Establishment of a deep-learning system to diagnose BI-RADS4a or higher using breast ultrasound for clinical application.

Although the categorization of ultrasound using the Breast Imaging Reporting and Data System (BI-RADS) has become widespread worldwide, the problem of inter-observer variability remains. To maintain uniformity in diagnostic accuracy, we have developed a system in which artificial intelligence (AI) can distinguish whether a static image obtained using a breast ultrasound represents BI-RADS3 or lower or BI-RADS4a or higher to determine the medical management that should be performed on a patient whose breast ultrasound shows abnormalities. To establish and validate the AI system, a training dataset consisting of 4028 images containing 5014 lesions and a test dataset consisting of 3166 images containing 3656 lesions were collected and annotated. We selected a setting that maximized the area under the curve (AUC) and minimized the difference in sensitivity and specificity by adjusting the internal parameters of the AI system, achieving an AUC, sensitivity, and specificity of 0.95, 91.2%, and 90.7%, respectively. Furthermore, based on 30 images extracted from the test data, the diagnostic accuracy of 20 clinicians and the AI system was compared, and the AI system was found to be significantly superior to the clinicians (McNemar test, p < 0.001). Although deep-learning methods to categorize benign and malignant tumors using breast ultrasound have been extensively reported, our work represents the first attempt to establish an AI system to classify BI-RADS3 or lower and BI-RADS4a or higher successfully, providing important implications for clinical actions. These results suggest that the AI diagnostic system is sufficient to proceed to the next stage of clinical application.

Tumor budding and fibrotic focus-proposed grading system for tumor budding in invasive carcinoma no special type of the breast.

Tumor budding grade is a very useful histological prognostic indicator for colorectal cancer patients. Recently, it has been also reported as a significant prognostic indicator in invasive breast carcinoma patients. Our group and others have previously reported that the presence of a fibrotic focus in the tumor is a very useful histological finding for accurately predicting the prognosis in patients with invasive carcinoma of no special type (ICNST) of the breast. The purpose of the present study was to investigate whether a grading system incorporating tumor budding in a fibrotic focus is superior to the conventional grading system for tumor budding to accurately predict outcomes in patients with ICNST. According to our new grading system, we classified the tumors into grade I (164 cases), grade II (581 cases), and grade III (110 cases), and the results clearly demonstrated the significant superiority of the new grading system over that of conventional tumor budding alone for accurately predicting outcomes in patients with ICNST. Our findings strongly suggest that tumor cells and tumor-stromal cells interaction play very important roles in tumor progression rather than tumor cells alone.

[Clinical Outcomes of Five Cases of Occult Breast Cancer in Which the Primary Site Was Not Detected in the Breast-by-Breast MRI].

Occult breast cancer is rare in practice. We studied the clinical outcomes of 5 occult breast cancers, including 2 with Luminal and 3 with non-Luminal subtypes, for which the primary site was not detected in the breast-by-breast MRI. The percentage of occult breast cancers that we encountered at our hospital was 0.11%. The mean age was 54 years. The Ki-67 labeling index value was 30% or higher for all the patients except one. Four patients were administered neoadjuvant chemotherapy and all but one patient received non-mastectomy and axillary dissection plus radiotherapy. We observed recurrent cases in one example each of the Luminal and HER2 subtypes, and both patients were less than 40 years old. The estimates of the probability of 5 year recurrence-free survival and 5 year overall survival were 40.0% and 66.7%, respectively. One recurrence case was a patient negative for ER and positive for HER2 wherein a breast cancer lesion appeared in the breast during post-treatment follow-up. Intrabreast relapse, which is itself rare in occult breast cancer, was observed 4 years postoperatively after standard treatment. Although there was no deviation according to subtype rate, the Ki-67 labeling index value was high and the prognosis was poor in our 5 cases.

Neo-Bioscore in Guiding Post-surgical Therapy in Patients With Triple-negative Breast Cancer Who Received Neoadjuvant Chemotherapy.

