Pembrolizumab response in stage IV luminal-type breast cancer with high microsatellite instability: a case report.

BACKGROUND: Pembrolizumab (PEM), an immune checkpoint inhibitor (ICI), is often used for triple-negative breast cancer, but can also be used to treat solid tumors that exhibit high microsatellite instability (MSI-High). However, patients with breast cancer rarely have MSI-High, the use of PEM in such cases in clinical practice is uncertain due to lack of sufficient supporting data. Here, we report the case of a premenopausal woman in who received PEM for MSI-High luminal-type breast cancer. CASE PRESENTATION: A 40-year-old premenopausal Asian woman was diagnosed with stage IIA (T2N0M0) breast cancer and had an Oncotype DX recurrence score of 38. After surgery, she received 4 courses of chemotherapy with docetaxel and cyclophosphamide. After 3 months of tamoxifen therapy, the patient complained of abdominal pain due to right iliac metastasis, and biopsy of the metastatic lesion showed of luminal type; she was sequentially treated with fulvestrant, a CDK4/6 inhibitor, and an anticancer drug (TS1), but over the next year, metastasis to the bone and para-aortic lymph nodes increased. Tumor was MSI-High; PEM was started, and after three courses, bone metastases were reduced, para-aortic lymph node metastases resolved, opioids were discontinued, and the patient returned to society; PEM was administered for 1 year with no worsening of bone metastases on imaging. Asymptomatic brain metastasis less than 1 cm was detected and gamma knife was performed. Six months after completion of PEM, the patient is working with no new lesions. CONCLUSION: We report a case of luminal-type breast cancer with bone metastases and MSI-High, which was treated with PEM and showed a rapid therapeutic response.

Real-World Outcomes of Treating Advanced Breast Cancer Patients With Palbociclib: A Multicenter Retrospective Cohort Study in Japan-The KBCOG-14 Study.

BACKGROUND: Clinical studies have shown that palbociclib improves progression-free survival in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) patients with advanced breast cancer (ABC). However, there are insufficient data on its use in a real-world setting in Japan. The aim of this study was to investigate the effectiveness, predictive factors, and safety of palbociclib among Japanese patients in routine clinical practice. METHODS: Between December 1, 2017, and April 30, 2019, we recruited patients from 9 hospitals and retrospectively evaluated the data on HR+/HER2- patients with ABC who received palbociclib for at least 1 week. The correlation between time-to-treatment discontinuation (TTD) and clinical background was investigated via univariate and multivariate analyses using Cox hazards models. RESULTS: A total of 177 women were available for analysis. Of these patients, 58 (33%) patients were treated with palbociclib with an aromatase inhibitor and 117 (66%) patients were treated with palbociclib and a selective estrogen receptor degrader. Approximately three-fourths of the patients (n = 130, 73%) received palbociclib as third- or later-line therapy. One-third of the patients had 3 or more metastatic sites (n = 59, 33%), and one-third of the patients had liver metastasis (n = 59, 33%). The median follow-up duration at the time of data cutoff was 8.9 months, the median TTD was 6.3 months, and the median overall survival was not reached. Liver metastasis (hazard ratio [HR]: 1.54 [95% confidence interval {CI}: 1.03-2.27]), high serum lactate dehydrogenase (LDH) level (>300 U/L) (HR: 2.58 [95% CI: 1.49-4.26]), and high neutrophil-to-lymphocyte ratio (NLR) (⩾3.0) (HR: 1.76 [95% CI: 1.13-2.69]) were significantly associated with shorter TTD. The most common hematologic adverse event was neutropenia, which occurred in 93% of the patients. CONCLUSION: Based on the results of the pivotal phase 3 trials, the median TTD recorded in this study was shorter than expected. Our results suggest that liver metastasis, serum LDH level, and NLR may be predictive factors for HR+/HER2- ABC treatment outcomes.

Body mass index and menopausal disorders during menopause affect vasomotor symptoms of postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes.

