In the 1990s, the number of newly registered tuberculosis patients in Japan was about 40,000 per year. It has been gradually decreasing and the number of new patients became 10,235 in 2022 with the incidence rate of 8.2 per 100,000 population. However it is still occasionally encountered even in recent years. Herein, we report a case of human epidermal growth factor receptor 2(HER2)-enriched breast cancer patient developed pulmonary tuberculosis just after finishing neoadjuvant chemotherapy and was successfully treated for both disease simultaneously. A 68 years old woman presented due to right breast mass was diagnosed with hormonal receptor-negative, HER2-positive invasive ductal carcinoma. Neoadjuvant chemotherapy with paclitaxel, trastuzumab and pertuzumab was started. After 12 courses of chemotherapy, CT scan revealed disappearance of the right breast tumor and infiltrating shadow in the left lower lung field. Sputum polymerase chain reaction test for tuberculosis was positive. Anti-tuberculosis chemotherapy was started. Four days after starting isoniazid, partial mastectomy was performed under local anesthesia and radiation therapy for the breast was omitted. There are no signs of recurrence of breast cancer and pulmonary tuberculosis for 5 years. Chemotherapy for breast cancer and premedication with corticosteroid may have inhibited cellular immunity, causing endogenous relapse of tuberculosis.

The Japanese Society for Sentinel Node Navigation Surgery conducted a multi-institutional prospective cohort study to compare sentinel node biopsy (SNB) with SNB followed by axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel lymph node (SLN). Female patients with breast cancer with cT1-3N0-1M0 were eligible. In cases of one to three positive micro- or macrometastases in the SLN confirmed by histological or molecular diagnosis, SNB alone (SNB group) or additional ALND (ALND group) was performed under physician’s discretion. The primary endpoint was the 5-year regional node (RN) recurrence rate in the SNB group. Propensity score matching (PSM) was performed to compare the prognosis between the two groups. Of the 871 eligible cases registered between 2013 and 2016, 308 underwent SNB alone. At the median follow-up of 6.3 years, 5-year RN recurrence rate was 2.7

CONTEXT:Aromatase inhibitors (AIs) cause bone loss and increase fracture risk in women with hormone receptor-positive early-stage breast cancer (HR + EBC). Bone antiresorptive agents are recommended for patients at risk of fragility fractures. Eldecalcitol, combined with bisphosphonate, increases bone mineral density (BMD) in primary osteoporosis. OBJECTIVE:To determine the effect of eldecalcitol (0.75 ug/day) add-on therapy to risedronate (17.5 mg/week) on bone quantity and quality in women treated with AI. DESIGN:Open-label randomized control trial. SETTING:Postmenopausal women with HR + EBC (TNM stage 0-3A) treated with risedronate for more than 12 months. PATIENTS:Two hundred patients were enrolled; 196 patients were eligible for the full analysis set after excluding those without follow-up BMD data. Participants were advised to take vitamin D and calcium, yet many were vitamin D deficient or insufficient. INTERVENTION:Participants were randomly assigned in a 1:1 ratio to receive either eldecalcitol add-on therapy or risedronate monotherapy. MAIN OUTCOME MEASURE:The primary outcome was the group difference in the change of lumbar spine (LS)-BMD in 24 months. Secondary outcomes included femoral neck (FN)-BMD, total hip (TH)-BMD, trabecular bone score (TBS), and the incidence of vertebral and nonvertebral fractures. RESULTS:The increase at LS-, FN-, and TH-BMD at 24 months was larger in the add-on therapy group than in the monotherapy group, with a group difference (add-on therapy minus monotherapy) estimate of 0.020 g/cm2 [95% confidence interval (CI): 0.010-0.029 g/cm2, P < .001] for LS-BMD. The incidence rate ratio (add-on therapy/monotherapy) for morphometric vertebral fractures was 0.292 (95% CI: 0.080-1.061, P = .061). No group difference was detected in the change in TBS. CONCLUSION:Eldecalcitol add-on therapy increased LS-BMD in osteopenic to osteoporotic postmenopausal women treated with an AI and risedronate.

