The Japanese breast cancer society clinical practice guidelines for breast cancer screening and diagnosis, 2022 edition.

This article provides updates to readers based on the newly published Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer Screening and Diagnosis, 2022 Edition. These guidelines incorporate the latest evaluation of evidence from studies of diagnostic accuracy. For each clinical question, outcomes for benefits and harms were established, and qualitative or quantitative systematic reviews were conducted. Recommendations were determined through voting by a multidisciplinary group, and guidelines were documented to facilitate shared decision-making among patients and medical professionals. The guidelines address screening, surveillance, and pre- and postoperative diagnosis of breast cancer. In an environment that demands an integrated approach, decisions are needed on how to utilize modalities, such as mammography, ultrasound, MRI, and PET/CT. Additionally, it is vital to understand the appropriate use of new technologies, such as tomosynthesis, elastography, and contrast-enhanced ultrasound, and to consider how best to adapt these methods for individual patients.

Utility of B-Mode, Color Doppler and Elastography in the Diagnosis of Breast Cancer: Results of the CD-CONFIRM Multicenter Study of 1351 Breast Solid Masses.

The usefulness of color Doppler ultrasound (CD) in distinguishing between benign and malignant breast lesions remains controversial. Our prior study, the Japan Association of Breast and Thyroid Sonology (JABTS) BC-04 study (malignant: 839, benign: 569), found CD was useful in breast cancer diagnosis, and we developed CD diagnostic criteria. The first aim of the current study (the CD-CONFIRM study) was to evaluate the usefulness of the CD diagnostic criteria. The second aim was to evaluate the relationship between CD and elastography. We evaluated ultrasound images of breast masses from 13 institutions (malignant: 639, benign: 712). While the sensitivity of B-mode alone was very high and was not significantly improved with CD, the specificity was significantly improved with CD (61.2%-69.2%, p < 0.0001). Furthermore, the specificity of the combination of B-mode and CD improved significantly with the addition of elastography (72.8%-79.0%, p < 0.0001). This study found that the CD criteria are useful, and CD and elastography are independent.

Investigation of a Novel S-1 Administration Schedule for Treating Metastatic and Recurrent Breast Cancer (KBCOG13).

BACKGROUND/AIM: S-1, a 5-fluorouracil(5-FU) oral anti-cancer drug, has been traditionally used with a schedule of 4-week oral administration followed by 2-week rest for breast cancer treatment. We, herein, aimed to investigate the clinical efficacy and safety of a schedule of 2-week oral administration followed by 1-week rest for patients with metastatic breast cancer. PATIENTS AND METHODS: We enrolled patients with HER2-negative metastatic breast cancer who had not received prior chemotherapy. S-1 was administered consecutively for 2-weeks followed by a 1-week rest. RESULTS: Between September 1, 2013 and August 31, 2016, 32 patients were enrolled. The median follow-up time was 32.1 months. The median progression-free survival (PFS) was 9.4 months. Overall survival (OS) was 41.0 months, time to treatment failure (TTF) was 7.8 months, response rate (RR) was 31.3%, and disease control rate (DCR) was 78.1%. The incidence of grade 3 side-effects was not high. CONCLUSION: The 3-week schedule of S-1 can be considered useful as a treatment for patients with metastatic breast cancer, helping in maintaining a high quality of life.

B-mode ultrasound diagnostic flowchart for solid breast masses: JABTS BC-01 study.

PURPOSE: Breast ultrasound has been widely used as an essential examination for diagnosing breast cancer. However, standardized diagnostic criteria are as yet lacking. This study aimed to develop a simple diagnostic flowchart for beginners learning breast ultrasonography. The diagnostic flowchart was developed based on the recall criteria widely used in Japan. METHODS: We conducted a multicenter study to examine recall criteria usefulness in the diagnostic phase of breast disease. Women with ultrasound-visible breast masses who underwent B-mode breast ultrasound examination were recruited from 22 hospitals in Japan between September 2009 and January 2010. B-mode images were evaluated by members of the centralized image interpretation committee. We developed the new diagnostic flowchart based on the results. The usefulness of the diagnostic flowchart was assessed by employing datasets from the current study and another study which we conducted (BC-04 study). RESULTS: We evaluated 1045 solid masses (malignant: 495, benign: 550). Multivariate analysis showed that shape, margin, echogenic halo, interruption of the mammary gland interface, and depth width ratio were significant findings for distinguishing between benign and malignant masses. We modified the recall criteria and developed our novel diagnostic flowchart using these findings. The sensitivity and specificity of the new flowchart (current study: 0.97, 0.45; BC-04 study dataset: 0.95, 0.45) were similar to those of experts (current study: 0.96, 0.54; BC-04 study dataset: 0.98, 0.38). CONCLUSION: We developed a simple diagnostic flowchart for breast ultrasound. This flowchart is anticipated to be applicable to educating beginners learning breast ultrasound.

