Effect of bisphosphonate and denosumab treatment on TBS in Japanese breast cancer patients with AIBL.

INTRODUCTION: Bisphosphonates and denosumab increase bone mineral density (BMD) for osteoporosis treatment in patients with aromatase inhibitor-associated bone loss (AIBL). This study aimed to directly compare bisphosphonates with denosumab in treating patients with AIBL and to determine the effect of denosumab on the trabecular bone score (TBS). MATERIALS AND METHODS: Thirty-nine patients with AIBL receiving osteoporosis treatment (21 in the bisphosphonates group and 18 in the denosumab group) were retrospectively evaluated for changes in lumbar spine and femoral BMD, lumbar spine bone quality (assessed by TBS), and blood bone metabolic markers. The Mann-Whitney and Wilcoxon tests were used for statistical evaluation. RESULTS: After 24 months of treatment, the lumbar spine BMD change rate was 5.82 ± 1.10% with bisphosphonates and 10.49 ± 1.20% with denosumab, with the change rate of denosumab significantly increasing over that of bisphosphonates. The change rate in femoral BMD was 2.69 ± 1.16% with bisphosphonates and 2.95 ± 1.26% with denosumab, with no significant difference between the two groups. The rate of decrease in tartrate-resistant acid phosphatase isoform 5b was significantly higher in the denosumab group. The change rate in TBS at 24 months of treatment was 0.53 ± 1.26% in the bisphosphonates group and 1.08 ± 1.33% in the denosumab group, with no significant difference between the two groups. After 24 months, TBS remained stable. CONCLUSION: Both bisphosphonates and denosumab may increase BMD, improve bone metabolism, and inhibit bone quality loss in patients with AIBL.

Endoscopic mastectomy followed by immediate breast reconstruction with fat grafting for breast cancer.

BACKGROUND: Although endoscopic mastectomy has been associated with good tolerance and enhanced patient satisfaction, limitations such as the implant or flap size for reconstruction with small incisions remain unresolved. Fat grafting (FG) can expand tissue volume with pinhole skin incisions. Herein, we evaluated the safety and efficacy of endoscopic mastectomy followed by immediate FG. METHODS: Patients who underwent endoscopic mastectomy with immediate FG reconstruction from 2015 to 2021 were retrospectively evaluated to establish surgical outcomes and prognosis. RESULTS: Twenty-three patients with clinical stage 0 or I breast cancer underwent unilateral endoscopic mastectomy with immediate FG. The median age was 45 years (41-55), and the median body mass index was 19.3 kg/m2 (15.8-26.6). Endoscopically performed procedures included skin-sparing mastectomies in 18 patients (78%) and nipple-sparing mastectomies in five patients (22%). The median procedure duration was 295 min (242-346). The median specimen weight was 133 g (71-334), and the median grafted fat volume was 200 mL (136-320). No patient required reoperation or additional procedures for complications. One patient experienced recurrence at a median follow-up of 56.1 months and underwent resection; the patient was alive without recurrence 54 months post-resection. CONCLUSION: To the best of our knowledge, this is the first report of endoscopic mastectomy with immediate FG for reconstruction. When compared with other immediate autologous reconstructions, our strategy could minimize the skin incision and procedure duration, as well as limit complications. Further prospective investigations are needed to evaluate oncological safety, surgical outcomes, and patient satisfaction.

Clinicopathological Characteristics and Prognosis of Triple-Negative Apocrine Carcinoma: A Case-Control Study.

Background: With a prevalence of only 1% among all breast cancers in Japan, apocrine carcinoma (AC) is a rare type of breast cancer, and its clinicopathological characteristics remain unclear. The aim of this study was to evaluate the characteristics and prognosis of AC, in relation to the presence or absence of androgen receptor (AR). Methods: We conducted a retrospective multi-center case-control study (Yokohama Clinical Oncology Group (YCOG): YCOG1701 study) in Japan. A total of 53 patients were registered who were diagnosed with AC between 2000 and 2017 in YCOG-affiliated hospitals. Results: The median age of the patients was 67 (43 - 94) years, and the median observation time was 6.1 years. Among the 53 cases, 24 had triple-negative pure AC (TN-PAC; AR-positive), whereas 29 had other types of AC (other-AC; estrogen receptor-positive and/or human epidermal growth factor receptor 2-positive or AR-negative). Tumor size was smaller (1.4 vs. 2.1 cm, P = 0.024) and metastasis occurred in fewer nodes (12.5% vs. 37.9%, P = 0.036) in the TN-PAC group than in the other-AC group. The number of patients who were administered perioperative adjuvant chemotherapy did not significantly differ between the two groups (TN-PAC/other-AC = 50.0%/55.2%, P = 0.525); however, there was no recurrence in the TN-PAC group, compared to five cases with relapse in the other-AC group. Conclusions: AR-positive AC patients showed a favorable prognosis without adjuvant chemotherapy, even with the TN subtype. A clinical trial exploring the possibility of treatment de-escalation is anticipated.

