Clinicopathological, immunohistochemical and treatment features of metachronous versus synchronous bilateral breast carcinoma

Objectives. The purpose of this study was to assess and compare the clinicopathological, molecular pathology, treatment and survival characteristics in patients with metachronous bilateral breast cancer (mBBC) and synchronous breast cancer (sBBC). Materials and methods. A cohort of 658 patients with breast cancer treated at the Coltea Clinical Hospital, Surgery Department, between January 2015 and December 2019 and followed-up until August 2020 was studied. Data pertaining to patients who were diagnosed as having bilateral breast cancer were retrospectively reviewed and collected. A 3-months interval was used to distinguish metachronous from synchronous tumors. Among patients with bilateral breast cancer, assessment parameters included patient characteristics, histological and molecular pathology features and the performed treatment that were statistically evaluated comparing the first and second tumor of each group and among groups. Survival analysis was performed comparing mBBC and sBBC patients. SPSS was used for data analysis. Outcomes. Of the 658 patients with primary breast cancer, 35 (5.3%) patients were diagnosed as having bilateral breast cancer (25 (3.8%) mBBC and 10 (1.5%) sBBC). When clinical and histopathological parameters were statistically evaluated, age, menopausal status, tumor size, number of invaded nodes and anatomic stage were found to be significant between the tumors of the metachronous group and tumor size, pathologic T(tumor) and stage between tumors of the synchronous group. Hormonal receptor (HR) status concordance was higher in the synchronous group (85.7%, p = 0.010), with a higher percentage of ER positive (71.4%) and PR positive (71.4%) concordance of the tumors. In terms of survival analysis, there was a difference in overall survival (OS, p = 0.005), disease-free survival (DFS, p = 0.011) and distant relapse-free survival (p = 0.003) between mBBC and sBBC. The mean disease-free survival for patients in whom metachronous tumor occurred within less than 5 years was 63.3 months, for sBBC patients was 39.6 months, whereas for patients with more than 5 years was 437.9 months (p = 0.012, Log Rank). Discordant biomarker defined subgroup (ER,HER2) patients were associated with better disease-free survival (p = 0.047, Log Rank) and better distant relapse-free survival (p = 0.015, Log Rank) in overall patients. In terms of loco-regional relapse-free survival, although mBBC and sBBC patients showed no statistical significant difference earlier in the time course (p = 0.088, Breslow; p = 0.054 Tarone-Ware), among mBBC patients was observed a better outcome (p = 0.027, Log Rank). Conclusions. Based on survival analysis, patients in whom metachronous tumor developed after more than 5 years, had a better distant relapse-free survival. Patients with synchronous bilateral breast cancer were associated with worse disease outcome based on overall survival analysis and disease free-survival rates with more frequent rates of distant metastasis. Outcome of patients in whom metachronous tumor was diagnosed within less than 5 years might be similar to synchronous tumors. Patients with discordant ER,HER2 status showed a better disease outcome. Although concordance in HR status and molecular subtype, did not show statistical significant differences, it is a subject which deserves further clinical observation.

Genomic heterogeneity of multifocal NSCLC.

e21595 Background: Distinguishing multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) remains a common diagnostic dilemma but critical for developing a therapeutic strategy. Methods: In this study, we analyse genomic features of 584 tissue samples from 258 NSCLC patients with > 1 surgically-resected tumor. NGS was performed using panels of 1021/59 genes. Results: Among 80 patients with definite diagnosis, 23 patients (46 tumors) were diagnosed with IPM. And 57 patients (145 tumors) were MPLC, consisting of 53 synchronous and 3 metachronous tumor pairs. Among 23 IPM tumor pairs, we identified at least one shared somatic mutation. By contrast, 93%(53/57) MPLC tumor pairs exhibited entirely unique mutation profiles in each tumor. Of 57 MPLCs, 4(7%) had no driver alteration ( EGFR, KRAS, BRAF, ALK, ERBB2, MET Exon 14). 9(16%) had a driver in only one of the tumors. In the remaining 44 MPLCs, 40 had unique driver mutation in each tumor. 50%(20/40) had distinct EGFR mutations, the most common combination was L858R and delins in exon 19. Specifically, 8(20%) patients resided ≥3 unique driver mutations simultaneously. This observation indicated that multiple lesions in the same individual can be driven by distinct molecular events. In contrast, 21 available IPM tumor pairs shared the same driver mutation. Pathogenic germline mutations were also analysed. Two were found in 2 MPLCs, involving PLAB2 and BLM, which were both null variants. While there were no pathogenic germline mutations found in IPMs. Regarding the MSI status, all samples from either MPLCs and IPMs displayed MSS, unexpectedly. To further verify the findings above, the remaining 393 samples with uncertain diagnosis were classified into group M (no shared mutation, 218 samples /97 patients) and I (≥1 shared mutation, 175 samples/81 patients). We find the similarity results among all available patients, driver mutation profiles exhibited completely unique and multiple in group M and fully consistent in group I. Conclusions: Taken together, our analyses indicated that the genomic heterogeneity of multifocal NSCLC may be a potential strategy for differentiating IPM and MPLC. This may hold implications for prioritizing therapeutic strategies.

