Background Ovarian cancer (OvC) constitutes significant management challenges primarily due to its late-stage diagnosis and the development of resistance to chemotherapy. The standard treatment regimen typically includes carboplatin and paclitaxel, with the addition of poly (ADP-ribose) polymerase inhibitors for patients with high-grade serous ovarian cancer (HGSOC) harboring BRCA1/2 mutations. However, the variability in treatment responses suggests the need to investigate factors beyond BRCA1/2 mutations, such as DNA repair mechanisms and epigenetic alterations. Notably, homologous recombination repair deficiency (HRD) is observed in an additional 20% of HGSOC cases, indicating a broader spectrum of DNA repair defects. Existing commercial HRD assays have certain limitations, prompting a global effort to develop new genomic and functional tests through academic research. Materials and methods This study investigates, in the 187 high-grade serous and endometrioid tumors from the MITO16/MaNGO-OV-2 trial, academic HRD genomic tests in conjunction with a RAD51 immunofluorescence assay to assess functional activation of HRD. Additionally, the study incorporates analysis of microRNA-506 (miR-506) expression as a putative epigenetic effector. Results The RAD51 test identified HRD in 73% of the samples and genomic HRD testing in 57%, with HRD identified in 45% of samples by both tests. The significant discrepancy between the two assays emphasizes the need to refine tumor classification for HRD. A three-group genomic classification unveiled superior progression-free survival (PFS) in high- and mild-HRD tumors compared with negative-HRD tumors. High concordance between RAD51 and genomic testing in high-HRD tumors suggests a subset of ‘super-HRD’ tumors exhibiting superior PFS. High expression of miR-506 may be used to further refine HRD status. Conclusions The study underscores the complexities of HRD assessment and advocates for a combined genomic and functional approach to enhance predictive accuracy in OvC treatment responses.

BACKGROUND: Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications.METHODS: This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed.RESULTS: Sixty-five advanced EGFR-mutated NSCLC patients treated with osimertinib in first- (n = 56) or in second-line (n = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification (n = 8), EGFR C797S (n = 3), and SCLC transformation (n = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively.CONCLUSIONS: Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.

Triple-negative breast cancer (TNBC) that do not achieve pathological complete response (pCR) have unfavorable prognosis. The RAD51 score is a functional assay able to identify Homologous Recombination Repair (HRR)-deficient tumors. In this setting, it may add prognostic value and guide post-neoadjuvant treatments.

In our retrospective analysis, Notch signalling pathway was associated with resistance to anti-vascular endothelial growth factor (VEGF) therapy in patients with metastatic colorectal cancer (mCRC). We tested whether radiomics might select treatment-naïve mCRC patients responding to bevacizumab, beyond clinical and genomic (Notch Intracellular Cleaved Domain (NICD)/JAG1 expression) parameters.

Preoperative chemoradiotherapy can enhance antitumor immunity through increasing T-cell activation and tumor infiltration. These effects could potentially sensitize tumors to immunotherapies, including checkpoint inhibitors. We explored whether preoperative therapy for locally advanced rectal cancer induces immunologic changes. We analyzed by immunohistochemistry 55 locally advanced rectal cancers from the STAR-01 cohort. Paired pre- and post-operative specimens were available for 25 out of 55 patients. The multicenter STAR-01 study enrolled patients treated with preoperative chemoradiation with or without oxaliplatin. The immunoistochemical analysis was performed with a panel of immune cells and associated factors as CD3, CD20, CD4/CD8, PD1 and FoxP3. The pattern of tumor infiltrating lymphocytes (TILs) and related infiltrating lymphocytes (RILs) was also evaluated. Response to preoperative chemoradiotherapy was assessed according to tumor regression grade (TRG sec. Ryan –AJCC Eight ed.). The expression level of CD3+, CD20+, FoxP3+ and PD1+ cells were not significantly different after therapy. The TILs and RILs immunosuppressive cells were higher in better responder (TRG0), although we did not find any statistical significance given the small sample size. Decreasing CD4/CD8 ratio on post-operative samples was significantly associate with TRG 0 (p <0.01). The increase of lymphocyte CD8+ was related to a good pathological response after chemoradiotherapy. Our data suggest that chemoradiotherapy may induce an enrichment of CD8+ T lymphocytes in good responders. The new frontier of best treatment could be the use of specific immune cells (T lymphocytes) to activate the system's response immune against disease.

