# IMMUNOHISTOCHEMICAL CLASSIFICATION OF HUMAN BREAST TUMOR

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 1991 · $161,930

## Abstract

This proposal addresses the important issue of hormone therapy
failures among post-menopausal women with estrogen receptor-
positive ER(+) breast cancer with or without progesterone receptors
(PR).  Clinical correlation studies have shown that the current
methods of sub-classification of ER(+) tumors based on the
presence/absence of proteins which are markers of estrogen action
(ex. PR) are inadequate for precise differentiation of truly
hormone-responsive from hormone-resistant ER(+) tumors.  The level
of prediction error (30% ER+/PR+ failures and 25-30% ER+/PR-
responders to hormone therapy) translates to significant
proportions because 75% of 100,000 newly diagnosed cases of breast
cancer will be ER(+) and 50-60% of these will be PR(+).  A precise
sub-classification of primary biopsies of ER(+) tumors will be
valuable for early selection of potential hormone therapy failures
when the tumor burden is small so that alternative therapies can
be administered to benefit the patient.  With the help of
polyclonal antibodies (Pab) to ER, in-vitro hormone incubation
procedure and immunohistochemistry (IF) developed in our lab we
have identified two varieties of ER in human cancers which,
although capable of binding estrogens with high affinity, are
defective in their nuclear binding function.  Preliminary clinical
correlation data have also revealed a preponderance of these
defective ER among those breast cancers which are hormone resistant
and of non-defective ER among those which are responsive to hormone
therapy.  Based on these results and of previous investigations
emphasizing a correlation between defective ER and hormone-
independent growth WE PROPOSE THAT A SUB-CLASSIFICATION OF ER(+)
TUMORS BASED ON NUCLEAR BINDING CHARACTERISTICS MAY DISCERN TRULY
HORMONE-DEPENDENT TUMORS FROM RESISTANT ONES.

Our SPECIFIC GOALS , therefore, are: (1) To develop novel
monoclonal antibodies (Mabs) to identify and discriminate among the
defective/non-defective ER based on their epitope differences;
(2) To immunotype with Pabs and IF, the ER in established ER(+)
human breast cancer cell lines with known hormone response data;
(3) To attempt establishment of primary cultures from malignant
fluids of patients with ER(+) tumors who failed hormone therapy and
to immunotype ER with Pabs; (4) To immunotype sequential biopsies
of ER(+) tumors (primary vs recurrent) to find out if recurrences
become enriched in cells with defective ER; to increase patient
population for clinical response to hormone therapy.

## Key facts

- **NIH application ID:** 3175910
- **Project number:** 5R01CA037944-06
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **SAM.gov UEI:** C1F5LNUF7W86
- **Principal Investigator:** SHANTHI RAAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $161,930
- **Award type:** 5
- **Project period:** 1989-01-01 → 1992-12-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175910

## Citation

> US National Institutes of Health, RePORTER application 3175910, IMMUNOHISTOCHEMICAL CLASSIFICATION OF HUMAN BREAST TUMOR (5R01CA037944-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175910. Licensed CC0.

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