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

The 2022 revision of the Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for surgical treatment of breast cancer was updated following a systematic review of the literature using the Medical Information Network Distribution Service (MINDS) procedure, which focuses on the balance of benefits and harms for various clinical questions (CQs). Experts in surgery designated by the JBCS addressed five areas: breast surgery, axillary surgery, breast reconstruction, surgical treatment for recurrent and metastatic breast cancer, and other related topics. The revision of the guidelines encompassed 4 CQs, 7 background questions (BQs), and 14 future research questions (FRQs). A significant revision in the 2022 edition pertained to axillary management after neoadjuvant chemotherapy in CQ2. The primary aim of the 2022 JBCS Clinical Practice Guidelines is to provide evidence-based recommendations to empower patients and healthcare professionals in making informed decisions regarding surgical treatment for breast cancer.

Analysis of prognosis in different subtypes of invasive lobular carcinoma using the Japanese National Cancer Database-Breast Cancer Registry.

PURPOSE: Many studies have shown that the prognosis of invasive lobular carcinoma (ILC) is better than that of invasive ductal carcinoma (IDC). However, both disorders exhibit different prognoses according to molecular subtype, and the prognosis of ILC subtypes might depend on their hormone receptor positivity rate. This study clarified the prognosis of ILC and IDC in each subtype and examined the effectiveness of adjuvant chemotherapy (CT) in luminal ILC. METHODS: We planned the analysis using data from the Breast Cancer Registry in Japan. Because it was presumed that there are differences in characteristics between ILC and IDC, we created matched cohorts using exact matching to compare their prognoses. We compared the prognosis of ILC and IDC for each subtype. We also compared the prognosis of luminal ILC between the CT and non-CT groups. RESULTS: For all subtypes, the disease-free survival (DFS) and overall survival (OS) of ILC were poorer than those of IDC. In the analysis by each subtype, no statistically significant difference was found in DFS and OS in luminal human epidermal growth factor 2 (HER2), HER2, and triple-negative cohorts; however, luminal ILC had significantly poorer DFS and OS than luminal IDC. The CT effects on the prognosis of luminal ILC were greater in more advanced cases. CONCLUSION: Luminal ILC had a poorer prognosis than luminal IDC, contributing to the worse prognosis of ILC than that of IDC in the overall cohort. Different therapeutic approaches from luminal IDC are essential for a better prognosis of luminal ILC.

Characteristics of female breast cancer in japan: annual report of the National Clinical Database in 2018.

Information regarding patients who were treated for breast cancer in 2018 was extracted from the National Clinical Database (NCD), which is run by Japanese physicians. This database continues from 1975, created by the Japanese Breast Cancer Society (JBCS). A total of 95,620 breast cancer cases were registered. The demographics, clinical characteristics, pathology, surgical treatment, adjuvant chemotherapy, adjuvant endocrine therapy, and radiation therapy of Japanese breast cancer patients were summarized. We made comparisons with other reports to reveal the characteristics of our database. We also described some features in Japanese breast cancer that changed over time. The unique characteristics of breast cancer patients in Japan may provide guidance for future research and improvement in healthcare services.

Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.

PURPOSE: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. METHODS: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. RESULTS: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC. CONCLUSION: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.

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.

Clinicopathological features of male patients with breast cancer based on a nationwide registry database in Japan.

BACKGROUND: Male breast cancer (MBC) is rare; however, its incidence is increasing. There have been no large-scale reports on the clinicopathological characteristics of MBC in Japan. METHODS: We investigated patients diagnosed with breast cancer in the Japanese National Clinical Database (NCD) between January 2012 and December 2018. RESULTS: A total of 594,316 cases of breast cancer, including 3780 MBC (0.6%) and 590,536 female breast cancer (FBC) (99.4%), were evaluated. The median age at MBC and FBC diagnosis was 71 (45-86, 5-95%) and 60 years (39-83) (p < 0.001), respectively. MBC cases had a higher clinical stage than FBC cases: 7.4 vs. 13.3% stage 0, 37.2 vs. 44.3% stage I, 25.6 vs. 23.9% stage IIA, 8.8 vs. 8.4% stage IIB, 1.9 vs. 2.4% stage IIIA, 10.1 vs. 3.3% stage IIIB, and 1.1 vs. 1.3% stage IIIC (p < 0.001). Breast-conserving surgery was more frequent in FBC (14.6 vs. 46.7%, p = 0.02). Axillary lymph node dissection was more frequent in MBC cases (32.9 vs. 25.2%, p < 0.001). Estrogen receptor(ER)-positive disease was observed in 95.6% of MBC and 85.3% of FBC cases (p < 0.001). The HER2-positive disease rates were 9.5% and 15.7%, respectively (p < 0.001). Comorbidities were more frequent in MBC (57.3 vs. 32.8%) (p < 0.001). Chemotherapy was less common in MBC, while endocrine therapy use was similar in ER-positive MBC and FBC. Perioperative radiation therapy was performed in 14.3% and 44.3% of cases. CONCLUSION: Japanese MBC had an older age of onset, were more likely to be hormone receptor-positive disease, and received less perioperative chemotherapy than FBC.

