Abemaciclib-induced lung damage leading to discontinuation in brain metastases from breast cancer: A case report.

BACKGROUND: This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer. It presents a unique case of a woman with estrogen receptor-positive, HER2-negative breast cancer who developed brain metastasis. The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discontinuation due to drug-induced lung damage (DILD). CASE SUMMARY: In this comprehensive case summary, we present the clinical course of a woman in her 60s, who 11 years following primary breast cancer surgery, was diagnosed with multiple brain metastases. As a third-line systemic therapy, she underwent treatment with abemaciclib and letrozole. This treatment approach yielded a near-partial response in her metastatic brain lesions. However, abemaciclib administration ceased due to the emergence of DILD, as confirmed by a computed tomography scan. The DILD improved after 1 mo of cessation. Despite ongoing therapeutic efforts, the patient's condition progressively deteriorated, ultimately resulting in death due to progression of the brain metastases. CONCLUSION: This case underscores the challenge of managing adverse events in responsive brain metastasis patients, given the scarcity of therapeutic options.

Factors affecting prognosis in patients treated with bevacizumab plus paclitaxel as first-line chemotherapy for HER2-negative metastatic breast cancer: an international pooled analysis of individual patient data from four prospective observational studies.

BACKGROUND: Bevacizumab (BV) plus paclitaxel (PTX) is a treatment option in patients with HER2-negative metastatic breast cancer (mBC). We conducted an international pooled analysis with individual patient data to evaluate the effectiveness of BV + PTX as a first-line treatment for HER2-negative mBC patients under routine practice. METHODS: A total of 2,474 mBC patients treated with BV + PTX from four prospective observational studies were analyzed. The primary endpoint was overall survival (OS). The other endpoints including identifying independent prognostic factors and validation of the modified Prognostic Factor Index (PFI) developed in the ATHENA trial. RESULTS: Median follow-up time was 10.9 months (M). Median OS were 21.4 M (95% confidential interval 19.8-22.7 M). The seven independent prognostic factors (tumor subtype, age, ECOG performance status (PS), disease-free interval (DFI), liver metastases, number of metastatic organs, and prior anthracycline and/or taxane treatment) for OS found in this analysis included the five risk factors (RFs [DFI < 24 months, ECOG PS 2, liver metastases and/or > 3 metastasis organ sites, TNBC, prior anthracycline and/or taxane therapy]). High- (> 3 RFs [median OS 12.6 M]) and intermediate-risk groups (2 RFs [median OS 18.0 M]) had a significantly worse prognosis than the low-risk group (< 1 RF [median OS 27.4 M]), (p < 0.0001). CONCLUSIONS: This international pooled analysis showed the effectiveness of first-line BV + PTX for HER2-negative mBC patients identifying seven independent prognostic factors as real-world evidence. The usefulness of the modified PFI developed in the ATHENA trial in predicting OS among patients receiving BV + PTX was also verified.

Phase Ib/II study of nivolumab combined with palliative radiation therapy for bone metastasis in patients with HER2-negative metastatic breast cancer.

Radiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4-29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23-58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1-6.1 months) and 2.0 months (95% CI 1.2-3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted.Trial registration number and date of registration UMIN: UMIN000026046, February 8, 2017; ClinicalTrials.gov: NCT03430479, February 13, 2018; Date of the first registration: June 22, 2017.

Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study.

BACKGROUND: The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting. METHODS: This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model. RESULTS: Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56 years (95% CI 2.27-2.74), while it was 2.87 years (95% CI 2.20-4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70-2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14-2.75) and 2.91 years (95% CI 2.61-4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56-1.46). CONCLUSIONS: Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting. TRIAL REGISTRATION: This study is registered with Clinical Trials.gov (NCT 02,551,263).

Prospective observational study of bevacizumab combined with paclitaxel as first- or second-line chemotherapy for locally advanced or metastatic breast cancer: the JBCRG-C05 (B-SHARE) study.

