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.

[Two Cases of Recurrent Colon Cancer with BRAF Mutation].

We report 2 cases of recurrent colon cancer with BRAF mutation. Case 1, a 75-year-old man, had rapid progress of multiple liver metastasis 5 months after curative resection, and died on 37 days after recurrence without induction of systemic therapy. Case 2, a 67-year-old man with diagnosis of peritoneal dissemination at 8 months after curative resection, received encorafenb and cetuximab (doublet-therapy) with certain effect, nevertheless advanced triplet-therapy with binimetinib was forced to pause due to severe skin disorders and he died on 123 days after recurrence. We considered that closed follow- up should be required after curatively resected colorectal cancers with BRAF mutation for early detection of recurrence, and prompt induction and evaluation of systemic treatment also should be required after unresectable recurrence including careful management with the attention to the features of doublet and triplet-therapy.

[Could Preoperative Conditions Be Preserved or Improved by the Support of Preoperative ONS Administration in Patients with Gastric Cancer?]

INTRODUCTION: In our hospital, we measure the body composition of patients undergoing gastrointestinal surgery. For patients who have a skeletal muscle mass(SMM)of less than 90% of the ideal, we provide them with guidance on having oral nutritional supplements(ONS)and self-exercise therapy. Therefore, we perform operations after taking measures on preserving/improving patient's preoperative conditions. This study was aimed to evaluate the effects on body weight, SMM, and fat mass(FM)in the patients scheduled for gastrectomy. PATIENTS AND METHODS: From January 2017 to December 2020, we retrospectively analyzed 64 gastric cancer patients whose body composition changes were measured at the time of initial diagnosis and immediately before surgery. The body composition was measured by a nutritionist using the BIA method, while the self-exercise therapy was instructed by a rehabilitation therapist. RESULTS: A total of 64 patients were divided into 2 groups: ONS group(36 patients)and Non-ONS group(28 patients). The median preoperative ONS administered to the ONS group was 15 packs. Body weight change showed a significant difference between the 2 groups(+0.73% and -0.91%[p<0.01]in the ONS group and Non-ONS group respectively). SMM change showed no significant difference between the 2 groups(+1.18% and +0.64%[p=0.19]in the ONS group and Non-ONS group respectively). Likewise, FM change showed no significant difference between the 2 groups(-1.08% and -3.50%[p=0.39]in the ONS group and Non-ONS group respectively). CONCLUSION: This study suggested that SMM and FM could be preserved, and body weight could be increased by the support of preoperative ONS administration even in patients with gastric cancer close to having sarcopenia.

[A Case of Rectal Neuroendocrine Tumor with a Major Axis of 10.7 mm with Lymph Node Metastasis].

The case is a 50-year-old woman. Colonoscopy performed by a local doctor for the purpose of stool occult blood positive revealed a 15 mm tumor in the lower rectum, biopsy showed chromogranin positive, synaptophysin positive, and Ki-67 index<1% showed a neuroendocrine tumor(NET), G1 was diagnosed and introduced. Colonoscopy revealed a smooth- surfaced circular hemispherical tumor with a lower edge 30 mm from the anal margin and 20 mm from the dentate line, and EUS showed 10.7×5.2 mm in layers 2 to 3. It was visualized as a well-defined hypoechoic tumor. Contrast-enhanced CT examination showed a 12×5 mm mass showing a contrast-enhancing effect, and no lymphadenopathy or distant metastasis was observed. Contrast-enhanced MRI showed no evidence of pelvic lymphadenopathy. Based on the above, it was diagnosed that NET, G1, and infiltration to the submucosa exceeding 10 mm. Although endoscopic resection as a diagnostic treatment was also an option, we determined surgical resection policy, therefore we performed laparoscopic rectal intersphincteric resection and upper D2 dissection. Histopathological findings showed a tumor of 11×8 mm infiltrating the submucosa( 5,000µm)with metastasis to the pararectal lymph nodes, and the diagnosis was T1b, N1, Ki-67 index 3%, Ly1, V1a, NET G2, pStage ⅢB. Her postoperative course was uneventful, and 6 months later, we performed her artificial anal closure. One year after the operation, there are frequent bowel movements but no fecal incontinence and she is alive without recurrence. For rectal NET with a tumor diameter of 10 mm or more, radical surgery with dissection is recommended because of the high risk of lymph node metastasis. In this case lymph node metastasis was observed surgical resection according to the above reason, but endoscopic resection was possible except that the preoperative size exceeded 10 mm to 0.7 mm and the distance from the anus was short, therefore it took some thought to decide the policy.

C-Reactive Protein and Absolute Lymphocyte Count Can Predict Overall Survival of Patients Treated With Eribulin.

