Long-Term Survival Outcomes and Risk Factors for Axillary and Locoregional Recurrence in Japanese Patients with Sentinel Node-Positive Breast Cancer Treated in Accordance with the ACOSOG Z0011 Strategy.

INTRODUCTION: In 2018, we reported the results of a study to assess the feasibility of applying the ACOSOG Z0011 criteria to Japanese patients with early-stage breast cancer (median follow-up, 3 years). Their results over the longer term can now be presented. Risk factors for axillary and locoregional recurrence in Z0011-eligible patients are unknown. METHODS: Long-term survival outcomes were investigated by analyzing data from patients enrolled in the feasibility study. Data from the feasibility study patients, and from patients eligible for the Z0011 strategy after its introduction into clinical practice, were subjected to multivariate logistic regression analysis to identify risk factors for axillary and locoregional recurrence. RESULTS: Regarding long-term outcomes for the feasibility study patients (n = 189), distant disease-free survival rates at 5 and 7 years were 90.4 ± 2.1% and 85.9 ± 2.6%, respectively, and overall survival rates at 5 and 7 years were 97.3 ± 1.2% and 95.3 ± 1.7%, respectively. Analysis of data from these patients plus the 93 who received Z0011 in clinical practice (total, n = 282) identified the following independent risk factors for axillary recurrence: absence of high axillary tangential irradiation (OR, 5.87 [95% CI, 1.09-31.35], p = 0.04) and number of positive sentinel lymph nodes (OR, 4.65 [95% CI, 1.11-19.48], p = 0.04). Only high Ki67 labeling index (OR, 5.92 [95% CI, 1.31-26.70], p = 0.02) was identified as an independent risk factor for locoregional recurrence. CONCLUSION: Long-term survival outcome results of the feasibility study show that the Z0011 strategy can be used to treat Japanese patients with early-stage breast cancer. Our findings regarding risk factors suggest that high axillary tangent irradiation is necessary for the prevention of axillary recurrence and that irradiation, including of the regional lymph nodes, should be considered, especially in patients with high Ki67 index values.

Predictive factors for response to neoadjuvant chemotherapy: inflammatory and immune markers in triple-negative breast cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients. However, the TIL level can be determined at a few facilities. By contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily and objectively determined from the results of full blood counts. We conducted a retrospective study to investigate whether TILs, NLR, and PLR predict NAC efficacy and whether NLR and PLR could be surrogate markers for TILs in TNBC. METHODS: Of the 266 patients diagnosed with TNBC between 2013 and 2019, 66 who underwent radical surgery after sequential administration of anthracycline and taxane as NAC were included in the study. TILs, NLR, and PLR were evaluated as predictors of pathologic complete response (pCR) using cutoff values determined from receiver operating characteristic curves. RESULTS: The cutoff values of TILs, NLR, and PLR were 20%, 2.6, and 180, respectively. High TIL level was associated with low NLR (P = 0.01) and low PLR (P = 0.01). High TIL level (odds ratio [OR] 4.28 [95% CI 1.40-13.1]; P = 0.01), low NLR (OR 5.51 [95% CI 1.60-18.9]; P = 0.01), and low PLR (OR 3.29 [95% CI 1.13-9.57]; P = 0.03) were associated with pCR. Low NLR predicted pCR independently (OR 6.59 [95% CI 1.45-30.0]; P = 0.01). CONCLUSIONS: TILs, NLR, and PLR predicted NAC efficacy against TNBC. TIL level was associated with NLR and PLR. NLR was an independent predictive factor and may be a useful surrogate marker for TILs when predicting pCR.

[A Case of Chronic Expanding Hematoma of the Lower Abdomen after Reconstruction of Deep Inferior Epigastric Perforator Flap for Breast Cancer].