Fibroblast growth factor receptors (FGFRs) are a highly conserved family of transmembrane receptor tyrosine kinases with multiple roles in the regulation of key cellular processes. Specific FGFR mutations have been observed in several types of cancers, including gastric carcinoma and cholangiocarcinoma. Dose escalation data of 24 Japanese patients with solid tumors treated with Tasurgratinib (previously known as E7090), a potent, selective FGFR1-3 inhibitor, was reported in a phase I, first-in-human, single-center study. Based on the safety, pharmacokinetic, and pharmacodynamic profiles observed in this study, the recommended dose of 140 mg once daily was selected for the expansion part (Part 2), a multicenter expansion of the dose-finding study restricted to patients with tumors harboring FGFR gene alterations. Safety and preliminary efficacy were assessed in Part 2. Pharmacodynamic pharmacogenomic markers (serum phosphate, FGF23, and 1,25-(OH)2-vitamin D, circulating tumor DNA) and pharmacokinetic profiles were also evaluated. A total of 16 patients were enrolled in Part 2, six with cholangiocarcinoma and 10 with gastric cancer. The most common treatment-emergent adverse events were hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, and paronychia. Five partial responses (83.3%) in cholangiocarcinoma patients and one partial response (11.1%) in gastric cancer patients were observed; median progression-free survival was 8.26 months (95% confidence interval [CI] 3.84, not evaluable [NE]) and 3.25 months (95% CI 0.95, 4.86), and overall survival was 22.49 months (95% CI 6.37, NE) and 4.27 months (95% CI 2.23, 7.95), respectively, in the two groups. In conclusion, Tasurgratinib 140 mg has a tolerable safety profile with good clinical efficacy in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements.

In patients undergoing mastectomy for locally advanced breast cancer, surgical skin flap reconstruction is sometimes required in order to cover large skin defects. Generally, we reconstruct by using latissimus dorsi or rectus abdominis when the direct closure is difficult. These constructions are difficult and have various complications. Our facility started rhomboid flap reconstruction after mastectomy. We report the result of rhomboid flap reconstruction. Five patients were performed rhomboid flap reconstruction. Three of 5 patients were cutaneous invasion, 1 patient was skin metastasis after mastectomy, and the other patient was Paget's disease. Regarding post operative complications, there were 2 cases of surgical site infection, 2 cases of skin necrosis and 1 case of seroma. The median length of postoperative hospital stay was 9 days. Median follow-up period was 381 days(221-508 days). Only 1 patient progressed. The median progression-free survival was 332 days(221-508 days). Rhomboid flap reconstruction is effective way for the improvement of the QOL of the patients with advanced breast cancer because the long term result was not bad and we can repair large skin defect easily.

乳腺葉状腫瘍に乳癌が併存することは非常に稀である．今回われわれは，小葉癌が併存した葉状腫瘍の1例を経験した．症例は51歳，女性．3年半前の乳腺超音波検診で左乳房ED区域に20mm大の粗大石灰化を含む低エコー腫瘤を認め，針生検で乳管腺腫と診断され経過観察を行っていたが，左乳頭血性分泌が出現したため再診，超音波検査で増大傾向があり，画像ガイド下乳腺腫瘍吸引術ではfibroepithelial lesionであったが，乳管上皮の過形成傾向があり左乳腺部分切除術を行った．組織学的所見では多数の拡張乳管内に葉状腫瘍が増殖しており，葉状腫瘍の上皮成分は高度過形成でその中に非浸潤性小葉癌の増殖巣を認め，0.5mmの範囲で微小浸潤を伴っていた．