PURPOSE: To investigate the effectiveness and safety of bevacizumab-paclitaxel combination therapy as first- or second-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer in daily clinical practice. METHODS: In this prospective multicenter observational study, bevacizumab-paclitaxel was administered at the discretion of attending physicians. Cohorts A and B had hormone receptor-positive and triple-negative breast cancer (TNBC), respectively. Primary endpoint was overall survival (OS). Multivariate analyses were conducted to identify prognostic factors. RESULTS: Between November 2012 and October 2014, 767 patients were enrolled from 155 institutions across Japan. Effectiveness was analyzed in 754 eligible patients (cohort A, 539; cohort B, 215) and safety in 750 treated patients (median observation period, 19.7 months). Median OS (95% CI) was 21.7 (19.8-23.6) months in eligible patients; 25.2 (22.4-27.4) months and 13.2 (11.3-16.6) months in cohorts A and B, respectively; and 24.4 (21.9-27.2) months and 17.6 (15.2-20.0) months in patients receiving first- and second-line therapy, respectively. Factors affecting OS (hazard ratio 95% CI) were TNBC (1.75, 1.44-2.14), second-line therapy (1.35, 1.13-1.63), ECOG performance status ≥ 1 (1.28, 1.04-1.57), taxane-based chemotherapy (0.65, 0.49-0.86), cancer-related symptoms (0.56, 0.46-0.68), and visceral metastasis (0.52, 0.40-0.66). Incidences of grade ≥ 3 AEs hypertension, neutropenia, peripheral neuropathy, proteinuria, and bleeding were 35.7%, 27.2%, 7.2%, 3.7%, and 0.3%, respectively. CONCLUSIONS: In Japanese clinical practice, combined bevacizumab-paclitaxel was as effective as in previous studies. Factors that independently predicted poor prognosis in the present study are consistent with those identified previously. TRIAL REGISTRATION: Trial no. UMIN000009086.

Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients: extended follow-up of JBCRG-cohort study 01.

BACKGROUND: Previous large trials of trastuzumab (TZM) demonstrated improved outcomes in patients with HER2-positive early breast cancer. However, its effectiveness and safety in Japanese patients is not yet clear. Recently, new anti-HER2 agents were developed to improve treatment outcomes, but the patient selection criteria remain controversial. PURPOSE: The aim of this study was to evaluate the long-term effectiveness of TZM therapy as perioperative therapy for HER2-positive operable breast cancer in daily clinical practice and to create a recurrence prediction model for therapeutic selection. METHODS: An observational study was conducted in Japan (UMIN000002737) to observe the prognosis of women (n = 2024) with HER2-positive invasive breast cancer who received TZM for stage I-III C disease between July 2009 and June 2011. Moreover, a recurrence-predicting model was designed to evaluate the risk factors for recurrence. RESULTS: The 5- and 10-year disease-free survival (DFS) rates were 88.9 (95% CI 87.5-90.3%) and 82.4% (95% CI 79.2-85.6%), respectively. The 5- and 10-year overall survival (OS) rates were 96% (95% CI 95.1-96.9%) and 92.7% (95% CI 91.1-94.3%), respectively. Multivariate analysis revealed that the risk factors for recurrence were an age of ≥ 70 years, T2 or larger tumors, clinically detected lymph node metastasis, histological tumor diameter of > 1 cm, histologically detected lymph node metastasis (≥ n2), and the implementation of preoperative treatment. The 5-year recurrence rate under the standard treatment was estimated to be > 10% in patients with a score of 3 or greater on the recurrence-predicting model. CONCLUSION: The recurrence-predicting model designed in this study may improve treatment selection of patients with stage I-III C disease. However, further studies are needed to validate the scores generated by this model.

Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subset of breast cancer that results from overexpression of HER2 protein. Pertuzumab-a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2-was recently approved for adjuvant therapy and neoadjuvant therapy of HER2-positive early breast cancer. As pertuzumab and trastuzumab bind to different domains of the extracellular dimerization domain of HER2, a combination therapy of pertuzumab and trastuzumab is beneficial for the treatment of metastatic cancer, advanced local cancer, or early cancer by dual HER2 blockage. Many clinical trials have been performed using pertuzumab for breast cancer patients; these include the CLEOPATRA trial for palliative therapy, the APHINITY trial for adjuvant therapy, and the NeoSphere and the TRYPHAENA trials for neoadjuvant therapy. These trials revealed pertuzumab to be a safe and effective drug regardless of the patient age and hormone receptor status. Notably, pertuzumab use was associated with severe cardiac toxicity in some cases; however, the risk of pertuzumab-induced cardiac dysfunction was low. The most common adverse effect associated with pertuzumab-use was diarrhea, but most cases were not severe. Several different chemotherapeutic agents have been investigated to determine optimal chemotherapeutic combinations for dual HER2 blockage. Some exploratory analyses indicate that pertuzumab treatment offered little benefit to patients with node-negative and small primary tumors; pertuzumab treatment was also found not be cost-effective. Further research will reveal the appropriate usage of pertuzumab for treating a subset of eligible patients.

Effectiveness and safety of surgical glove compression therapy as a prophylactic method against nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy.

BACKGROUND: We have developed a surgical glove (SG)-compression therapy and reported that this method significantly reduced the overall occurrence of grade 2 or higher nanoparticle albumin-bound-paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) from 76.1% to 21.4%. In this multicenter single-arm confirmatory study, we investigated the efficacy and safety of SG-compression therapy for the prevention of nab-PTX-induced PN, compared with the incidence of grade 2 or higher PN in published literature as controls. PATIENTS AND METHODS: Primary breast cancer patients who received 260 mg/m2 of nab-PTX were eligible for this study. Patients wore two SGs (one size smaller than the tight-fitting size) in each hand for 90 min. PN was evaluated at each treatment cycle using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The temperature of each fingertip was measured using thermography. RESULTS: Between October 2016 and June 2017, 58 patients were evaluated. The incidence of CTCAE grade 2 or higher PN was as low as 13.8% following SG-compression therapy. A goodness-of-fit test proved that the overall incidence of 13.8% grade 2 or higher PN in this study was comparable to the hypothesis-predicted value (13%). No adverse events, including compression intolerance or skin disorders caused by use of SG, were observed. SG-compression therapy significantly reduced the temperature of each fingertip by 1.3°C-2.3 °C compared to pre-chemotherapy level. CONCLUSIONS: This study suggested the safety and efficacy of SG-compression therapy for the amelioration of CIPN. CLINICAL TRIAL NUMBER: UMIN 000024836.

Clinical Predictive Factors for the Efficacy of Everolimus in Patients With Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer: A Multicenter Retrospective Cohort Study in Japan.

PURPOSE: To investigate the clinical predictive factors for the efficacy of everolimus (EVE) for advanced/metastatic breast cancer (AMBC). METHODS: Routine practice data of consecutive patients with AMBC who received EVE at 5 institutions in western Japan were retrospectively analyzed in this cohort study (study registration no.: UMIN 000032569). The correlation among time to treatment failure (TTF), overall survival (OS), and clinical background was investigated via univariate and multivariate analyses using Cox hazards model for the clinically important variables. RESULTS: A total of 134 patients were included in the analysis. The median TTF and OS were 5.2 months (95% confidence interval [CI]: 4.1-6.4) and 27.3 months (95% CI: 23.7-30.9), respectively. Multivariate analysis showed that dose reduction of EVE from any initial dose was associated with a longer TTF (hazard ratio [HR]: 0.52; 95% CI: 0.32-0.84, P = .007). Meanwhile, very low hormone sensitivity (ie, relapse within the first 2 years during adjuvant endocrine therapy or progression within 3 months of endocrine therapy immediately before EVE) was associated with a shorter TTF (HR: 2.48; 95% CI: 1.49-4.10, P < .001). In the analysis of stratified treatment outcomes, TTF was longer in the group with <3 liver metastases and in groups other than the very low hormone sensitivity group, regardless of the treatment line of EVE. CONCLUSIONS: Low hormone sensitivity and ⩾3 liver metastases were important prognostic factors for the efficacy of EVE. EVE may be less effective in patients with AMBC with these factors, and as such, chemotherapy should be administered instead.

