Breast cancer is the most common cancer and the second leading cause of cancer death in women worldwide. Novel biomarkers for early diagnosis, treatment, and prognosis in breast cancer are needed and extensively studied. Metabolites, which are small molecules produced during metabolic processes, provide links between genetics, environment, and phenotype, making them useful biomarkers for diagnosis, prognosis, and disease classification. With recent advancements in metabolomics techniques, metabolomics research has expanded, which has led to significant progress in biomarker research. In breast cancer, alterations in metabolic pathways result in distinct metabolomic profiles that can be harnessed for biomarker discovery. Studies using mass spectrometry and nuclear magnetic resonance spectroscopy have helped identify significant changes in metabolites, such as amino acids, lipids, and organic acids, in the tissues, blood, and urine of patients with breast cancer, highlighting their potential as biomarkers. Integrative analysis of these metabolite biomarkers with existing clinical parameters is expected to improve the accuracy of breast cancer diagnosis and to be helpful in predicting prognosis and treatment responses. However, to apply these findings in clinical practice, larger cohorts for validation and standardized analytical methods for QC are necessary. In this review, we provide information on the current state of metabolite biomarker research in breast cancer, highlighting key findings and their clinical implications.

Background: In patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost. Methods: We retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR).DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test. Results: Total 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated.The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (P = 0.374). Furthermore, the IBTR did not differ between the hypofractionated RT and conventional RT groups (P = 0.374) after matching. The 3-year overall survival was not different between two groups (both 100%). Hypofractionated RT saved 26.6% of the total cost of RT compared to conventional RT. Additionally, the acute skin toxicity rate (≥ grade 2) was also not significantly different between the groups (hypofractionated RT: 10.1% vs. conventional RT: 2.2%). Conclusion Hypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Post-partum galactocele is a common benign disease among breastfeeding women, whereas retromammary and peri-implant galactocele are relatively rare conditions. Herein, a 34-yearold, 1 month-postpartum female, who had augmentation mammoplasty and a 1-month history of breast pump use, presented with left breast enlargement for 2 weeks. An initial left breast US revealed hyperechoic peri-implant fluid collection. Additional US-guided fine needle aspiration was done using a 21G-needle, draining the milk component in the process, and cytologic results revealed numerous crystals, suggestive of galactocele. Various diseases, especially breast implant-associated anaplastic large cell lymphoma, can cause peri-implant fluid collection in an augmented breast. Thus, correlating imaging features with clinical information and cytologic analysis plays an important role in appropriate management.

Purpose: Nanoxel®-M is a low-molecular-weight, non-toxic, biodegradable, docetaxel-loaded methoxy-poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PDLLA) micellar formulation. We conducted a multicenter trial to evaluate the safety and toxicity of Nanoxel®-M and the quality of life (QoL) of Korean breast cancer patients treated with this formulation. Methods: Patients received adjuvant Nanoxel®-M with a schedule comprising four alternating cycles of doxorubicin with cyclophosphamide, followed by either Nanoxel®-M or Nanoxel®-M with cyclophosphamide after surgery for early breast cancer. We analyzed hematological and non-hematological toxicity profiles and alterations in patient QoL using the Korean version of the European organization for research and treatment of cancer core 30-item quality of life questionnaire. Fifty-five operable breast cancer patients with stage II or III disease were enrolled from four centers in Korea. Results: Regarding safety and toxicity profiles, grade 3/4 toxicity presented as anemia in 0.5%, neutropenia in 61.8%, febrile neutropenia in 4.5%, mucositis in 1.4%, and edema in 0.5% of patients during 220 total cycles. However, all-grade thrombocytopenia was not observed among hematological toxicities. No grade 3/4 nausea, vomiting, diarrhea, hand foot syndrome, dyspnea, allergic reaction, edema, or peripheral neuropathy were observed. Furthermore, no vehicle-related hypersensitivity reactions occurred when using Nanoxel®-M. Conclusion Our findings indicate that Nanoxel®-M could be used to treat operable breast cancer patients, compare favorably with docetaxel in terms of hypersensitivity reactions and the incidence of taxane-induced peripheral neuropathy, and is associated with a similar incidence of febrile neutropenia.