AIM: Patients with triple-negative breast cancer (TNBC) who have not achieved pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) were considered for adjuvant capecitabine. This study was to explore the utility of the Neo-Bioscore in guiding post-surgical therapy in TNBC. PATIENTS AND METHODS: The Neo-Bioscore was calculated for patients with non-metastatic primary breast cancer who received NAC at National Cancer Center Hospital East, Japan. RESULTS: A total of 329 patients were evaluated. The Neo-Bioscore stratified prognosis after NAC better than clinical or pathological stage. The Neo-Bioscore performed well in the selection of patients with TNBC with excellent prognoses despite non-pCR; no death was observed in patients who had a Neo-Bioscore of 2, the lowest score in those with TNBC. CONCLUSION: The Neo-Bioscore can improve the prognostic stratification of patients after NAC for breast cancer over clinical and pathological staging and may enable the identification of patients with non-pCR TNBC who can avoid additional adjuvant chemotherapy.

Use of eribulin as an earlier-line chemotherapy for patients with HER2-negative metastatic breast cancer.

Background: Previous prospective studies have shown that eribulin improves the survival in patients with metastatic breast cancer (MBC). However, the optimal timing of its administration to achieve the longest extended survival and the efficacy of using eribulin monotherapy as earlier-line chemotherapy are yet unclear. Methods: We identified all consecutive female patients with MBC who received any chemotherapeutic intervention for metastatic disease at our institution between July 2012 and December 2017, excluding patients with HER2-positive disease. Those who received eribulin monotherapy for MBC were classified under the eribulin cohort, whereas those who never received eribulin were included in the non-eribulin (Non-E) cohort. Among the patients in the eribulin cohort, those who received eribulin as the first- or second-line chemotherapy for MBC were further classified under the earlier-line eribulin (EE), and otherwise classified under the later-line eribulin (LE) cohorts. The survival of patients was assessed using the log-rank test. A multivariable Cox proportional hazards model was used to assess the independent efficacy and timing of eribulin monotherapy. The inverse probability of treatment weighting (IPTW) estimate was utilized to compare the EE and LE cohorts. Results: Of the 507 patients who were initially screened, 226 were included after an intensive chart review: 93, 49, and 84 patients were included in the Non-E, EE, and LE cohorts, respectively. The eribulin cohort showed significantly longer overall survival than the Non-E cohort (30.3 vs. 22.2 months, p = 0.0217). No significant difference was observed in the progression-free survival of the EE and LE cohorts (3.4 vs. 4.4 months, p = 0.1337) after adjusting for clinically relevant factors using IPTW estimates. LE cohort showed good overall survival (OS) compared with patient group of Non-E and EE by log-rank testing (p = 0.0398), although multivariate analysis did not demonstrate eribulin administration timing as an independent prognostic factor of OS. OS was defined from the initiation of first-line chemotherapy date. Conclusions: Our data provided additional insights regarding the use of eribulin monotherapy as earlier-line chemotherapy. However, the optimal timing of eribulin monotherapy for MBC was not determined in the current study.

Taxane-based combinations as adjuvant chemotherapy for node-positive ER-positive breast cancer based on 2004-2009 data from the Breast Cancer Registry of the Japanese Breast Cancer Society.

BACKGROUND: Adding taxane to an anthracycline-based regimen improves survival in node-positive breast cancer patients, as shown by clinical trials and meta-analyses. However, no studies have analyzed the number of metastatic lymph nodes in patients with estrogen receptor (ER)-positive cancer. This study investigated whether adding a taxane to an anthracycline-based regimen improved prognosis in node-positive, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients in a real-world setting. METHODS: Using Japanese Breast Cancer Society registry data, we compared disease-free survival (DFS) of patients with ER-positive, HER2-negative breast cancer, excluding those receiving neoadjuvant chemotherapy, between those who received an anthracycline-based regimen followed by a taxane-based regimen (A + T) and those who received only an anthracycline-based regimen (A w/o T), stratified by lymph node status. A Cox proportional hazards model was used to evaluate DFS in both groups. RESULTS: There were 4566 eligible patients with ER-positive, HER2-negative breast cancer. During the median follow-up period of 60 months, there were 481 recurrences and 149 deaths. There was no significant difference in DFS between the A + T and A w/o T groups among patients with 1-3 positive nodes, while there was a significant difference among patients with ≥ 4 positive nodes. CONCLUSIONS: In patients with ER-positive, HER2-negative breast cancer, adding taxane to an anthracycline regimen did not improve DFS in patients with metastasis in 1-3 lymph nodes. We considered that the group without the addition of taxane might be present in patients with ER-positive, HER2-negative lymph node metastases.

Assessment of Upper Limb Physiological Features in Patients with Lymphedema After Breast Surgery Using Multiple Instruments.

