthy people formed the control group. Demographic, anthropometric characteristics, food consumption frequency form and exercise status were recorded with all groups. Data analysis was done by SPSS 22. RESULTS: In the study group, mean carbohydrate percentage was lower, while fat, fat percentage, monosaccharide, glucose, fructose, omega3(n3), saturated fatty acids(SFA), monounsaturated fatty acids (MUFA), vitamin A, C, E, B6, biotin and copper values were significantly higher (p<0.05). Recurrence was observed in seven patients (7.1%) during the follow-up period, hormone receptor levels (ER) and vitamin B2 intake (accuracy 93.9%) were inversely related to the recurrence of the disease (p=0.02). CONCLUSIONS: While the percentage of carbohydrate taken was lower in study group; total fat, n3, SFA, MUFA, monosaccharide, glucose, fructose, water-soluble fiber, B6, biotin and copper values were higher. Further studies are needed for vitamin B2 deficiency in patients with recurrence.

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. METHODS: In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. CONCLUSIONS: In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition.

Intraoperative palpation of sentinel lymph nodes can accurately predict axilla in early breast cancer.

Recent randomized trials have shown that completion axillary lymph node dissection (ALND) is not required in all patients with a positive sentinel lymph node (SLN) who will receive radiation therapy. Although routine intraoperative pathologic assessment (IPA) becomes unnecessary and less indicated by breast surgeons in the United States and some European countries, it is still widely used all around the world. In this prospective study, the feasibility of intraoperative nodal palpation (INP) as opposed to IPA of the SLN has been analyzed. Between March 2014 and June 2015, 305 patients with clinical T1-2/N0 breast cancer from two different breast clinics (cohort A; [n = 225] and cohort B; [n = 80]) who underwent any breast surgery with sentinel lymph node biopsy (SLNB) were included in this study. Surgeons evaluated the SLNs by manual palpation before sending for IPA, and findings compared with the final pathology. The positive predictive values (PPV) of INP and IPA were 81.8% and 97.9%, respectively, whereas the negative predictive values (NPV) of INP and IPA were 83% and 92.4%. The accuracies of INP and IPA were 82.6% and 94.1%, respectively. If patients with SLNB including micrometastasis were also considered in the final pathologic assessment (FPA) (-) group that would not require a further axillary dissection, the revised NPV of INP and FPA were found to be 92.6% and 98.1%, respectively. The revised accuracy of INP also found to be increase to 86.9%. Our study, which is the only prospective one about palpation of dissected SLNs in the literature, suggests that INP can help to identify patients who do not need ALND, which encourages omitting IPA in cT1-2 N0 breast cancer.

Improved False-Negative Rates with Intraoperative Identification of Clipped Nodes in Patients Undergoing Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy.

BACKGROUND: Identification and resection of a clipped node was shown to decrease the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for patients presenting with initially node-positive breast cancer. METHODS: Between March 2014 and March 2016, a prospective trial analyzed 98 patients with axilla-positive locally advanced breast cancer (T1-4, N1-3) to assess the feasibility and efficacy of placing clips into most suspicious biopsy-proven node. The study considered blue, radioisotope active, and suspiciously palpable nodes as sentinel lymph nodes (SLNs). RESULTS: The SLN identification rate was 87.8%. The median age of the patients with an SLNB (n = 86) was 44 years (range 28-66 years). Of these patients, 77 (88.4%) had cT1-3 disease, and 10 (11.6%) had cT4 disease. The majority of the patients (n = 66, 76.7%) had cN1, whereas 21 patients (23.3%) had cN2 and cN3. A combined method was used for 37 patients (43%), whereas blue dye alone was used for the remaining patients (57%). The clipped node was the SLN in 70 patients (81.4%). For the patients with cN1 before NAC, the FNR was found to be 4.2% (1/24) when the clipped node was identified as an SLN. However, the FNR was estimated to be as high as 16.7% (1/6) for the patients with cN1 before NAC when the clipped node was found to be a non-SLN. CONCLUSIONS: The study results also suggest that axillary dissection could be omitted for patients presenting initially with N1 disease and with a negative clipped node as the SLN after NAC due to the low FNR.

Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01.

BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49-0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46-0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(-) (HR 0.64; 95% CI 0.45-0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38-0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23-0.98; p = 0.04). CONCLUSION: In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.