Characteristics of ultrasonographic images of ductal carcinoma in situ with abnormalities of the ducts.

PURPOSE: Although the number of ductal carcinoma in situ (DCIS) cases has increased with the spread of breast cancer screening in Japan, there are very few reports that summarize ultrasound image features of DCIS. The Japan Association of Breast and Thyroid Sonology (JABTS) investigated the incidence of DCIS with masses and non-mass abnormalities and the characteristics of US images in a retrospective, multicenter, observational study (JABTS BC-02 study). The purpose of this report is to clarify the proportion of DCIS with abnormalities of the ducts with each ultrasound finding and the characteristics of US images. METHODS: The JABTS BC-02 study population was comprised of patients who were examined by ultrasonography, underwent surgery, and were histopathologically diagnosed with DCIS at each study site between January 2008 and December 2012. The US images of DCIS and pathology and clinical information were retrospectively collected from 16 institutions in Japan. The US images were evaluated by 22 experts on the Central Image Interpretation Committee of JABTS. RESULTS: Abnormalities of the ducts were noted in 78 (10.5%) of 705 US images of DCIS. Of the 78 cases, the distribution of abnormalities of the ducts was focal or segmental. The second characteristic was the presence of internal echoes in dilated ducts. All cases were accompanied by intraductal solid echoes, and 40 cases (51.3%) were accompanied by echogenic foci. In addition, intraductal solid echoes were continuous or multiple in 72 cases (92.4%), and the shape of the solid echoes was broad-based and/or irregular in 62 cases (79.5%). CONCLUSION: DCIS cases with duct abnormalities on ultrasound were investigated in this study. The important characteristics were as follows: (1) the distribution of ductal dilatation was focal or segmental, (2) solid parts were present in the dilated ducts, (3) the distribution of internal echoes was continuous or multiple, (4) the shape of solid echoes was broad-based and/or irregular, and (5) internal echoes were sometimes accompanied by echogenic foci. Accurate evaluation of these findings may be useful for diagnosing DCIS. Although the duct abnormalities are included in "ASSOCIATED FEATURES" in ACR BI-RADS ATLAS (USA), we emphasize that this concept is very important for understanding US characteristics of DCIS.

Safety and Relative Dose Intensity of Dose-dense Doxorubicin and Cyclophosphamide Followed by Dose-dense Paclitaxel.

BACKGROUND/AIM: Dose-dense doxorubicin and cyclophosphamide (ddAC) followed by dose-dense paclitaxel (ddP) (ddAC-P) has improved disease-free survival of patients with breast cancer. The aim of this study was to evaluate the safety and relative dose intensity (RDI) of ddAC-P administered together with pegfilgrastim. PATIENTS AND METHODS: Between May 2015 and Aug 2017, 44 patients were retrospectively reviewed; they were administered 4 cycles of ddAC, followed by 4 cycles of ddP. Pegfilgrastim (3.6 mg) was administered in every cycle. RESULTS: The mean RDIs for ddAC-P, ddAC, and ddP were 95.0%, 94.5%, and 93.3%, respectively. The prevalence of high RDIs (≥85%) for ddAC-P, ddAC, and ddP was 90.9%, 84.1%, and 88.6%, respectively. Seven of the 10 patients with low RDIs experienced grade 1 or 2 fever. CONCLUSION: DdAC-P administered together with pegfilgrastim (3.6 mg) appears to be feasible and maintains RDI in most of Japanese patients with breast cancer. Rapid evaluation and proper management of fever may prevent low RDI.

Multicenter Prospective Study of Color Doppler Ultrasound for Breast Masses: Utility of Our Color Doppler Method.