Background: Objective assessment of upper limb physiological features may allow for early detection and proper intervention for lymphedema after breast surgery. However, the development of diagnostic instruments and standard measurement procedures are required. Methods and Results: Four instruments (Venustron, Softmeasure, Myoton Pro, and iBDent), tape measurement, and water volumetry were investigated in this study. Inter-limb differences in physiological data were obtained from 40 patients with lymphedema after breast surgery and 38 control subjects. Four instruments and tape measurements were performed at four points. Inter-limb differences between patients with lymphedema and control subjects were determined. All measurements took <20 minutes with minimal pain reported. Inter-limb differences in water volumetry and tape measurements, especially when measured at 5 cm distal to the cubital fossa, were increased in International Society of Lymphology (ISL) stage II cases. All four instruments showed high reproducibility in standard silicon sample measurement. On the other hand, data from human samples were varied, and the utility for assessment of lymphedema was not determined. Conclusion: Water volumetry and tape measurement at 5 cm distal to the cubital fossa were useful to assess lymphedema in ISL stage II cases. Four instruments used in this study were feasible in clinical practice. In addition, inconsistent data from human tissue were not due to sensor limitations, rather, acquisition of accurate data from human tissue seemed to be difficult due to anatomical factors. In addition to high-quality sensor, development of system that produce accurate and reproducible results from human tissue is required.

Invasive breast cancers in adolescent and young adult women show more aggressive immunohistochemical and clinical features than those in women aged 40-44 years.

BACKGROUND: Limited knowledge exists concerning the clinicopathological features of breast cancers (BCs) occurring in adolescent and young adult (AYA) women. We evaluated tumor characteristics in AYA women in comparison with those in middle-aged premenopausal women. METHODS: From consecutive AYA patients (< 35-year-old) with invasive BC in a single institute, 82 patients first treated with surgery were examined. As the control group, 82 tumors from middle-aged premenopausal patients (40-44 years) were selected by matching pathological T and N factors. We compared habitual factors, immunohistochemical parameters, and patient outcome between the two groups. RESULTS: Most of the study population (148 of 164, 90.2%) were in the early clinical stages (stage I or II). In the AYA group, the number of childbirths was smaller (p < 0.0001), while the volume of alcohol consumption was larger (p < 0.0001), and palpable primary tumors were more frequent (p < 0.01) than in the control group. The positivities of estrogen receptor, progesterone receptor, and androgen receptor were lower (p < 0.001, p = 0.03, and p < 0.001, respectively), and the triple-negative (TN) BCs rates were higher (p < 0.01) in the AYA group. Distant recurrence-free survival (DRFS) curves were different in the whole population (p = 0.02) and in hormone receptor-positive cases (p = 0.01). CONCLUSIONS: We confirmed that BCs occurring in AYA women had more aggressive features than those of the older premenopausal women in terms of a high proportion of TN subtypes and a lower DRFS.

Clinicopathological predictive factors for ipsilateral and contralateral events following initial surgery to treat ductal carcinoma in situ.

BACKGROUND: Ipsilateral breast tumor recurrence (IBTR) after partial breast resection and contralateral breast tumor recurrence (CBTR) have been shown to occur relatively frequently in patients with ductal carcinoma in situ (DCIS). However, there is only limited data from Japanese institutes to support this. METHODS: Of 301 consecutive DCIS patients, 179 patients underwent a mastectomy, and the other 122 underwent partial resection in the National Cancer Center Hospital, Tokyo, with a median follow-up period of 2,106 days. We reviewed clinicopathological parameters including age, menopausal status, body mass index, family history (FH) of breast cancer, tumor size, histological subtype, nuclear grade (NG), hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, treatment, and the surgical margin status of partially resected specimens. The risk associated with each of these parameters for IBTR in 122 patients who underwent partial resections, and for CBTR in a total of 301 patients were calculated using Cox proportional hazard general linear models. RESULTS: Of the 122 patients who underwent partial breast resection, IBTR occurred in 7 (5.7%). The risk of IBTR was higher or tended to be higher in younger patients or those with lower NG tumors, but did not change significantly with respect to margin status or irradiation. Amongst the entire cohort of 301 patients, CBTR occurred in 18 cases (6.0%). CBTR occurred significantly more frequently in patients with a FH of breast cancer and with HR+/HER2- subtype tumors by univariate analyses, and tumor subtype was an independent risk factor for CBTR by multivariate analysis. CONCLUSIONS: The local recurrence rate was low following partial resection of DCIS. Younger age was a risk factor for IBTR, whereas the HR+/HER2- tumor subtype and a FH of breast cancer were risk factors for CBTR.

