Are Androgen and Estrogen Receptors in DCIS Patients Prognostic Indicators of Relapse Independently of Treatment?

Ductal carcinoma in situ (DCIS) is a highly heterogenous tumor that is now more frequently diagnosed because of the increased number of screening programs. Women with DCIS are mainly treated with conservative surgery almost always followed by radiotherapy. Although conventional biomarkers, i.e. ER, PgR, Ki67, and HER2, have been extensively investigated in invasive tumors, little is known about their role in DCIS, especially that of the androgen receptor (AR). In the present study, the expression of conventional biomarkers and AR was determined by immunohistochemistry in 85 DCIS samples from patients monitored for a maximum of 13 years: 43 patients were treated with quadrantectomy and 42 patients underwent quadrantectomy and radiotherapy. Of these, 5 and 11 patients relapsed, respectively. Our findings showed that ER and PgR were higher in nonrelapsed than in relapsed patients (P=0.025 and 0.0038). In contrast, AR expression and the AR/ER ratio were higher in relapsed patients than in the nonrelapsed group (P=0.0069 and 0.0012). At the best cut-off value of 1.1, the AR/ER ratio showed an overall accuracy of 92% and 80% in predicting in situ relapse or progression to invasive carcinoma in DCIS patients treated with surgery and those treated with surgery plus radiotherapy, respectively. AR would therefore appear to be an independent prognostic biomarker in the latter group. Our preliminary results highlight the potentially important role of the AR/ER ratio as a predictive indicator of DCIS relapse, independently of treatment.

First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer.

BACKGROUND: CHEK2 is a multi-cancer susceptibility gene whose common germline mutations are known to contribute to the risk of developing breast and prostate cancer. CASE PRESENTATION: Here, we describe an Italian family with a high number of cases of breast cancer and other types of tumour subjected to the MLPA test to verify the presence of BRCA1, BRCA2 and CHEK2 deletions and duplications. We identified a new 23-kb duplication in the CHEK2 gene extending from intron 5 to 13 that was associated with breast cancer in the family. The presence and localisation of the alteration was confirmed by a second analysis by Next-Generation Sequencing. CONCLUSIONS: This finding suggests that CHEK2 mutations are heterogeneous and that techniques other than sequencing, such as MLPA, are needed to identify CHEK2 mutations. It also indicates that CHEK2 rare variants, such as duplications, can confer a high susceptibility to cancer development and should thus be studied in depth as most of our knowledge of CHEK2 concerns common mutations.

Intra-operative radiological margins assessment in conservative treatment for non-palpable DCIS: correlation to pathological examination and re-excision rate.

What constitutes an adequate surgical margin in partial mastectomy is still controversial: intra-operative specimen radiogram is commonly used during partial mastectomy for nonpalpable lesions in order verify the adequacy of the resection but what margin is to be considered "adequate" is still debatable. An intraoperative specimen mammogram was performed during all consecutive conservative resections for nonpalpable DCIS and a 15-mm radiological margin was considered "adequate". Margins were pathologically assessed and classified as "negative", "close" or "positive" and the rate of margin involvement constitued the main outcome of the study. Among 272 conservative interventions, 80.51% had negative margins at final pathology, 3.31% had close margins and 16.18% had positive margins. An intraoperative "adequate" margin of 15 mm as defined on intraoperative specimen mammogram granted a high rate of histologically negative margin at primary surgery; this finding was paralleled by confirmation of the treatment as conservative in 95% of cases.