Objectives The objective of this study was to develop and validate a state-of-the-art, deep learning (DL)-based model for detecting breast cancers on mammography. Methods Mammograms in a hospital development dataset, a hospital test dataset, and a clinic test dataset were retrospectively collected from January 2006 through December 2017 in Osaka City University Hospital and Medcity21 Clinic. The hospital development dataset and a publicly available digital database for screening mammography (DDSM) dataset were used to train and to validate the RetinaNet, one type of DL-based model, with five-fold cross-validation. The model's sensitivity and mean false positive indications per image (mFPI) and partial area under the curve (AUC) with 1.0 mFPI for both test datasets were externally assessed with the test datasets. Results The hospital development dataset, hospital test dataset, clinic test dataset, and DDSM development dataset included a total of 3179 images (1448 malignant images), 491 images (225 malignant images), 2821 images (37 malignant images), and 1457 malignant images, respectively. The proposed model detected all cancers with a 0.45-0.47 mFPI and had partial AUCs of 0.93 in both test datasets. Conclusions The DL-based model developed for this study was able to detect all breast cancers with a very low mFPI. Our DL-based model achieved the highest performance to date, which might lead to improved diagnosis for breast cancer.

The cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib, have been approved in Japan. However, the selection criteria for these drugs have not been established. Hence, we aimed to identify the risk factors for CDK4/6 inhibitor-induced intolerable adverse events requiring dose reduction or therapy cessation and to establish useful markers for choosing the appropriate CDK4/6 inhibitor, based on the incidence of the intolerable adverse events. This retrospective cohort analysis included patients with advanced breast cancer who received 125 mg/d palbociclib or 300 mg/d abemaciclib. We defined significant adverse events (SAEs) as side effects requiring dose reduction or therapy cessation. Thirty-six percent of the patients who received palbociclib (9/25) and 27.3% of those who received abemaciclib (9/33) experienced SAEs. In palbociclib and abemaciclib groups, baseline white blood cell (WBC) counts and serum albumin (ALB) levels, respectively, were significantly lower in patients who experienced SAEs than in those who did not (palbociclib: p = 0.007; abemaciclib: p = 0.004). According to the receiver operating characteristic curve analysis, the optimal cutoff values for baseline WBC count and ALB level were 5700/µL and 4.0 g/dL, respectively. Among patients with ALB levels >4.0 g/dL, the incidence of abemaciclib-induced SAEs was significantly lower than that of the palbociclib-induced SAEs (1/17 (5.9%) vs. 6/14 (42.9%), odds ratio: 11.0, 95% confidence interval: 1.07-583, p = 0.0281). Thus, a baseline WBC count ≤5700/µL and ALB level ≤4.0 g/dL may be risk factors for palbociclib and abemaciclib-induced SAEs, respectively. Also, high ALB levels can serve as a useful marker for choosing abemaciclib.