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

Hereditary breast cancer is known for its strong tendency of inheritance. Most hereditary breast cancers are related to BRCA1/BRCA2 pathogenic variants. The lifelong risk of breast cancer in pathogenic BRCA1 and BRCA2 variant carriers is approximately 65% and 45%, respectively, whereas that of ovarian cancer is estimated to be 39% and 11%, respectively. Therefore, understanding these variants and clinical knowledge on their occurrence in breast cancers and carriers are important. BRCA1 pathogenic variant breast cancer shows more aggressive clinicopathological features than the BRCA2 pathogenic variant breast cancer. Compared with sporadic breast cancer, their prognosis is still debated. Treatments of BRCA1/BRCA2 pathogenic variant breast cancer are similar to those for BRCA-negative breast cancer, mainly including surgery, radiotherapy, and chemotherapy. Recently, various clinical trials have investigated poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor treatment for advanced-stage BRCA1/BRCA2 pathogenic variant breast cancer. Among the various PARP inhibitors, olaparib and talazoparib, which reached phase III clinical trials, showed improvement of median progression-free survival around three months. Preventive and surveillance strategies for BRCA pathogenic variant breast cancer to reduce cancer recurrence and improve treatment outcomes have recently received increasing attention. In this review, we provide an information on the clinical features of BRCA1/BRCA2 pathogenic variant breast cancer and clinical recommendations for BRCA pathogenic variant carriers, with a focus on treatment and prevention strategies. With this knowledge, clinicians could manage the BRCA1/BRCA2 pathogenic variant breast cancer patients more effectively.

PURPOSE: The role of the host immunologic environment is crucial in cancer progression. Recent studies revealed that neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), are possible surrogate markers of outcome in various cancers. In breast cancer, the therapeutic effect of neoadjuvant chemotherapy (NAC) differs in patients, and higher response rate reflects better outcomes. This study aimed to determine the predictive value of peripheral blood NLR and PLR for NAC response along with their prognostic role in breast cancer. METHOD: A total of 105 patients with breast cancer treated with NAC between 2009 and 2017 were analyzed retrospectively. NAC response and prognosis (disease-free-survival [DFS], progression-free-survival [PFS] and overall survival [OS]) according to NLR and PLR were evaluated. According to the optimal cut-off values for NAC response obtained from receiver operating characteristic (ROC) curves, patients satisfying both low NLR and PLR levels (low-ratio group) were compared to those who did not (high-ratio group). RESULTS: The NLR cut-off value was ≤ 2.21 (area under the ROC curve [AUC], 0.617; 95% confidence interval [CI], 0.517–0.710; p=0.030) with 94.1% sensitivity and 38.0% specificity. The PLR cut-off value was ≤ 143.36 (AUC, 0.618; 95% CI, 0.518–0.711; p = 0.040) with 85.3% sensitivity and 39.4% specificity. The low-ratio group demonstrated a better NAC response (p = 0.006) in multivariate analysis than the high-ratio group. The low-ratio group showed better DFS and PFS (p = 0.046 and p = 0.040, respectively) and longer OS (p = 0.078) in univariate survival analysis than the high-ratio group. In multivariate analysis, the low-ratio group had significantly better PFS (p = 0.049) and higher DFS (p = 0.054) than the high-ratio group. CONCLUSIONS: The combination of NLR and PLR showed improved prediction of NAC response, revealing their potential as screening tools, significant prognostic role in breast cancer patients who receive NAC. Further studies with subgroup analysis, larger population and longer follow up duration are required.
Biomarkers ; Blood Cell Count ; Breast Neoplasms ; Breast ; Drug Therapy ; Follow-Up Studies ; Humans ; Mass Screening ; Methods ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity

PURPOSE: For early detection of breast cancer, tests with high sensitivity and specificity are needed. Metabolomics, the study of chemical processes involving metabolites, can be used to identify diagnostic biomarkers for a variety of types of cancers. In this study we identified biomarkers of breast cancer by profiling urinary metabolites. METHODS: We performed metabolite profiling of 30 urine samples from 14 patients with breast cancer and 16 healthy controls by liquid chromatography–mass spectrometry. An orthogonal partial least squares-discriminant analysis (OPLS-DA), Student's t-test, and receiver operating characteristic (ROC) analysis were performed to identify metabolites that were potential diagnostic biomarkers for breast cancer. RESULTS: The OPLS-DA showed clear separation between the two groups. Of the 95 metabolites detected, 24 potential biomarkers were identified by Student's t-test. A ROC analysis showed that concentrations of N-(2-furoyl) glycine, histidine, and D-tagarose were significantly higher (area under the ROC curve [AUC] >0.7) and those of trigonellinamide, L-galacto-2-heptulose, creatinine, and xanthine were significantly lower (AUC ≥0.8) in the patients with breast cancer than in the healthy controls. CONCLUSION Measurement of the concentrations of urinary metabolites can be used to screen for early breast cancer. We plan to explore diagnostic biomarkers of breast cancer in blood and urine further in a larger study.