Experts' opinion: Recommendations for retesting breast cancer metastases for HER2 and hormone receptor status

Abstract The human epidermal growth factor receptor 2 (HER2) and hormone receptor status of recurrent breast cancer may change between the tumor and metastases from negative to positive and vice versa, potentially affecting the treatment regimen. Retesting of metastases may therefore be crucial to allow appropriate selection of patients for whom targeted therapy is indicated; however, retesting is not routinely performed. This article recommends that metastases be retested for HER2 and hormone receptor status and provides practical guidance on when and how to retest, as agreed by a panel of expert pathologists with extensive experience of HER2 and hormone receptor testing

Chromogenic in situ hybridisation for the assessment of HER2 status in breast cancer: an international validation ring study

ABSTRACT: INTRODUCTION: Before any new methodology can be introduced into the routine diagnostic setting it must be technically validated against the established standards. To this end, a ring study involving five international pathology laboratories was initiated to validate chromogenic in situ hybridisation (CISHTM) against fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) as a test for assessing human epidermal growth factor receptor-2 (HER2) status in breast cancer. METHODS: Each laboratory performed CISHTM, FISH and IHC on its own samples. Unstained sections from each case were also sent to another participating laboratory for blinded retesting by CISHTM ('outside CISHTM'). RESULTS: A total of 211 invasive breast carcinoma cases were tested. In 76 cases with high amplification (HER2/CEP17 ratio >4.0) by FISH, 73 cases (96%) scored positive (scores [greater than or equal to] 6) by 'outside CISHTM'. For FISH-negative cases (HER2/CEP17 ratio <2.0), 94 of 100 cases (94%) had CISHTM scores indicating no amplification (score GBP5), and only three cases were positive by CISHTM; in the three remaining cases, no CISHTM result could be obtained. For cases with low-level amplification using FISH (HER2/CEP17 ratio 2.0-4.0), 20 of 35 had CISHTM scores indicating gene amplification. Inter-laboratory concordance for was also very high: 95% for normal HER2 copy number (1-5 copies); and 92% for cases with HER2 copy numbers [greater than or equal to] 6. CISHTM intra-laboratory concordance with IHC was 92% for IHC-negative cases (IHC 0/1+) and 91% for IHC 3+ cases. Among IHC 2+ cases, CISHTM was 100% concordant with samples showing high amplification by FISH, and 94% concordant with FISH-negative samples. CONCLUSION: These results show that CISHTM inter-and intra-laboratory concordance to FISH and IHC is very high, even in equivocal IHC 2+ cases. Therefore, we conclude that CISHTM is a methodology that is a viable alternative to FISH in the HER2 testing algorith

Biological Markers Predictive of Invasive Recurrence in DCIS

DCIS is a heterogeneous group of non-invasive cancers of the breast characterized by various degrees of differentiation and unpredictable propensity for transformation into invasive carcinoma. We examined the expression and prognostic value of 9 biological markers with a potential role in tumor progression in 133 patients with pure DCIS treated with breast conserving surgery alone, between 1982–2000. Histology was reviewed and immunohistochemical staining was performed. Pearson correlation coefficient was used to determine the associations between markers and histopathological features. Univariate and multivariate analysis examined associations between time to recurrence and clinicopathologic features and biological markers

Estrogen and progesterone receptor levels in nonneoplastic breast epithelium of breast cancer cases versus benign breast biopsy controls

<p>Abstract</p> <p>Background</p> <p>Previous studies and biological mechanisms of carcinogenesis suggest that the steroid receptor content of benign breast epithelium may be related to breast cancer risk. The objective in this study was to compare the levels of estrogen receptor-α (ER) and progesterone receptor (PR) in nonneoplastic breast epithelium between breast cancer cases and biopsy controls.</p> <p>Methods</p> <p>Between 1995 and 1997 at two sites (Women's College Hospital in Toronto and Kingston General Hospital), 667 women who were scheduled for diagnostic excisional breast biopsies completed a questionnaire providing personal information and agreed to allow analysis of routinely resected tissue. Histological slides with nonneoplastic epithelium were available for 101 cancer cases and 200 biopsy controls in Toronto and for 105 cancer cases and 119 controls in Kingston. Nonneoplastic epithelium was examined with immunohistochemical assays to determine the percent of epithelial cells staining for ER and PR. Unconditional logistic regression was used to calculate odds ratios (OR) stratified by study site.</p> <p>Results</p> <p>The ER content of nonneoplastic tissue was higher in cases than biopsy controls in unadjusted analyses; after adjustment for age, however, a weak association remained in only one of the study sites. After adjustment for age, the PR content of nonneoplastic tissue was slightly lower in breast cancer cases than controls in one study site. Furthermore, this inverse association was confined to women with PR negative breast cancer in comparison to the controls. No interaction between ER and PR content of nonneoplastic tissue was observed in relation to the odds of having breast cancer.</p> <p>Conclusion</p> <p>The results of this study are consistent with only a slight indication of increased ER levels in nonneoplastic tissue in breast cancer cases relative to controls. This study contributes to the understanding of breast cancer by examining both ER and PR in nonneoplastic tissue. Limitations remain, however, such as the necessity of using as controls women with benign breast changes, difficulties in selecting the appropriate tissue for analysis, and tissue sampling concurrent to diagnosis.</p