Background: The development of resistance to endocrine therapy appears to have become a major clinical problem of hormone receptor (HR) positive breast cancer. Drug resistance is associated with changes of the tumor microenvironment due to tumor hypoxia. Eribulin, a nontaxane, synthetic microtuble dynamics inhibitor, induces G2/M cell cycle arrest. Interestingly, it also has some unique anticancer effects in breast cancer cells, such as improvement of tumor perfusion and hypoxia. In this study, we investigated the effect of eribulin for endocrine therapy resistant breast cancer. Materials and Methods: We established hypoxia resistant HR positive/human epithelial growth receptor 2 (HER2) negative breast cancer cell lines, via continuous culturing in hypoxic environment. Parental and hypoxia resistant cell lines were treated with eribulin, followed by estrogen receptor (ER), epithelial-mesenchymal transition (EMT) and hypoxia related gene and protein expression changes in each surviving cells by quantitative real-time polymerase chain reaction (qPCR) and western blot, respectively. In addition, proliferation assay was conducted in these breast cancer cell lines treated with tamoxifen alone and tamoxifen plus eribulin. For the in vivo experiment, we produced subcutaneous xenografts of each cell lines. We treated these tumors with tamoxifen alone and tamoxifen plus eribulin, and analyzed their growth activity and protein expression by immunohistochemical study of surgically resected tissues. Results: Though parental HR positive/HER2 negative breast cancer cell lines displayed an epithelial-like cuboidal phenotype, hypoxia resistant cell lines displayed a mesenchymal-like spindle-shaped phenotype. In addition, hypoxia resistant cell lines significantly decreased the expression of epithelial and ER related markers, and exhibited a higher level of resistance to tamoxifen treatment. On the other hand, eribulin treatment for hypoxia resistant cell lines increased epithelial and ER related gene and protein expressions, and enhanced the anticancer effect of tamoxifen. In in vivo xenograft models, eribulin treatment for hypoxia resistant tumor with resistance to tamoxifen induced re-expression of ER. Also, hypoxia resistant tumor after administration of eribulin became effective with tamoxifen treatment. Conclusions: Eribulin improve the tumor microenvironment changed by hypoxia, and induce re-expression of ER in hypoxia resistant breast cancer cells. Eribulin treatment for HR positive breast cancer with resistance to endocrine therapy makes possibility of re-administration of endocrine therapy. Citation Format: Wataru Goto, Shinichiro Kashiwagi, Misato Fujioka, Sae Ishihara, Yuka Asano, Tamami Morisaki, Satoru Noda, Tsutomu Takashima, Masaichi Ohira, Kosei Hirakawa. Eribulin treatment for hormone receptor positive breast cancer cells with resistant to endocrine therapy promotes re-expression of estrogen receptor [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-15.

PurposeTo gauge the effects of treatment practices on prognosis for older patients with HER2-positive early breast cancer, particularly to determine whether adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. This is a prospective cohort study which accompanies the RESPECT that is a randomized-controlled trial (RCT).MethodsPatients who declined the RCT were treated based on the physician's discretion. We studied the 1) trastuzumab-plus-chemotherapy group, 2) trastuzumab-monotherapy group, and 3) non-trastuzumab group (no therapy or anticancer therapy without trastuzumab). The primary endpoint was disease-free survival (DFS), which was compared using the propensity-score method. Relapse-free survival (RFS) and health-related quality of life (HRQoL) were assessed.ResultsWe enrolled 123 patients aged over 70 years (median: 74.5). Treatment categories were: trastuzumab-plus-chemotherapy group (n = 36, 30%), trastuzumab-monotherapy group (n = 52, 43%), and non-trastuzumab group (n = 32, 27%). The 3-year DFS was 96.7% in trastuzumab-plus-chemotherapy group, 89.2% in trastuzumab-monotherapy group, and 82.5% in non-trastuzumab group. DFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted hazard ratio; HR: 3.29; 95% CI: 1.15–9.39; P = 0.026). The RFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted HR = 7.80; 95% CI: 2.32–26.2, P < 0.0001). There were no significant intergroup differences in the proportions of patients showing HRQoL deterioration at 36 months (P = 0.717).ConclusionTrastuzumab-treated patients had better prognoses than patients not treated with trastuzumab without deterioration of HRQoL. Trastuzumab monotherapy could be considered for older patients who reject chemotherapy.

症例は38歳，女性．乳児期にPrader-Willi症候群（PWS）と診断されていた．スクリーニング検査にて甲状腺右葉に結節性病変を指摘され，精査加療目的に当科を紹介受診．甲状腺癌が強く疑われたため，手術加療の方針となった．精神発達遅延のため興奮状態となることがあり，全身麻酔導入に難渋した．手術は甲状腺右葉+峡部を摘出し，術中迅速診断にて甲状腺乳頭癌の診断であったため，頸部リンパ節郭清を追加した．術前CTではリンパ節腫大は認めなかったが，病理学的には9個の転移リンパ節を認めた．術後2年9カ月経過した現在，明らかな再発は認めていない．PWS患者における悪性新生物の報告は極めて少なく，本症例は甲状腺乳頭癌の本邦で初めての報告となる．