Prognostic impact of postoperative radiotherapy in patients with breast cancer and with pT1-2 and 1-3 lymph node metastases: A retrospective cohort study based on the Japanese Breast Cancer Registry.

AIM: Postmastectomy radiotherapy (PMRT) is the standard treatment for locally advanced breast cancer. However, the effectiveness of PMRT in patients with pT1-2 and N1 tumours remains controversial. Therefore, this study aimed to determine the prognostic impact of PMRT in patients with breast cancer and with pT1-2 and 1-3 lymph node metastases. METHODS: Using data from the Japanese National Clinical Database from 2004 to 2012, we evaluated the association of PMRT with locoregional recurrence (LRR), any recurrence, and mortality. We enrolled patients who had undergone mastectomy and axillary node dissection and were diagnosed with pT1-2 and N1. We compared clinicopathological factors and prognosis between patients who received (PMRT group) and those who did not receive (No-PMRT group) PMRT. RESULTS: Among 8914 patients enrolled, 492 patients belonged to the PMRT group and 8422 to the No-PMRT group. The median observation time was 6.3 years. There was no significant difference in the incidences of LRR (4.0% versus 5.0%, P = 0.61), recurrence (13.8% versus 11.8%, P = 0.23) and breast cancer death (6.0% versus 4.3%, P = 0.08) at 5 years between the groups. Multivariable analysis revealed that LRR was significantly associated with tumour size, number of node metastases and triple-negative subtype but not with PMRT. CONCLUSIONS: The LRR rate in the No-PMRT group was 5.0% at 5 years among patients with T1-2 and N1. PMRT did not significantly influence LRR in patients with T1-2 and N1. However, PMRT administration should be tailored considering the individual risks of tumour size, 3 node metastases and triple-negative subtype.

Surgical treatment trends and identification of primary breast tumors after surgery in occult breast cancer: a study based on the Japanese National Clinical Database-Breast Cancer Registry.

BACKGROUND: Occult breast cancer (OBC) is classified as carcinoma of an unknown primary site, and the adequate therapy for OBC remains controversial. This retrospective study aimed to reveal the transition in breast cancer therapy and the frequency of primary breast tumors after resection in clinical OBC (cT0N+) patients using the Japanese Breast Cancer Registry database. METHODS: We enrolled OBC patients with cT0N+ from the registry between 2010 and 2018. On the basis of the period of diagnosis, OBC patients were divided into the following two groups: 2010-2014 and 2015-2018. We described the transition in treatments and tumor characteristics. After breast resection, the frequency of pathological identification of primary tumors and tumor sizes was assessed. RESULTS: Of the 687,468 patients registered, we identified 148 cT0N+ patients with a median age of 61 years. Of these patients, 64.2% (n = 95) received breast surgery (2010-2014: 79.1%, 2015-2018: 50.0%). Axillary lymph node dissection was performed in 92.6% (n = 137, 2010-2014: 91.6%, 2015-2018: 93.4%). The breast tumor size in the resected breast was 0-7.0 cm (median: 0 cm, 2010-2014: 0-7.0 cm [median: 0 cm], 2015-2018: 0-6.2 cm [median: 0 cm]). The pathological identification rate of the primary tumor was 41.1% (n = 39, 2010-2014: 40.4%, 2015-2018: 42.1%). CONCLUSIONS: Breast surgery for cT0N+ decreased between 2010 and 2018. Despite the high identification rate of primary tumors, most tumors were small, and there was no significant change in the identification rate or invasive diameter of the identified tumors after 2010.