BRCA2 reversion mutation confers resistance to olaparib in breast cancer.

Key Clinical Message: A rare missense mutation was identified as a reversion mutation using cancer genomic profiling and a suspected mechanism underlying resistance to olaparib in breast cancer. Abstract: A 34-year-old woman with breast cancer and BRCA2: p.Gln3047Ter was treated with olaparib. After tumor progression, cancer genomic profiling testing using liquid biopsy revealed BRCA2 p.Gln3047Ter and p.Gln3047Tyr, with 48.9% and 0.37% allele frequency, respectively. These findings shed light on reversion mutation as a mechanism of resistance to olaparib in breast cancer.

Granulomatous mastitis in a male breast: A case report and review of literature.

Granulomatous mastitis (GM) is a rare disease, particularly among men. Herein, we present a case of GM diagnosed in a 63-year-old male patient who showed reduction in the tumor size during 3 months of observation.

The Modified Glasgow Prognostic Score and Prognostic Nutritional Index as Prognostic Markers in Patients With Metastatic Breast Cancer Treated With Eribulin.

AIM: To examine the role of the Modified Glasgow Prognostic Score (mGPS) and Prognostic Nutritional Index (PNI) as prognostic markers for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: We investigated the associations of clinico-pathological factors with time-to-treatment failure (TTF) and overall survival (OS) in 110 patients with MBC treated with eribulin. RESULTS: C-Reactive protein >1 mg/dl, albumin <3.5 g/dl, mGPS=2, and PNI <40 were significant predictors of shorter TTF in univariate analyses. PNI <40 remained a significant and independent predictor of shorter TTF in multivariate analyses. De novo tumor, visceral metastases, C-reactive protein >1 mg/dl, albumin <3.5 g/dl, mGPS=2, and PNI <40 were significant predictors of poor OS at the univariate level. A PNI <40 was a significant and independent predictor of poor OS in multivariate analyses. CONCLUSION: PNI is a reliable predictor of TTF and OS in patients with MBC treated with eribulin.

Primary breast lymphoma initially diagnosed as invasive ductal carcinoma: A case report.

A malignant tumor in the breast may not be conclusive of breast cancer. It is important to keep the possibility of primary breast lymphoma in rare scenarios. For the diagnosis of primary breast lymphoma, immunohistochemical staining is necessary.

Bromodomain-containing Protein 4 Is a Favourable Prognostic Factor in Breast Cancer Patients.

AIM: To evaluate the association between bromodomain-containing protein 4 (BRD4) expression and clinicopathological factors and prognosis in human breast cancer specimens. PATIENTS AND METHODS: We used tissue microarrays constructed from samples of patients (n=183) who underwent surgery. We validated the association between BRD4 expression and prognosis in solid tumours, including breast cancer, using The Cancer Genome Atlas (TCGA) database. RESULTS: Immunohistochemical staining showed that BRD4 was widely distributed in breast cancer tissues. BRD4 was strongly expressed in 19.7% of patients but BRD4 staining intensity was not correlated with other clinicopathological factors. Most importantly, patients with a strong BRD4 expression had a significantly longer disease-specific survival than those with a weak BRD4 expression (100.0% vs. 91.3% at 5 years, p=0.027). mRNA expression analysis showed similar results (91.2% vs. 80.2% at 6 years, p=0.047). CONCLUSION: Strong BRD4 expression was associated with a significantly better prognosis in breast cancer tumours.

First-line Gemcitabine Versus Treatment of Physician's Choice for Metastatic Breast Cancer: A Prospective Cohort Study.

BACKGROUND/AIM: This study aimed to investigate the efficacy of first-line gemcitabine monotherapy for metastatic breast cancer (MBC) and its effect on health-related quality of life (HRQoL) compared with treatment of physician's choice (TPC). PATIENTS AND METHODS: We enrolled 96 patients into the first-line gemcitabine group (n=47) or other treatment of physician's choice (TPC) group (n=49) from May 2010 to April 2013. HRQoL was evaluated every 4 weeks. RESULTS: There was no significant difference in the median time to treatment failure (5.3 vs. 4.6 months, hazard ratio=0.87, p=0.546) and the incidence rates of grade 3/4 haematological toxicity (10.6% vs. 8.1%, p=0.677) and grade 3/4 non-haematological toxicity (4.2% vs. 8.1%, p=0.429) between the gemcitabine and TPC groups. Changes in HRQoL from baseline to 12 weeks were not significantly different. CONCLUSION: Gemcitabine achieves similar efficacy and HRQoL benefit to other chemotherapy and can be used as first-line treatment for MBC.

