Safety of a short-term infusion of fosnetupitant in patients with gastrointestinal and breast cancer: a prospective study.

BACKGROUND: Fosnetupitant, a neurokinin-1 receptor antagonist, is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Previous phase III trials demonstrated the non-inferiority of its 30-minute infusion to fosaprepitant in efficacy and a favorable safety profile. METHODS: This was a single-arm, phase II study to investigate the safety of a 15-minute infusion of fosnetupitant in patients with gastrointestinal and breast cancer. Patients who had received their dose of fosnetupitant in a 30-minute infusion without developing an allergic reaction were eligible and received their next fosnetupitant dose for 15 minutes. The primary endpoint was the incidence of an allergic reaction during the first 15-minutes infusion, and the secondary endpoints were the incidence of injection site reaction (ISR), the incidence of a grade ≥ 3 treatment-related adverse event (TRAE) with fosnetupitant, and complete response (CR) rate. RESULTS: The study period was from February 17, 2023 to June 20, 2023. In an exploratory analysis, medical records from the end of the study period to December 31, 2023 were retrospectively evaluated to assess the time-saving effect and safety of the short-term infusion of fosnetupitant. Fifty-six patients with gastrointestinal and 14 patients with breast cancer were enrolled, one of whom with breast cancer did not receive study treatment at her own request. No allergic reactions occurred during the 15-minutes infusion. Furthermore, there were no allergic reactions across all 280 short-term injections (Table 1). Additionally, no ISR or grade 3 or higher TRAE were reported. The CR rate was 87.0%. CONCLUSION: Short-term infusion of fosnetupitant, administered over 15 minutes, was demonstrated to be safe and effective for patients receiving HEC or MEC (Japan Registry of Clinical Trials Trial ID: jRCT1041220144).

Clinical benefit of post-trastuzumab deruxtecan treatment in patients with HER 2-positive unresectable or metastatic breast cancer: A single-institution retrospective observational study.

PURPOSE: Trastuzumab deruxtecan (T-DXd) can improve the prognosis of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, data on treatment recommendations after T-DXd are lacking. Thus, this study aimed to evaluate the treatment options after T-DXd and their effectiveness. METHODS: Patients with HER2-positive MBC were included in this study. Data from clinical records were retrospectively analyzed. The primary outcome was time to treatment failure (TTF). Secondary endpoints were TTF of each treatment and first-line treatment after interstitial lung disease (ILD) and overall survival (OS). RESULTS: A total of 29 patients were included. Among them, 18 (62%) were hormone receptor-positive. All patients had a median TTF (mTTF) of 3.5 months (95% confidence interval (CI) 2.1-10.03). The mTTF of each treatment, including HER2 tyrosine kinase inhibitor (HER2 TKI), other anti-HER2 treatments, and other treatments, was 2.6, 8.8, and 3.8 months, respectively. No significant differences were observed between treatments, but regimens that include trastuzumab showed a longer TTF than TKI. However, the mTTF among patients who developed T-DXd-related ILD was 2.33 months (95% CI 0.7-not reached), which was shorter than that among those who did not develop ILD (3.83 months, 95% CI 2.1-10.03, hazard ratio: 2.046, 95% CI 0.760-5.507, p = 0.258). The median OS was 14.9 months (95% CI 11.07-29.17). CONCLUSION: Treatments after T-DXd showed a shorter mTTF. Regimens that include trastuzumab may be more effective post-T-DXd treatment than HER2 TKI. Further data are needed to establish the best sequential treatment after T-DXd.

The Absence of Cancer in the Location of a Breast Tissue Marker After Neoadjuvant Chemotherapy may Predict Pathological Complete Response with High Accuracy: Results from a Phase II Trial.