Prediction of postoperative disease-free survival and brain metastasis for HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab using a machine learning algorithm.

PURPOSE: This study aimed to develop mathematical tools to predict the likelihood of recurrence after neoadjuvant chemotherapy (NAC) plus trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: Data of 776 patients from a multicenter retrospective cohort study were collected. All patients had HER2-positive breast cancer and received NAC plus trastuzumab between 2001 and 2010. Two mathematical tools using a machine learning method were developed to predict the likelihood of disease-free survival (DFS) (DFS model) and brain metastasis (BM) (BM model) within 5 years after surgery. For validation, bootstrap analyses were conducted. The area under the receiver operating characteristics curve (AUC) was calculated to examine the discrimination. RESULTS: The AUC values were 0.785 (95% CI 0.740-0.831, P < 0.001) for the DFS model and 0.871 (95% CI 0.830-0.912, P < 0.001) for the BM model. Patients with low-risk DFS or BM events, as predicted by the models, showed better 5-year DFS and BM rates than those with high-risk DFS or BM events (89% vs. 61% for the DFS model, P < 0.001; 99% vs. 87% for the BM model, P < 0.001). These models maintained discrimination abilities in both luminal and non-luminal subtypes, providing prognostic information independent of pathological response. Bootstrap validation confirmed the high generalization abilities of the models. CONCLUSIONS: The DFS and BM models have a high accuracy to predict prognosis among HER2-positive patients treated with NAC plus trastuzumab. Our models can help optimize adjuvant therapy and postoperative surveillance.

Survival Outcomes of Retreatment with Trastuzumab and Cytotoxic Chemotherapy for HER2-Positive Recurrent Patients With Breast Cancer Who Had Been Treated with Neo/adjuvant Trastuzumab Plus Multidrug Chemotherapy: A Japanese Multicenter Observational Study.

BACKGROUND: There are little data on the usefulness of trastuzumab (TZM) retreatment as the first-line treatment for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer recurrence after perioperative treatment with TZM. AIM: To clarify the outcome and safety of TZM retreatment in patients with recurrent HER2-positive breast cancer. METHOD: An observational study was conducted on patients who relapsed after primary systemic therapy with TZM using the central registration system. The primary end point was progression-free survival (PFS). Secondary end points consisted of the response rate, overall survival (OS), and safety. RESULT: In total, 34 patients were registered between July 2009 and June 2012. The median follow-up time was 23.7 months (2-24 months). The 1- and 2-year PFS rates were 46.9% (95% confidence interval (95% CI): 29.2%-62.9%) and 29.8% (95% CI: 15.0%-46.3%), respectively (median 10.6 months). The median PFS time for patients receiving TZM combined with CTx was 13.9 months. The 1-and 2-year OR rates were 93.9 (95% CI: 77.9%-98.4%) and 84.8% (95% CI: 67.4%-93.4%). Trastuzumab-induced grade 3/4 adverse events were not observed. CONCLUSIONS: This study suggests that the PFS and OS in Japanese patients who relapsed after perioperative TZM therapy improved or were similar to those in previous reports. Differences in patient backgrounds and treatments must be considered when interpreting the results. Trastuzumab should be used combination with CTx and/or HTx for retreatment. Retreatment with TZM is safe.Trial registration: UMIN000002738.