Predicting Nonsentinel Lymph Node Metastasis in Breast Cancer: A Multicenter Retrospective Study.

BACKGROUND: Sentinel lymph node (SLN) biopsy has been the standard modality for breast cancer patients with clinically node negative disease. In patients who undergo axillary lymph node dissection (ALND) due to SLN metastasis, the harvested nodes (non-SLNs) often contain no metastasis. Here, we evaluated the predictive factors associated with non-SLN metastasis in breast cancer patients. MATERIALS AND METHODS: This was a retrospective study of patients with operable cT1-3, cN0 invasive breast cancer who underwent SLN biopsy followed by ALND due to SLN metastasis. The clinicopathologic factors and predictive factors of non-SLN metastasis were analyzed. The optimal cutoff for the Ki67 index and the number of positive and negative SLNs that were predictive of non-SLN metastasis were evaluated using receiver operating characteristic curves. RESULTS: The median number of SLN and non-SLN was 3 and 11, respectively. Of the 150 patients, 52 (35.0%) had metastases in non-SLNs. The optimal cutoffs for the Ki67 index and the number of positive and negative SLNs were of 12%, 2, and 1, respectively. In the univariate analysis, the Ki67 index and the number of positive SLNs≥2 and negative SLNs≤1 were higher in the non-SLN + group than that in the non-SLN - group. The number of negative SLNs was as a predictive factor for non-SLNs metastasis in the multivariate analysis. CONCLUSIONS: The number of negative SLNs predicts the risk of non-SLN metastasis in breast cancer. When deciding on whether to omit ALND, the number of positive and negative SLNs should be considered.

Aldehyde Dehydrogenase 1-related Genes in Triple-negative Breast Cancer Investigated Using Network Analysis.

BACKGROUND/AIM: Aldehyde dehydrogenase 1 (ALDH1) is known as a breast cancer stem cell (CSC) marker. This study aimed to identify genes associated with ALDH1. MATERIALS AND METHODS: ALDH1-positive and -negative breast cancer cells were isolated using laser capture microdissection from five tissue samples of ALDH1-positive breast cancer patients. Messenger RNA expression levels were compared between ALDH1-positive and -negative cells. RESULTS: We found 104 differentially expressed genes between ALDH1-positive and -negative cells. Gene ontology and pathway analysis revealed that these genes were correlated with CSC functions and pathways. Network analyses identified 10 genes that were closely associated with ALDH1. We validated these 10 genes utilizing The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium cohort, and found that they were associated with ALDH1 expression and correlated with Wnt pathway signaling. CONCLUSION: The 10 genes we identified could be potential targets for CSC therapy of breast cancer.

Development of an invasive ductal carcinoma in a contralateral composite nipple graft after an autologous breast reconstruction: a case report.

BACKGROUND: Nipple-areola complex (NAC) reconstruction is a technique used in breast reconstructive surgery, which is performed during the final stage of breast reconstruction after total mastectomy of primary breast cancer. Composite nipple grafts utilizing the contralateral NAC are common; however, to our knowledge, there are no reports of new primary invasive ductal carcinoma development within the graft. Here, we describe one such case for the first time. CASE PRESENTATION: A 54-year-old woman was referred to us by the Department of Plastic and Reconstructive Surgery in our medical center for further evaluation of right nipple erosion. She had undergone total mastectomy of the right breast following a breast cancer diagnosis 15 years ago, at which time tumor biological profiling revealed the following: estrogen receptor (ER), positive; progesterone receptor (PgR), negative; and human epidermal growth factor receptor 2 (HER2), undetermined. She received adjuvant chemotherapy and endocrine therapy. She defaulted endocrine therapy for a few years, and 7 years after surgery, she underwent autologous breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. In the following year, NAC reconstruction was performed using a composite graft technique. Seven years after the NAC reconstruction, erosion appeared on the nipple grafted from its contralateral counterpart; scrape cytology revealed malignancy. The skin on the right side of her chest around the NAC and subcutaneous fat tissue consisted of transferred tissue from the abdomen, as the DIEP flap and grafted nipple were located on the graft skin. The right nipple carcinoma arose from the tissue taken from the left nipple. Magnetic resonance imaging (MRI) or computed tomography showed no malignant findings in the left breast. As the malignant lesion seemed limited to the area around the grafted right nipple on MRI, surgical resection with sufficient lateral and deep margins was performed around the right nipple. Pathological findings revealed invasive ductal carcinoma with comedo ductal components infiltrating the graft skin and underlying adipose tissue. Immunohistochemistry revealed positive for ER, PgR, and HER2. CONCLUSIONS: To our knowledge, this is the first case involving the development of invasive ductal carcinoma in a nipple graft constructed on the skin of a DIEP flap, with the origin from the contralateral breast's nipple.