Clinicopathological features of multifocal gastric carcinoma: A retrospective study.

453 Background: The occurrence of multifocal gastric carcinoma (MGC) is growing in China, while relevant study remains limited. This study aimed to collect more information of MGC for further research. Methods: Patients with MGC treated at China National Cancer Center from January 2010 to December 2017 were enrolled in this retrospective study. A 6-month interval was used to separate synchronous and metachronous foci. Results: 103 patients were included. 88 (85.4%) were males. 96 (93.2%) patients had two foci and 7 (6.8%) had three or more foci, contributing a total of 216 tumor foci. 185 (85.6%) foci were adenocarcinoma, 18 (8.3%) were intraepithelial neoplasia, 2 (0.9%) were lymphoepithelioma-like carcinoma and 1 (0.5%) was small cell carcinoma. Intestinal, diffuse, and mixed type accounted for 49.7%, 14.6% and 11.4% respectively, with 24.3% unknown.In 96 patients with 2 foci, 56 (58.3%) patients had synchronous diseases, and 40 (41.7%) had metachronous diseases. The median age at the diagnosis of first tumor was 62 (55-71) years. The median diagnosis interval of metachronous tumor foci was 41.4 (23.5-88.3) months. The locations and sizes of foci are shown in Table. In synchronous cases, 6 foci of accessory tumor were less than 1cm including one being 0.4 cm. In metachronous cases, 4 foci of second tumor were less than 1 cm. 51 (49.5%) patients were current smokers or ex-smokers, and 44 (42.7%) were regular alcohol consumers. 26 (25.2%) patients had a first-relative family history, including 14 (13.6%) having a family history of gastrointestinal carcinoma. Conclusions: The second gastric tumor should be thoroughly detected to avoid missed diagnosis, since the accessory tumor might be rather small. Further genetic research is warranted to explore the potential pathogenesis of MGC. [Table: see text]

WT1 gene mutation in exone 7 in boy with disturbance of the sex formation and the bilateral nephroblastoma

The case of observing a patient with WT1 gene mutation in exone 7 with bilateral Wilms metachronous tumor, disturbance of the sex formation in the form of scrotal hypospadias and bilateral abdominal cryptorchidism, without nephropathy, is presented. The child underwent surgical operations: left-sided nephrectomy, resection of the lower pole of the right kidney, bilateral orchiopexy and two-stage hypospadias correction. 7 years after the start of treatment and 3 years after the final operation, the condition of the child was estimated as satisfactory. The presented case by the results of the molecular genetic study has no previously described analogues and requires further observation.

DESCRIPTION OF THE CASE OF METACHRONOUS CANCER OF THE CERVICAL ESOPHAGUS AFTER EXTIRPATION OF THE ESOPHAGUS WITH PRE-STERNUM ESOPHAGOPLASTY BY THE RIGHT HALF OF THE COLON

Repeated development of a metachronous tumor in the esophagus resected because of cancer is usually observed in later periods. The period of time between the plasticity of the esophagus and the appearance of tumor can reach several tens of years. Optimal for patients with cancer of their own esophagus after esophagoplasty is early and radical surgical treatment with an individual approach to choosing surgical tactics to achieve the possible high quality of life.