The patient was a 64-year-old woman. The patient was operated for left breast cancer(pT2N0M0, stage ⅡA, Luminal A). Eight years after surgery, CT findings revealed lung metastasis in the S8 and S9 areas of the left lung. The patient was treated with a combination of abemaciclib and letrozole, which resulted in a partial response(PR). One year after treatment, the lung metastases remained small, but multiple interstitial shadows appeared in both lower lung fields. The patient was diagnosed with drug-induced interstitial lung disease(Grade 1), and abemaciclib withdrawal and steroid therapy were initiated. After 3 months of treatment with prednisolone at 30 mg/day, the interstitial shadows tended to improve on CT, but a liver abscess was found in the S8 area of the right lobe of the liver. Prednisolone was tapered and abemaciclib was resumed at a dose of 200 mg/day, resulting in scarring of the lung injury and resolution of the liver abscess. The patient's PR was maintained for 18 months after relapse. We report a case of liver abscess during treatment of abemaciclib-induced interstitial lung disease.

Abstract Purpose: While the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) are associated with prolonged progression-free survival (PFS) and overall survival (OS), the influence of previous chemotherapy on blood cell counts may necessitate an evaluation of baseline ALC and NLR in patients receiving first-line chemotherapy. Methods: Patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) who received first-line eribulin chemotherapy in two phase 2 trials (BIRICHEN and OMC-BC 03) were retrospectively analyzed. HER2-negative MBC patients who received first-line chemotherapy other than eribulin (treatment of physician’s choice; TPC) at the Osaka Medical and Pharmaceutical University Hospital between March 2013 and March 2017 were also analyzed for comparison. Results: In the eribulin group, the median OS (mOS) was 30.9 and 17.8 months in the high-(H-)ALC (≥1500/μL; n=33) and low-(L-)ALC (<1500/μL; n=26) groups, respectively (hazard ratio [HR], 0.52; 95% confidence interval [CI]: 0.27-1.01), whereas it was 30.9 months and 15.4 months in the L-NLR (<2.5; n=23) and H-NLR (≥2.5; n = 36) groups, respectively (HR, 0.49; 95% CI: 0.25-0.95). In the TPC group, neither ALC nor NLR was associated with OS or PFS extension. After propensity-score matching, the mOS in the eribulin group was 32.0 and 19.6 months, respectively, in the H- and L-ALC groups (HR, 0.43; 95% CI: 0.18-0.99), while OS in the L- and H-NLR groups showed no significant differences in the eribulin group (HR, 0.65; 95% CI: 0.27-1.58). Conclusions: ALC is a prognostic marker for first-line eribulin chemotherapy, but not for other agents.

