Preventive effect of dexamethasone premedication on the development of infusion-related reaction in breast cancer patients receiving trastuzumab.

AIM: To clarify the incidence and risk factors of infusion-related reactions (IRRs) caused by trastuzumab in breast cancer patients and verify the preventive effects of dexamethasone. METHODS: All breast cancer patients newly treated with trastuzumab at the Osaka Medical and Pharmaceutical University Hospital from 1 January 2017 to 31 December 2020 were included. The electronic medical records were retrospectively reviewed. The outcome measure was the occurrence of IRRs of grade 1 or higher during trastuzumab infusion. Only dexamethasone and anticancer drugs administered concomitantly before trastuzumab were used as explanatory variables. RESULTS: The 176 patients included in the study received 2320 infusions. Fifty-eight patients (33.0%) experienced IRRs, and IRRs occurred in 80 (3.4%) of the total 2320 infusions. Owing to the hierarchical structure of the data, the independence of the observed values was evaluated using the intraclass correlation coefficient. Multivariate multilevel logistic regression analysis showed that premedication with dexamethasone lowered the risk of trastuzumab-induced IRRs (mg, per 1 unit, odds ratio [OR] = 0.61, 95% confidence interval [95% CI] 0.43-0.85, P = .003). In addition, preoperative status (OR = 38.9, 95% CI 5.4-278.7, P < .001) and high-dose trastuzumab (mg/kg, per 1 unit, OR = 60.6, 95% CI 20.1-182.9, P < .001) were independent risk factors for IRRs. CONCLUSION: The results of this study suggest that premedication with dexamethasone exhibits preventive effects on trastuzumab-induced IRRs in breast cancer patients. Future studies are needed to determine the optimal dose of dexamethasone to prevent IRRs and the impact of dexamethasone on the efficacy of trastuzumab in breast cancer.

[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].

The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.

[A Case of Severe Drug-Induced Lung Injury during Preoperative Chemotherapy for Breast Cancer in the Early Stages of the COVID-19 Epidemic].

Drug-induced interstitial lung disease(DILD)is defined as a drug-related respiratory disorder that occurs during drug administration. For diagnosis, it is important to differentiate similar diseases. We report a case of severe drug-induced lung injury during preoperative chemotherapy for breast cancer in the early stages of the COVID-19 epidemic, which was difficult to diagnose. The patient was a 48-year-old woman. The chief complaint was fever and dyspnea. She was diagnosed with left breast cancer(ER 30-40%, PR 0%, HER2 1+, Ki-67 84%), cT4bN1M0, cStage ⅢB and was treated with dose-dense AC therapy and docetaxel sequentially as preoperative chemotherapy. On the 21st day of the first course of docetaxel, the patient developed respiratory failure. A CT scan of the chest showed diffuse ground-glass shadows in the bilateral lung fields, suggesting severe viral pneumonia caused by COVID-19, and the patient was admitted to the isolation ward and managed with an intubated ventilator. PCR and LAMP were negative, and COVID-19 was ruled out. Based on the clinical course and CT findings, we started steroid pulse therapy with DILD in mind. The patient was extubated on the 5th day after the onset of the disease because the steroid pulse therapy was successful and her respiratory condition was stable. Preoperative chemotherapy was stopped, and a left mastectomy and axillary dissection were performed. In this case, COVID-19 should have been suspected first, but we were able to minimize the interruption of treatment by taking early action and keeping DILD in mind.

[Maintenance of Long-Term Stable Disease(SD)in Metastatic Breast Cancer with Eribulin - A Case Report of Long-Term SD in Japan].

This case report discusses a 48-year-old woman with metastatic breast cancer: T4c(10.5 cm)N2bM1,(OSS, LYM), stage IV, estrogen receptor(ER)(+), progesterone receptor(PgR)(+), human epidermal growth factor receptor-2(HER2) (-), and Ki-67 17.2%. Administration of eribulin was initiated after treatment with anthracycline and taxane. Thereafter, 28 courses of eribulin maintained a SD state for over a year and improved the quality of life(QOL). Eribulin is effective for both prolonging life and improving QOL, which are the main goals in the treatment of metastatic or recurrent cancer. Therefore, this evidence suggests that eribulin can be effective in various clinical situations.

