Long-Term Outcomes of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy (N-1 Study, Phase II Trial) in Patients With Operable Breast Cancer.

BACKGROUND: We previously reported that S-1 and low-dose docetaxel (DOC) (N-1 study, phase II trial) could be a well-tolerated and effective neoadjuvant chemotherapies (NACs) for patients with operable breast cancer. Herein, we analyzed the long-term outcomes and developed clinicopathological and molecular predictors of pathological complete response (pCR). PATIENTS AND METHODS: Eighty-three patients received S-1 (40 mg/m2 orally on days 1-14) and DOC (40 mg/m2 intravenously on day 1) every 3 weeks for 4 to 8 cycles. Disease-free survival (DFS) and overall survival (OS) were analyzed for each population with a pCR status. To assess the relationship between pCR and clinicopathological factors such as tumor-infiltrating lymphocytes (TILs, 1+ <10%, 2+ 10%-50%, and 3+ >50%) and nuclear grade (NG), microarray was used to compare the microRNA profiles of the pCR and non-pCR groups using core needle biopsy specimens. RESULTS: With a median follow-up duration of 99.0 (range, 9.0-129.0) months, the 5-year DFS and OS rates were 80.7% and 90.9%, respectively. The 5-year OS rate of the pCR group was significantly better than that of the non-pCR group (100% vs. 86.2%, p = .0176). Specifically, in triple-negative patients, the difference was significant (100% vs. 60.0%, p = .0224). Multivariate analysis revealed that high TILs (≥2-3+) and NG 2-3 independently predicted pCR. Microarray data revealed that 3 miRNAs (miR-215-5p, miR-196a-5p, and miR-196b-5p) were significantly upregulated in the pCR group. CONCLUSION: Our NAC regimen achieved favorable long-term outcomes and significantly improved OS in the pCR group. High TILs, NG 2-3, and some miRNAs may be predictors of pCR.

Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients.

NTRODUCTION/BACKGROUND: Some reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. PATIENTS AND METHODS: This retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Data from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). CONCLUSION: HER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.

Axillary lymphangioma that developed following COVID-19 vaccination: a case report.

BACKGROUND: Extensive vaccination programs are being implemented worldwide for coronavirus disease 2019 (COVID-19). With the spread of vaccination, swelling of the lymph nodes after vaccination is frequently seen. We encountered a patient who developed left axillary lymphadenoma following vaccine administration. CASE PRESENTATION: The patient was a Japanese woman in her 80 s who had previously undergone surgery for right breast cancer. She received two injections of the Pfizer-BioNTech COVID-19 vaccine in her left arm. Approximately 3 months later, she complained of left axillary swelling, and imaging resulted in a diagnosis of left axillary lymphangioma. In accordance with the patient's wishes, we performed axillary mass resection. The pathological diagnosis was lymphangioma. CONCLUSION: Our examination findings indicated that congestion of the axillary lymph vessels might have been caused by upper-arm injections of the COVID-19 vaccine.

Drug-induced interstitial pneumonia during perioperative chemotherapy for breast cancer.

PURPOSE: Drug-induced interstitial pneumonia (DIP) that occurs during chemotherapy for breast cancer is a rare but a serious adverse event. Treatments of DIP requires interruption of breast cancer treatment, which may affect the patient's prognosis. However, there are few reports which discuss DIP during breast cancer treatments. Purpose of this report is to make clear how DIP occurred and influenced breast cancer treatment in our hospital. PATIENTS AND METHODS: A total of 74 patients who started perioperative chemotherapy in Tokushima Municipal Hospital for breast cancer from January 2019 to December 2020 were evaluated for DIP. Patients' and tumors' characteristics, and regimens which caused DIP were investigated. The clinical courses of the DIP patients were also followed up. RESULTS: Twelve of the 74 patients developed DIP. All 12 patients had histories of cyclophosphamide administration;however, the causative drug could not be determined. Ten of the 12 patients were treated with steroids, and all the patients recovered ultimately from the interstitial pneumonia. While chemotherapy was administered in six patients after mild DIP, no relapse of pneumonia was observed. CONCLUSION: DIP during perioperative chemotherapy for breast cancer was resolved with appropriate treatment. Patients were able to resume breast cancer treatment with minimal interruption. J. Med. Invest. 69 : 107-111, February, 2022.

Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study).

BACKGROUND: To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. PATIENTS AND METHODS: Patients were treated with docetaxel (40 mg/m2 intravenously on day 1) and S-1 (40 mg/m2 orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. RESULTS: Ninety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. CONCLUSION: The S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.

Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.