Long-Term Outcomes of Immediate Autologous Breast Reconstruction for Breast Cancer Patients.

BACKGROUND: There is limited information on the oncological outcomes of immediate autologous breast reconstruction in the Asian population. This study aimed to evaluate the oncological outcomes of immediate one-stage autologous breast reconstruction using a free perforator flap for breast cancer patients at a single institution in Japan. METHODS: We retrospectively reviewed 239 patients who underwent immediate one-stage autologous breast reconstruction using a free perforator flap after skin- or nipple-sparing mastectomy. The whole breast was pathologically analyzed in 5-mm sections. Clinical and pathological data were collected from medical records. RESULTS: For tumor stage among the 239 patients, 101 (42.3%) had stage 0, 127 (53.1%) had stage I and II, and 11 (4.6%) had stage III. Twenty-three patients (9.6%) had margin involvement in the surgical specimen. Adjuvant chemotherapy was performed in 75 patients (30%), and endocrine therapy was administered in 153 patients (64%). Radiation therapy was performed in 15 patients (6.3%) because of multiple lymph node metastases or margin involvement. With a median follow-up time of 73 mo, local recurrence was found in 3.3%, distant metastases in 2.5%, and contralateral breast cancer in 3.7%. All patients with local recurrence did not receive radiation therapy as adjuvant treatment. CONCLUSIONS: Among the patients who underwent immediate one-stage autologous reconstruction after breast surgery, 3.3% had local recurrence. For patients with margin involvement, radiation therapy is a promising option.

Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness.

PURPOSE: Aldehyde dehydrogenase1 (ALDH1) is widely accepted as a stem cell marker for normal breast as well as in breast cancer. Although the clinical impact of ALDH1 was observed in our previous study, we do not know how ALDH1 affects stem cell features resulting in worsening of prognosis in breast cancer. The purpose of this study is to explore ALDH1-related gene and its function on cancer stem cell (CSC). METHODS: In five cases of ALDH1-positive triple-negative breast cancer, mRNA expression profile was compared between ALDH1-positive and ALDH1-negative cells by Affymetrix microarray analysis after microdissection. Among the genes modulated in ALDH1-positive cells, we focused on H19, which encodes a long non-coding RNA, in this study. An in-vitro study was conducted with H19 siRNA in HCC1934 and iCSCL10A cell lines. The association of H19 with prognosis was examined in 180 breast cancer cases. RESULTS: Network analysis revealed the existence of five genes related with H19, including miR-103, miR-107, let-7, miR-29b-1, and Trx. In-vitro analysis showed that suppression of H19 using siRNA reduces sphere formation capacity in both HCC1934 and iCSCL10A cell lines. In clinical studies, H19 expression was associated with hormone negativity, tumor size, and nodal status. Patients with H19 expression had significantly poor disease-free survival (DFS) (26.3 vs. 64.8% at 5 years, p = 0.001) and overall survival (OS) (28.9 vs. 68.3% at 5 years, p = 0.004). The effect of H19 expression on prognosis was the most significant in triple-negative breast cancer compared to that in other subtypes (20.0 vs. 65.4% at 5 years DFS, p = 0.012, 20.0 vs. 69.2% at 5 years OS, p = 0.016). CONCLUSION: This study indicated that H19 was associated with stem cell phenotype in ALDH1-positive breast cancer. H19 regulates CSC and is associated with poor prognosis in breast cancer patients, particularly in triple-negative subtype.

[Evaluation of measurement method of a bacterial sepsis marker, procalcitonin].

Procalcitonin (PCT) is a novel biomarker for diagnosis and severity evaluation of bacterial sepsis. PCT measurement methods provided by Wako Pure Chemical Industries, Ltd. include a fully automated chemiluminescent immunoassay system SphereLight Wako and fully automated immunoanalyzer microTASWako i30 for a quantitative measurement, and immunochromatographic assay method, B R A H M S PCT-Q kit. This time, basic performance of SphereLight Wako and microTASWako i30 was evaluated as quantitative determination methods for PCT. The lower limit of detection for the both methods was 0.02 ng/ml. Correlation coefficients of 0.993 to 0.997 indicated good correlation between the two methods. The both methods allow quick and easy measurement of PCT, therefore they are helpful for diagnosis and severity evaluation of bacterial sepsis.