Background: Eribulin demonstrated improving overall survival of HER2-negative metastatic breast cancer in EMBRACE trial. Recently, ad hoc analysis of the trial showed that immune response markers such as absolute lymphocyte count (ALC) was associated with prognosis. However, blood cell count must be influenced by previous chemotherapy because the trial was targeted for late-line treatment.Previously we had conducted two phase 2 trials that estimated efficacy of eribulin as the first-lien chemotherapy for HER2-negative metastatic breast cancer in Japan. Base line ALC and NLR were examined for the participants of these trials to determine whether they were also associated with prognosis in the first-line setting. Patients and Methods: A total of 59 patients were enrolled this study including 35 patients of BIRICHEN trial (UMIN000006086; SpringerPlus 2016;5:164) for only first-line chemotherapy with eribulin and 24 patients who treated as the first-line chemotherapy in OMC-BC03 trial targeted for first and second line chemotherapy (UMIN000009568; Cancer Chemother Pharmacol 2018; 81:923). Pretreatment blood cell counts were collected from case report form and compared with survival data. Cutoff value of ALC was set at 1500/mm3 and that of NLR was set at 3 in accordance with ad hoc analysis of EMBRACE trial. The ethics committees of Osaka Medical College and Osaka City University approved the present study. Results: Median value of ALC was 1690/mm3(Quartile Q1,Q3: 1014, 2012) and that of NLR was 2.17(Q1,Q3: 1.54, 2.99). In comparison with ALC, overall survival (OS) was 132.6 months in the ALC-high group(>=1500;n=33) versus 76.4 months in the ALC-low group (< 1500; n=26). Hazard ratio(HR) was 0.52(95%CI; 0.27-1.01) with border line significancy. Progression free survival(PFS) is 28.0 months in the ALC-high group versus 20.4 months in the ALC-low group. HR was 0.91(95% CI; 0,51-1.60) without statistically significant difference. In NLR, OS was 20.7 months in the NLR-low group(<3;n=45) versus 4.6 months in the NLR-high group. HR was 0.40 (95%CI; 018-0.90) with statistical significance. PFS was 6.2 months in the NLR-low group versus 10.8 months in the NLR-high group (>=3; n=14). HR was 0.57 (95%CI; 0.25-1.30) without statistically significant difference. Conclusions: In the post hoc analysis of the EMBRACE trial, patients who assigned eribulin group with ALC 1500 or higher had better OS than those with ALC less than 1500, but no difference was observed in PFS. In addition, those with NLR less than 3 had better PFS and OS than those with NLR 3 or more. In comparison with the capecitabine group, although low NLR was a good prognostic factor not only in eribulin group but also in capecitabine group, high ALC was suggested to be a particular prognostic factor of eribulin. However, since EMBRACE study was a late line setting, there could be an effect of myelosuppression by pretreatment. Our first-line results did not affect bone marrow function by prior chemotherapy, but similar results were obtained. ALC may be a prognostic factor of eribulin regardless of the treatment line, suggesting that eribulin exerts its effect by acting on the immune microenvironment. Citation Format: Tsutomu Takashima, Kosei Kimura, Hidemi Kawajiri, Shinichiro Kashiwagi, Shinya Tokunaga, Shigehiko Nishimura, Satoru Noda, Hiroyo Oku, Ayana Ikari, Tomo Tominaga, Saki Maezawa, Junna Sakane, Mitsuhiko Iwamoto. High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin as the first-line chemotherpy. Combined analysis of two phase 2 study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-06.

Abstract Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a group of chronic relapsing inflammatory conditions. Although IgG4-RD can occur in various organs, it is rarely observed in mammary glands. Here, we report a case of IgG4-related mastitis (IgG4-RM) that needed to be differentiated from breast cancer. A 54-year-old woman was examined for a tumor in her left breast. Mammary ultrasonography revealed an irregular hypoechoic tumor measuring 45.0 × 43.0 × 32.0 mm in size. A core-needle biopsy of the left breast tissue revealed a high degree of mixed T and B lymphocytic and plasma cell infiltration, as well as interstitial fibrosis. IgG4-RD was diagnosed based on hematological examination that revealed an abnormal IgG4 value of 332 mg/dl. All the clinical diagnostic criteria for IgG4 were met, resulting in a definitive diagnosis of IgG4-RM.

For qualitative diagnosis of breast mass, core needle biopsy(CNB)and fine-needle aspiration biopsy cytology(FNAC)are widely used. Overseas, vacuum-assisted biopsy(VAB)is often the first choice for qualitative diagnosis, and its proper use has become a clinical issue. In addition, with the progress of diagnostic imaging in recent years, the chances of finding micro-lesions such as ductal carcinoma in situ(DCIS)are increasing. Since a sufficient amount of tissue sample is required for these diagnoses and abundant biopsy materials are required, tissue biopsy by VAB may be desirable. The advantage of tissue biopsy with VAB is that accurate definitive diagnosis is possible by collecting a sufficient amount of tissue to obtain pretreatment tissue information. On the other hand, there is concern that patient stress may occur, such as hematoma formation after puncture and invasion by a thick puncture needle. It is lightweight and has an ergonomic design that provides stable grip. New technological innovations in this device may contribute to the reduction of patient stress, and are expected to be used in the future. We outline the experience of using BD EleVationTM in breast suction tissue biopsy at our institution.