Long-term results of fluorescence and indigo carmine blue dye-navigated sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy is widely applied for the management of clinically node-negative breast cancer, and a radioisotope with a blue dye are most often used as tracers. Fluorescence of indocyanine green could also potentially be used as tracer. This study aimed to demonstrate the long-term survival results of fluorescence-guided sentinel lymph node biopsy. PATIENTS AND METHODS: Patients with clinically node-negative breast cancer who underwent surgery as initial treatment were included in this study. Both fluorescence of indocyanine green and indigo carmine blue dye were used as tracers. Axillary lymph node dissection was omitted unless metastasis was pathologically proven in sentinel nodes. Breast cancer recurrence and death were recorded and prognostic factors were identified using disease-free survival and overall survival data. RESULTS: A total of 565 patients were analyzed. There were 14 (2.5%) patients whose sentinel nodes could not be identified, yielding an identification rate of 97.5%. Axillary dissection was performed in 90 patients. Forty-three recurrences including 6 ipsilateral axilla recurrence and 13 deaths were observed during the median 83 months of follow-up period. Seven-year disease-free and overall survival were 92.4% and 97.3%, respectively. Multivariate analyses demonstrated that pre-menopausal status and invasive lobular carcinoma were significant unfavorable prognostic factors of disease-free survival. Half of ipsilateral axilla recurrences occurred within 5 years after surgery and these recurrences were correlated with inappropriate adjuvant therapy. CONCLUSION: Fluorescence-guided sentinel lymph node biopsy demonstrated favorable prognostic results and could be alternative to the radioisotope for clinically node-negative breast cancer.

Annual report of the Japanese Breast Cancer Registry for 2017.

BACKGROUND: The Japanese Breast Cancer Society Registry started in 1975; it was transferred to the registry platform of the National Clinical Database in 2012. We provide the annual data and an analysis of the Breast Cancer Registry for 2017. METHODS: Patients' characteristics and pathological data of the 95,203 registered Japanese breast cancer patients from 1,427 institutes in 2017 were obtained. Trends in age at diagnosis and pathological stage were determined during the most recent 6 years (2012-2017). RESULTS: The mean onset age was 60.2 years with bimodal peaks at 45-49 years and 65-69 years. A short-term trend of the most recent 6 years of data caused the second, older peak. At diagnosis, 32.4% of breast cancer patients were premenopausal. The distribution of stages revealed that the proportion of early stage breast cancer (stage 0-I) increased up to 60%. At the initial diagnosis, 2.2% of patients presented with metastatic disease. Sentinel node biopsy without axillary node dissection was performed without neoadjuvant chemotherapy (NAC) in 68.8%, and with NAC in 31.1%, of patients. For patients without NAC, lymph node metastasis was less than 3% if the tumor size was less than 1 cm. The proportion of node-negativity decreased to 79.5% when tumor size was 2.1-5 cm. CONCLUSIONS: This analysis of the registry provides new information for effective treatment in clinical practice, cancer prevention, and the conduct of clinical trials. Further development of the registry and progress in collecting prognostic data will greatly enhance its scientific value.

Annual report of the Japanese Breast Cancer Society registry for 2016.

The Japanese Breast Cancer Society (JBCS) registry began data collection in 1975, and it was integrated into National Clinical Database in 2012. As of 2016, the JBCS registry contains records of 656,896 breast cancer patients from more than 1400 hospitals throughout Japan. In the 2016 registration, the number of institutes involved was 1422, and the total number of patients was 95,870. We herein present the summary of the annual data of the JBCS registry collected in 2016. We analyzed the demographic and clinicopathologic characteristics of registered breast cancer patients from various angles. Especially, we examined the registrations on family history, menstruation, onset age, body mass index according to age, nodal status based on tumor size and subtype, and proportion based on ER, PgR, and HER2 status. This report based on the JBCS registry would support clinical management for breast cancer patients and clinical study in the near future.

A population-based recurrence risk management study of patients with pT1 node-negative HER2+ breast cancer: a National Clinical Database study.

PURPOSE: Recurrence risk management of patients with small (≤ 2 cm), node-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains challenging. We studied the effects of adjuvant chemotherapy and/or trastuzumab and survival outcomes among these patients, using data from the population-based Japanese National Clinical Database (NCD). METHODS: We identified a cohort of 2736 breast cancer patients with HER2+ pT1N0 disease: 489 pT1a, 642 pT1b, and 1623 pT1c. The median observation period was 76 months, and the 5-year follow-up rate was 48.2%. The number of events was 212 for disease-free survival (DFS), 40 for breast cancer-specific survival, and 84 for overall survival (OS). RESULTS: There were 24.5% of pT1a, 51.9% of pT1b, and 63.3% of pT1c patients who were treated systemically after surgery. OS in pT1b (logrank test; p = 0.03) and DFS in pT1c (logrank test; p < 0.001) were significantly improved in treated compared with untreated patients. In the Cox proportional hazards model, treated patients had significantly longer OS than untreated patients in pT1b (hazard ratio (HR) 0.20) and pT1c (HR 0.54) groups. Estrogen receptor-negative tumors was also a significant predictor of survival in pT1c (HR 2.01) but not pT1ab patients. Furthermore, HR was greater in patients aged ≤ 35 years (3.18) compared to that in patients aged 50-69 years in the pT1b group. CONCLUSIONS: NCD data revealed that systemic treatment improved OS in pT1bc but not in pT1a node-negative HER2+ breast cancer patients. Future observational research using big-sized data is expected to play an important role in optimizing treatment for patients with early-stage breast cancer.