The aim of this study was to identify an objective way to define a long-term survivors (LTS) and short-term survivors (STS) in patients with surgically resected lung adenocarcinoma (ADK), and secondly to find peculiar clinicopathological features in these two groups of patients. all patients who underwent major lung resection for lung ADK from 2000 to 2015 were studied. LTS and STS were extrapolated considering the overall survival (OS) and pathological tumour stage: the first and the fourth quartile of those patients with cancer-related death were considered for statistical analysis. from 600 ADK patients we found 79 STS and 77 LTS;clinico-pathologic baseline characteristics are presented in Table 1.Considering STS patients, smoking habit, histotype, tumour necrosis, pleural invasion and pathological stage were significantly associated with OS at univariate analysis (Fig.1). In LTS patients, smoking habit, neoadjuvant chemotherapy, tumour-infiltrated lymphocytes and pathological stage were significantly associated with OS (Fig.2). On multivariate analysis, smoking status, lymphoid infiltrate, pleural invasion and stage remained significantly associated with OS (Table 2).Table 1VariableFull sampleaSTS (N=79)aLTS (N=77)ap-valueAge at diagnosis (median)68 (62-74)68 (61-74)69 (64-75)0.301Gender (M:F)110:46 (70.5%:29.5%)60:19 (24,1%:75,9%)27:50 (35,1%:64,9%)0.131Smoking status<0.001Never smoker23 (19,6%)5 (6,8%)18 (27,3%)Smoker + Former smoker117 (81,4%)69 (93,2%)48 (72,7%)Other previous primary tumor0.936Yes43 (27,6%)22 (27,8%)21 (27,3%)No113 (72,4%)57 (72,2%)56 (72,7%)Side0.079Right70 (44,9%)30 (38,0%)40 (51,9%)Left86 (55,1%)49 (62,0%)37 (48,1%)Histotype0.085Lepidic5 (3,2%)0 (0,0%)5 (6,5%)Papillary21 (13,5%)11 (13,9%)10 (13,0%)Acinar37 (23,7%)16 (20,3%)21 (27,3%)Micropapillary18 (11,5%)8 (10,1%)10 (13,0%)Solid75 (48,1%)44 (55,7%)31 (40,3%)Grade0.034G12 (1,3%)0 (0,0%)2 (2,6%)G223 (14,7%)7 (8,9%)16 (20,8%)G3131 (84,0%)72 (91,1%)59 (76,6%)Lymphatic invasion0.864Yes101 (64,7%)51 (67,1%)50 (65,8%)No51 (32,7%)25 (32,9%)26 (34,2%)Blood invasion0.128Yes47 (30,1%)28 (36,4%)19 (25,0%)No106 (67,9%)49 (63,6%)57 (75,0%)Pleural invasion0.439PL078 (50,0%)37 (46,8%)41 (53,2%)PL141 (26,3%)24 (30,4%)17 (22,1%)PL220 (12,8%)8 (10,1%)12 (15,6%)PL317 (10,9%)10 (12,7%)7 (9,1%)Necrosis0.419Yes70 (46,7%)37 (50,0%)33 (43,4%)No80 (53,3%)37 (50,0%)43 (56,6%)Lymphoid infiltrate0.787Absent57 (37,0%)27 (35,1%)30 (39,0%)Mild63 (40,9%)34 (44,2%)29 (37,7%)Moderate21 (13,6%)9 (11,7%)12 (15,6%)Marked13 (8,4%)7 (9,1%)6 (7,8%)Neoadjuvant chemotherapy0.371Yes11 (7,1%)7 (8,9%)4 (5,2%)No145 (92,9%)72 (91,1%)73 (94,8%) Open table in a new tab Table 295% CIVariablesp-value.HRSmoking Habit0,0032,3171,3254,052Histotype0,817,951,6201,459Tumor Necrosis0,065,667,4341,025Limphoyd Infiltrate0,0241,5981,0632,402Neoadjuvant CHT0,160,502,1921,313Pleural Invasion0,021,421,201,879Stage0,002,480,305,755 Open table in a new tab Our findings suggest that the unexpected survival of STS and LTS ADK-patients is determined by a concert of clinical and pathological features. Biological characterization of these kind of patients will likely improve the understanding of their unusual course.

