HER2 Support Group Forums - View Single Post - a cheap, readily available and reproducible way to distinguisn triple positives and

Lani · 05-13-2009, 09:28 AM

therefore be better able to predict their prognosis and determine best treatment

Immunohistochemistry Tests Distinguish Breast Cancer Subtypes
[Eureka News Service]

A panel of four immunohistochemistry tests can distinguish luminal A and B breast cancer subtypes.
No simple immunohistochemical test has been available to distinguish luminal A from B, which are the most common of five breast cancer subtypes defined by gene expression profiling. Luminal B is characterized by more proliferating cells and worse patient prognoses.
In the current study, Torsten O. Nielsen, M.D., Ph.D., of the University of British Columbia in Vancouver, and colleagues subtyped 357 breast tumors by gene expression profiling and tested them for Ki67 expression by immunohistochemistry to determine a cut point that distinguished between luminal A and B tumors. They then examined 2,847 independent breast tumors with four immunohistochemical tests, including estrogen and progesterone receptor expression, Ki67 expression, and HER2 status.
The researchers found that Ki67 was expressed in 13 percent or less of the cells in luminal A tumors. Using that cut point for Ki67 expression, the four immunohistochemistry tests could distinguish between luminal A and luminal B subtypes in the independent series of breast cancers.
"Although we consider breast cancer molecular subtyping by gene expression profiling to be the gold standard, we nevertheless believe that there is an immediate need for well-defined and validated immunopanels for worldwide clinical diagnostic use," the authors conclude.

based on:
EARLY VIEW: OPEN ACCESS: Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer
[Journal of the National Cancer Institute]
Background: Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival.
Methods: Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan-Meier curves and multivariable Cox regression.
Results: Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor-positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal-HER2 positive. Luminal B and luminal-HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer-specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal-HER2 subtypes.
Conclusion: Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.

So tamoxifen alone did much more poorly in triple positives, but the majority still survived 10 years.

This is the first time I have seen a Ki-67 cut-off point other than + or -.

Glad to see people working on this as before triple positive seemed to be an orphan type of breast cancer, as it did not fit into the established "breast cancer subtypes" well.

05-13-2009, 09:28 AM	#1
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	a cheap, readily available and reproducible way to distinguisn triple positives and therefore be better able to predict their prognosis and determine best treatment Immunohistochemistry Tests Distinguish Breast Cancer Subtypes [Eureka News Service] A panel of four immunohistochemistry tests can distinguish luminal A and B breast cancer subtypes. No simple immunohistochemical test has been available to distinguish luminal A from B, which are the most common of five breast cancer subtypes defined by gene expression profiling. Luminal B is characterized by more proliferating cells and worse patient prognoses. In the current study, Torsten O. Nielsen, M.D., Ph.D., of the University of British Columbia in Vancouver, and colleagues subtyped 357 breast tumors by gene expression profiling and tested them for Ki67 expression by immunohistochemistry to determine a cut point that distinguished between luminal A and B tumors. They then examined 2,847 independent breast tumors with four immunohistochemical tests, including estrogen and progesterone receptor expression, Ki67 expression, and HER2 status. The researchers found that Ki67 was expressed in 13 percent or less of the cells in luminal A tumors. Using that cut point for Ki67 expression, the four immunohistochemistry tests could distinguish between luminal A and luminal B subtypes in the independent series of breast cancers. "Although we consider breast cancer molecular subtyping by gene expression profiling to be the gold standard, we nevertheless believe that there is an immediate need for well-defined and validated immunopanels for worldwide clinical diagnostic use," the authors conclude. based on: EARLY VIEW: OPEN ACCESS: Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer [Journal of the National Cancer Institute] Background: Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival. Methods: Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan-Meier curves and multivariable Cox regression. Results: Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor-positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal-HER2 positive. Luminal B and luminal-HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer-specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal-HER2 subtypes. Conclusion: Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes. So tamoxifen alone did much more poorly in triple positives, but the majority still survived 10 years. This is the first time I have seen a Ki-67 cut-off point other than + or -. Glad to see people working on this as before triple positive seemed to be an orphan type of breast cancer, as it did not fit into the established "breast cancer subtypes" well.