J Cancer 2014; 5(2):156-165. doi:10.7150/jca.7668 This issue

Research Paper

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

Jyothi S. Prabhu1✉, Aruna Korlimarla1, Krisha Desai1, Annie Alexander1, Rohini Raghavan1, CE Anupama1, Nandini Dendukuri3, Suraj Manjunath2, Marjorrie Correa4, N Raman5, Anjali Kalamdani5, MSN Prasad5, K.S Gopinath5, B.S. Srinath6, T.S. Sridhar1

1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India
2. Department of Surgical Oncology, St. John's Medical College and Hospital, Bangalore, India
3. Department of Medicine, McGill University, Montreal, Quebec, Canada, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
4. Department of Pathology, St. John's Medical College and Hospital, Bangalore, India
5. Rangadore Memorial Hopsital, Bangalore, India
6. Shankara Cancer Hospital and Research Centre, Bangalore, India

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Prabhu JS, Korlimarla A, Desai K, Alexander A, Raghavan R, Anupama CE, Dendukuri N, Manjunath S, Correa M, Raman N, Kalamdani A, Prasad MSN, Gopinath KS, Srinath BS, Sridhar TS. A Majority of Low (1-10%) ER Positive Breast Cancers Behave Like Hormone Receptor Negative Tumors. J Cancer 2014; 5(2):156-165. doi:10.7150/jca.7668. Available from https://www.jcancer.org/v05p0156.htm

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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.

Keywords: ER 1-10 %, gene expression, q-RT-PCR, FFPE, Breast Cancer