Two rare cases of endosalpingiosis in the axillary sentinel lymph nodes: evaluation of immunohistochemical staining and one-step nucleic acid amplification (OSNA) assay in patients with breast cancer.

Benign inclusions, such as endosalpingiosis, in an axillary sentinel lymph node (SLN) can be misdiagnosed as metastatic breast carcinoma. However, endosalpingiosis is rare in lymph nodes above the diaphragm. Among 792 patients with breast carcinoma who underwent sentinel lymph node biopsy at our center, 2 patients have experienced benign glandular inclusions in 3 SLNs, and all of these glandular inclusions were lined with columnar and ciliated epithelial cells. Immunohistochemistry revealed that the epithelial cells were positive for Müllerian markers (e.g., PAX8 and WT-1) and negative for mammary markers (e.g., mammaglobin, GCDFP-15, and GATA3), which confirm the diagnosis of endosalpingiosis. The epithelial cells were positive for CK19 but the one-step nucleic acid amplification assay revealed negative results for the axillary SLNs. Although endosalpingiosis is rare in axillary SLNs, care is needed to identify these rare cases and avoid unnecessary axillary lymph node dissection, overstaging, and overtreatment.

Prognostic factors for breast cancer patients with T1-2 tumor and 1-3 positive axillary nodes treated using total mastectomy without radiotherapy.

Prospective randomized trials have demonstrated that postmastectomy radiotherapy (PMRT) improves not only locoregional recurrence-free survival, but also overall survival for node-positive breast cancer patients. Subset analyses in previous trials have shown that improvement of overall survival with PMRT is not always demonstrated for patients with 1-3 positive nodes. Indications for PMRT are still marginal for patients with pathological invasion 5 cm in diameter and 1-3 positive nodes. The aim of this study was to clarify poor prognostic factors for breast cancer patients with pathological invasion size 5 cm and 1-3 positive nodes. Participants comprised 428 breast cancer patients with T1-2 tumor and 1-3 positive axillary nodes (pT1-2 N1) treated using total mastectomy without radiotherapy. Correlations between clinicopathological characteristics and 10-year Kaplan-Meier estimates of locoregional recurrence-free survival, disease-free survival, and overall survival were retrospectively analyzed. Median follow-up was 98 months. Locoregional recurrence was observed in 20 patients (4.7%), and distant recurrence was observed in 70 patients (16.4%). Disease-free survival rate was 80.8%, and overall survival rate within the study period was 90%. Multivariate analysis demonstrated that favorable prognostic factors for locoregional recurrence-free survival were the presence of chemotherapy and positive hormone receptor status, and for disease-free survival were presence of chemotherapy, pT1 tumor, and single positive node. Physicians may consider these favorable prognostic factors in decision to eliminate PMRT from patients with the borderline indications.

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.

Prognostic Impact of Discordance in Hormone Receptor Status Between Primary and Recurrent Sites in Patients With Recurrent Breast Cancer.

INTRODUCTION: Recent retrospective studies have reported discordance rate of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses between primary and recurrent tumors and prognostic values of discordance. However, the results of these reports may possibly include analytical error. PATIENTS AND METHODS: We analyzed 153 patients from whom pathological specimens of tumor tissues were available from both primary and recurrent sites. For all specimens, immunohistochemistry was performed for these statuses with a standardized method. Two experienced pathologists evaluated these specimens in a blinded fashion. RESULTS: The discordance rates for estrogen receptor, progesterone receptor, and HER2 were 18%, 26%, and 7%, respectively. Subtype changes based on HR and HER2 status occurred in 21% of patients. Clinical outcome was significantly worse in the patients with the tumors that were primarily HR-positive (HR(+)) converted to HR-negative (HR(-)) at recurrent sites than in the patients with the tumors in which HR status did not change or converted from HR(-) to HR(+) (P = .001). Clinical outcome was also significantly worse in the patients with the primarily HR(+) tumor that converted to triple negative in the recurrence sites than in the patients with a constantly HR(+) tumor (P < .001). By the Cox multivariate analyses, loss of HR expression and conversion to triple negative at the recurrence sites were independent indicators of worse clinical outcome. CONCLUSION: Discordance in HR and HER2 status often occurred between primary and recurrent breast cancer and had independent prognostic impact in the patients with recurrent breast cancer.

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.

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.

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.

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.