The use of color Doppler ultrasound (CD) for distinguishing between benign and malignant breast lesions remains controversial. This study (JABTS BC-04 study) was aimed at confirming the usefulness of our CD diagnostic criteria. We evaluated ultrasound images of 1408 solid breast masses from 16 institutions in Japan (malignant: 839, benign: 569). Multivariate analysis indicated that vascularity (amount of blood flow), vascular flow pattern ("surrounding marginal flow" or "penetrating flow") and the incident angle of penetrating flow were significant findings for distinguishing between benign and malignant lesions. However, the sensitivity and specificity of B-mode alone did not improve significantly with CD addition (97.6% → 97.9%, 38.3% → 41.5%, respectively). We explored the causes of these negative results and found that age should have been considered when evaluating vascularity. Simulation experiments suggested that specificity is significantly improved when age is taken into consideration (38.3% → 46.0%, p < 0.001) and we thereby improved our diagnostic criteria.

Patient preference study comparing hypofractionated versus conventionally fractionated whole-breast irradiation after breast-conserving surgery.

OBJECTIVE: To compare patient preferences and acute adverse events of hypofractionated (HF) and conventionally fractionated (CF) whole-breast irradiation (WBI) after breast-conserving surgery in our institution. METHODS: We conducted a patient preference study comparing CF-WBI (50 Gy/25 fractions) and HF-WBI (41.6 Gy/16 fractions) after breast-conserving surgery. Eligible patients selected either type of fractionation following an explanation from the radiation oncologist. In this report, we analyzed the selection rate and acute toxicities. RESULTS: Between June 2009 and December 2013, 348 patients (349 breasts) were identified as eligible for the study. Among them, 259 patients (260 breasts [74.5%]) selected CF-WBI and 89 patients (89 breasts [25.5%]) selected HF-WBI. Factors significantly associated with the selection of HF-WBI were older age (P = 0.028) and no adjuvant chemotherapy (P = 0.041). Regarding acute adverse events, Grade 2 (G2) or higher radiation dermatitis was less frequently observed in HF-WBI than in CF-WBI (13.8% vs. 29.4%; P = 0.004). In addition, G2 or higher breast pain was only observed in the CF-WBI group (6.9%; P = 0.012). There were no significant differences in the presence of fatigue, wound pain or radiation pneumonitis of G2 or higher between the groups. CONCLUSIONS: In this study, in which patients themselves selected the irradiation method, more patients tended to select CF-WBI. The frequency of G2 or higher dermatitis and breast pain was significantly lower in the HF-WBI group than in the CF-WBI group. Our results support the evidence for recommending HF-WBI after breast-conserving surgery while presenting aspects of patient preferences.

Ultrasound Image Classification of Ductal Carcinoma In Situ (DCIS) of the Breast: Analysis of 705 DCIS Lesions.

The Japan Association of Breast and Thyroid Sonology (JABTS) proposed, in 2003, a conceptual classification system for non-mass abnormalities to be applied in addition to the conventional concept of masses, to facilitate detecting ductal carcinoma in situ (DCIS) lesions. The aim of this study was to confirm the utility of this system and to clarify the distribution of these findings in DCIS lesions. Data on 705 surgically treated DCIS lesions from 16 institutions in Japan were retrospectively reviewed. All 705 DCIS lesions could be classified according to the JABTS classification system. The most frequent findings were hypo-echoic areas in the mammary gland (48.6%), followed by solid masses (28.0%) and duct abnormalities (10.2%) or mixed masses (8.1%). Distortion (1.3%), clustered microcysts (1.4%) and echogenic foci without a hypo-echoic area (2.5%) were uncommon. These results suggest that the concept of non-mass abnormalities is useful in detecting DCIS lesions.

[A case of locally advanced and metastatic breast cancer successfully treated with combination therapy of paclitaxel and bevacizumab].

The patient was a 53-year-old woman with a large left breast tumor. Triple-negative breast cancer with bilateral axillary lymph-node metastasis and bone metastasis was diagnosed. The primary treatment consisted of chemotherapy with a combination of paclitaxel(PTX 80mg/m 2)and bevacizumab(Bev 10 mg/kg). After chemotherapy, the tumor shrunk and showed an obvious decrease in size, eventually disappearing. After therapy, an ulcer was detected on the left breast, and mastectomy and axillary lymph node dissection were performed. The patient's postoperative course was uneventful and she has been receiving chemotherapy at our outpatient clinic. Thus, combination therapy with PTX and Bev may be useful for the local control of advanced breast cancer.

Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status.

OBJECTIVE: For patients with HER2-positive breast cancer, the prognostic impact of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear when stratified by hormonal receptor (HR) status; however, the impact of pCR on survival when stratified by hormonal receptor (HR) status is uncertain. PATIENTS AND METHODS: This multicenter retrospective study investigated the predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive breast cancer who received NAC. pCR was defined as no invasive residual tumor in the breast or axilla. RESULTS: Median follow-up was 55 months. Multivariate analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent predictors of pCR. Five-year recurrence-free survival was higher in HR-negative patients with pCR (93%) than in those without pCR (68%), and pCR was independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year recurrence-free survival was not different between HR-positive patients with pCR (94%) and those without pCR (84%), and pCR was not significantly prognostic (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive group (hazard ratio, 0.63; p = 0.56). CONCLUSION: Our study suggested that the HER2-positive HR-positive patients had a good prognosis despite the lower achievement rate of pCR, whose prognostic impact was smaller than that in the HER2-positive HR-negative patients. The treatment strategy for HER2-positive breast cancer can be stratified by HR status.

Diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography of breast cancer in detecting axillary lymph node metastasis: comparison with ultrasonography and contrast-enhanced CT.

PURPOSE: The purpose of this retrospective study was to evaluate the diagnostic performance of positron emission tomography/computed tomography (PET/CT) with fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose (FDG) in comparison with that of ultrasonography and contrast-enhanced computed tomography (CT) in detecting axillary lymph node metastasis in patients with breast cancer. MATERIALS AND METHODS: Fifty patients with invasive breast cancer were recruited. They had received no neoadjuvant chemotherapy and underwent PET/CT, ultrasonography and contrast-enhanced CT before mastectomy. The clinical stage was I in 34 patients, II in 15 patients, and III in one patient. The images of these modalities were interpreted in usual practice before surgery and the diagnostic reports were reviewed for analysis. Sensitivity, specificity, positive predictive value, and negative predictive value of each modality were obtained taking histopathological results of axillary lymph node dissection or sentinel lymph node biopsy as the reference standard. RESULTS: Axillary lymph node metastasis was confirmed in 15 of 50 patients by histopathological studies. PET/CT identified lymph node metastasis in three of these 15 patients. The overall sensitivity and specificity, positive predictive value, and negative predictive value of PET/CT in the diagnosis of axillary lymph node metastasis were 20, 97, 75, and 74%, and those of ultrasonography were 33, 94, 71, and 77% and those of contrast-enhanced CT were 27, 97, 80, and 76%, respectively. CONCLUSIONS: PET/CT showed poor sensitivity and high specificity in the detection of axillary lymph node metastasis of breast cancer. Diagnostic performance of PET/CT was not superior to that of ultrasonography and contrast-enhanced CT.

Mucinous carcinoma of the breast: MRI features of pure and mixed forms with histopathologic correlation.

OBJECTIVE: The purpose of this study was to describe the MRI features of the pure and mixed forms of mucinous carcinoma of the breast and the histopathologic correlation. MATERIALS AND METHODS: Seventeen pure and three mixed mucinous tumors of the breast were examined with T2-weighted MRI and triple-phase dynamic MRI. MR images were reviewed for evaluation of the signal intensity and enhancement patterns of tumors and for correlation with the histopathologic findings. RESULTS: The presence of very high signal intensity on T2-weighted images was a common feature of pure and mixed mucinous tumors. Fourteen pure tumors and one mixed tumor had very high signal intensity, and three pure and two mixed tumors had very high signal intensity and isointensity on T2-weighted images. The enhancement pattern during the early phase varied with the cellularity of pure tumors and with the distribution of nonmucinous components in mixed tumors. Hypocellular pure mucinous tumors had a typical pattern of gradual enhancement. CONCLUSION: Hypercellular pure mucinous tumors exhibit strong early enhancement and may be difficult to differentiate from mixed mucinous tumors. The distinction between the pure and mixed forms of mucinous carcinoma is important because mixed mucinous carcinoma more frequently undergoes lymph node metastasis and has a poorer prognosis than does pure mucinous carcinoma.