Prognosis of isolated locoregional recurrence after early breast cancer with immediate breast reconstruction surgery: a retrospective multi­institutional study.

BACKGROUND: The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population. METHODS: This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS). RESULTS: Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3 months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS. CONCLUSIONS: Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients.

Impact of immediate breast reconstruction on perioperative therapy: insights from a Japanese Nationwide Registry.

BACKGROUND: Immediate breast reconstruction (IBR) is a common oncoplastic procedure used in breast cancer surgery. This study aims to investigate compliance with prosthetic breast reconstruction guidelines and its impact on perioperative treatment. METHODS: We reviewed data from the National Clinical Database-Breast Cancer Registry between January 2019 and December 2020. We compared perioperative treatment implementation between the IBR and non-IBR groups by subtype matching for age, menopausal status, T stage, N stage, and histology. RESULTS: A total of 8,860 patients with breast cancer who underwent IBR (6,075 breast prostheses, 2,492 autologous tissues, and 293 others) were identified. The compliance rate with the guidelines for prosthetic breast reconstruction was 97.7%. After matching, chemotherapy for luminal A-like diseases was significantly less frequent in the IBR group than in the non-IBR group (16.3% vs 20.5%, p < 0.001), and radiotherapy was less frequent in luminal A-like and HER2-positive patients (7.2% vs 9.0%, p = 0.010 and 7.1% vs 11.4%, p = 0.005, respectively). Among the 1-3 node-positive cases, fewer patients with prosthetic IBR received radiotherapy than those without IBR (15.7% vs 26.4%, p < 0.001). CONCLUSION: Prosthetic breast reconstruction was performed with strict adherence to the Japanese guidelines. The implementation rates of chemotherapy and radiotherapy were lower in the specific IBR group than those in the non-IBR group. Therefore, large-scale, long-term follow-up data are required.

A nomogram to predict the pathological complete response in patients with breast cancer based on the TILs-US score.

BACKGROUND: The tumor-infiltrating lymphocytes-ultrasonography score is a calculation system for predicting lymphocyte-predominant breast cancers in surgical specimens. A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score was developed to predict the pathological complete response in breast cancer treated with neoadjuvant chemotherapy. METHODS: A retrospective evaluation was conducted on 118 patients with breast cancer treated with neoadjuvant chemotherapy at Hiroshima University Hospital. Tumor-infiltrating lymphocytes-ultrasonography scores ≥4 were classified as high. A nomogram was developed using a stepwise logistic regression model for pathological complete response (ypT0 ypN0), based on the smallest Akaike information criterion. The predictive ability and clinical usefulness of the nomogram were also evaluated. RESULTS: Among 118 patients, 34 (28.8%) achieved a pathological complete response, and 52 (44.1%) exhibited high tumor-infiltrating lymphocytes-ultrasonography. In multivariate logistic regression analysis, high tumor-infiltrating lymphocytes-ultrasonography (odds ratio, 6.01; P < 0.001), clinical complete response (odds ratio, 4.83; P = 0.004) and hormone receptor (odds ratio, 3.48; P = 0.038) were independent predictors of pathological complete response. A nomogram based on tumor-infiltrating lymphocytes-ultrasonography score, clinical complete response, hormone receptor and clinical N status was developed. The nomogram showed an area under the curve of 0.831 and a bias-corrected area under the curve of 0.809. The calibration plot showed a good fit between the expected and actual pathological complete response values. Decision curve analysis also showed the clinical utility of the nomogram for predicting pathological complete responses. CONCLUSIONS: A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score exhibited a favorable predictive ability for pathological complete response in patients with breast cancer, which can be useful in predicting the residual disease status after neoadjuvant chemotherapy.

Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy.

BACKGROUND: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. METHODS: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. RESULTS: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74-1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. CONCLUSION: IBR after NAC is a safe procedure with an acceptable postoperative complication profile.

Impact of radiation therapy for breast cancer with involved surgical margin after immediate breast reconstruction: A multi-institutional observational study.

INTRODUCTION: Involved surgical margins are risk factors for local recurrence and re-excision is often difficult, particularly in patients with breast cancer undergoing immediate breast reconstruction (IBR). However, the magnitude of the effect of radiation therapy on preventing local recurrence for breast cancers with involved margins has not been sufficiently assessed. MATERIALS AND METHODS: We retrospectively assessed sites of involved surgical margins and local recurrence after mastectomy with IBR in patients with early breast cancer between 2008 and 2016. The effect of postoperative radiation therapy was evaluated in patients with involved margins, adjusted for nuclear grade, lymphatic invasion, surgical procedures, and primary systemic therapy. RESULTS: A total of 274 (5.8 %) out of 4726 patients who underwent mastectomy with IBR had involved surgical margins: 133, 68, 88, and 26 had involvement of the skin, deep margin, lateral margins, and nipple, respectively (including duplicates). Radiation therapy was administered to 54 patients with involved margins. In patients with involved margins, 7-year cumulative incidences of local recurrence were 1.9 % and 12.6 % with and without radiation therapy, respectively (adjusted hazard ratio, 0.17; 95 % CI, 0.04-0.80). Local recurrence occurred in 28 patients, and the sites were skin, subcutaneous tissue, muscle, and nipple-areola complex in 7, 17, 1, and 3 patients, respectively. Among them, 23 (82.1 %) were associated with involved margin sites. CONCLUSIONS: Radiation therapy meaningfully reduced the incidence of local recurrence in patients with breast cancer with margin involvement after mastectomy with IBR. Most local recurrences occurred at involved margin-related sites.

Nipple-areolar complex malposition in breast reconstruction after nipple-sparing mastectomy: a multi-institutional retrospective observational study in Japan.

BACKGROUND: Position of the nipple-areolar complex (NAC) is an important factor in the esthetic impression of the breast, and NAC malposition is often an issue in breast reconstruction after nipple-sparing mastectomy (NSM). The purpose of this study was to evaluate the degree of NAC malposition depending on several factors using data quantified with the Mamma Balance application (Medic Engineering K.K., Kyoto, Japan). METHODS: Patients who underwent unilateral breast reconstruction after NSM at eight hospitals in Japan between 2007 and 2020 were retrospectively investigated. Using Mamma Balance, NAC malposition was quantified separately in horizontal and vertical directions using patient photographs from pre-operatively and 6-24 months post-operatively. The degree of malpositioning was then statistically compared using various factors. RESULTS: The NAC deviated more cranially and medially with implants than that with flaps. Cases with latissimus dorsi flap showed lateral malposition more often than cases with deep inferior epigastric artery perforator flap. With flaps, lateral incisions showed more lateral malposition, and peri-areolar incisions tended to show more medial NAC malposition. In cases with severe post-operative infection of the implant, the NAC tended to deviate cranially. In radiation cases, the NAC deviated cranially. No significant difference was observed according to the degree of breast ptosis or use of the pull-down operation. Only a very weak correlation was observed between a larger amount of mastectomy and more cranial NAC malposition with both flaps and implants. CONCLUSIONS: This study provides insights into the tendencies and characteristics of NAC malposition.

Cross-Correlation of Confocal Images for Excised Breast Tissues of Total Mastectomy.

OBJECT: The purpose of this study is to develop an image artifact removal method for radar-based microwave breast imaging and demonstrates the detectability on excised breast tissues of total mastectomy. METHODS: A cross-correlation method was proposed and measurements were conducted. A hand-held radar-based breast cancer detector was utilized to measure a breast at different orientations. Images were generated by multiplying the confocal image data from two scans after cross-correlation. The optimum reconstruction permittivity values were extracted by the local maxima of the confocal image intensity as a function of reconstruction permittivity. RESULTS: With the proposed cross-correlation method, the contrast of the imaging result was enhanced and the clutters were removed. The proposed method was applied to 50 cases of excised breast tissues and the detection sensitivity of 72% was achieved. With the limited number of samples, the dependency of detection sensitivity on the breast size, breast density, and tumor size were examined. CONCLUSION AND SIGNIFICANCE: The detection sensitivity was strongly influenced by the breast density. The sensitivity was high for fatty breasts, whereas the sensitivity was low for heterogeneously dense breasts. In addition, it was observed that the sensitivity was high for extremely dense breast. This is the first detailed report on the excised breast tissues.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

Long-Term Outcomes of Breast Cancer Patients with Local Recurrence After Mastectomy Undergoing Immediate Breast Reconstruction: A Retrospective Multi-institutional Study of 4153 Cases.

