[A case of resection margin involvement gastric carcinoma that relapsed late after additional gastrectomy].

We report a case of a patient with resection margin involvement gastric carcinoma that recurred 5.5 years after additional resection. A 64-year-old man underwent distal gastrectomy for advanced gastric carcinoma (sig+por2, pSE, pN0, pStage IIB) in January 2008. A total gastrectomy was performed 2 months after the initial gastrectomy because of proximal resection line involvement, and curative resection was obtained. Adjuvant chemotherapy with S-1 was completed, and follow-up surveillance was finished 5 years after the additional surgery. In November 2013, the patient experienced bouts of vomiting, and a computed tomography (CT) scan showed an abdominal abscess that had spread to the liver and communicated with the intestine. Despite abscess drainage and antibiotic therapy, infection control was difficult and the patient died 20 days after hospitalization. An autopsy showed the recurrence lesions had diffusely spread to the peritoneum and was also disseminated around the Roux-Y jejunum. These findings suggest that peritoneal recurrence might lead to penetration of the intestine and abscess formation.

[A case of metachronous triple cancer treated with a multimodal approach including surgical resection].

We report a patient with metachronous triple cancer of the hypopharynx, esophagus, and tongue. A 37-year-old man with hypopharyngeal cancer underwent hypopharyngolaryngectomy and cervical lymphadenectomy in 1999. Submental lymphadenectomy following adjuvant radiotherapy was performed for lymph node recurrence in 2000. The patient then underwent esophagectomy for esophageal cancer in 2004. Subsequently, the patient underwent 2 partial resections and 1 subtotal resection of the tongue for tongue cancer in 2005, 2007, and 2008, respectively. The pathological findings for each cancer were squamous cell carcinoma. Two rounds of radiotherapy were performed for bone metastasis of the esophageal cancer and for the local recurrence of the tongue cancer. A total of 7 lines of chemotherapy, including superselective arterial infusion chemotherapy, were administered to treat the recurrences. The patient died in 2013, but he showed long-term survival of 13 years from the first operation owing to the multimodality treatment.

[A case of advanced gastric cancer successfully treated with second-line chemotherapy followed by curative conversion gastrectomy].

We report a case of advanced gastric cancer that was successfully treated with second-line chemotherapy followed by curative conversion gastrectomy. The patient was a 71-year-old man. Endoscopic examination revealed a type 3 gastric cancer in the lower third of the stomach. Abdominal computed tomography (CT) revealed multiple lymph node metastases and metastasis to the peritoneal cavity. The clinical diagnosis was cT4N3aP1H0M1(LYM), cStage IV. The patient was treated with S-1 (80 mg/m² on days 1-28, every 6 weeks [q6w]) in November 2009. Temporarily, both the size of the primary lesion and the swelling of the lymph nodes were markedly reduced. However, after 10 courses of chemotherapy, the primary lesion was found to be enlarged again. The patient was then treated with S-1(80 mg/m², on days 1-14, every 6 weeks [q3w]) plus CPT- 11 (150 mg/m² on day 1, q3w) as the second-line chemotherapy. After 8 courses, an abdominal CT showed no peritoneal or lymph node metastases, but gastric endoscopy revealed the presence of a residual primary lesion. After staging laparoscopy, distal gastrectomy with D2 lymphadenectomy was performed. The histological diagnosis was ypT3 (SS) N1M0, Stage IIB. Analysis of the histological features of the primary tumor and peritoneal metastases resulted in their classifications as Grade 1a and Grade 3, respectively. After surgery, there were no serious adverse events. The patient has been in good health without recurrence for over 3 years after surgery.

CCND1 Copy Number Variation in Circulating Tumor DNA from Luminal B Breast Cancer Patients.

BACKGROUND/AIM: Abnormalities in the cyclin D1-CDK4/6 complex have been implicated in breast cancer proliferation and resistance to treatment. Recently, new drugs have been developed to target CDK4/6. Meanwhile, liquid biopsy has received great interest in oncology. In this study, we analyzed cyclin D1 gene (CCND1) copy number variation (CNV) in circulating tumor DNA (ctDNA) from luminal B breast cancer patients. PATIENTS AND METHODS: This study included 31 patients with luminal B breast cancer who underwent resection. We analyzed CCND1 CNV in ctDNA by digital droplet PCR. RESULTS: Of the 31 luminal B breast cancers, CCND1 CNV was positive in 5 cases. Patients with CCND1 CNV positivity had significantly shorter recurrence-free survival than patients with negative CCND1 CNV. CONCLUSION: CCND1 CNV in ctDNA was associated with poor prognosis in patients with luminal B breast cancer. This biomarker could be a useful prognostic factor.

A novel germline mutation of TP53 with breast cancer diagnosed as Li-Fraumeni syndrome.

TP53 is a tumor suppressor gene and, when dysfunctional, it is known to be involved in the development of cancers. Li-Fraumeni syndrome (LFS) is a hereditary tumor with autosomal dominant inheritance that develops in people with germline pathogenic variants of TP53. LFS frequently develops in parallel to tumors, including breast cancer. We describe a novel germline mutation in TP53 identified by performing a multi-gene panel assay in a breast cancer patient with bilateral breast cancer.

Validity of the prognostication tool PREDICT version 2.2 in Japanese breast cancer patients.

