TO THE EDITOR: Whenever possible, guideline recommendations should be based on compelling published evidence. Where a recommendation is not supported by such evidence, the guidelines should explicitly state the weaknesses in the evidence, whether the recommendation is based on unpublished evidence, or whether the authors have made a pragmatic decision. This information is particularly important if the recommendations have implications for health care resources. The American Society of Clinical Oncology and the College of American Pathologists guidelines on human epidermal growth factor receptor 2 (HER2) testing 1,2 are largely based on published evidence and are an important contribution to improving reproducibility and standardization of assessment.One of the new recommendations introduced in the recent guidelines 2 is the novel concept of histopathological concordance. Repeat testing on excision specimens is recommended if the preoperative core biopsy result is HER2 negative and the tumor is grade 3, which comprises more than a third of breast cancers, and for certain other combinations of grade, histological type, estrogen receptor status, and HER2 status. No evidence is provided to support this recommendation, which has significant financial and practical implications.Those studies showing relatively low levels of concordance of HER2 status between core biopsy and excision specimens included tumors diagnosed before publication of the 2007 HER2 guidelines. 1 More recent studies show that rates of concordance for HER2 between core biopsy and excision specimens of 98% to 99% are achievable. [3][4][5][6]7 To further address this issue, we have reviewed three concordance studies 6,8,9 in which HER2 status has been assessed on both core and subsequent excision specimens and in which data on relevant histologic features including tumor type, histological grade, size, and hormone receptor status are available. Of the 530 tumors, 11 (2%) had a different HER2 status identified in the core biopsy and excision specimens. Ten cases were negative in the core and positive in the excision; six cases were 2ϩ on immunohistochemistry and fluorescent in situ hybridization negative in the core and 2ϩ on immunohistochemistry and fluorescent in situ hybridization positive with ratios between 2.0 and 3.3 on excision. In three cases, the core biopsy was negative (0ϩ or 1ϩ), and the excision was HER2 positive. In one case, the core was positive, and the excision was negative. In these cases, the reason for discordance was often either HER2 amplification around the cutoff for positivity or tumor heterogeneity consistent with other studies. 3,9,10 Furthermore, we have reviewed 3,054 breast cancer tumor tissue samples consecutively reported in routine practice in Nottingham in the last 4 years (2010 to 2013). Ninety-eight cases (3%) had HER2 status assessed on core biopsy and the corresponding tumor excision specimen. Of those 98, the HER2 status of the index tumor was changed in two, and both were in the borderline result category (rat...

KLHL7 appears to play an important role in BC progression. High KLHL7 protein expression identified a subgroup of BC with aggressive behaviour and provided independent prognostic information.

High RAPH1 expression is correlated with aggressive breast cancer phenotypes and provides independent prognostic value in invasive breast cancer.