BACKGROUND: It is difficult to determine pathological complete response (pCR) before surgery in clinical complete response (cCR) cases by imaging alone. We designed a prospective study to evaluate whether a breast tissue marker placed in a tumor before neoadjuvant chemotherapy (NAC) can predict a pCR, possibly removing the need for surgery. METHODS: We recruited patients with primary invasive breast cancer assigned to undergo curative surgery and possible NAC. A breast marker (UltraClip®) was placed in the primary tumor before standard NAC. We evaluated the probability of no cancer in the marker but cancer in removed specimens from a cCR group. RESULTS: A total of 102 patients were enrolled. Patients were categorized by cancer stage and subtypes. Seventy-two patients (70.6%) received standard NAC; 23 (34.3%) attained cCR, of whom pCR was obtained in 12 (52.2%). The probability of no cancer in the marker's location but cancer in the removed specimens was 4.3% (95% confidence interval, 0.1-21.9). The false-negative rate was 9.1% (1/11), and the negative predictive value was 92.3% (12/13). In only one case, no cancer was found in the marker's location, but cancer cells were present in the removed specimen. CONCLUSIONS: The absence of cancer in the location of a breast tissue marker after NAC predicted pCR with high accuracy. Therefore, the rebiopsy of a marker's location might mean surgery is unnecessary.

Retrospective study on the effectiveness of medroxyprogesterone acetate in the treatment of ER-positive/HER2-negative post-menopausal advanced breast cancer: an additional analysis of the JBCRG-C06 Safari study.

BACKGROUND: Only old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment. METHODS: This was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan-Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate. RESULTS: From the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer. CONCLUSION: In actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.

Satisfaction survey on a preoperative explanation method using three-dimensional breast imaging for breast cancer patients considering breast-conserving surgery.

PURPOSE: Although one of the essential factors in surgical shared decision-making is the body image, the breast morphology after breast-conserving surgery is particularly difficult to explain in a uniform manner due to large individual differences. METHODS: Patients with breast cancer eligible for breast-conserving surgery (BCS) were recruited between June 2020 and October 2021. We surveyed the patients' satisfaction with our method of explaining the likely breast morphology after BCS using three-dimensional (3D) breast imaging in the form of a questionnaire. RESULTS: A total of 162 patients were enrolled, and 137 (84.6%) answered the questionnaire. One hundred and sixteen patients (84.6%) answered that they were very satisfied or satisfied with our explanation method, and 100 (73.0%) patients were very satisfied or satisfied with the 3D breast imaging. Some patients answered that 3D breast imaging helped them prepare for BCS, or on the contrary, made them choose mastectomy with breast reconstruction because the deformation likely with BCS was considered unacceptable. Only a few patients who underwent BCS felt that their postoperative morphology was more deformed than the preoperatively imagined one. CONCLUSION: Our results suggest that our preoperative explanation method using 3D breast imaging was useful for shared decision-making.

Subgroup analysis of Japanese patients in a phase III randomized, controlled study of neoadjuvant atezolizumab or placebo, combined with nab-paclitaxel and anthracycline-based chemotherapy in early triple-negative breast cancer (IMpassion031).

BACKGROUND: In the global phase III IMpassion031 study, neoadjuvant atezolizumab plus nab-paclitaxel/anthracycline-based chemotherapy improved pathological complete response in patients with early stage triple-negative breast cancer. Here, we report primary analysis results from a subgroup of Japanese patients. METHODS: Patients with histologically documented, previously untreated, stage cT2-cT4, cN0-cN3, cM0 triple-negative breast cancer were randomized 1:1 to receive intravenous atezolizumab 840 mg or placebo every 2 weeks in combination with chemotherapy consisting of nab-paclitaxel intravenous 125 mg/m2 once a week, followed by doxorubicin intravenous 60 mg/m2 and cyclophosphamide intravenous 600 mg/m2 every 2 weeks. Patients then underwent surgery. Pathological complete response (ypT0/is ypN0) in the intention-to-treat and PD-L1-positive (≥1% PD-L1-expressing tumor-infiltrating immune cells) populations were co-primary endpoints. RESULTS: This subanalysis (data cutoff: 3 April 2020) included 36 patients from Japan (intention-to-treat; atezolizumab arm, n = 17; placebo arm, n = 19). Pathological complete response occurred in 41% (n = 7; 95% confidence interval, 18-67) of patients in the atezolizumab arm and 37% (n = 7; 95% confidence interval, 16-62) in the placebo arm. In the PD-L1-positive population, pathological complete response occurred in 50% (n = 5; 95% confidence interval, 19-81) of patients in the atezolizumab arm and 45% (n = 5; 95% confidence interval, 17-77) in the placebo arm. Treatment-related grade 3-4 adverse events occurred in 71% and 68% of patients in the respective arms. CONCLUSION: Atezolizumab added to neoadjuvant chemotherapy numerically improved pathological complete response versus placebo in this small exploratory analysis of Japanese patients with early stage triple-negative breast cancer, a trend directionally consistent with the global study results. No new safety signals were identified.