Preoperatively diagnosed ductal carcinoma in situ: risk prediction of invasion and effects on axillary management.

BACKGROUND: Preoperatively diagnosed ductal carcinoma in situ (DCIS) has the potential to have occult invasion. The predictors of invasive carcinoma underestimation in patients with DCIS diagnosed by preoperative percutaneous biopsy were identified and the effects of underestimation on axillary management were evaluated. METHODS: Medical records of 280 patients preoperatively diagnosed as DCIS who underwent surgery were retrospectively analyzed. The patients were divided into non-invasive and invasive carcinoma groups according to the final pathological diagnosis. Risk predictors of invasive carcinoma underestimation and axillary lymph node (ALN) metastasis were analyzed. The axillary status estimated by pathological diagnosis and one-step nucleic acid amplification (OSNA) assay was evaluated. RESULTS: The presence of an invasive carcinoma was overlooked in 104 (37.1 %) patients. A clinically palpable mass was an independent risk predictor of invasive carcinoma underestimation by multivariate analysis. There was no risk predictor of ALN metastasis. No ALN metastasis was seen in non-invasive carcinoma group. Six (6.2 %) patients in invasive carcinoma group had macro- or micrometastasis in sentinel lymph nodes (SLNs). Non-SLN metastasis was observed in 3 patients of them. Fourteen patients with only isolated tumor cells (ITCs) or only OSNA-positive SLNs had no metastasis in non-SLNs. CONCLUSIONS: SLN biopsy and, if necessary, subsequent ALN dissection (ALND) should be performed in patients with DCIS who have a risk predictor of underestimation. ALND can be avoided in patients who have histologically negative or ITC-positive SLNs, regardless of the presence of invasion on final pathological diagnosis.

Clinicopathological features of breast angiosarcoma.

BACKGROUND: Breast angiosarcomas are rare neoplasm. Due to its rarity, our therapeutic strategy is extremely limited. Therefore, we investigated the clinicopathologic features and examined the treatment for angiosarcoma compared with some literatures. METHODS: We conducted a retrospective chart and slide review of all patients in our division seen from 1997 to 2012 with a diagnosis of primary or secondary breast angiosarcoma at the National Cancer Center Hospital (Tokyo, Japan). RESULTS: Nine patients were diagnosed with breast angiosarcoma (six primary and three secondary cases). The median age of patients with primary angiosarcoma was 39 years (range 27-65 years). The median tumor size was 6.78 cm (range 3.0-8.8 cm). In the primary tumor, 4 patients had total mastectomy and 2 had a breast conserving surgery. 3- and 5-year disease-free survival (DFS) of the patients with primary angiosarcoma was 20 and 0 %. 5-year surviving rate of primary angiosarcoma was 50 %. In all patients with secondary angiosarcoma, recurrence was observed in all cases. But one case obtained long-term survival in local control therapy. CONCLUSIONS: Our study demonstrates breast angiosarcoma exhibits high recurrence rates. Tumor size and surgical margin may be important factor to obtain long-term survival. In this point of view, total mastectomy with adequate tumor margin with early detection is desired. In case of recurrence, if it is local, surgery may be potentially curative.

Intensive vs. Standard Post-Operative Surveillance in High-Risk Breast Cancer Patients (INSPIRE): Japan Clinical Oncology Group Study JCOG1204.

This Phase III trial aims to determine the superiority of intensive follow-up to standard follow-up in terms of overall survival in high-risk breast cancer patients, who are expected to have recurrence rates of over 30% within 5 years after surgery. Eligible patients are randomized either to the intensive follow-up group or to the standard follow-up group; the former will undergo physical examination, bone scintigraphy, chest computed tomography, abdominal computed tomography, brain magnetic resonance imaging/computed tomography and frequent tumor marker evaluations, whereas the latter will undergo physical examination at the same frequency and tumor markers will be evaluated once a year. Mammography once a year is planned for both groups. The primary endpoint is overall survival. Patient accrual was started in November 2013. A total of 1700 patients will be enrolled for 3 years and followed up for 7 years after closure of accrual. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429.