BACKGROUND: Adverse events related to endocrine therapies have a major impact not only on patients' quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs). PATIENTS AND METHODS: For this prospective cohort study (SAVS-JP, UMIN000002455), 391 postmenopausal Japanese estrogen receptor-positive breast cancer patients who were treated with adjuvant anastrozole were recruited from 28 centers. The PRO assessment was obtained from a self-reported questionnaire at baseline, 3, 6, 9 and 12 months between August 2009 and April 2012. Vasomotor symptoms, comprising hot flashes, night sweats, and cold sweats, were categorized into four grades (none, Grade 1: mild, Grade 2: moderate, Grade 3: severe). Pre-existing symptoms were only included if they had become worse than at baseline. RESULTS: Hot flashes, night sweats, and cold sweats at baseline were reported by 20.5, 15.1, and 8.2 % of the patients, respectively, and new appearance or worsening of symptoms in comparison with baseline by 38.4, 29.3, and 28.7 %, respectively. About 80 % of newly occurring symptoms were Grade 1, and less than 5 % were Grade 3. Vasomotor symptoms were reported by 201 out of 362 patients (55.5 %) during the first year and the mean time to onset was 5.6 months. Patients with vasomotor symptoms were significantly younger (mean 62.8 years, range 38-86 vs 64.7 years, range 37-84; p = 0.02), had higher body mass index (BMI) (23.4 kg/m2, range 15.8-39.9 vs 22.4 kg/m2, range 15.8-34.9; p = 0.01), had vasomotor symptoms sooner after menopause (12.4 years, range 0-51 vs 15.1 years, range 1-37; p = 0.002), and had more menopausal disorders during menopause (63.3 vs 36.7 %; p = 0.002). Multivariate analysis showed that BMI [odds ratio (OR) 1.09 per unit of increase, 95 % confidence interval (CI) 1.02-1.16; p = 0.009] and experiencing menopausal disorders (OR 2.11, 95 % CI 1.35-3.30; p = 0.001) were significantly associated with vasomotor symptoms. CONCLUSION: High BMI and experiencing menopausal disorders at menopause were found to be significantly associated with the occurrence of vasomotor symptoms. These findings are expected to prove useful for the management of postmenopausal Japanese women treated with aromatase inhibitors.

[A Case of Granulocyte-Colony Stimulating Factor Producing Breast Cancer That Caused Rapid Progression].

We report a case of granulocyte-colony stimulating factor(G-CSF)producing breast cancer in a 54-year-old woman. Eight months after surgery, multiple liver and pulmonary metastases appeared. They progressed rapidly in 2 weeks and she had a high fever of 38 degrees. Serum G-CSF was high, and positive cells were found by immunostaining of the primary tumor. Chemotherapy was initially successful but she died 4 months after relapse.

Risk factors for joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes.

BACKGROUND: Endocrine treatment-related adverse events have a strong impact on patients' quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently recognized side effect of aromatase inhibitors, evaluation of associated risk factors may yield significant findings. PATIENTS AND METHODS: A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers for assessment of patient-reported outcomes (PROs) in this prospective cohort study (SAVS-JP, UMIN000002455). Patients completed the self-report questionnaire at baseline and after 3, 6, 9, and 12 months of treatment for evaluation of frequency of treatment-related joint symptoms (arthralgia, decrease in range of joint motion, and joint stiffness). RESULTS: We obtained PROs from 362 patients (92.6 %) at baseline and at one or more subsequent points. New or worsening from baseline of joint symptoms were reported by 260 patients (71.8 %). More than 90 % of the symptoms were mild or moderate and nearly 80 % had occurred by 6 months. Multivariate analysis showed that a short time span after menopause [odds ratio (OR) 0.95, 95 % confidence interval (CI) 0.90-0.99; P = 0.02] and adjuvant chemotherapy (OR 2.29, 95 % CI 1.06-4.95; P = 0.03) were significant independent risk factors for joint symptoms. No significant relationships between body mass index (BMI) and joint symptoms were identified. Eighteen patients discontinued treatment during the 1st year and eight of them reported joint symptoms. CONCLUSION: Taking into consideration that PROs may yield higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials, we found that a short time span after menopause and use of adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These findings might prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors in postmenopausal Japanese women.