ABSTRACTObjectivesTo introduce a new sonographic marker of intrathoracic liver herniation in fetuses with left‐sided congenital diaphragmatic hernia (CDH).MethodsIn a consecutive series of fetuses with isolated CDH, an ultrasound volume of the fetal abdomen was acquired. On this volume, offline calculation of the angle formed by the midline of the abdomen (joining the center of the vertebral body to the abdominal insertion of the umbilical cord) and a second line joining the center of the vertebral body to the intra‐abdominal convexity of the umbilical vein was carried out to give the umbilical vein deviation angle (UVDA). The UVDA was measured in a group of normal fetuses selected as controls. At follow‐up, the presence of liver herniation was investigated in all cases of CDH. UVDA values were compared between the CDH group and controls, and between CDH ‘liver‐up’ vs ‘liver‐down’ cases. A receiver–operating characteristics (ROC) curve was constructed to identify a cut‐off value of the UVDA with the highest accuracy in predicting liver herniation in the CDH group.ResultsBetween 2009 and 2015, 22 cases of left‐sided CDH were included in the study group, of which nine cases had liver herniation. Eighty‐eight normal fetuses were recruited as controls. The UVDA was significantly higher in the cases vs controls (15.25 ± 7.91° vs 7.68 ± 1.55°; P < 0.0001). Moreover, the UVDA was significantly increased in CDH fetuses with liver‐up vs liver‐down (21.77 ± 8.79° vs 10.75 ± 2.10°; P < 0.0001). On ROC curve analysis the UVDA showed good prediction of liver herniation (area under the ROC curve, 0.94; P < 0.0001) with the best cut‐off of 15.2°, yielding a sensitivity of 89% and a specificity of 100% (P < 0.0001).ConclusionsIn fetuses with CDH, umbilical vein bowing may be quantified by measuring the UVDA using three‐dimensional ultrasound. This sonographic marker seems to be an accurate predictor of liver herniation in left‐sided CDH. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

This case report refers to ovarian metastases from renal clear cell carcinoma (RCC) in a 46-year-old woman with a history of abdominal pain and urinary incontinence. A pelvic ultrasound revealed a heterogeneous, large, right-sided solid/multi-cystic ovarian mass, suggesting diagnosis of borderline or malignant epithelial ovarian tumor. At staging, abdominal CT incidentally revealed an enlarged left kidney with a lesion, consistent with renal carcinoma. At the time of surgery, a frozen section of ovarian neoplasm was performed to confirm diagnosis of primary epithelial borderline ovarian tumor or metastatic renal carcinoma. Macroscopically. the right ovary had been entirely replaced by a multiloculated cystic lesion with clear serous fluid, solid septa, and centrally, a solid gray area. Imprint cytology, performed during an intraoperative study of the lesion, showed cohesive clusters of neoplastic cells with clear abundant and vacuolated cytoplasm, pleomorphic, medium or large nuclei, and evident nucleoli. Histological examination revealed an epithelial neoplasm, characterized by large cells with clear optically empty cytoplasm that lined the alveolar and cystic spaces. A prominent vascular component with sinusoidal features was also present. These findings and the clinical data of the simultaneous renal lesion were consistent with an intraoperative diagnosis of ovarian metastatic renal carcinoma. Permanent sections revealed that the ovarian lesion showed the same pathological features as those observed in frozen sections. Immunohistochemical analysis of the ovarian tumor showing positivity for CD10 and renal clear cell marker (RCC Ma), while the presence of RCC in a nephrectomy specimen confirmed ovarian metastatic renal carcinoma. In conclusion, although ovarian metastasis of RCC is very rare, diagnosis can be made by careful histological examination, immunohistochemical study, plus clinical data.