Intraductal papillomas on core biopsy can be upgraded to malignancy on subsequent excisional biopsy regardless of the presence of atypical features.

Intraductal papillary lesions of the breast constitute a heterogeneous entity, including benign intraductal papilloma (IDP) with or without atypia and malignant papillary carcinoma. Differentiating between these diagnoses can be challenging. We re-evaluated core biopsy specimens that were diagnosed as IDP and the corresponding surgical excision specimens, and assessed the potential risk for the diagnosis to be modified to malignancy based on excision. By sorting the pathology database of the National Cancer Center Hospital, Tokyo, we identified 146 core biopsy cases that were histologically diagnosed as IDP between 1997 and 2013. The re-evaluated diagnosis was IDP without atypia in 79 (54%) patients, IDP with atypia in 66 (45%), and ductal carcinoma in situ (DCIS) in 1 (1%). Among the 34 patients (23%) who underwent surgical excision subsequent to core biopsy, histological diagnosis was upgraded to carcinoma, excluding lobular carcinoma in situ (LCIS), in 14 (41%) cases, including 4 (33%) of 12 IDPs without atypia and 10 (45%) of 22 IDPs with atypia. Complete surgical excision should be kept in mind for all IDPs diagnosed on core biopsy, not only IDPs with atypia but IDPs without atypia, especially when clinical or imaging diagnosis findings cannot rule out the possibility of malignancy, because papillary lesions comprise a variety of morphological appearances.

Predictive Factors for Non-Sentinel Lymph Node Metastasis in Patients With Clinically Node-Negative Ipsilateral Multiple Breast Cancer Treated With Total Mastectomy.

BACKGROUND: Recent clinical trials have shown that axillary lymph node dissection can be omitted even with positive sentinel nodes (SN) unless the patient undergoes total mastectomy without irradiation. The aim of our study was to identify predictive factors for non-SN metastasis among patients with solitary or multiple breast cancer treated with total mastectomy. PATIENTS AND METHODS: Clinically node-negative breast cancer patients with pathologically node-positive disease treated with total mastectomy and axillary dissection after SN biopsy were retrospectively analyzed. Significant pathologic predictive factors for positive non-SN metastasis were also examined. RESULTS: There were 47 multiple and 143 solitary breast cancer patients. Pathologic diagnosis demonstrated that smaller invasion size but larger tumor size, including adjacent noninvasive cancer, was observed in multiple breast cancer. The number of involved SNs and the rate of non-SN metastasis were similar between the multiple and solitary groups. Regarding predictive factors for non-SN metastasis, lymphatic invasion and SN macrometastasis were significant factors in the solitary group, and pathologic invasion size > 2 cm was the only significant factor in the multiple group. CONCLUSION: Larger pathologic invasion size was important for predicting non-SN metastasis in multiple breast cancer.

Utility of intraoperative frozen section examinations of surgical margins: implication of margin-exposed tumor component features on further surgical treatment.

OBJECTIVE: In patients who underwent breast-conserving surgery, we attempted to identify the histological characteristics of margin-exposed tumor components on intraoperative frozen section examinations that were predictive of residual tumor components in additionally resected specimens. METHODS: Of 1835 patients who underwent breast-conserving surgery, we identified 220 patients who had positive surgical margins determined by intraoperative frozen section examinations and who had undergone immediate additional resections. Two observers (M.K., H.T.) reviewed the slides of frozen sections and confirmed the presence of tumor components. RESULTS: In additionally resected specimens, residual tumors were detected in 115 cases (52.3%) but not in 105 cases (47.7%). The primary tumor characteristics of extensive intraductal component (+), younger age, invasive lobular carcinoma and pathological T3 classification were significantly associated with the residual tumor components. The margin-exposed tumor components of the maximum diameter, number of positive margins and histological type were correlated with the residual tumors. Multivariate analysis showed that the maximum tumor diameter was an independent risk factor for residual tumors. CONCLUSIONS: Diagnosis of positive margins by intraoperative frozen section examinations was useful for predicting residual tumors, and three histological properties of the margin-exposed tumor components were correlated with the status of residual tumor components. Although it was impossible to clearly identify the single main factor for predicting patients for whom additional resections were not necessary, it may be possible to consider stratification of additional surgical therapy according to the characteristics of margin-exposed tumor components on intraoperative frozen section examinations.

Oncological safety of breast-conserving surgery after primary systemic chemotherapy in cT3-4 breast cancer patients.

