Half Dose Pegfilgrastim for Patients With Breast Cancer During Chemotherapy: A Case-series.

BACKGROUND/AIM: This study aimed to show the trend of neutrophil counts and frequency of febrile neutropenia after changing pegfilgrastim from 3.6 mg to 1.8 mg. PATIENTS AND METHODS: This case-series study was performed between April 2016 and December 2021 at Hyogo Prefectural Amagasaki General Medical Center. All patients who reduced their normal dose of 3.6 mg pegfilgrastim to 1.8 mg due to adverse events or markedly elevated neutrophil counts were included. Any type of chemotherapy was acceptable. Patients who dropped out within 1 month of receiving 1.8 mg pegfilgrastim were excluded. The primary outcome was the neutrophil counts after receiving 1.8 mg pegfilgrastim. The secondary outcome was febrile neutropenia, which was evaluated by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: The study included seven patients who used a regimen of dose-dense epirubicin and cyclophosphamide, trastuzumab, pertuzumab, and docetaxel, docetaxel, or docetaxel and cyclophosphamide. After using 1.8 mg pegfilgrastim, neutrophil counts changed from a mean of 18,944 [standard deviation (SD)=-7,768] to only 4,447 (SD=1,224). The patients experienced grades 1 to 3 adverse events during the use of 1.8 mg and 3.6 mg pegfilgrastim doses, including febrile neutropenia, and pain. Four patients (57%) complained of grade 1 or 2 fatigue and anorexia. After switching from 3.6 mg pegfilgrastim to 1.8 mg, three patients (42%) experienced adverse events. CONCLUSION: In patients who experienced adverse events due to markedly elevated neutrophil counts with pegfilgrastim, reducing the dose of pegfilgrastim by half may reduce adverse events.

Promoters of BRCA testing under insurance coverage for non-metastatic breast cancer patients in Japan: a retrospective cohort study.

BACKGROUND: We investigated the barriers to and promoters of taking BRCA testing, after the start of national healthcare insurance coverage for non-metastatic breast cancer patients in Japan. PATIENTS AND METHODS: This was a multi-center, retrospective, cohort study. We included stage 0 to III breast cancer patients who were diagnosed and met the criteria for insurance coverage of BRCA testing between April 2020 and December 2021. We examined the association between BRCA testing and possible exposures: breast cancer diagnosis at 45 years or younger, triple-negative breast cancer (TNBC) diagnosis at the age of 60 or younger, two or more primary breast cancers, family history of breast cancer or ovarian cancer in the third degree of relatives, male breast cancer, medical expense limits, and parity. We used logistic regression analysis. RESULTS: We included 222 patients and 123 (55.4%) of them underwent the test. In univariate analysis, a family history of ovarian cancer (odds ratio (OR) 10.59; 95% CI 1.35-82.96, p = 0.025), diagnosis of breast cancer at the age of 45 or younger (OR 2.78; 95% CI 1.52-5.14, p = 0.0009), and diagnosis of TNBC at the age of 60 or younger (OR 3.95; 95% CI 1.55-10.07, p = 0.004) were associated with taking the test. After multivariate logistic regression analysis, a family history of ovarian cancer (adjusted OR 12.80; 95% CI 1.51-108.80, p = 0.0195), diagnosis of breast cancer at the age of 45 or younger (adjusted OR 4.43; 95% CI 1.98-9.90, p = 0.0003), and TNBC at the age of 60 or younger (adjusted OR 5.28; 95% CI 1.90-14.66, p = 0.0014) were consistently associated. CONCLUSION: For non-metastatic breast cancer patients whose BRCA testing is covered by insurance, costs would no longer be a definite barrier. Physicians should keep in mind that a family history of ovarian cancer, breast cancer diagnosis at 45 years of age or younger and TNBC diagnosis at 60 years of age or younger are strong promoters.