Background: The 2016 WHO classification of CNS tumors included molecular parameters in addition to histology to redefine many tumor entities. Low-grade glioma (LGG) are divided into isocitrate dehydrogenase (IDH) wild type or mutant. Absence of IDH mutation is a rare event in LGG, and IDH wild type are considered a provisional entity. The technique used to assess IDH mutation is essential to determine the real impact of this tumor type. Methods: The observation of a particularly favorable outcome in a group of 42 patients with a diagnosis of IDH wild type LGG (OS = 93.7 months) led us to retest IDH mutation with a more sensitive technique. Next Generation Sequencing (NGS) was used to retest IDH status in tumor samples, the results of NGS assay were compared with previous findings. Results: Initial assessment of IDH mutation in this 42 patients had been performed using PCR in 19 cases and immunohistochemistry in 2 cases. twenty-one (50%) of the 42 initial IDH wild type LGGs were discovered to be IDH mutant when tested with NGS. Four patients had R132H mutation while in the remaining 17 cases a rare IDH mutation was detected. In particular 4 patients showed IDH2 mutation, 5 patients had IDH1 R132C mutation, 5 patient had IDH1 R132G mutation and 3 patients had IDH1 R132S mutation. Median OS of NGS confirmed IDH mutated LGG was 164.0 months vs 32.2 months for NGS IDH wild type LGG reflecting the very distinct clinical course of these two entities. Conclusions: Repeating testing in IDH wild type LGG cases is crucial, as well as the technique used to assess this mutation. NGS is able to assess IDH mutations in 50% of patients previously misdiagnosed. IDH wild type LGG remains a rare entity with dismal prognosis. Legal entity responsible for the study: N/A Funding: None Disclosure: All authors have declared no conflicts of interest.

Background: Glioblastoma (GBM) remains an incurable disease. Radiotherapy and temozolomide are the backbone of the treatment. Clinical and molecular factors are essential to define prognosis. Methods: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). We perform a prospective evaluation about prognostic factors in GBM patients treated with temozolomide concurrent with and adjuvant to radiotherapy. Results: One hundred sixty-nine GBM patients (median age, 60 years; range 29 – 82) were prospectively evaluated. MGMT methylation status was available in 140 patients. Combining gender and MGMT methylation status we obtained four groups of patients: 36 male pts with methylated MGMT (25.7%), 47 male pts with unmethylated MGMT (33.6%), 32 female pts with methylated MGMT (22.9%), 25 female pts with unmethylated MGMT (17.9%). Results of univariate analysis are summarized in the Table. Overall survival (OS) was significantly different between methylated male and methylated female (p = 0.028), methylated male and unmethylated female (p = 0.031), unmethylated male and methylated female (p = 0.002), methylated female and unmethylated female (p < 0.001). In multivariate analysis, gender and MGMT methylation considered together (met female vs met male HR = 0.459; 95% CI 0.242 – 0.827; p = 0.017), age (HR 1.025; 95% CI 1.002 – 1.049; p = 0.032) and Karnofsky Performance Status (KPS) (HR 0.965; 95% CI 0.948 – 0.982; p < 0.001) were significantly correlated with OS.Table348P Results of univariate analysisnmOS95%CImethylated male3116.39.2-23.4unmethylated male4115.611.8-19.5methylated female26nrunmethylated female2117.011.8-22.2total11917.015.2-18.9 Open table in a new tab Conclusions: The median overall survival is consistently higher for female pts with methylated MGMT, treated with temozolomide concurrent with and adjuvant to radiotherapy. When considered simultaneously with MGMT methylation status, gender might impact on clinical outcome and should be considered as a prognostic factor. Legal entity responsible for the study: N/A Funding: None Disclosure: All authors have declared no conflicts of interest.