PURPOSE: The aim of this study was to retrospectively assess the oncological safety of breast-conserving surgery (BCS) after primary systemic chemotherapy (PST) in terms of local recurrence (LR) in cT3-4 patients. METHODS: The subjects were 146 cT1-2 patients who underwent BCS after PST, and 169 patients with cT3-4 primary breast cancer. Of the 169 patients with cT3-4 disease, 20 underwent surgery first, and 149 underwent surgery after PST (mastectomy: 101 patients; BCS: 48 patients). The LR-free survival (LRFS) was analyzed using a Kaplan-Meier analysis. We evaluated the predictors using Cox proportional hazards modeling for LR after PST. RESULTS: There was no significant difference in 5-year LRFS between the cT1-2 and cT3-4 groups that underwent BCS after PST (98.6 vs. 92.5 %; P = 0.074). The 5-year LRFS was 94.7 % in the group that underwent initial surgery and 93.0 % in the PST group (P = 0.845) in the cT3-4 patients, while the 5-year LRFS rates were 93.2 % in the BCS subgroup and 92.5 % in the mastectomy subgroup (P = 0.958). In a multivariate analysis, the histological type, hormone negativity and a higher histological grade were independent predictors of LR after PST. CONCLUSIONS: BCS after PST may be oncologically acceptable for cT3-4 breast cancers in terms of the LR compared with initial surgery or mastectomy after PST.

Mucinous breast carcinoma with a lobular neoplasia component: a subset with aberrant expression of cell adhesion and polarity molecules and lack of neuroendocrine differentiation.

We investigated whether some mucinous carcinomas (MUCs) are associated with lobular neoplasia (LN) components, and if so, whether this subset has any distinct biological properties. MUC specimens from 41 patients were stratified into pure and mixed types. The LN components adjacent to MUC lesions were examined histopathologically. We also tested immunohistochemically for E-cadherin, ß-catenin, and the neuroendocrine markers chromogranin A and synaptophysin; and compared results between MUCs with and without LN. Of 41 patients with MUC, LN was detected in 12 patients (29%); LN alone was the noninvasive component in 8 patients (20%). Decreased E-cadherin and ß-catenin expression in the MUC component was detected in 2 (17%) and 7 (58%) cases, respectively, of MUC with LN, compared with 0% (P = 0.080) and 21% (P = 0.018) in MUCs without LN. Neuroendocrine factors were frequently detected in MUCs with LN (42%) and without LN (52%), but tended to be less frequent in MUCs with only LN components (25%) than in other MUCs (55%; P = 0.133). MUCs associated with LN components appear to be a biologically characteristic subset that frequently shows decreased cell-cell adhesion, cell polarity molecules and lack of neuroendocrine differentiation.

Locoregional recurrence risk factors and the impact of postmastectomy radiotherapy on patients with tumors 5 cm or larger.

BACKGROUND: Locoregional recurrence (LRR) after mastectomy reduces the patient's quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps achieve locoregional control and reduces LRR. However, in patients with large tumors, the question of which variables affect the likelihood of LRR and the role of PMRT have been subjects of substantial controversy. This study investigated what the risk factors are for LRR and the efficacy of PMRT in this patient population. METHODS: This retrospective study examined 589 cases of invasive breast carcinoma with tumors 5 cm or larger from 1998 to 2008. We divided the study population into 3 groups: patients with negative nodes, 1-3 positive nodes, and ≥4 positive nodes. The relationship between various clinicopathological variables and LRR was examined, and the relationship between LRR and PMRT was estimated. RESULTS: During the median follow-up of 44.2 months, 38 (6.5 %) patients experienced LRR. In the multivariate analysis, independent risk factors for LRR included pectoral invasion in patients with 1-3 positive nodes, severity of lymphatic invasion, estrogen receptor-negative status, and a nodal ratio of positive/excised nodes >0.50 in patients with ≥4 positive nodes. In patients without positive nodes, none of the examined variables were significantly associated with LRR. Although patients treated with PMRT had good outcomes, there was no significant difference. CONCLUSIONS: With systemic therapy and adequate lymph node dissection, PMRT by itself was of limited value in establishing locoregional control. Due to the very low incidence of LRR observed, PMRT was not necessary for patients with large tumors without lymph node metastasis. Further examination and consensus about the indications for PMRT in patients with 1-3 metastatic nodes are needed.

Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed.