Multiplexed assessment of the Southwest Oncology Group-directed intergroup breast cancer trial S9313 by AQUA shows that both high and low levels of HER2 are associated with poor outcome

Malini Harigopal, William E. Barlow, Greg Tedeschi, Peggy L. Porter, I. Tien Yeh, Charles Haskell, Robert Livingston, Gabriel N. Hortobagyi, George Sledge, Charles Shapiro, James N. Ingle, David L. Rimm, Daniel F. Hayes

Research output: Contribution to journalArticle

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Abstract

Assessment of key breast cancer tissue biomarkers is often done using nonquantitative methods. We hypothesized that use of continuous analysis of expression with the AQUA method of automated quantitative analysis will provide prognostic information beyond that attainable with conventional methods. A tissue microarray was made from 2123 of 3122 patients accrued to SWOG 9313, in which sequential doxorubicin (A) and cyclophosphamide (C) was compared with combination AC and in which all patients except premenopausal estrogen receptor (ER)-negative patients received tamoxifen. Multiplexed assays of 1) HER2 and estrogen receptor and 2) progesterone receptor (PgR) and p53 were performed on the two slides using the immunofluorescence-based AQUA method of automated quantitative analysis. Both ER and PgR showed unimodal distributions and significantly predicted disease-free survival when tested as continuous variables and adjusted for node status, tumor size, treatment, and menopausal status (P = 0.005 and P < 0.001, respectively). HER2, measured as a continuous variable, showed a biphasic effect on disease-free survival. Both high and low expressers of HER2 have worse outcomes (when low levels are equivalent to that seen in normal breast ducts). In patients who were uniformly treated with AC chemotherapy and tamoxifen (when indicated), both ER and PgR, assessed as continuous variables, were highly prognostic, whereas p53 expression was not. This assay method may provide a new companion diagnostic approach for targeted therapies.

Original languageEnglish (US)
Pages (from-to)1639-1647
Number of pages9
JournalAmerican Journal of Pathology
Volume176
Issue number4
DOIs
StatePublished - Apr 2010

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Breast Neoplasms
Progesterone Receptors
Estrogen Receptors
Tamoxifen
Disease-Free Survival
Estrogen Receptor beta
Tumor Biomarkers
Doxorubicin
Cyclophosphamide
Fluorescent Antibody Technique
Breast
Drug Therapy
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Multiplexed assessment of the Southwest Oncology Group-directed intergroup breast cancer trial S9313 by AQUA shows that both high and low levels of HER2 are associated with poor outcome. / Harigopal, Malini; Barlow, William E.; Tedeschi, Greg; Porter, Peggy L.; Yeh, I. Tien; Haskell, Charles; Livingston, Robert; Hortobagyi, Gabriel N.; Sledge, George; Shapiro, Charles; Ingle, James N.; Rimm, David L.; Hayes, Daniel F.

In: American Journal of Pathology, Vol. 176, No. 4, 04.2010, p. 1639-1647.

Research output: Contribution to journalArticle

Harigopal, M, Barlow, WE, Tedeschi, G, Porter, PL, Yeh, IT, Haskell, C, Livingston, R, Hortobagyi, GN, Sledge, G, Shapiro, C, Ingle, JN, Rimm, DL & Hayes, DF 2010, 'Multiplexed assessment of the Southwest Oncology Group-directed intergroup breast cancer trial S9313 by AQUA shows that both high and low levels of HER2 are associated with poor outcome', American Journal of Pathology, vol. 176, no. 4, pp. 1639-1647. https://doi.org/10.2353/ajpath.2010.090711
Harigopal, Malini ; Barlow, William E. ; Tedeschi, Greg ; Porter, Peggy L. ; Yeh, I. Tien ; Haskell, Charles ; Livingston, Robert ; Hortobagyi, Gabriel N. ; Sledge, George ; Shapiro, Charles ; Ingle, James N. ; Rimm, David L. ; Hayes, Daniel F. / Multiplexed assessment of the Southwest Oncology Group-directed intergroup breast cancer trial S9313 by AQUA shows that both high and low levels of HER2 are associated with poor outcome. In: American Journal of Pathology. 2010 ; Vol. 176, No. 4. pp. 1639-1647.
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