Factors associated with overall survival after recurrence in patients with ER-positive/HER2-negative postmenopausal breast cancer: an ad hoc analysis of the JBCRG-C06 Safari study.

BACKGROUND: The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence. METHODS: The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. RESULTS: A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years). CONCLUSION: The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.

Expression of ASC splice variant found in Japanese patients with palindromic rheumatism is regulated by rs8056505 single nucleotide polymorphism and interleukin-1 beta.

BACKGROUND: Palindromic rheumatism (PR) is an infrequent form of periodic arthritis. Based on the similarity of the pathogenesis of PR to autoinflammatory syndromes, we previously found that the dominant-active splice variant of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a CARD (ASC), which lacks exon 2 (Δexon2), is expressed in Japanese patients with PR. OBJECTIVE: Elucidation of the mechanism of Δexon2 ASC production and the effect of IL-1ß on splicing. METHODS: The genomic DNA of Japanese patients with PR was sequenced. The effect of the observed single nucleotide polymorphisms (SNPs) on ASC splicing was determined via exon trapping using THP-1 cells stimulated with interleukin-1 beta (IL-1ß) or ceramide. To investigate the genes that affect alternative splicing via IL-1ß, we analyzed the transcriptome of IL-1ß-treated THP-1 cells using RNA sequencing. RESULTS: We found the rs8056505 A->G SNP located in the 5'-untranslated region of the genomic ASC gene in patients and that Δexon2 expression was induced by this SNP, whereas it was suppressed by IL-1ß or ceramide. We detected 131,426 transcripts and identified 52 differentially expressed genes (DEGs) consisting of 41 downregulated genes and 11 upregulated genes in IL-1ß-stimulated THP-1 cells. The splicing-related gene MASCRNA was the most significantly induced gene by IL-1ß. CONCLUSIONS: We propose a cyclic expression model in which ASC alternates between wild-type and Δexon2 expression regulated by the rs8056505 G allele and splicing factors induced by IL-1ß. This cycle may be correlated with the formation of periodic PR pathologies.

Impact of post-diagnosis weight change on survival outcomes in Black and White breast cancer patients.

PURPOSE: To evaluate weight change patterns over time following the diagnosis of breast cancer and to examine the association of post-diagnosis weight change and survival outcomes in Black and White patients. METHODS: The study included 2888 women diagnosed with non-metastatic breast cancer in 2000-2017 in Chicago. Longitudinal repeated measures of weight and height were collected, along with a questionnaire survey including questions on body size. Multilevel mixed-effects models were used to examine changes in body mass index (BMI). Delayed entry Cox proportional hazards models were used to investigate the impacts of changing slope of BMI on survival outcomes. RESULTS: At diagnosis, most patients were overweight or obese with a mean BMI of 27.5 kg/m2 and 31.5 kg/m2 for Blacks and Whites, respectively. Notably, about 45% of the patients had cachexia before death and substantial weight loss started about 30 months before death. In multivariable-adjusted analyses, compared to stable weight, BMI loss (> 0.5 kg/m2/year) showed greater than 2-fold increased risk in overall survival (hazard ratio [HR] = 2.60, 95% CI 1.88-3.59), breast cancer-specific survival (HR = 3.05, 95% CI 1.91-4.86), and disease-free survival (HR = 2.12, 95% CI 1.52-2.96). The associations were not modified by race, age at diagnosis, and pre-diagnostic weight. BMI gain (> 0.5 kg/m2/year) was also related to worse survival, but the effect was weak (HR = 1.60, 95% CI 1.10-2.33 for overall survival). CONCLUSION: BMI loss is a strong predictor of worse breast cancer outcomes. Growing prevalence of obesity may hide diagnosis of cancer cachexia, which can occur in a large proportion of breast cancer patients long before death.

