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The data from our study seem to be generally comparable with the relatively scarce published data on clinicopathological parameters of MBC and AMBC.

We investigated the expression of tumor-associated antigens (TAA) of the cancer/testis (C/T) gene family in cervical squamous cell carcinomas. First, we focused on the HeLa cervical cancer derived cell line, and we found that it expresses MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A12, GAGE-3/6, LAGE-1, and PRAME genes, encoding defined C/T TAA. In contrast, no expression of MAGE-A10, BAGE, GAGE-1/2, or NY-ESO-1 genes was observed. Corresponding gene products could also be detected by immunoblotting and immunocytochemistry, taking advantage of monoclonal antibodies recognizing discrete TAA. Capitalizing on these data, a monoclonal antibody predominantly recognizing MAGE-A4 TAA in paraffin-embedded sections (57B) was used to investigate the C/T gene expression in clinical tumor samples. A group of 60 patients was studied, and 57B positivity was detectable to different extents in 33% of the cases (20/60). In 13 of them (21%), staining of over 50% of the tumor cells was evident, whereas healthy cells always scored negative. Remarkably, MAGE-A4 expression was significantly (p < 0.05) more frequently detectable in poorly differentiated tumors (8/13) than in well-differentiated or moderately differentiated cancers (3/15 and 9/32, respectively) and in stage FIGO II as compared with stage FIGO Ib tumors (12/23 and 5/24, respectively, p = 0.04). Interestingly, staining was mostly nuclear in well-differentiated tumors, but involved both nuclei and cytoplasm in less differentiated cancers. Positivities of comparable frequency were also detectable in a smaller series of specimens upon staining with MAGE-A1- or NY-ESO-1/LAGE-1-specific reagents. Considering the high tumor specificity of C/T TAA, our data provide the rationale for the design of immunotherapy procedures targeting these antigens in cervical cancers.

BackgroundNeratinib is an irreversible pan-HER tyrosine kinase inhibitor that inhibits PI3K/Akt and MAPK signaling pathways after HER2 receptor activation. The ExteNET study showed that neratinib significantly improved 5-year invasive disease-free survival (iDFS) in women who completed trastuzumab-based adjuvant therapy for early breast cancer (EBC). We assessed the prognostic and predictive significance of PIK3CA alterations in patients in ExteNET.MethodsParticipants were women aged ≥ 18 years (≥ 20 years in Japan) with stage 1–3c (modified to stage 2–3c in February 2010) operable breast cancer, who had completed (neo)adjuvant chemotherapy plus trastuzumab ≤ 2 years before randomization, with no evidence of disease recurrence or metastatic disease at study entry. Patients were randomized to oral neratinib 240 mg/day or placebo for 1 year. Formalin-fixed, paraffin-embedded primary tumor specimens underwent polymerase chain reaction (PCR) PIK3CA testing for two hotspot mutations in exon 9, one hot-spot mutation in exon 20, and fluorescence in situ hybridization (FISH) analysis for PIK3CA amplification. The primary endpoint (iDFS) was tested with log-rank test and hazard ratios (HRs) estimated using Cox proportional-hazards models.ResultsAmong the intent-to-treat population (n = 2840), tumor specimens were available for PCR testing (991 patients) and PIK3CA FISH (702 patients). Overall, 262 samples were PIK3CA altered: 201 were mutated (77%), 52 (20%) were amplified, and 9 (3%) were mutated and amplified. iDFS was non-significantly worse in placebo-treated patients with altered vs wild-type PIK3CA (HR 1.34; 95% CI 0.72–2.50; P = 0.357). Neratinib’s effect over placebo was significant in patients with PIK3CA-altered tumors (HR 0.41; 95% CI 0.17–0.90, P = 0.028) but not PIK3CA wild-type tumors (HR 0.72; 95% CI 0.36–1.41; P = 0.34). The interaction test was non-significant (P = 0.309).ConclusionsAlthough there was a greater absolute risk reduction associated with neratinib treatment of patients with PIK3CA-altered tumors in ExteNET, current data do not support PIK3CA alteration as a predictive biomarker of response to neratinib in HER2-positive EBC.Trial registrationClinicalTrials.gov, NCT00878709. Trial registered April 9, 2009.Electronic supplementary materialThe online version of this article (10.1186/s13058-019-1115-2) contains supplementary material, which is available to authorized users.

AimTo immunohistochemically evaluate the expression of MAGE-A1, MAGE-A, and NY-ESO-1 cancer/testis (C/T) tumor antigens in medullary breast cancer (MBC) tumor samples and to analyze it in relation to the clinicopathological features.MethodsThis retrospective study included samples from 49 patients: 40 with typical MBC and 9 with atypical MBC. Tumor specimens were obtained from patients operated on in the University Hospital for Tumors and the Sisters of Mercy University Hospital, Zagreb, Croatia, from 1999 to 2005. Standard immunohistochemistry was used on archival paraffin-embedded MBC tissues.ResultsMAGE-A1, MAGE-A, and NY-ESO-1 antigens were expressed in 33% (16/49), 33% (16/49), and 22% (11/49) of patients, respectively. No difference between the groups with and without C/T tumor antigen expression in age at diagnosis, tumor size, axillary lymph node metastasis, adjuvant therapy, and HER-2 expression was identified. Significantly more patients died in the MAGE-A-positive group than in the MAGE-A-negative group (P = 0.010), whereas a borderline significance was found between MAGE-A1-positive and the MAGE-A1-negative group (P = 0.079) and between NY-ESO-1-positive and NY-ESO-1-negative group (P = 0.117). Overall survival, as evaluated by the Kaplan-Meier curves, was lower in MAGE-A1- (P = 0.031), MAGE-A- (P = 0.004), NY-ESO-1-positive groups (P = 0.077).ConclusionExpression of C/T antigens may represent a marker of potential prognostic relevance in MBC.