[Clinical significance of neutrophil to lymphocyte ratio in colorectal cancer patients receiving adjuvant chemotherapy combined with polysaccharide-K].

The neutrophil to lymphocyte ratio (N/L ratio) has been reported to be related to the prognosis of various types of cancer. In particular, a high N/L ratio has been suggested to be associated with poor outcome. We investigated the changes in N/L ratio during treatment in 12 patients who had undergone surgery for colorectal cancer and were receiving postoperative adjuvant therapy with a combination of chemotherapy and polysaccharide-K (PSK). The patients were stratified into 2 groups according to the preoperative N/L ratio (cut-off ratio was 2.5): high N/L (≥2.5) and low N/L (<2.5). The changes in N/L ratio and other clinical parameters over time were investigated. In patients with a high preoperative N/L ratio, the use of postoperative PSK-chemotherapy controlled the N/L ratio at low levels. The N/L ratio tended to remain low in patients with low preoperative N/L ratios. No difference in outcome was observed between patients with high and low N/L ratios. In patients who underwent colorectal cancer surgery, postoperative adjuvant therapy with a combination of chemotherapy and PSK succeeded in controlling the N/L ratio at low levels. Further studies with more patients are required to explore the outcomes associated with changing N/L ratios.

[Response to neoadjuvant chemotherapy in breast cancer as assessed by subtype].

The aim of this study was to investigate the responses to neoadjuvant chemotherapy (NAC) in breast cancer according to subtype. The study included 69 women who received NAC at our hospital between January 2004 and January 2013. Complete response( CR) was achieved in 14 patients( 20.3%) and partial response( PR) was achieved in 37 patients (53.6%).CR and PR rates according to subtype were as follows: 0% and 57.1% for the luminal type, 0% and 66.7% for the luminal-human epidermal growth factor receptor (HER)-2 type, 16% and 56% for the triple negative type, and 58.8% and 41.2% for the HER2 type, respectively. The CR rate was the highest among patients with HER2-type breast cancer. Trastuzumab was additionally administered to 12 patients with HER2-type breast cancer, and the CR rate among these patients was significantly higher after trastuzumab treatment( 75%).Thus, it is important to select a treatment strategy for breast cancer on the basis of the subtype diagnosed.

Sentinel lymph node biopsy using CT lymphography in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a standard surgical procedure for patients with early breast cancer. The combination of radioisotope (RI) and dye staining is the most accurate method for identification of sentinel lymph nodes (SLN). However, institutions without RI centers perform SLNB by blue dye alone. The identification rate with the dye method alone is inferior to the RI combination method. In our institution, the identification rate of SLNBs by the dye method alone was 95%. So we started this study of SLNB using computed tomographic lymphography (CTLG). PATIENTS AND METHODS: Three hundred twenty-four patients with primary breast cancer and no clinical evidence of lymph node metastasis were studied. Identification of SLN was performed by CTLG and the dye-staining method. The identification rate of SLNs was analyzed for relation with the clinicopathological findings. RESULTS: The SLN identification rate was 98.5% with CTLG and 98.8% when combined with the dye-staining method. The identification rate with CTLG was significantly lower in the initial cases. CTLG identified the SLNs in all cases 6 months after its induction. Multi-route multi-SLN patterns, in which SLNs were easily missed by the dye method, were detected in 9.6% of the patients. There was a significant difference in the SLN metastasis rates; partial enhancement of the SLN with CTLG had the consequence that the metastasis-positive rate was high. CONCLUSION: The SLN identification rate was improved by combining the dye-staining method and CTLG. CTLG has a superior spatial resolution activity for detecting SLNs precisely; making CTLG available for the prediction of metastases has been suggested. It is possible to perform SLNB with high accuracy by using CTLG in the institutions that do not have RI.