A phase II study of sequential treatment with anthracycline and taxane followed by eribulin in patients with HER2-negative, locally advanced breast cancer (JBCRG-17).

PURPOSE: The sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC. METHODS: In this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative. RESULTS: A preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade ≥ 3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%). CONCLUSION: Sequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.

Efficacy of the eribulin, pertuzumab, and trastuzumab combination therapy for human epidermal growth factor receptor 2-positive advanced or metastatic breast cancer: a multicenter, single arm, phase II study (JBCRG-M03 study).

Purpose To date, it is not clear which anticancer agent is useful in combination with trastuzumab and pertuzumab As the first and second selective regimens for advanced or metastatic breast cancer (AMBC), this multicenter, open-label, phase II trial (JBCRG-M03: UMIN000012232) presents a prespecified analysis of eribulin in combination with pertuzumab and trastuzumab. Methods We enrolled 50 patients with no or single prior chemotherapy for HER2-positive AMBC during November 2013-April 2016. All patients received adjuvant or first-line chemotherapy with trastuzumab and a taxane. The treatment comprised eribulin on days 1 and 8 of a 21-day cycle and trastuzumabplus pertuzumab once every 3 weeks, all administered intravenously. While the primary endpoint was the progression-free survival (PFS), secondary endpoints were the response rate and safety. Results Of 50 patients, 49 were eligible for safety analysis, and the full analysis set (FAS) included 46 patients. We treated 8 (16%) and 41 (84%) patients in first- and second-line settings, respectively. While 11 patients (23.9%) had advanced disease, 35 (76.1%) had metastatic disease. The median PFS was 9.2 months for all patients [95% confidence interval (CI): 7.0-11.4]. In the FAS, 44 patients had the measurable lesions and the complete response rate (CR) was 17.4%, and partial response rate (PR) was 43.5%. The grade 3/4 adverse events were neutropenia (5 patients, 10.2%), including febrile neutropenia (2 patients, 4.1%), hypertension (3 patients, 6.1%), and other (1 patient). The average of the left ventricular ejection fraction did not decline markedly. No symptomatic left ventricular systolic dysfunction was observed. Conclusions In patients with HER2-positive AMBC, eribulin, pertuzumab, and trastuzumab combination therapy exhibited substantial antitumor activity with an acceptable safety profile. Hence, we have started a randomized phase III study comparing eribulin and a taxane in combination with pertuzumab and trastuzumab for the treatment of HER2-positive AMBC. Trial registration ID: UMIN-CTR: UMIN000012232.