A 49-year-old woman who had surgery for left breast cancer and subsequently underwent a two-stage deep inferior epigastric perforator(DIEP)flap reconstruction. One month postoperatively, she became aware of abdominal distention and visited a local hospital. CT scan revealed subcutaneous fluid accumulation with capsular formation in the lower abdomen. Imaging findings and physical examination showed no abdominal wall scar hernia. After multiple puncture aspirations, fluid accumulation was observed again, and the possibility of a chronic expanding hematoma was considered. Later, hematoma removal, including the capsules, was performed; pathological findings showed no evidence of malignancy. No fluid retention was observed postoperatively. In cases where imaging evaluation reveals hematoma formation with capsules, hematoma removal, including the capsules, should be performed to avert the possibility of a chronic expanding hematoma.

Risk of Abemaciclib-induced Liver Injury in Hormone Receptor-positive, HER2-negative Metastatic Breast Cancer: A Retrospective Analysis.

BACKGROUND/AIM: The efficacy of endocrine therapy combined with abemaciclib for hormone receptor-positive, HER2-negative metastatic breast cancer has been established through pivotal clinical trials. However, abemaciclib-induced liver injury (AILI) can be a cause for dose reduction or discontinuation. Therefore, it is critical to understand the risk factors for AILI. PATIENTS AND METHODS: This retrospective study analyzed data from patients who had received abemaciclib combined with endocrine therapy for metastatic breast cancer as first- or second-line therapy at our hospital between December 2018 and October 2021. Relevant data were extracted from their medical records. Logistic regression analysis was performed to identify characteristics associated with AILI. RESULTS: Of the 52 eligible patients, 12 (23%) received an aromatase inhibitor (AI), and 40 (77%) received fulvestrant, concomitantly with abemaciclib. Fifteen (29%) of the patients developed liver injury after starting abemaciclib. Univariate analysis revealed the following risk factors for AILI: age ≥65 years (p=0.047), fatty liver disease (p=0.047), and concomitant use of an AI (p=0.002). Concomitant use of an AI was identified by multivariate analysis as an independent risk factor for AILI [odds ratio (OR)=10.23, 95% confidence interval (CI)=2.02-51.91, p=0.005]. CONCLUSION: Concomitant use of an AI could be the most significant factor associated with increased risk of AILI. Future research on the mechanism by which the use of an AI plus abemaciclib can cause liver injury, and prospective studies to validate our findings regarding AILI risk factors, are warranted.

Pegfilgrastim-induced vasculitis of the subclavian and basilar artery complicated by subarachnoid hemorrhage in a breast cancer patient: a case report and review of the literature.

BACKGROUND: Pegfilgrastim (PEG) is a sustained-duration pegylated form of filgrastim, a granulocyte-colony stimulating factor agent that is widely used as prophylaxis against febrile neutropenia during chemotherapy. We report the case of a breast cancer patient who developed PEG-induced vasculitis complicated by subarachnoid hemorrhage (SAH) and review the relevant literature. CASE PRESENTATION: A 48-year-old woman had undergone surgery for breast cancer and was receiving docetaxel and cyclophosphamide as adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2); on day 4 of treatment, PEG had been administered. On day 14, she was admitted to hospital with fever, general malaise, and neck pain, and her C-reactive protein level was found to be high (12.65 mg/dL). Although infection was initially suspected, antimicrobial treatment was ineffective and other laboratory test results were negative for this. Contrast-enhanced computed tomography on day 22 showed thickened vessel walls in the left subclavian artery, the origin of the common carotid artery, and the thoracoabdominal aorta. On day 26, magnetic resonance imaging of the head to investigate possible causes of headache showed signs consistent with SAH, and magnetic resonance angiography images showed irregularity in the basilar artery wall; the findings of both studies were considered to be due to PEG-induced vasculitis. Once treatment with prednisolone 40 mg/day had started, the wall thickening and irregularity improved. CONCLUSION: Although an uncommon adverse effect, vasculitis affecting vessels of various sizes may be caused by PEG. To the best of our knowledge, this report is the first to describe a case of G-CSF-induced vasculitis complicated by SAH. In cases of persistent high fever and elevated inflammatory response after PEG administration and in the absence of infection, clinicians should consider the possibility of drug-induced vasculitis.