BACKGROUND: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of, and factors associated with, local recurrence (LR) after IBR. METHODS: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. RESULTS: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p < 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p = 0.002). CONCLUSIONS: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR.

Physicians' perception about the impact of breast reconstruction on patient prognosis: a survey in Japan.

BACKGROUND: One barrier to the widespread use of breast reconstruction (BR) is physicians' perception that BR adversely affects breast cancer prognosis. However, there is limited information regarding physicians' understanding of the impact of BR on patient prognosis and which physicians have misunderstandings about BR. METHODS: We conducted an e-mail survey regarding the impact of BR on the prognosis of patients with breast cancer among members of the Japanese Breast Cancer Society. RESULTS: Of 369 respondents, 99 (27%) said that they believe BR affects patient prognosis. Female respondents and those who treat fewer new breast cancer patients per year were more likely to state that they believe BR affects patient prognosis (P = 0.006 and 0.007). Respondents who believed that BR affects patient prognosis underestimated 5-year overall survival rates in patients who receive BR and subsequently have local or regional recurrence in different sites. CONCLUSION: Our survey demonstrated that a quarter of respondents believe that BR affects patient prognosis and underestimate survival rates in patients who receive BR and have subsequent local or regional recurrence. Because of the lack of evidence regarding the impact of BR on patient prognosis, educating physicians by providing accurate knowledge regarding BR and patient prognosis is highly recommended.

18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Predicts Tumor Immune Microenvironment Function in Early Triple-negative Breast Cancer.

BACKGROUND/AIM: The maximum standardized uptake value (SUVmax) obtained using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is presumed to indicate tumor and active immune cells in the tumor immune microenvironment (TIME) based on their glycolysis activity. Therefore, this study investigated whether the metabolic parameter SUVmax could provide information regarding TIME in triple-negative breast cancer (TNBC) patients. PATIENTS AND METHODS: Fifty-four patients with TNBC underwent FDG PET/CT before neoadjuvant chemotherapy. Pretreatment biopsy specimens were pathologically evaluated. Expression statuses of CD8, forkhead box P3 (FOXP3), programmed cell death-1 (PD-1), and programmed cell death-ligand 1 (PD-L1) were assessed by immunohistochemistry. The relationships between immunological factors, including the tumor-infiltrating lymphocyte (TIL) grade and SUVmax or pathological complete response (pCR), were investigated. RESULTS: CD8, FOXP3, PD-1, and PD-L1 were high in 15 (27.8%), 39 (72.2%), 18 (33.3%), and 26 (48.2%) patients, respectively. SUVmax was significantly correlated with tumor size, Ki-67 labeling index, and CD8/FOXP3 ratio. Multiple linear regression analysis indicated that tumor size and the CD8/FOXP3 ratio predicted SUVmax. Seventeen patients (31.5%) achieved a pCR; TILs, the CD8/FOXP3 ratio, PD-1, and PD-L1 were significantly correlated with pCR rate. Multivariate analysis indicated that the CD8/FOXP3 ratio was the only independent predictive factor for pCR. CONCLUSION: SUVmax could provide metabolic information regarding TIME for TNBC patients and might be beneficial for formulating a treatment strategy and predicting pCR after neoadjuvant chemotherapy.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

PURPOSE: Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. METHODS: A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. RESULTS: The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106 CFU/mL, cycle 3: 4.61 × 106 CFU/mL, cycle 4: 5.85 × 106 CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. CONCLUSION: FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

Classification of Local Recurrence After Nipple-Sparing Mastectomy Based on Location: The Features of Nipple-Areolar Recurrence Differ from Those of Other Local Recurrences.