Compression therapy using surgical gloves does not prevent paclitaxel-induced peripheral neuropathy: results from a double-blind phase 2 trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of paclitaxel (PTX). There is no known prophylactic measure, although there are some reports of prevention with compression therapy using surgical gloves. On account of its predominantly subjective symptoms, it is difficult to exclude bias when assessing for CIPN. In this study, we assessed the effectiveness of the same procedure for the prevention of paclitaxel-induced PN based on a double-blind study design. METHODS: The patients with early and recurrent breast cancer (with no prior PTX exposure) initiating weekly chemotherapy with PTX 80 mg/m2 were enrolled. Each patient donned two gloves on each hand at every PTX infusion. Two one-size-smaller gloves were donned on one hand (study side) and two normal-size gloves were donned on the other hand (control side) during 90 min from 30 min before the infusion to 30 min after the end of the infusion. Study side are blind for both patients and assessing physicians according to determination of the study side by research nurses in the chemotherapy unit. The primary outcome was the difference in the frequency of CIPN (motor/sensory) determined by the physician using the common terminology criteria for adverse events (CTCAE v4.0), with an evaluation at each cycle of PTX infusion. McNemar test was used to assess the primary outcome. RESULTS: Between July 2017 and November 2018, 56 patients were enrolled and 49 patients were evaluated. Overall, Grade ≥ 2 PN (sensory) was observed in 30.6 and 36.7% in the study and control sides, respectively (McNemar p = 0.25). PN (motor) was observed in 4.1 and 6.1% in the study and control sides, respectively (McNemar p = 1.0). CONCLUSION: Surgical glove compression therapy showed no statistically significant effect on the incidence of PTX-induced PN. TRIAL REGISTRATIONS: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry managed by the National University Hospital Council of Japan ( UMIN000027944 ). Registered 26 June 2017.

A systematic literature review of prognostic factors in patients with HR+/HER2- advanced breast cancer in Japan.

BACKGROUND: Breast cancer is the most prevalent cancer in women in Japan and the fifth in mortality. This systematic review summarized the evidence for prognostic factors for patients with HR+/HER2- advanced and metastatic breast cancer in Japan. METHODS: MEDLINE and EMBASE were searched with keywords 'breast neoplasms' AND 'Japan' AND 'advanced' or equivalent, and Japan Medical Abstract Society database with 'breast cancer' AND 'advanced/metastatic' for publications from January 2010 to October 2019. ASCO, ESMO, ABC4 abstracts and WHO website were hand searched. The endpoints of interest were overall survival, progression-free survival, tumour response and post-progression survival. Factors were evaluated based on the consistency in direction and the strength (hazard ratios) of association. RESULTS: Searches identified 4530 publications, of which 27 were eligible. All were observational studies. Among the endpoints, overall survival was the most commonly assessed (n = 22) and evaluated further. Ki-67 expression, progesterone receptor expression status, tumour grade and lymph node metastases were consistently associated with poor overall survival in univariate analysis but not in multivariate analysis. Short disease-free interval, the number of metastatic organs and liver metastasis were consistently associated with poor overall survival in both of univariate and multivariate analysis. The association was strong for liver metastasis (hazard ratio ≥2.8 in the majority of studies) and moderate for disease-free interval and the number of metastatic organs (hazard ratio 1.3-2.8 in the majority of studies). CONCLUSIONS: Disease-free interval, the number of metastatic organs and liver metastasis were identified as independent prognostic factors for overall survival. These findings may help clinical decision-making to improve outcomes in patients with HR+/HER2- advanced and metastatic breast cancer.

Differences in baseline risk estimated by physicians and patients with early breast cancer.

BACKGROUND: Physicians recommend adjuvant therapy to patients based on baseline risk. A common recognition for baseline risk between patients and physicians is critical for successful adjuvant therapy. We prospectively investigated the differences in estimated baseline risk between physicians and patients with early breast cancer. METHODS: This analysis was performed at a single institution in Japan. Early breast cancer patients over 18 years old were enrolled after surgery. After explaining the pathological results, physicians asked each patient about an estimated baseline risk. Differences in estimated baseline risk were defined as the baseline risk estimated by patients minus the baseline risk estimated by physicians. The primary endpoint was that the number of patients who estimate baseline risk higher than physicians was higher than those who estimate a lower baseline risk. The secondary endpoints were differences in estimated baseline risk by stage, subtype and the influence of patient factors to differences in estimated baseline risk. RESULTS: From July 2017 to December 2018, 262 patients were enrolled. Among the 262 patients, 190 estimated a higher baseline risk than physicians, 53 estimated a lower baseline risk and 19 estimated the same. Overall, patients estimated a significantly higher baseline risk than physicians (P < 0.001). Differences in estimated baseline risk was significantly smaller in patients who knew the term 'baseline risk' than patients who did not (P = 0.0037). Differences in estimated baseline risk were also significantly smaller in patients with stage II breast cancer than patients with stage I (P = 0.0239). However, there were no statistically significant differences of differences in estimated baseline risk according to other factors. CONCLUSIONS: Patients with early breast cancer estimated a significantly higher baseline risk than physicians. Physicians should accurately explain baseline risk to patients for shared decision making.

