A Majority of Low (1-10%) ER Positive Breast Cancers Behave Like Hormone Receptor Negative Tumors

作者：Prabhu Jyothi S^*; Korlimarla Aruna; Desai Krisha; Alexander Annie; Raghavan Rohini; Anupama C E; Dendukuri Nandini; Manjunath Suraj; Correa Marjorrie; Raman N; Kalamdani Anjali; Prasad M S N; Gopinath K S; Srinath B S; Sridhar T S

来源：Journal of Cancer, 2014, 5(2): 156-165.

DOI：10.7150/jca.7668

• ER 1-10 %
• gene expression
• q-RT-PCR
• FFPE
• Breast Cancer

Background: The 2010 guidelines by ASCO-CAP have mandated that breast cancer specimens with >= 1% positively staining cells by immunohistochemistry should be considered Estrogen Receptor (ER) positive. This has led to a subclass of low-ER positive (1-10%) breast cancers. We have examined the biology and clinical behavior of these low ER staining tumors.
Methods: We have developed a probabilistic score of the "ER-positivity" by quantitative estimation of ER related gene transcripts from FFPE specimens. Immunohistochemistry for ER was done on 240 surgically excised tumors of primary breast cancer. Relative transcript abundance of 3 house-keeping genes and 6 ER related genes were determined by q-RT PCR. A logistic regression model using 3 ER associated genes provided the best probability function, and a cut-off value was derived by ROC analysis. 144 high ER (> 10%), 75 ER negative and 21 low-ER (1-10%) tumors were evaluated using the probability score and the disease specific survival was compared.
Results: Half of the low-ER positive tumors were assigned to the ER negative group based on the probability score; in contrast 95% of ER negative and 92% of the high ER positive tumors were assigned to the appropriate ER group (p<0.0001). The survival of the low-ER group was intermediate between that of the high ER positive and ER negative groups (p<0.05).
Conclusion: Our results suggest that the newly lowered ASCO-CAP criteria for ER positivity, leads to the false categorization of biologically ER negative tumors as ER positive ones. This may have particular relevance to India, where we have a much higher proportion of ER negative tumors in general.

• 出版日期2014
• 单位McGill