BACKGROUND: Little information is available about the clinical and pathologic characteristics of local recurrence (LR) after nipple-sparing mastectomy according to the locations of LR. METHODS: This study classified 99 patients into the following two groups according to the location of LR after nipple-sparing mastectomy: nipple-areolar recurrence (NAR) group and other locations of LR (oLR) group. The study evaluated whether the location of LR was associated with disease-free survival (DFS) after LR resection. RESULTS: For about half of the patients (44.4 %) with NAR, the primary cancer was estrogen receptor (ER)-negative and human epidermal growth factor receptor 2 (HER2)-positive. Conversely, in most of the patients with oLR (79.2 %), the primary cancer was ER-positive and HER2-negative. Among the LR tumors, the frequency of noninvasive carcinoma in the NAR tumors was significantly higher than in the oLR tumors (51.9 % vs 4.2 %, respectively). During a median follow-up period of 46 months, the location of LR was not associated with DFS after LR. In the NAR group, the presence or absence of LR tumor invasiveness was the only factor associated with DFS. In the oLR group, age at primary surgery was the only factor associated with DFS. CONCLUSION: This multi-institutional retrospective study demonstrated that the features of NAR, such as the characteristics of the primary and recurrent tumors and the prognostic factors after LR resection, were quite different from those of oLR.

Effect of Secondary Prophylactic G-CSF on the Occurrence of Febrile Neutropenia in Breast Cancer.

BACKGROUND/AIM: Docetaxel and cyclophosphamide (TC) combination therapy is widely used as adjuvant chemotherapy for early-stage breast cancer and is associated with a high incidence of febrile neutropenia (FN). Granulocyte colony-stimulating factor (G-CSF) is recommended in the primary prevention of febrile neutropenia (FN). This study aimed to evaluate the FN-suppressing effect of G-CSF in patients with breast cancer receiving TC. PATIENTS AND METHODS: We performed 272 treatment cycles after FN onset in 106 patients with breast cancer receiving TC. We retrospectively evaluated the effect of G-CSF as secondary prophylaxis. The frequency of FN was calculated based on the treatment cycles to adjust for differences in the number of cycles per case and FN occurrence. RESULTS: FN occurred in 58 cycles (21.3%). The incidence of FN with and without secondary prophylactic G-CSF was 10.1% and 25.9%, respectively (p=0.003). Multivariate analysis showed secondary prophylactic G-CSF administration to be an independent predictor of FN incidence [odds ratio (OR)=0.33, 95% confidence interval (CI)=0.14-0.74, p=0.007]. CONCLUSION: Secondary prophylaxis with G-CSF is recommended for patients with breast cancer undergoing TC chemotherapy to reduce the incidence of FN.

Dual-phase FDG PET/CT for predicting prognosis in operable breast cancer.

PURPOSE: We aimed to investigate the role of dual-phase FDG PET/CT in predicting the prognosis of patients with operable breast cancer. METHODS: We retrospectively reviewed the data of 998 patients who underwent radical treatment for breast cancer. Before treatment, PET/CT scans were performed 1 and 2 h after FDG administration. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumor and the retention index (RI) were calculated. PET recurrence risk (PET-RR) was determined based on the SUVmax1 and RI, and disease-free survival (DFS) and overall survival (OS) were evaluated according to the metabolic parameters. Propensity score matching was performed to adjust for biological characteristics. RESULTS: The cut-off values for SUVmax1 and RI were 3 and 5%, respectively. The 5-year DFS was 94.9% and 86.1% (P < 0.001), and the 5-year OS was 97.6% and 92.7% (P < 0.001) in the low and high PET-RR groups, respectively. In multivariate analysis, high T status, nodal metastasis, the triple-negative subtype, and high PET-RR were independent factors of poor DFS. Propensity score matching revealed similar findings (5-year DFS 91.8% vs. 88.6%, P = 0.041 and 5-year OS 97.1% vs. 94.2%, P = 0.240, respectively). CONCLUSION: The combined parameters of SUVmax1 and RI on dual-phase FDG PET/CT were useful for predicting prognosis of patients with breast cancer. Patients with a high SUVmax1 and a negative time course of FDG uptake had a favorable prognosis.

The tumor-infiltrating lymphocyte ultrasonography score can provide a diagnostic prediction of lymphocyte-predominant breast cancer preoperatively.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) are known to predict the therapeutic effect in breast cancer. Although a preoperative tissue biopsy can be used to evaluate TILs, TILs that are heterogeneously distributed might require examination of all preoperative tissue biopsy samples. We have recently reported that the TIL ultrasonography (US) score, as determined by characteristic US findings, provides excellent predictive performance for lymphocyte predominant breast cancer (LPBC). We herein aimed to determine whether the preoperative TIL-US score can more accurately predict LPBC than preoperative tissue biopsy. METHODS: We assessed 161 patients with invasive breast cancer that were treated with curative surgery between January 2014 and December 2017. Stromal lymphocytes were examined on preoperative tissue biopsy tissues and surgical pathological specimens. Breast cancer samples with ≥ 50% stromal TILs were defined as pre-LPBC (preoperative tissue biopsy) and LPBC (surgical pathological specimens). Useful factors for predicting LPBC were searched among clinicopathological factors. RESULTS: The TIL-US score cutoff value for predicting LPBC was 4 points based on the receiver operating characteristic curves (area under the curve: 0.88). Several significant predictors for LPBC were revealed by the undertaken multivariate logistic regression analysis (odds ratios: TIL-US score, 26.8; pre-LPBC, 18.6; HER2, 9.2; all, p < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.74, 0.89, 0.85, 0.67, and 0.92 for the TIL-US score, respectively, and 0.51, 0.98, 0.87, 0.91, and 0.86 for the pre-LPBC, respectively. CONCLUSION: TIL-US scores can predict LPBC preoperatively and are characterized by a significantly high sensitivity and negative predictive value.

The ratio of CD8 + lymphocytes to tumor-infiltrating suppressive FOXP3 + effector regulatory T cells is associated with treatment response in invasive breast cancer.

PURPOSE: FOXP3 + and CD8 + are recognized markers of tumor-infiltrating lymphocytes (TILs) for breast cancer. FOXP3 + TILs are composed of effector Tregs (eTregs) and other subpopulations that are classified by their differences in suppressive function. In this prospective study, we evaluated Treg subpopulations and CD8 + TILs in breast cancer. METHODS: 84 patients with breast cancer were enrolled. Fresh TILs were extracted andTregs were classified into eTregs (CD4+FOXP3highCD45RA-), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs using flow cytometry. The suppression strength of each Treg subpopulation was analyzed. The association between TIL subpopulations, clinicopathological characteristics, and response to chemotherapy was evaluated. RESULTS: The mean CD8/eTreg ratio value was 7.86 (interquartile range: 4.08-12.80). The proliferation function of eTregs was significantly suppressed compared with that of the other subpopulations (proliferation rates: control: 89.3%, + naiiveTreg: 64.2%, + non-Treg: 78.2% vs eTreg 1.93%; all P < 0.05). The patients with high with a high CD8 + /eTreg ratio achieved excellent pathological complete response (pCR) rate of neoadjuvant chemotherapy (90.2%) and the CD8/eTreg ratio were independent predictive factors for pCR (odds ratio:18.7(confidence interval 1.25-279) P < 0.05). A detailed assessment of the CD8/eTreg ratio for each patient who underwent NAC revealed that high CD8/eTreg ratio showed a significantly higher pCR rate compared to patients with a low CD8/FOXP3 ratio (39.6% vs 13.3, P < 0.05) in triple negative subtype patients with stromal TILs < 50%. CONCLUSIONS: A high CD8/eTreg ratio enhances pCR rate in patients with invasive breast cancer.