Predictive analysis of breast cancer response to neoadjuvant chemotherapy through plasma metabolomics.

PURPOSE: Preoperative chemotherapy is a critical component of breast cancer management, yet its effectiveness is not uniform. Moreover, the adverse effects associated with chemotherapy necessitate the identification of a patient subgroup that would derive the maximum benefit from this treatment. This study aimed to establish a method for predicting the response to neoadjuvant chemotherapy in breast cancer patients utilizing a metabolomic approach. METHODS: Plasma samples were obtained from 87 breast cancer patients undergoing neoadjuvant chemotherapy at our facility, collected both before the commencement of the treatment and before the second treatment cycle. Metabolite analysis was conducted using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry (LC-MS). We performed comparative profiling of metabolite concentrations by assessing the metabolite profiles of patients who achieved a pathological complete response (pCR) against those who did not, both in initial and subsequent treatment cycles. RESULTS: Significant variances were observed in the metabolite profiles between pCR and non-pCR cases, both at the onset of preoperative chemotherapy and before the second cycle. Noteworthy distinctions were also evident between the metabolite profiles from the initial and the second neoadjuvant chemotherapy courses. Furthermore, metabolite profiles exhibited variations associated with intrinsic subtypes at all assessed time points. CONCLUSION: The application of plasma metabolomics, utilizing CE-MS and LC-MS, may serve as a tool for predicting the efficacy of neoadjuvant chemotherapy in breast cancer in the future after all necessary validations have been completed.

Intronless Pabpc6 encodes a testis-specific, cytoplasmic poly(A)-binding protein but is dispensable for spermatogenesis in the mouse†.

Besides ubiquitous poly(A)-binding protein, cytoplasmic 1 (PABPC1), testis-specific PABPC2/PABPt (in humans, referred to as PABPC3), and female and male germline-specific PABPC1L/ePAB, have been reported in the mouse testis. Recent in silico analysis additionally identified testis-specific Pabpc6 in the mouse. In this study, we characterized PABPC6 and its mutant mice. PABPC6 was initially detectable in the cytoplasm of pachytene spermatocytes, increased in abundance in round spermatids, and decreased in elongating spermatids. PABPC6 was capable of binding to poly(A) tails of various mRNAs and interacting with translation-associated factors, including EIF4G, PAIP1, and PAIP2. Noteworthy was that PABPC6, unlike PABPC1, was barely associated with translationally active polysomes and enriched in chromatoid bodies of round spermatids. Despite these unique characteristics, neither synthesis of testicular proteins nor spermatogenesis was affected in the mutant mice lacking PABPC6, suggesting that PABPC6 is functionally redundant with other co-existing PABPC proteins during spermatogenesis.

Efficacy and safety of dose-dense neoadjuvant chemotherapy with nab-paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer.

OBJECTIVE: Dose-dense chemotherapy has shown a better prognosis than standard interval chemotherapy in adjuvant settings for high-risk breast cancer. This study aimed to evaluate the efficacy and safety of dose-dense nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide as neoadjuvant chemotherapy for human epidermal growth factor 2 (HER2)-negative operable breast cancer. METHODS: Patients with histologically confirmed stage I-III HER2-negative breast cancer were enrolled in this study. Patients received nanoparticle albumin-bound paclitaxel (260 mg/m2) followed by epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 2 weeks with pegfilgrastim. The primary endpoint was the pathological complete response rate. Patients also underwent prophylactic management for peripheral neuropathy, which involved a combination of cryotherapy, compression therapy using elastic stockings and medications including goshajinkigan. RESULTS: Among the 55 patients enrolled in this study, 13 (23.6%) achieved pathological complete response, of whom 10/26 (38.5%) patients had triple-negative disease and 3/29 (10.3%) had luminal disease. The objective response was observed in 46 (83.6%) patients. Of the 36 patients who were initially planned for mastectomy, 11 (30.6%) underwent breast-conserving surgery after neoadjuvant chemotherapy. The most common grade 3-4 adverse events were myalgia (14.5%), fatigue (12.7%) and elevated transaminase levels (9.1%). No patients experienced febrile neutropenia. Eight (14.5%) patients discontinued treatments due to adverse events. CONCLUSIONS: Neoadjuvant dose-dense biweekly nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide was effective, especially in patients with triple-negative disease, and feasible with pegfilgrastim support.

Acute arterial occlusive disease due to tumor thrombus from lung metastasis of breast cancer with cartilaginous and osseous metaplasia: a case report.

BACKGROUND: Tumor embolization due to venous infiltration of breast cancer pulmonary metastases is very rare. CASE PRESENTATION: A 72-year-old female was diagnosed with triple-negative breast cancer. Neoadjuvant chemotherapy was discontinued because of progressive disease, and a right mastectomy with sentinel lymph node biopsy was performed. The pathological analysis of surgical specimens revealed carcinoma with cartilaginous and/or osseous metaplasia. At 22 months after surgery, lung metastasis was observed, and 6 months after initiating treatment for lung metastases, she complained of sudden numbness in the left-lower limb with trouble walking. Ultrasonography showed an embolism in the left popliteal artery, and contrast computed tomography showed enlarged lung metastases and infiltration of the left-upper lobe disease into the left superior pulmonary vein and left atrium. Acute arterial occlusive disease in the left-lower limb caused by the tumor embolism was suspected, so an endovascular thrombectomy was performed. Tumor emboli were removed by embolectomy catheter. CONCLUSION: This report of lung metastasis from breast cancer with cartilaginous and/or osseous metaplasia and acute lower-limb artery occlusion due to a tumor thrombus adds useful information to the literature on these extremely rare cases.

Large Nipple Volume as a Risk Factor of Nipple-areola Complex Necrosis Following Nipple-sparing Mastectomy.

BACKGROUND: Nipple-areola complex (NAC) necrosis, which is caused by local ischemia, remains one of the complications associated with nipple-sparing mastectomy. Obesity, smoking, diabetes mellitus, and immediate breast reconstruction have been identified as risk factors of NAC necrosis. The current study examined the correlation between NAC necrosis and nipple volume. MATERIALS AND METHODS: A total of 83 patients who underwent NSM for primary breast cancer from January 2016 to December 2019 were retrospectively analyzed. Nipple volume was determined using the formula: volume (cc) = length × width × height (mm), with measurements determined using contrast-enhanced magnetic resonance imaging. Total and partial NAC necrosis was defined as full-thickness necrosis requiring surgical procedures and epidermal necrosis managing local wound care, respectively. RESULTS: NAC necrosis was observed in 30 patients (36%), with 3 and 27 patients having total and partial necrosis, respectively. Large nipple volume (56% vs. 24%, p = 0.006), as well as smoking and immediate breast reconstruction (57 vs. 28%, p = 0.017; 48% vs. 20%, p = 0.009, respectively), were significantly correlated with NAC necrosis. Multivariate analysis identified nipple volume as an independent risk factor for NAC necrosis (OR, 3.75; 95% CI, 1.23-11.44; p = 0.02). Smoking (OR, 4.68; 95% CI, 1.37-15.94; p = 0.014) and immediate breast reconstruction (OR, 3.43; 95% CI, 1.05-11.23; p = 0.042) were also independently associated with NAC necrosis. CONCLUSIONS: This study suggested that a large nipple volume could be one of the risk factors for NAC necrosis following NSM.