Background: Glioblastoma (GBM) remains an incurable disease. Radiotherapy and temozolomide are the backbone of the treatment. Clinical and molecular factors are essential to define prognosis. Methods: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). We perform a prospective evaluation about prognostic factors in GBM patients treated with temozolomide concurrent with and adjuvant to radiotherapy. Results: One hundred sixty-nine GBM patients (median age, 60 years; range 29 – 82) were prospectively evaluated. MGMT methylation status was available in 140 patients. Combining gender and MGMT methylation status we obtained four groups of patients: 36 male pts with methylated MGMT (25.7%), 47 male pts with unmethylated MGMT (33.6%), 32 female pts with methylated MGMT (22.9%), 25 female pts with unmethylated MGMT (17.9%). Results of univariate analysis are summarized in the table 1.Table: M1nmOS95%CImethylated male3116.39.2 -23.4unmethylated male4115.611.8 - 19.5methylated female26nrunmethylated female2117.011.8 - 22.2total11917.015.2 - 18.9 Open table in a new tab Overall survival (OS) was significantly different between methylated male and methylated female (p = 0.028), methylated male and unmethylated female (p = 0.031), unmethylated male and methylated female (p = 0.002), methylated female and unmethylated female (p < 0.001). In multivariate analysis, gender and MGMT methylation considered together (met female vs met male HR = 0.459; 95% CI 0.242 – 0.827; p = 0.017), age (HR 1.025; 95% CI 1.002 – 1.049; p = 0.032) and Karnofsky Performance Status (KPS) (HR 0.965; 95% CI 0.948 – 0.982; p < 0.001) were significantly correlated with OS. Conclusions: The median overall survival is consistently higher for female pts with methylated MGMT, treated with temozolomide concurrent with and adjuvant to radiotherapy. When considered simultaneously with MGMT methylation status, gender might impact on clinical outcome and should be considered as a prognostic factor.

Background: To predict the response to immunotherapy, tissue and circulating cytotoxic lymphocytes, potentially targeted by anti-PD-1/PD-L1 drugs, were simultaneously assessed in NSCLC. Methods: Twenty-six advanced NSCLC patients receiving nivolumab were included. Tissue samples were immunohistochemically analyzed to quantify PD‐L1 (H‐score) and CD3, CD8, CD4 and PD-1 positive TILs. Peripheral blood (PB) immune profile at baseline (T0) and after 2 (T1) and 4 (T2) cycles of bi-weekly nivolumab was performed by FACS analysis of CD3, CD8, CD4, NK (CD56), Treg (FOXP3) and MDSC. Changes in their number, and functional (PD-1, Granzyme B, Perforin) and proliferative (Ki67) hallmarks were determined. Integrated tissue and circulating parameters were correlated to treatment response (RECIST 1.1). Results: At tissue level, in association with variable PD-L1 degrees, low PD-1 expression in CD8pos TILs was present in 100% of patients with clinical benefit (CB, n 9) compared to only 20% of non-responders (NR, p < 0.001). At baseline, PB of CB patients showed higher number of NK, which tended to increase at T1 and T2, while in NR a progressive decline in NK, CD3, CD8 and CD4 was observed (p < 0.05). Moreover, a significant 2.5-fold increase in the incidence of circulating CD8pos/PD-1pos cells was detected at baseline in CB vs NR (p < 0.001). Saturation of PD-1 sites was apparent in PB of both groups following nivolumab. Cycling Ki67poscytotoxic lymphocytes were higher in CB at baseline (12.4%), T1 and T2 while in NR proliferating CD8 (T0: 7.7%) progressively decreased to halve at T2 (p < 0.001). Intriguingly, one of the two patients with a complete response had the highest baseline value of both PD-1pos (176.3/μl) and Ki67pos CD8 cells (52%); conversely NR patients with rapidly progressive disease displayed the lowest range of both Ki67 labelling (1.3-3.9%) and PD-1 expression (18.3-22.4/μl). Conclusions: The inhibitory and activating PD-1 pathways, respectively translated in low tissue PD-1posCD8pos TILs, to escape PD-L1 pressure and high peripheral blood PD-1posCD8pos, rescued by PD-1 targeting, may identify a specific immune profile predictive of the response to immunotherapy. Legal entity responsible for the study: University Hospital of Parma Funding: AIRC project grant Disclosure: All authors have declared no conflicts of interest.