Comparison of CK-IHC assay on serial frozen sections, the OSNA assay, and in combination for intraoperative evaluation of SLN metastases in breast cancer.

BACKGROUND: Intraoperative evaluations of sentinel lymph node (SLN) metastases are performed for providing appropriate and immediate axillary treatments in breast cancer patients who do not meet Z0011 criteria; however, standard intraoperative procedure has not yet been established. METHODS: We consecutively performed intraoperative evaluation for SLN metastases using both a cytokeratin immunohistochemistry (CK-IHC) assay on serial frozen sections and a one-step nucleic acid amplification (OSNA) assay of the remaining whole node in patients with invasive breast cancer. In this article, we compared the intraoperative diagnostic ability of CK-IHC assay, the OSNA assay, and in combination. RESULTS: Between August 2009 and May 2017, 1,103 SLNs from 499 consecutive clinically node-negative invasive breast cancers were intraoperatively evaluated for SLN metastases using an OSNA and CK-IHC assay. The detection rates of SLN metastases by the OSNA and CK-IHC assays and in combination were 11.8, 12.1, and 14.5%, respectively. The concordance rate between the intraoperative SLN findings of the OSNA and CK-IHC assays was 94.9% (95% confidence interval 93.6-96.2%). The false negative rate for the OSNA assay was 3.1% (30/973), including 3 (0.3%) macrometastases and 27 (2.8%) micrometastases, and for the CK-IHC assay was 2.7% (26/969), including 1 (0.1%) OSNA ++ and 25 (2.6%) OSNA +. CONCLUSIONS: The CK-IHC assay and the OSNA assay have compatible diagnostic abilities in intraoperative evaluations for SLN metastases. The low incidence of false negative results with limited disease burden suggests that both assays can be reliable techniques for intraoperative diagnoses of SLN metastases in breast cancer patients.

Pathological complete response rate in hormone receptor-negative breast cancer treated with neoadjuvant FEC, followed by weekly paclitaxel administration: A retrospective study and review of the literature.

While tumor size, the presence of inflammatory carcinoma and lymph node involvement are the main prognostic factors of women with locally advanced breast cancer, the prognostic value of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) status has not been fully clarified. The present study examined the therapeutic efficacy of a neoadjuvant fluorouracil, epirubicin and cyclophosphamide regimen (FEC), followed by weekly paclitaxel and/or trastuzumab administration, in the treatment of hormone receptor-negative breast cancer patients. Between April 2012 and February 2014, 14 patients with hormone receptor-negative local breast cancer (triple-negative type, 9 patients; HER2 type, 5 patients) were included in the study. In all cases, the histological type of the primary cancer was invasive ductal carcinoma. Among the 14 women who received the regimen, 5 presented with stage I cancer (35.7%), 3 with stage IIA (21.4%), 3 with stage IIB (21.4%), 1 with stage IIIB (7.1%) and 2 with stage IIIC (14.3%), according to the American Joint Committee on Cancer staging system. With regard to the tumor-node-metastasis classification, 5 patients were T1N0M0 (35.7%), 3 were T2N0M0 (21.4%), 3 were T2N1M0 (21.4%), 2 were T3N3M0 (14.3%) and 1 was T4N1M0 (7.1%). The pathological response was evaluated using resected tissue following neoadjuvant chemotherapy, according to the criteria established by the Japanese Breast Cancer Society. Patients were classified into pathological responders (grades 2 and 3, 71.4% of all patients) and non-responders (grade 1, 28.6% of all patients). A pathological complete response (pCR) was achieved in 50.0% of all cases (7/14); 44.4% of triple-negative-type cases (4/9) and 60.0% of HER2-type cases (3/5). Hematological and non-hematological toxicity was reversible and manageable. No patients withdrew from treatment, and favorable compliance was achieved. The present study demonstrated that neoadjuvant FEC followed by weekly administration of paclitaxel and/or trastuzumab induces a high pathological response and a high pCR rate in patients with hormone receptor-negative breast cancer. Due to the high clinical benefit rate and acceptable safety profile, this regimen should be considered an acceptable neoadjuvant treatment option for hormone receptor-negative breast cancer.

Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer.

There are limited studies reported that describe the efficacy of eribulin and trastuzumab in the treatment of recurrent breast cancer. The present study examined the therapeutic efficacy of eribulin and trastuzumab in the treatment of recurrent breast cancer. Between October 2011 and August 2013, 5 recurrent breast cancer patients who were treated with eribulin and trastuzumab were included in the study. The cancer stages in the 5 women who received this regimen were stage IIIB in 1 (20%) and stage IV in 4 (80%). The sites of recurrence were the lung in 3 patients, liver in 2, bone in 1, brain in 1, supraclavicular lymph nodes in 1, infraclavicular lymph nodes in 1 and mediastinal lymph nodes in 1. The median number of prior treatment regimens was 5 (range, 5-11). Complete response was achieved in 0 patients, 1 achieved partial response, 3 had stable disease, and 1 had progressive disease. The overall response rate was 20%, and the clinical benefit rate was 80%. Patients also reported grade 3/4 neutropenia (80.0%). However, hematological toxicity was reversible and manageable. The most common grade 3/4 nonhematological toxicities were fatigue (20.0%), peripheral neuropathy (20.0%) and appetite loss (20.0%). No patients withdrew from treatment, and favorable compliance was achieved in the study. The results indicated that eribulin and trastuzumab have the potential to be one of the drugs for treatment of recurrent breast cancer.

Evaluation of the Clinical Utility of the ICG Fluorescence Method Compared with the Radioisotope Method for Sentinel Lymph Node Biopsy in Breast Cancer.

PURPOSE: This study compared the clinical utility of indocyanine green (ICG) fluorescence and radioisotope (RI) for sentinel lymph node (SLN) detection in breast cancer. METHODS: Women with node-negative breast cancer underwent SLN biopsy using ICG fluorescence and RI. The primary end point was the sensitivity of ICG fluorescence compared with RI in the patients with tumor-positive SLNs. Secondary end points included detection rates for SLN, the additive effect of ICG fluorescence to RI, signature of positive SLNs according to tier, and adverse events related to ICG administration. RESULTS: A total of 847 women with clinical node-negative breast cancer underwent SLN biopsy, and 821 patients were included in the per-protocol analysis. SLN mapping was performed using ICG fluorescence and RI. The overall detection of SLNs using ICG fluorescence was identical to RI (97.2 vs. 97.0 %, P = 0.88), and the combination of both methods achieved a significant improvement compared with RI alone (99.8 vs. 97.0 %, P < 0.001). The detection rate for tumor-positive SLN was 93.3 % for ICG fluorescence and 90.0 % for RI, and the sensitivity of the ICG fluorescence method was 95.7 % (95 % CI 91.3-98.3, P = 0.11). The additional use of ICG significantly improved positive SLN detection for RI (97.2 vs. 90.0 %, P < 0.001). There were no serious adverse events related to hypersensitivity to ICG. CONCLUSIONS: The ICG fluorescence method may be an acceptable alternative to SLN detection using RI in breast cancer.

Pathological response rate in hormone-positive breast cancer patients treated with neoadjuvant FEC and triweekly docetaxel: a case series.