BACKGROUND/AIM: We investigated the efficacy of neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and C-reactive protein (CRP) in predicting overall survival of metastatic breast cancer patients treated with eribulin. PATIENTS AND METHODS: Overall, 74 patients treated with eribulin were enrolled and their baseline levels of NLR, ALC, and CRP retrieved. Cutoff values of NLR, ALC, and CRP were set at 3.0, 1500/µl, and 0.3 mg/dl, respectively. Overall survival (OS) was compared according to marker levels. RESULTS: The OS of NLR-low, ALC-high, and CRP-low groups at baseline was significantly longer than that of NLR-high, ALC-low, and CRP-high groups (p=0.0027, p=0.0013, and p=0.0164, respectively). The combination of ALC and CRP was significantly associated with OS by multivariate analysis (p=0.048). CONCLUSION: Baseline levels of NLR, ALC, and CRP were significantly associated with OS in patients treated with eribulin. The combination of ALC and CRP improved the predictive efficacy compared to individual markers.

Prognostic Significance of Neutrophil-to-lymphocyte Ratio in Luminal Breast Cancers With Low Levels of Tumour-infiltrating Lymphocytes.

BACKGROUND/AIM: This study aimed to improve the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and tumour-infiltrating lymphocytes (TILs). PATIENTS AND METHODS: In this retrospective study, NLR and TIL data from 677 operated breast cancer patients were analysed. The cut-off value of NLR was set at 2.72, and TIL levels were classified as low (<10%), intermediate (≥10 to <50%), and high (≥50%). RESULTS: Recurrence-free survival (RFS) was significantly longer in patients with low NLR (n=459) than in those with high NLR (n=218) (p=0.0383). In ER-positive/HER2-negative and TIL-low breast cancers, there were significant associations between NLR levels and RFS (p=0.0129) or overall survival (OS) (p=0.0046). On multivariate analysis, NLR was a significant and independent factor for OS (hazard ratio=3.78; 95% confidence interval=1.21-14.17; p=0.022). CONCLUSION: These data may be useful for predicting patient prognosis and understanding the clinical significance of immune status in breast cancers.

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

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

A Single-centre, Retrospective, Observational Analysis of Fulvestrant for Recurrent/metastatic Breast Cancer According to Metastatic Site.

BACKGROUND/AIM: Factors influencing fulvestrant efficacy may be useful in selecting the optimal treatment regimen for postmenopausal Japanese women with metastatic/recurrent HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated progression-free and overall survival (PFS and OS) in 100 fulvestrant-treated patients according to metastatic site. RESULTS: Median PFS was significantly better in patients with non-visceral (bone and regional metastases; 22.8 months) vs. visceral metastasis (lung, liver, and other organs; 8.2 months; p=0.024), although median OS did not differ (p=0.922). Median PFS in patients with lung metastasis (20.8 months) and non-visceral metastasis (22.8 months) were comparable; patients with liver metastasis (6.1 months) and other organ metastases (3.7 months) had worse prognoses. CONCLUSION: Patients with non-visceral metastases had a better prognosis than those with visceral metastases. Fulvestrant induced a longer PFS in patients with non-visceral metastasis, and also in those with lung metastasis without liver or other organ involvement.

Prognostic significance of tumor-infiltrating lymphocytes may differ depending on Ki67 expression levels in estrogen receptor-positive/HER2-negative operated breast cancers.

BACKGROUND: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been established in breast cancers with estrogen receptor (ER)-negative and human epithelial growth factor receptor 2 (HER2)-negative or HER2-positive subtypes; however, its utility concerning the ER + /HER2 - subtype remains unclear. METHODS: We evaluated the prognostic value of TILs by analyzing 717 invasive breast cancer operation cases. TILs were classified into three groups based on the proportion of area within the tumor: low ( < 10%), intermediate (10-50%), and high ( > 50%). Disease-free survival (DFS) and overall survival (OS) were calculated according to TIL levels. RESULTS: Although there was no significant association between TIL levels and DFS or OS in all patients, high TILs were significantly associated with favorable DFS in Ki67-high (n = 238, p = 0.035) but not in Ki67-low (n = 470, p = 0.46) breast cancers. Multivariable analysis showed that high TILs were a significant and independent factor for DFS (HR 0.34; 95% CI 0.10-0.87; p = 0.023) among the Ki67-high group. In the ER + /HER2 - subtype, high-TILs showed favorable DFS in the Ki67-high group, although this was not statistically significant (p = 0.48); in contrast, unfavorable DFS was observed in the Ki67-low group (p = 0.027). CONCLUSIONS: In Ki67-high breast cancers, high TILs were associated with favorable DFS, irrespective of subtype, but increasing TIL levels correlated with worse DFS in the Ki67-low group with the ER + /HER2 - subtype. These results highlight variation in TIL prognostic significance between Ki67-high and -low breast cancers, particularly for the ER + /HER2 - subtype.