Introduction: Outcomes for women with pT1aN0M0 breast cancers (BC) may vary by biologic subtype. A higher proportion of HER2-positive BCs diagnosed in the interval between scheduled screening rounds has been proposed to account for the more aggressive behaviour of interval cancers (IC) compared with screen-detected (SD) tumors. No data are available on the prognostic role of HER2-positive status in a general population of pT1aN0M0 breast tumors with known screening status. Methods: All incident pT1aN0M0 BCs (n=874), systematically collected by the Cancer Registries of Emilia Romagna Region (northern Italy) and diagnosed in women aged 50-69 from 2003 to 2009 were evaluated. Screening status was ascertained by reference to the Emilia Romagna Breast Cancer Screening Program (ERBSP) database. Patients unexposed to screening, with HER2 unknown primary tumor and/or who received adjuvant chemotherapy or trastuzumab were excluded from analysis. Results: Twenty percent of patients had HER2-positive tumors. Fifty-three percent of the entire study population were SD cancers, while 18% were ICs. Tumors with high histologic grade, high proliferative rate, negative estrogen receptor status, or HER2-positive status were more likely to be diagnosed in the interval between screening. At a median follow-up of 84 months, the 5-year invasive disease-free survival (IDFS) rates were 89% and 95% in patients with HER2-positive and HER2-negative tumors, respectively (P = 0.025). Notably, HER2-positive ICs showed poorer IDFS than HER2-positive SD tumors (84% vs. 95%, respectively; P = 0.04). No difference in IDFS rates were observed between HER2-positive SD cancers and HER2-negative SD cancers. Multivariable analysis of candidate prognostic factors for IDFS will be reported. Conclusions: In a general population of pT1aN0M0 early BCs with known screening status, IC detection may identify patients with HER2-positive pT1aN0M0 tumors in whom the rate of recurrence justifies consideration for systemic, anti-HER2, adjuvant therapy. Citation Format: Musolino A, Michiara M, Boggiani D, Sikokis A, Rimanti A, Pellegrino B, Silini EM, Campanini N, Barbieri E, Sgargi P, Falcini F, Pinto C. Prognostic impact of HER2 overexpression/amplification in women with pT1a N0 M0 breast cancer with known screening status: Results from a multicenter population-based cancer registry study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-23.

Background: Although human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis, patients (pts) with pT1a N0M0 breast cancers (BCs) have an excellent outcome across all subtypes. Interval cancers (ICs) have poorer survival than screen-detected (SD) tumours, and an association has been reported between ICs and HER2 overexpression. We aimed to determine, in a general population of pT1a N0M0 BCs with known screening status, whether HER2-positive ICs have a poorer outcome than HER2-positive SD cancers. Methods: We evaluated all incident pT1a N0M0 BCs (n = 874) collected in the Emilia-Romagna region (Italy) from 2003 to 2009 and diagnosed in women aged 50-69. Pts unexposed to screening, with unknown HER2 status and/or treated with adjuvant trastuzumab were excluded from analysis. Results: Sixty-one percent of the BCs were SD, whereas 19% were ICs. BCs with high histologic grade, hormone receptor-enegative or HER2-positive status (odds ratio = 1.7; 95% confidence interval [CI]: 1.1-2.7) were more likely ICs. Median follow-up was 115 months. The 10-year invasive disease-free survival (iDFS) for HER2-positive ICs was lower than that for HER2-positive SD cancers: 75.0% (95% CI: 55.5%-94.5%) versus 93.8% (95% CI: 86.5%-100%). An interaction between ICs and HER2-positive status was found for poorer iDFS after adjusting for prognostic variables (HR = 5.3; 95% CI: 1.6-16.7). Conclusions: IC detection may identify pts with HER2-positive pT1a N0M0 tumours in whom the rate of recurrence justifies consideration for conventional, anti-HER2, adjuvant treatment. (C) 2017 Elsevier Ltd. All rights reserved.