The significance of biopsy scar excision at the time of skin- or nipple-sparing mastectomy with immediate breast reconstruction.

BACKGROUND: Neoplastic seeding (NS) can occur after tissue biopsy, which is a clinical issue especially in mastectomy with immediate reconstruction. This is because postoperative radiation is not usually given and local recurrence of preserved skin flap may increase. The purpose of this study is to investigate the importance of preoperative evaluation of NS and the validity of biopsy scar excision. PATIENTS AND METHODS: We retrospectively analysed 174 cases of mastectomy with immediate breast reconstruction. The primary endpoint is the frequency of clinical and pathological NS and the secondary endpoint is the problem of excision of needle biopsy site. RESULTS: Three cases (1.7%) had preoperative clinical findings of NS. Pathological examination revealed NS in all three cases. Biopsy scars could be excised in 115 cases among 171 cases without clinical NS. Pathological NS was found in 1 of 66 (1.5%) cases of which pathological examination was performed. Biopsy scars could not be excised in the remaining 56 cases: the biopsy scar could not be identified in 41 cases, and there was concern about a decrease in flap blood flow after excision in 15 cases. In 12 of these 15 cases, the scars were close to the skin incision; excision of these scars might have triggered skin necrosis between the incision and the biopsy scar excision site. No postoperative complications were observed. CONCLUSIONS: It is important to preoperatively evaluate clinical NS, and biopsy scars should be excised in clinical NS cases. Even in cases without clinical NS, biopsy scar excision should be considered. It is also important to perform a biopsy in consideration of the incision design for reconstructive surgery.

[Japanese Subgroup Data in Global Clinical Trials for Breast Cancer].

Number of the approved drugs for breast cancer with global clinical trials including Japanese subjects is increasing. Attending to global clinical trials could shorten the drug lag period, which is expected to contribute to the implementation of best clinical practice. It is well known that some ethnic factors and the number of the subjects included in the trials may influence the interpretations of the efficacy and safety of drugs in regional subgroup data. In this article, we review the cases of interpretations of Japanese subgroup data in breast cancer global clinical trial results. We also refer to the potential ethnic factors in breast cancer clinical practice in Japan.

Patient-reported outcomes and objective assessments with arm measurement and bioimpedance analysis for lymphedema among breast cancer survivors.

PURPOSE: Lymphedema (LE) decreases the quality of life of breast cancer patients. Objective quantification of PRO may improve the discordance between patient-reported outcomes (PROs) and objective assessments of LE by establishing a standard follow-up for LE. This study determined the prevalence of subjective and objective LE and evaluated the correlation between objective assessment and PRO of LE in primary breast cancer patients undergoing breast and axilla surgery. METHODS: Breast cancer patients who underwent sentinel lymph node biopsy (SN) or axillary lymph node dissection (ALND) more than 1 year after surgery were enrolled. We prospectively evaluated LE using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and two objective assessments (arm circumference and bioimpedance) and analyzed their correlations. RESULTS: Between November 2018 and January 2019, 631 patients (SN; n = 415, ALND; n = 216) were enrolled. The median age, body mass index, and duration from surgery was 56 years, 21.9 kg/m2, and 3.8 years, respectively. The prevalences of subjective and objective LE were 4.1% and 1.4% in the SN group and 51.8% and 24.1% in the ALND group, respectively. The objective assessments were weakly positively correlated with PRO-CTCAE. Arm circumference measurement correlated better than bioimpedance overall and was most strongly correlated with "frequency" (r = 0.485, p < 0.01). CONCLUSIONS: LE occurred in few SN patients. The prevalence of subjective LE was higher than that of objective LE. Arm circumference measurements better reflected PRO than did bioimpedance. These results underscore the limitation of LE detection by subjective or objective methods alone.