[A Case of Squamous Cell Carcinoma of the Breast].

Squamous cell carcinoma(SCC)of the breast is a rare disease. We encountered a case of SCC of the breast that relapsed in the early postoperative period and rapidly progressed thereafter. A 38-year-old woman visited our hospital presenting with a tumor in the left breast consisting of a 5-cm mass with an irregularly sharped wall. Fine needle biopsy examination showed squamous cell carcinoma. A modified radical mastectomy by Auchincloss's method was performed on the left breast. SCC was confirmed by histological examination. Two months later, local recurrence on the chest wall was found during adjuvant chemotherapy. Thereafter, the disease rapidly progressed, and finally, the patient died of respiratory failure caused by lung metastasis. The prognosis of SCC of the breast is recognized as being more unfavorable than that of invasive ductal carcinoma. We should develop an effective chemotherapeutic strategy for this disease.

[Is the LHRH Agonist Recommended for Fertility Preservation ?].

The POEMS reportedan effect of goserelin for fertility preservation. The Clinical Practice Guideline for Breast Cancer by The Japanese Breast Cancer Society indicates that the use of the LHRH agonist (LHRHa) for preventing chemotherapy-induced early menopause is a grade C-1 recommendation, and its use for fertility preservation is a grade C-2 recommendation. Results from previous studies on the effects of LHRHa for fertility preservation have varied owing to differences in chemotherapy regimens, definitions of ovarian failure, and dosages of tamoxifen. In the POEMS, the primary endpoint of ovarian failure at 2 years was significantly lower, and the secondary endpoint of pregnancy outcomes was better in the combination group; however, precise interpretation is difficult because many cases were excluded. Currently, it is not necessary to revise The Clinical Practice Guideline; however, desirable results from future studies may allow the recommendation of a specific dosage of LHRHa for fertility preservation.

Breast conserving surgery using volume replacement with oxidized regenerated cellulose: a cosmetic outcome analysis.

We evaluated the cosmetic outcome of volume replacement with oxidized regenerated cellulose (ORC) after breast-conserving surgery (BCS) and also examined factors that may have influenced the results. Ninety-four patients who underwent BCS with ORC replacement between January 2010 and August 2012 participated in this study. The cosmetic outcomes of these patients were evaluated using scores based on the criteria of the Japan Breast Cancer Society. We evaluated cosmetic scores with regards to several clinical factors and the occurrence of complications after this procedure. The mean score of the cosmetic outcome of all patients was 9.5 points of 12 points. Thirty-seven patients were categorized as "Excellent," 34 were "Good," 22 were "Fair," and 1 was "Poor." Patient age, body mass index, weight of the specimen, and ORC amount were not significantly different between patients with favorable cosmetic scores and those without. However, the weight of the removed specimen was slightly higher in patients with an unfavorable cosmetic score. Although acute dermatitis and eczema was observed in 15% and 3% of patients, all of them were improved with conservative treatment. Cosmetic scores were significantly higher in patients without complications than in patients with complications. In conclusion, ORC replacement after BCS is a simple and reliable procedure. The selection of indication and prevention of complications are important for obtaining a better cosmetic outcome. This is the first report to cosmetically evaluate a relatively large number of patients that have undergone ORC replacement after BCS.

Validation of online calculators to predict the non-sentinel lymph node status in sentinel lymph node-positive breast cancer patients.

