e12072 Background: The aim of this study was to investigate the correlation of immunologic factors including the expression of PD-1/PD-L1, PTEN, and the density of TILs, macrophages in the tumor area of breast cancer, using immunohistological staining and to evaluate the association between the immunologic factors and the clinical outcome for early breast cancer (EBC). Methods: A total of 97 EBC patients (pts) who underwent surgery from February 1995 to November 2005 were investigated.The postoperative adjuvant chemotherapies were routinely performed, adjuvant Tmab were not available in Japan within this period.The immunohistological staining was performed with the monoclonal antibodies for PD-1/PD-L1, PTEN, CD3, CD8, and CD163. Pathological analysis was performed to measure the expression area of each antibody, using images scanned by a CCD digital camera (Nikon), and the digitized data of the expression area (μm 2 ) were analyzed by ‘Win ROOF’ (version 5.7) software. The association between the immunologic factors and clinical outcome was statistically analyzed for over 10-years follow-up. Results: The density of CD3+TILs, CD8+TILs, CD163+ macrophages and non-expression of PTEN was significantly higher in triple negative breast cancer (TNBC). CD8+TIL density and PD-L1+/CD8+ expression were predictive factors for DFS and OS. Her2+ pts with PTEN expression and luminal/Her2- patients without PD-L1 expression had longer OS, compared to patients without PTEN expression (p=0.049) and with PD-L1 expression (p=0.036), respectively. Furthermore, the pts with PD-L1+/CD8+ expression had worse median PFS (p = 0.022) and median OS (p = 0.037), compared with pts without PD-L1+/CD8+ expression. Conclusions: Our results demonstrated that CD3+ TILs, CD8+ TILs, and CD163+ macrophages were shown to infiltrate the tumor area of EBC. In particular, TNBC had a higher rate of TIL infiltration within the tumor environment. PTEN expression and lack of PD-L1 expression were associated with favorable survival in Her2-positive and luminal/Her2-negative EBC patients, respectively. The PD-L1 expression combined with CD8+ density was significantly associated with an aggressive clinical outcome.
Salivary duct carcinoma (SDC) is a rare tumor occurring in the salivary gland. SDC is a highly aggressive tumor and its prognosis is extremely poor. Effective treatments in advanced SDC have not yet been established. Recently, immune checkpoint inhibitors have paved the way for the treatment of various malignancies. We examined the expressions of programed death ligand (PD-L) 1/PD-L2 and programed death (PD-1), and the correlation of clinicopathological findings.We examined 18 cases of SDC and conducted immunohistochemical staining using formalin-fixed paraffin-embedded full-face sections.The expression of PD-L1 and PD-L2 in tumor cells was observed in nine cases (50%) and 14 cases (78%), respectively. Cases with a high expression of PD-L1 and PD-L2 were found in four (22%) and seven cases (39%), respectively. The cases with a high expression of PD-L1 showed significantly shorter overall survival compared to those with low PD-L1 expression and null expression. We also examined the expression of PD-L1/PD-L2 and PD-1 of tumor-infiltrating mononuclear cells (TIMC) in stroma. The expressions of PD-L1 in tumor cells and stroma had a significant correlation. Association between the expressions of PD-L1 in tumor cells and those of PD-1 in stroma was significant. However, PD-L2 expression in the tumor had no significant correlation with expression in TIMCs. PD-L1, PD-L2 and PD-1 expressions in stroma were not associated with patient prognosis.High PD-L1 expression in SDC was strongly associated with unfavorable prognosis, indicating that PD-1/PD-L1 inhibitors could be effective in SDC.
860 Background: In patients with unresectable colorectal cancer, primary tumor resection is expected not only local control but also prolongation of survival time. However, in some cases, metastatic tumors have been known to rapidly progress after primary tumor resection. We examined clinical factors associated with acute metastatic progress after primary tumor resection, and it might lead to worse survival. Methods: We retrospectively analyzed 183 patients who were newly diagnosed with unresectable colorectal cancer in our institution between April 2007 and April 2016. Among all patients, 83 patients received resection of primary tumor without the presence of symptoms. They were divided into progression and non-progression group according to metastatic progression that evaluated CT scan from four to six weeks after surgery. We analyzed clinicopathological factors related to acute progression after primary tumor resection using Cox proportional hazards. Results: After resection of the primary tumor, 25 patients were classified into progression group and 58 patients were classified into non-progression group. In progression group, the median percent change in the sum of the longest diameters of target lesions was 29.6% (10.0-191.7%), and 22 (88.0%) patients showed to have new lesions after resection of the primary tumor. Multivariate analysis revealed LDH (HR 4.44, 95%CI 1.15-18.5, p = 0.02), number of liver metastasis (HR 3.28, 95% CI 1.09-10.0, p = 0.03) and RAS status (HR 3.08, 95% CI 1.05-9.46, p = 0.03) were independent baseline factors associated with acute progression after resection of the primary tumor. The median overall survival (OS) was 12.3 and 27.8 months in progression and non-progression group, respectively. Conclusions: Serum LDH, number of liver metastasis, and RAS mutation were baseline factors associated with acute progression of metastatic tumors after resection of primary tumor in patients with unresectable colorectal cancer. These results indicated that the resection of the primary tumor in patients with these factors might be avoided when they have no clinical symptoms.
Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC. All patients had histologically confirmed measurable ER-PgR-HER2- mBC and their human leukocyte antigen(HLA) / -A molecules were A2, A3, A11, A24, A26, A31, or A33. KRM-19(19mg/mL)was administrated subcutaneously every week for a total of 6 doses. Concurrent conventional chemo- and/or endocrine therapy were not permitted during treatment. This was an open-label, early phase II study. The primary endpoint was safety and anti-tumor immunologic effect, while the secondary endpoints were clinical responses and progression-free survival(PFS). The estimated enrollment was 10-15 and 8 patients were enrolled(Clinical trial registry number: UMIN000014616). Measurement of peptide-specific cytotoxic T lymphocyte and IgG responses were conducted before and after vaccination. The correlation between PFS and the increased IgG response and/or CTL levels were investigated.
Abstract In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using tumor markers or imaging tests. We aimed to investigate differences in clinicopathological features, prognosis, and treatment between asymptomatic and symptomatic MBCs. Patients with MBC were retrospectively divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtype: luminal, human epidermal growth factor receptor 2 positive, and triple negative. Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts in the asymptomatic group tended to or had longer post-recurrence survival (PRS) than those in the symptomatic group. In contrast, all cohorts and TN patients in the asymptomatic group tended to have or had longer overall survival (OS) than those in the symptomatic group, although no significant difference was observed in the luminal and HER2 subtypes. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of PRS. Regarding the luminal subtype, the asymptomatic group had longer chemotherapy duration than the symptomatic group, with no significant difference in OS between the groups. Asymptomatic and symptomatic MBCs differ in terms of subtypes and prognosis, and whether they require different treatment strategies for each subtype warrants further investigation.
A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins. This report depicts an extremely rare case of multiple synchronous sporadic GISTs in the stomach and jejunum.
Breast carcinoma rarely occurs in cases of foreign body granulomas following liquid silicone injection. Although the Food and Drug Administration (FDA) banned the use of all silicone injection products in 1992, liquid silicone injection for breast augmentation continues to be performed illegally. We herein report a case of breast carcinoma following liquid silicone injection in a 67-year-old female. A total of 45 years after liquid silicone injection, the patient had felt a breast mass in the right breast. Mammography showed a smooth mass that retracted the right nipple. Due to the presence of a marked acoustic shadow caused by the granulomas, evaluating the mass on ultrasonography was difficult. However, magnetic resonance imaging (MRI) showed a lobulated mass under the right nipple. The mass exhibited low signal intensity (SI) on T1-weighted images and intermingled high and low SI on T2-weighted images. Heterogeneous early enhancement with central low intensity was noted on dynamic contrast-enhanced MRI. Several oval-shaped low SI structures in the adipose tissue and disruption of the pectoralis major muscle were also observed. We diagnosed the patient with invasive ductal carcinoma based on a stereotactic-guided Mammotome® (a vacuum-assisted biopsy system manufactured by DEVICOR MEDICAL JAPAN, Tokyo, Japan) biopsy and subsequently performed mastectomy and axillary lymph node dissection (with a positive result for the sentinel node biopsy). Histologically, invasive ductal carcinoma was observed in the silicone granuloma. The development of foreign body granulomas following breast augmentation usually makes it difficult to detect breast cancer; thus, various devices are required to confirm the histological diagnosis of breast lesions. The stereotactic-guided Mammotome® biopsy system may be an effective device for diagnosing breast cancer developing in the augmented breast.
Aims HER2‐positive (HER2+) breast carcinoma (BC) cases are often treated similarly; however, they can be classified as either luminal B (LH) or non‐luminal type (NLH) BC, which have different prognoses. In this study, we investigated the clinicohistomorphological features of each HER2+ BC subgroup. Methods and results We classified 166 patients with HER2+ invasive BC into LH ( n = 110, 66.3%) and NLH groups ( n = 56, 33.7%). We further subclassified LH into patients with carcinomas expressing high levels of hormone receptors [LH‐high; Allred score, oestrogen receptor (ER) and/or progesterone receptor (PgR) 4–8, n = 89, 53.6%] or low levels (LH‐low; Allred score, ER and/or PgR 2 or 3, n = 21, 12.7%) for clinicohistomorphological characterisation. Morphological review showed that NLH included a percentage of patients with comedo necrosis, while LH patients had significantly more central scarring. In terms of immune responsiveness, NLH showed significantly higher rates of tumour‐infiltrating lymphocytes and healing. The LH‐high and NLH groups showed distinct characteristics (by both models, P < 0.05) and the LH‐low group appeared to demonstrate intermediate characteristics according to multinomial analyses using covariates reflecting tumour morphology and immune response outcomes. Conclusions These results support the classification of HER2+ BC into two major subgroups, LH‐high and NLH, based on tumour morphology and immune response; LH‐high proliferates via scirrhous and/or spiculated growth with a central scar, while the primary proliferation pattern of NLH is based on in‐situ carcinomas containing comedo necrosis with noticeable TILs and healing.