Impact of BMI for clinical outcomes in Japanese breast cancer patients.

OBJECTIVE: The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. METHODS: Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is <18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, >30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. RESULTS: From the database of our institution, we identified 3223 patients. The median follow-up period was 57 months (1-149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38-4.28; P < 0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15-6.44; P = 0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11-3.02; P = 0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15-11.04; P < 0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52-13.34; P < 0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02-4.89; P = 0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. CONCLUSION: Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.

A single-arm, phase 2 study of steroid-containing mouthwash for the prevention of everolimus-associated stomatitis in multiple tumor types.

BACKGROUND: Everolimus is a mammalian target of rapamycin inhibitor used in the treatment of multiple tumor types, and its most common toxicity, stomatitis, can affect patient quality of life. Recent studies in breast cancer have supported the efficacy of steroid mouthwash for the prevention of everolimus-associated stomatitis. However, a few studies have been reported to date, and none have examined this effect in other tumor types. METHODS: This single-arm phase 2 study was designed to evaluate the efficacy of steroid-containing mouthwash for the prevention of stomatitis in patients with multiple tumor types receiving everolimus. The primary outcome was incidence of grade ≥ 2 stomatitis at 8 weeks of everolimus with steroid-containing mouthwash prophylaxis. We also assessed the stability of steroid-containing mouthwash components. RESULTS: Twenty-nine patients were evaluated, of which 76% had breast cancer and 24% had neuroendocrine tumors originating in the lung, gastrointestinal tract, pancreas, or of unknown primary origin. Grade ≥ 2 stomatitis incidence at 8 weeks was 28.1% (90% CI 16.2-46.1); the higher confidence limit exceeded the prespecified threshold of 30%. No patients developed grade ≥ 3 stomatitis. Most stomatitis occurred behind the oral cavity, with no lesions observed on the lips or floor of the mouth. CONCLUSIONS: Our findings did not support a prophylactic effect of steroid-containing mouthwash on everolimus-associated stomatitis. Given the needs of prevention of everolimus-associated stomatitis in various tumor types, further studies in a larger population using a randomized controlled trial design are, therefore, required to confirm the efficacy of steroid-containing mouthwash.

Prediction of pathological margin status using preoperative contrast-enhanced MRI in patients with early breast cancer who underwent skin-sparing mastectomy.

Skin-sparing mastectomy (SSM) with immediate reconstruction is standard surgical treatment for early breast cancer with widespread ductal carcinoma in situ (DCIS). The local recurrence rate after SSM is up to 7.0%. We investigated prediction of the pathological margin using contrast-enhanced MRI, and evaluated the cut-off point to obtain the safety margin. We performed SSM with immediate reconstruction in 216 early breast cancer patients with widespread DCIS and/or invasive cancer from January 2014 to December 2015. Forty cases were retrospectively reviewed after excluding those with >15 mm between skin and tumor, determined by preoperative contrast-enhanced MRI, or involving reconstructive surgery for local recurrence, immeasurable lesion by preoperative contrast-enhanced MRI, or neoadjuvant chemotherapy. We defined a positive pathological margin as <1 mm from the cancer nest. We reviewed the distance between skin and tumor by MRI and pathological examination. To identify the cut-off for predicting a positive pathological margin, we performed sensitivity analysis using an ROC curve. The margin-positive rate by pathological examination was 27.5% (n = 11/40), with a moderate correlation of MRI margin and pathological margin (r = 0.44). The best cut-off point for margin positivity was 5 mm of MRI margin, with sensitivity and specificity of 54% and 86%, respectively (P = 0.009). This is the first prediction of pathological margin by preoperative contrast-enhanced MRI in early breast cancer patients with SSM. Care is required for SSM if the MRI margin is less than 5 mm due to pathological margin positivity.