PURPOSE: This study evaluated and compared the predictive values of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Stanford nomogram for predicting non-sentinel lymph node (SLN) metastasis in patients with SLN metastasis, which were the only nomograms available online, and verified their usefulness in the macrometastasis or micrometastasis/isolated tumor cell (ITC) subgroups. METHODS: Eighty-nine patients with a positive SLN biopsy who underwent axillary lymph node dissection were analyzed. The predicted probability of non-SLN metastasis was calculated using a computerized model from the websites for each nomogram. The results were compared using the area under the curve (AUC) of the receiver operating characteristics curve for each model. The false-negative and false-positive rates were also calculated. RESULTS: The AUC for the entire population was 0.701 with the MSKCC nomogram and 0.756 with the Stanford nomogram. The AUCs of macrometastasis and micrometastasis/ITC groups were 0.680 and 0.469 with the MSKCC nomogram, and were 0.676 and 0.574 with the Stanford nomogram, respectively. Although false-negative cases were not identified, the false-positive rates were high in both subgroups when using these nomograms. CONCLUSIONS: This independent comparison found no significant difference between the two nomograms. In this study, these nomograms could not reliably predict positive non-SLN in patients with SLN micrometastasis/ITC.

Axillary accessory breast cancer reconstructed by a thoracodorsal artery perforator flap: A case report.

INTRODUCTION: Primary accessory breast cancer is rare and most commonly occurs in the axilla. Due to its low incidence, few studies have discussed axillary reconstruction after accessory breast cancer resection. In the present report, we describe a patient who underwent axillary reconstruction with a thoracodorsal artery perforator (TAP) flap after resection, and reconstruction methods after resection of axillary accessory breast cancer are discussed based on current and previous reports. PATIENT CONCERNS: A 60-year-old woman presented with a 7-year history of a gradually growing lump in the left axilla. DIAGNOSIS: The patient was diagnosed with latent breast cancer, axillary lymph node metastasis, or carcinoma of the accessory axillary breast with axillary lymph node metastasis. INTERVENTIONS: After preoperative chemotherapy, tumor resection and axillary lymph node dissection were performed, followed by immediate axillary reconstruction using a TAP flap. The patient received postoperative adjuvant endocrine and radiation therapy (50 Gy). OUTCOMES: No recurrence or metastasis was observed for 5 years postoperatively. The reconstructed axilla was not bulky, and scar contracture was not observed, with a full range of motion of the shoulder joint. CONCLUSION: We described a patient who underwent immediate TAP flap reconstruction after resection of accessory breast cancer and axillary lymph node dissection, followed by postoperative radiation, which could cause scar contracture. The patient was followed up for more than 5 years after the operation and radiation therapy, and the appearance of the axilla and range of motion of the shoulder were good despite postoperative radiation.

Breast neuroendocrine tumor arising in the axilla of a man: a case report.

BACKGROUND: Accessory breast carcinomas of the axilla of males are rare, and primary breast neuroendocrine tumors (BNETs) are rare as well. We present a case of a BNET arising in the axilla of a man. CASE PRESENTATION: A 64-year-old Japanese man presented with a hard 15-mm mass in the axilla and axillary lymph node swelling. Histopathological examination of the incisional biopsy specimen revealed a neuroendocrine carcinoma. Therefore, wide radical excision of the axillary tumor and axillary lymph node dissection were performed. Hematoxylin and eosin staining showed that the solid tumor was mainly located in the subcutaneous adipose tissues and appeared to invade the skin. The tumor phenotypes were positive for CAM 5.2, synaptophysin, estrogen receptor, progesterone receptor, and GATA-binding protein 3; they were negative for human epidermal growth receptor 2. The neuroendocrine component comprised more than 90% of the tumor, and the Ki-67 index was 21%. These results indicated that the tumor was a BNET. This patient underwent adjuvant chemotherapy, endocrine therapy, and radiotherapy. CONCLUSIONS: BNET cases in males are rare. The clinical and histological criteria as well as treatment for these rare cases are discussed.

A Prospective Study Regarding the Efficacy and Safety of the BNT162b2 Vaccine in Patients With Solid Malignancies Undergoing Systemic Chemotherapy.