We recently reported that neoadjuvant 5-FU, epirubicin, and cyclophosphamide (FEC) followed by weekly paclitaxel and/or trastuzumab induced a high pathological complete response (pCR) rate in hormone-negative patients. The present study examined the therapeutic efficacy of neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab in the treatment of hormone-positive patients. Between February 2012 and December 2013, 16 hormone-positive patients with local breast cancer (luminal A type: six patients; luminal B type: two patients; luminal HER2 type: eight patients) were included in the study. The histological type of the primary cancer was invasive ductal carcinoma in all patients. The cancer stages in the 16 women who received this regimen were stage I in five (31.3%), IIA in four (25.0%), IIB in five (31.3%), IIIB in one (6.3%), and IIIC in one (6.3%). Regarding clinical TNM classification, five patients were T1N0M0, one was T1N1M0, three were T2N0M0, five were T2N1M0, one was T3N2M0, and one was T4N0M0. The pCR was evaluated using resected tissue after neoadjuvant chemotherapy according to the evaluation criteria of the Japanese Breast Cancer Society. Patients were classified into pathologic responders (grade 2: 50.0% of all patients: 2/6 of luminal A type; 6/8 of Luminal HER2 type) and nonresponders (grades 0 and 1: 50.0% of all patients: 4/6 of luminal A type; 2/2 of luminal B type; 2/8 of luminal HER2 type) according to the grade of the tumor. The pCR rate was 0%. Hematologic and nonhematologic toxicity was reversible and manageable. This study demonstrated that neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab did induce a high pathologic response in luminal HER2 type, but not in luminal A and B types, and did not induce a high pCR rate in the hormone-positive patients.

[A case of Paclitaxel-induced peripheral neuropathy successfully treated with duloxetine].

Here, we report about a 60-year-old woman with metastatic breast cancer who was successfully treated for paclitaxelinduced peripheral neuropathy with duloxetine. She was administered trastuzumab plus paclitaxel(PTX)combination therapy that was ultimately discontinued because of grade 3 peripheral neuropathy detected on day 15, according to the CTCAE (v4.0). She was administered duloxetine on day 90 after the end of the previous therapy because of the peripheral neuropathy. Thereafter, the peripheral neuropathy decreased to grade 1, which enabled PTX administration on her request. Further trials are required to confirm the efficacy of duloxetine.

[Effect of dexamethasone on vascular pain caused by the administration of fosaprepitant dimeglumine and epirubicin hydrochloride in patients with primary breast cancer].

Epirubicin hydrochloride injection is indicated as a therapy for patients with primary breast cancer. This drug has been reclassified as a drug with high emetic potential according to the American Society of Clinical Oncology Guidelines for Antiemetics in Oncology. Therefore, patients who receive this agent should also receive fosaprepitant dimeglumine, an anti-emetic agent. However, it has been reported that fosaprepitant induces vascular pain when used in anthracycline-based regimens administered via the peripheral veins. In order to relieve the fosaprepitant and epirubicin-induced vascular pain associated with vasculitis, dexamethasone was administered at the onset of vascular pain. There is a possibility that the fosaprepitant and epirubicin-induced pain may improve owing to the administration of dexamethasone; however, further trials are required to confirm the effect of this method.

Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan.

BACKGROUND: Bone metastasis (BM) is important for studying systemic spread of breast cancer. It often causes skeletal-related events (SREs) that worsen quality of life. We investigated the prevalence and risk factors for BM and SRE using a dataset from the Breast Oncology Research Network (BORN) in Japan. PATIENTS AND METHODS: We collected data on primary breast cancer patients with node-positive or node-negative disease at intermediate to high risk of recurrence. The risk factors affecting the BM-free rate, SRE-free rate and overall survival were analyzed by using the Cox proportional hazard model. RESULTS: Data of 1,779 patients who were diagnosed with breast cancer during 2003-2005 were collected from the BORN and 1,708 cases were used for analysis. The median follow-up duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate at 5 years was 89.2 %. The annual hazard ratio of BM development differs remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of 193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate analysis, clinical stage (P < 0.0001), number of lymph node (LN) metastases (P = 0.0029), tumor subtype (P = 0.034) and progesterone receptor status (P = 0.038) were independently significant risk factors for BM-free rate, but only clinical stage (P < 0.0001) and number of LN metastases (P = 0.0004) significantly correlated with SRE-free rate. CONCLUSIONS: This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.