Association Between Treated Periodontal Disease and Febrile Neutropenia in Perioperative Chemotherapy for Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: This study aimed to examine whether the incidence of febrile neutropenia (FN) during perioperative chemotherapy for breast cancer increased in patients with periodontal disease who had received prior dental treatment. METHODS: This retrospective cohort study conducted at a single tertiary care center included patients diagnosed with clinical stages I-III of breast cancer and had started neoadjuvant or adjuvant intravenous chemotherapy between July 2015 and November 2021. The exposure was periodontal disease (probing depth ≥6 mm) diagnosed by dentists before the start of chemotherapy. Almost all the patients received dental treatment and oral care before initiating chemotherapy. The primary outcome was FN incidence during chemotherapy. We used a multivariable logistic regression model adjusted for age, diabetes mellitus, chemotherapy regimen, and the mean relative dose intensity. RESULTS: Based on the eligibility criteria of this study, 141 women were included. The incidence of FN in the periodontal group (probing depth ≥6 mm) and control group (probing depth <6 mm) was 36.4% and 25.9%, respectively. The crude odds ratio (OR) for FN incidence was 1.63 (95% confidence interval [CI], 0.71-3.74; P = 0.24), and the adjusted OR was 1.52 (95% CI, 0.62-3.73; P = 0.36).  Conclusions: Occurrence of FN during perioperative chemotherapy for breast cancer is not a concern in patients undergoing dental treatment for periodontal disease before or during chemotherapy.

A case of pleomorphic adenoma of the breast on dynamic contrast-enhanced MR imaging.

Pleomorphic adenoma commonly develops in the salivary gland, but rarely in the breast. The dynamic contrast-enhanced MR imaging findings of pleomorphic adenoma of the breast have not been well described. We report a 43-year-old woman with pleomorphic adenoma of the left breast. The imaging findings, including those on dynamic contrast-enhanced MR imaging, included an oval mass with a smooth margin, which consisted of solid and cystic components. The solid component was hypo-intense on T1-weighted imaging, hyper-intense on short tau inversion recovery imaging, with no apparent restricted diffusion, and had heterogeneous enhancement with dark internal septation and a fast/plateau dynamic contrast enhancement pattern. The cystic component was slightly hyper-intense on T1-weighted imaging, slightly hypo-intense on short tau inversion recovery imaging and had no apparent restricted diffusion or contrast enhancement. Together with its rarity, the similarities of imaging findings and the pathologic findings of pleomorphic adenoma of the breast to those of other tumors make accurate preoperative diagnosis difficult. Therefore, through this case report, awareness of pleomorphic adenoma of the breast on dynamic contrast-enhanced MR imaging will facilitate appropriate surgery and postoperative observation based on an accurate diagnosis.

Baseline neutrophil-to-lymphocyte ratio and c-reactive protein predict efficacy of treatment with bevacizumab plus paclitaxel for locally advanced or metastatic breast cancer.

The effect of bevacizumab plus paclitaxel therapy on progression-free survival (PFS) is prominent; however, no overall survival (OS) benefit has been demonstrated. Our aim was to study the predictive efficacy of peripheral immune-related parameters, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in locally advanced and metastatic breast cancers. A total of 179 patients treated with bevacizumab plus paclitaxel were recruited from three institutes in the test cohort. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/µL, and 1.0 mg/dL, respectively, and baseline values of these factors were measured. The PFS of patients with NLR-low was significantly longer than that of patients with -high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.48, 95% confidence interval (95% CI), 0.31-0.73; p = 0.0004). OS of patients with NLR-low was significantly better than those with-high (22.2 vs. 13.5 months; HR, 0.57, 95% CI, 0.39-0.83; p = 0.0032). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with patients with -high (HR, 0.44, 95% CI, 0.28-0.68; p = 0.0001 and HR, 0.39, 95% CI, 0.26-0.61, p < 0.0001, respectively). In the validation cohort from two institutes (n = 57), similar significant improvements in PFS and OS were confirmed for patients with NLR-low (p = 0.0344 and p = 0.0233, respectively) and CRP-low groups (p < 0.0001 and p = 0.0001, respectively). Low levels of NLR and CRP at baseline were significantly associated with improved prognosis in patients treated with bevacizumab plus paclitaxel.