BACKGROUND/AIM: To prospectively evaluate the efficacy and safety of the BNT162b2 vaccine in solid cancer patients undergoing systemic chemotherapy (n=63). PATIENTS AND METHODS: COVID-19 anti-spike protein antibody levels were measured before the first BNT162b2 vaccination, just before the second BNT162b2 vaccination, one month after the second BNT162b2 vaccination, and 3 months after the second BNT162b2 vaccination. Anti-spike protein antibody seropositivity was set at ≥0.8 U/ml. RESULTS: Colorectal cancer was the most commonly observed primary disease (36.5%). ECOG-PS 0 was observed in the majority (52.4%) of patients. The overall response rate and the median (range) anti-spike protein antibody levels in the whole cohort at 3 months after the second BNT162b2 vaccination were 98.4% (62/63) and 206 (0.4-3,813) U/ml. None of the patients required postponement or discontinuation of systemic chemotherapy because of an adverse reaction. CONCLUSION: The BNT162b vaccine in solid cancer patients undergoing systemic chemotherapy is effective and safe.

Esthetic result of rhomboid flap repair after breast-conserving surgery for lower quadrant breast cancer lesion with skin invasion: report of two cases.

Breast-conserving surgery (BCS) has been increasingly performed as a standard operative strategy for patients with breast cancer. The primary purpose of BCS is to acquire both local control and good cosmetic results. An insignificant difference in cancer treatment results has been shown between BCS and total mastectomy. However, achieving sufficiently cosmetic results can be difficult, particularly in patients with tumors that are large or localized to the lower quadrant. To avoid breast deformities and asymmetries after BCS, immediate reconstruction using autologous tissue has been accepted as the standard option. Rhomboid skin and adipose flap repair is a simple, less invasive procedure than the myocutaneous flap, which has primarily been performed in patients with upper quadrant lesions. We herein report the cases of two patients with lower quadrant breast cancer with skin invasion, who underwent BCS with immediate breast repair using a rhomboid flap. This procedure is therefore worth considering as one of the first options for immediate repair after BCS.

New enzyme-targeting radiosensitizer (KORTUC II) treatment for locally advanced or recurrent breast cancer.

Kochi oxydol radiation therapy for unresectable carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in Japan. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide. The mixture is injected intratumorally just before radiation therapy (RT) several times. KORTUC II has the effect of neutralizing antioxidant enzymes, while increasing the oxygen tension into the tumor tissue, and achieves marked local effects without notable adverse events. The present report describes cases in which KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC). The present study included 30 patients with LABC (n=9) or LRBC (n=21) aimed at local control of tumors, who were followed up for ≥3 months after treatment. The irradiation dose and extent fields were determined by the attending physicians considering various patient factors, such as a performance status, prognosis and presence or absence of adjuvant therapy. The median irradiation dose was 60.4 Gy3.5 (43.6-76.1 Gy3.5) based on the calculation of equivalents of 2 Gy fractions, and the median total number of sensitizer injections was 5 (2-7) times. The median maximum tumor shrinkage was 97.0% and 15 patients (50%) were assessed to have achieved a clinical complete response. The proportion with loco-regional control at 1, 2 and 3 years was 100, 94.7 and 75.4%, respectively, and progression free survival after RT at 1 and 2 years was 59.0 and 24.1%, respectively. KORTUC II exhibited high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and promising RT method because it is safe and has an excellent radio-sensitizing effect.

Capecitabine in Combination with Endocrine Therapy as Maintenance Therapy after Bevacizumab Plus Paclitaxel Induction Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: KBCSG-TR1214.