INTRODUCTION: PREDICT is a prognostication tool that calculates the potential benefit of various postsurgical treatments on the overall survival (OS) of patients with nonmetastatic invasive breast cancer. Once patient, tumor, and treatment details have been entered, the tool will show the estimated 5-, 10-, and 15-year OS outcomes, both with and without adjuvant therapies. This study aimed to conduct an external validation of the prognostication tool PREDICT version 2.2 by evaluating its predictive accuracy of the 5- and 10-year OS outcomes among female patients with nonmetastatic invasive breast cancer in Japan. METHODS: All female patients diagnosed from 2001 to 2013 with unilateral, nonmetastatic, invasive breast cancer and had undergone surgical treatment at Kyushu University Hospital, Fukuoka, Japan, were selected. Observed and predicted 5- and 10-year OS rates were analyzed for the validation population and the subgroups. Calibration and discriminatory accuracy were assessed using Chi-squared goodness-of-fit test and area under the receiver operating characteristic curve (AUC). RESULTS: A total of 636 eligible cases were selected from 1, 213 records. Predicted and observed OS differed by 0.9% (p = 0.322) for 5-year OS, and 2.4% (p = 0.086) for 10-year OS. Discriminatory accuracy results for 5-year (AUC = 0.707) and 10-year (AUC = 0.707) OS were fairly well. CONCLUSION: PREDICT tool accurately estimated the 5- and 10-year OS in the overall Japanese study population. However, caution should be used for interpretation of the 5-year OS outcomes in patients that are ≥65 years old, and also for the 10-year OS outcomes in patients that are ≥65 years old, those with histologic grade 3 and Luminal A tumors, and in those considering ETx or no systemic treatment.

Comprehensive molecular profiling broadens treatment options for breast cancer patients.

Precision oncology with next generation sequencing (NGS) using tumor tissue with or without blood has begun in Japan. Tumor molecular profiling tests are available, including the OncoGuide™ NCC Oncopanel System and FoundationOne® CDx (F1CDx). Our purpose was to identify potentially actionable genetic alterations in breast cancer with this comprehensive tumor profiling test. We enrolled 115 patients with pathologically diagnosed advanced or metastatic breast cancer. Comprehensive tumor genomic profiling, microsatellite instability, and tumor mutational burden (TMB) were determined using F1CDx. Testing was successful in 109/115 cases (94.8%). Clinically actionable alterations were identified in 76% of advanced breast cancer patients. The most frequent short variants were in TP53 (48.6%), PIK3CA (38.5%), GATA3 (11.0%), PTEN (11.0%), and BRCA1 (10.1%), and structural variants were in ERBB2 (24.8%), MYC (21.1%), RAD21 (21.1%), CCND1 (11.9%), FGF19 (10.1%), and PTEN (10.1%). Regarding human epidermal growth factor receptor (HER)2 status, 106/109 samples (97.2%) were concordant between F1CDx and HER2 testing with immunohistochemistry/fluorescence in situ hybridization. However, ERBB2 amplification was newly detected in four samples and ERBB2 mutations were detected in five HER2-negative breast cancer samples. Oncogenic BRCA mutations were found in three samples with F1CDx among 27 germline testing-negative samples. The mean TMB in all samples was 6.28 mut/Mb and tended to be higher in luminal B and triple-negative breast cancer (mean = 8.1 and 5.9 mut/Mb, respectively) compared with other subtypes. In conclusion, we established a system for precision oncology and obtained preliminary data with NGS as the first step. The information in this clinical sequencing panel will help guide the development of new treatments for breast cancer patients.

Breast metastasis from pelvic high-grade serous adenocarcinoma: a report of two cases.

BACKGROUND: Metastatic tumors to the breast reportedly account for 0.5% to 2.0% of all malignant breast diseases. Such metastatic tumors must be differentiated from primary breast cancer. Additionally, few reports have described metastases of gynecological cancers to the breast. We herein report two cases of metastasis of pelvic high-grade serous adenocarcinoma to the breast. CASE PRESENTATION: The first patient was a 57-year-old woman with a transverse colon obstruction. Colostomy was performed, but the cause of the obstruction was unknown. We found scattered white nodules disseminated throughout the abdominal cavity and intestinal surface. Follow-up contrast-enhanced computed tomography (CT) showed an enhanced nodule outside the right mammary gland. Core needle biopsy (CNB) of the right breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. We diagnosed the patient's condition as breast and lymph node metastasis of a high-grade serous carcinoma of the female genital tract. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. The second patient was a 71-year-old woman with a medical history of low anterior resection for rectal cancer at age 49, partial right thyroidectomy for follicular thyroid cancer at age 53, and left lower lung metastasis at age 57. Periodic follow-up CT showed peritoneal dissemination, cancerous peritonitis, and pericardial effusion, and the patient was considered to have a cancer of unknown primary origin. Contrast-enhanced CT showed an enhanced nodule in the left mammary gland with many enhanced nodules and peritoneal thickening in the abdominal cavity. CNB of the left breast mass was conducted, and immunohistochemical staining of the mass suggested a high-grade serous carcinoma of female genital tract origin. After chemotherapy for stage IVB peritoneal cancer, tumor reduction surgery was performed. CONCLUSIONS: We experienced two rare cases of intramammary metastasis of high-grade serous carcinoma of female genital tract origin. CNB was useful for confirming the histological diagnosis of these cancers that had originated from other organs. A correct diagnosis of such breast tumors is important to ensure quick and appropriate treatment.