title: A Majority of Low (1-10%) ER Positive Breast Cancers Behave Like Hormone Receptor Negative Tumors.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India.
authors.forename: Jyothi S
authors.initials: JS
authors.lastname: Prabhu
authors.affiliation: 1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India.
authors.forename: Aruna
authors.initials: A
authors.lastname: Korlimarla
authors.affiliation: 1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India.
authors.forename: Krisha
authors.initials: K
authors.lastname: Desai
authors.affiliation: 1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India.
authors.forename: Annie
authors.initials: A
authors.lastname: Alexander
authors.affiliation: 1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India.
authors.forename: Rohini
authors.initials: R
authors.lastname: Raghavan
authors.affiliation: 1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India.
authors.forename: Ce
authors.initials: C
authors.lastname: Anupama
authors.affiliation: 3. Department of Medicine, McGill University, Montreal, Quebec, Canada, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors.forename: Nandini
authors.initials: N
authors.lastname: Dendukuri
authors.affiliation: 2. Department of Surgical Oncology, St. John's Medical College and Hospital, Bangalore, India.
authors.forename: Suraj
authors.initials: S
authors.lastname: Manjunath
authors.affiliation: 4. Department of Pathology, St. John's Medical College and Hospital, Bangalore, India.
authors.forename: Marjorrie
authors.initials: M
authors.lastname: Correa
authors.affiliation: 5. Rangadore Memorial Hopsital, Bangalore, India.
authors.forename: N
authors.initials: N
authors.lastname: Raman
authors.affiliation: 5. Rangadore Memorial Hopsital, Bangalore, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Kalamdani
authors.affiliation: 5. Rangadore Memorial Hopsital, Bangalore, India.
authors.forename: Msn
authors.initials: M
authors.lastname: Prasad
authors.affiliation: 5. Rangadore Memorial Hopsital, Bangalore, India.
authors.forename: K S
authors.initials: KS
authors.lastname: Gopinath
authors.affiliation: 6. Shankara Cancer Hospital and Research Centre, Bangalore, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Srinath
authors.affiliation: 1. Division of Molecular Medicine, St. John's Research Institute, Bangalore, India.
authors.forename: T S
authors.initials: TS
authors.lastname: Sridhar
keywords: Breast Cancer; ER 1-10 %; FFPE; gene expression; q-RT-PCR