Optimal treatment strategies for hormone receptor (HR)-positive, HER2-negative advanced and/or metastatic breast cancer (AMBC) remain uncertain. We investigated the clinical usefulness of adding capecitabine to maintenance endocrine therapy after induction chemotherapy and the efficacy of reinduction chemotherapy. Patients who had received bevacizumab-paclitaxel induction therapy and did not have progressive disease (PD) were randomized to maintenance therapy with endocrine therapy alone (group E) or endocrine plus capecitabine (1657 mg/m2/day on days 1-21, q4w) (group EC). In case of PD after maintenance therapy, patients received bevacizumab-paclitaxel reinduction therapy. Ninety patients were randomized. The median progression-free survival (PFS) under maintenance therapy (primary endpoint) was significantly longer in group EC (11.1 {95% CI, 8.0-11.8} months) than in group E (4.3 {3.6-6.0} months) (hazard ratio, 0.53; p < 0.01). At 24 months from the induction therapy start, the overall survival (OS) was significantly longer in group EC than in group E (hazard ratio, 0.41; p = 0.046). No difference was found in the time to failure of strategy (13.9 and 16.6 months in groups E and EC, respectively). Increased capecitabine-associated toxicities in group EC were tolerable. Addition of capecitabine to maintenance endocrine therapy may be a beneficial option after induction chemotherapy for HR-positive, HER2-negative AMBC patients.

De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer.

PURPOSE: Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. METHODS: We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. RESULTS: Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. CONCLUSION: This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.

[Clinical effect and positioning of capecitabine for metastatic breast carcinoma].

We evaluated the effect of capecitabine for metastatic breast carcinoma. Of 18 metastatic breast carcinoma patients experienced in our institution from November 2002 to July 2007, all patients had resisted the anthracycline or taxanes therapy before. Of these patients, 7 had liver, 6 had bone, and 5 had lung metastases. The capecitabine response in these 18 patients was evaluated as follows: PR in 4, long SD in 6, SD in 3, and PD in 5. In particular, 3 patients with liver metastases showed remarkable tumor regression. Compared to the 3rd-and 4th-line, 2nd-line capecitabine proved more effective. Hand-foot syndrome was found in 4 patients. Only one patient discontinued the therapy due to nausea. These results showed that capecitabine may be a useful treatment regimen for chemotherapy-resistant metastatic breast carcinoma patients.

Axillary Reconstruction with a Posterior Circumflex Humeral Artery Perforator Flap as a Salvage Surgery for Axillary Invasion of Advanced Breast Cancer.

A case of advanced breast carcinoma with large skin invasion that extended from the breast to the axilla and which was reconstructed with a meshed split skin graft for the chest defect and a posterior circumflex humeral artery perforator flap for the axillary area was described. When skin invasion of the breast cancer extends to the axillary area, reconstruction methods of the defect are probably complicated. The purpose of reconstruction is not only to close defects, but also to protect important tissues, such as axillary vessels and the brachial plexus. Moreover, thinner flaps are preferred to prevent a bulky contour. Many reconstruction methods can be used; however, if total mastectomy causes a large tissue defect from the breast to the axilla involving the subscapular artery, and only limited reconstruction is possible, a posterior circumflex humeral artery perforator flap can be an option to reconstruct the axilla.

A phase II, multicenter, single-arm trial of eribulin as first- or second-line chemotherapy for HER2-negative advanced or metastatic breast cancer: evaluation of efficacy, safety, and patient-reported outcomes.

PURPOSE: Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of eribulin for first- or second-line chemotherapy for HER2-negative MBC. MATERIALS AND METHODS: We performed a phase II, open-label, single-arm, multicenter study in Japan. Eligible patients were women with histologically confirmed HER2-negative MBC without chemotherapy or only one chemotherapy line for MBC. The primary endpoint was the overall response rate (ORR) and the secondary endpoints included the clinical benefit rate (ORR + stable disease for 6 months; CBR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and health-related quality of life (HRQoL). RESULTS: A total of 35 patients with HER2-negative MBC were enrolled between March 2013 and February 2017 (data cut-off July 31, 2017). The ORR was 37.1% (95% CI 21.1-53.2%). The CBR was 54.3% (95% CI 37.8-70.8%). The median PFS was 6.2 months (95% CI 2.7-9.4 months) and median OS was 21.4 months (95% CI 11.5-32.9 months). Common grade 3/4 adverse events were neutropenia (42.9%) but febrile neutropenia (2.9%). Although the majority of non-hematological adverse events were mild in severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared to maintain HRQoL of many patients. CONCLUSIONS: Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity for patients with HER2-negative MBC.