[Analysis of Five Days of Administration of S-1 Followed by a Two-Day Rest in Patients with Metastatic Breast Cancer].

Although S-1 is an effective oral anticancer drug in patients with metastatic breast cancer, it is difficult for some patients to continue taking S-1 because of its side effects in the approved regimen of 4 weeks of administration followed by a 2-week rest. When S-1 is administered for 5 days followed by a 2-day rest(5-day on/2-day off), the drug concentration is almost equal to that of the approved regimen, and it can be administered for longer without deterioration of its clinical effect. We retrospectively analyzed the effect and safety in 25 cases in which S-1 was administered using the "5-day on/2-day off" regimen in patients with metastatic breast cancer between November 2006 and August 2014 in our hospital. Patients were all female, and their median age was 68 years(44-87). ER was positive/negative in 15/10 cases, and PS 0/1/2were found in 8/ 10/7 cases. They had no prior chemotherapy and had measurable lesions. S-1 was administered at a dose of 80mg/m2 twice a day on a "5-day on/2-day off" schedule and was reduced when its side effects were appeared. The median treatment duration was 25(3-214)weeks, and CR/PR/long SD/SD/PD as clinical responses were observed in 0/8/5/5/7 cases. The overall response rate was 32% and clinical benefit rate was 52%. There was no difference in response rates whether visceral metastases were present or not. In terms of hematologic toxicity, anemia was seen in one case, and there were no cases of neutropenia. In non-hematologic toxicity, no more than Grade 3 side effects were shown. Discontinuance was observed in only one case because of diarrhea. A "5-day on/2-day off" regimen of S-1 in metastatic breast cancer is well tolerated, and we can continue administering it to elderly patients or those with poor PS without reducing QOL; thus, it can be considered as one of the effective metronomic treatments. In the future, a prospective study is warranted to ascertain these results.

Mesenteric vein thrombosis following impregnation via in vitro fertilization-embryo transfer.

Pregnancy is an acquired hypercoagulable state. Most patients with thrombosis that develops during pregnancy present with deep vein leg thrombosis and/or pulmonary embolism, whereas the development of mesenteric vein thrombosis (MVT) in pregnant patients is rare. We report a case of MVT in a 34-year-old woman who had achieved pregnancy via in vitro fertilization-embryo transfer (IVF-ET). At 7 wk of gestation, the patient was referred to us due to abdominal pain accompanied by vomiting and hematochezia, and she was diagnosed with superior MVT. Following resection of the gangrenous portion of the small intestine, anticoagulation therapy with unfractionated heparin and thrombolysis therapy via a catheter placed in the superior mesenteric artery were performed, and the patient underwent an artificial abortion. Oral estrogen had been administered for hormone replacement as part of the IVF-ET procedure, and additional precipitating factors related to thrombosis were not found. Pregnancy itself, in addition to the administered estrogen, may have caused MVT in this case. We believe that MVT should be included in the differential diagnosis of a pregnant patient who presents with an acute abdomen.

[A Case of Malignant Lymphoma of the Jejunum That Developed Stenosis and Perforation after a Complete Response to Chemotherapy].

A 57-year-old woman was admitted owing to epigastric pain.Abdominal computed tomography demonstrated a tumor in the origin of the jejunum.After an endoscopic biopsy, we diagnosed diffuse large B-cell lymphoma.We treated her with CHOP chemotherapy because pancreaticoduodenectomy is highly invasive.After 1 course of chemotherapy, the tumor was reduced.However, she developed a jejunal stenosis; therefore, we performed laparoscopic gastrojejunostomy.Furthermore, she developed perforated peritonitis on the sixth day after the surgery, and therefore, an emergency partial jejunum resection was performed.Histopathologically, viable lymphoma cells were not found in the resected intestine.She had a complete response 10 months after the surgery.Chemotherapy may cause intestinal stenosis and perforation requiring surgery; therefore, decisions about surgical procedures must be made carefully.