In fact, although not widely known since it is an extremely rare from of breast cancer, IBC (inflammatory breast cancer), not TNBC, is the most aggressive form of breast cancer with the most compromised survival. It is tested and explored in preclinical models via the SUM149 human IBC cell line, and/or through the MARY-X human IBC xenograft.

After IBC, TNBC (triple negative breast cancer) is the most prognosis- and outcome-compromised breast cancer type.

MDA-MB-468 is a basal BC cell line while MDA-MB-231 is a claudin-low cell line - a point Hamed Helal made above, to his credit - with claudin-3, claudinin-4 and claudinin-7 low, and typically with low Ki67 and E-cadherin, in contrast to MDA-MB-468 absent these and itself with high Ki-67 [1,2,3], and as I noted [4], MDA-MB-231 shows enrichment for markers associated with EMT and the expression of features associated with mammary cancer stem cells (CSCs), such as the CD44+CD24-/low phenotype, features NOT shared with MDA-MB-468, so they can be different in molecular and phenotypic behavior.

Many studies on potentially active agents for triple negative breast cancer disease have been conducted using, indifferently, MDA-MB-231 or MD-MD-468 (there are dozens of examples, many right here in ResearchGate), but MDA-MB-468 most closely maps basal tumors (EGFR-positivity and cytokeratins 5/6) while MDA-MB-231 closely maps not basality, but rather the new claudin-low (E-cadherin, claudin-3, claudinin-4 and claudinin-7 low) molecular subtype, and clearly these are vastly different in molecular and phenotypic behavior, with MDA-MB-468 being highly proliferative and prognostically highly compromised relative to MDA-MB-231, so it matters vastly which cancer cell line is chosen, and of course it will also matter vastly as to outcome obtained from any given preclinical study trying to determine the efficacy and responsivity of a particular therapeutic agent against one versus the other cell line, yet basic scientists often slur these together as "triple-negative" cell lines.

So MDA-MB-231 is characterized more critically by claudin-3 and claudinin-4 downregulation, low expression of the Ki-67 proliferation marker, enrichment for markers associated with EMT (the epithelial-mesenchymal transition), and, importantly, the expression of features associated with mammary cancer stem cells (CSCs), such as the CD44+CD24-/low phenotype, features NOT shared with MDA-MB-468. (As a final note, despite mistakenly being thought so, MDA-MB-435 is not a TNBC cell line, and indeed is not a breast cancer cell line at all, and is officially listed by all authoritative Cell Line Databanks/Registries (including ATCC among others) as a misidentified/misclassified melanoma cell line that should not be further used in the breast cancer context (see my paper: The Boundaries and Limitations of Preclinical Research: A Mini-Review [4]).

1. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010, 12:R68.

2. Neve RM, Chin K, Fridlyand J, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006, 10:515-527.

3. Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3:537-549.

4. Kaniklidis, C. The Boundaries and Limitations of Preclinical Research: A Mini-Review. (2013; publication pending: available from my ResearchGate Profile.

Constantine Kaniklidis

Director of Medical Research,

No Surrender Breast Cancer Foundation (NSBCF)

European Association for Cancer Research (EACR)

The most aggressiveBC type is Triple Negative Breast Cancer (TNBC). MDA-MB-231 is a TNBC cell line (Claudin low subtype)

In fact, although not widely known since it is an extremely rare from of breast cancer, IBC (inflammatory breast cancer), not TNBC, is the most aggressive form of breast cancer with the most compromised survival. It is tested and explored in preclinical models via the SUM149 human IBC cell line, and/or through the MARY-X human IBC xenograft.

After IBC, TNBC (triple negative breast cancer) is the most prognosis- and outcome-compromised breast cancer type.

MDA-MB-468 is a basal BC cell line while MDA-MB-231 is a claudin-low cell line - a point Hamed Helal made above, to his credit - with claudin-3, claudinin-4 and claudinin-7 low, and typically with low Ki67 and E-cadherin, in contrast to MDA-MB-468 absent these and itself with high Ki-67 [1,2,3], and as I noted [4], MDA-MB-231 shows enrichment for markers associated with EMT and the expression of features associated with mammary cancer stem cells (CSCs), such as the CD44+CD24-/low phenotype, features NOT shared with MDA-MB-468, so they can be different in molecular and phenotypic behavior.

Many studies on potentially active agents for triple negative breast cancer disease have been conducted using, indifferently, MDA-MB-231 or MD-MD-468 (there are dozens of examples, many right here in ResearchGate), but MDA-MB-468 most closely maps basal tumors (EGFR-positivity and cytokeratins 5/6) while MDA-MB-231 closely maps not basality, but rather the new claudin-low (E-cadherin, claudin-3, claudinin-4 and claudinin-7 low) molecular subtype, and clearly these are vastly different in molecular and phenotypic behavior, with MDA-MB-468 being highly proliferative and prognostically highly compromised relative to MDA-MB-231, so it matters vastly which cancer cell line is chosen, and of course it will also matter vastly as to outcome obtained from any given preclinical study trying to determine the efficacy and responsivity of a particular therapeutic agent against one versus the other cell line, yet basic scientists often slur these together as "triple-negative" cell lines.

So MDA-MB-231 is characterized more critically by claudin-3 and claudinin-4 downregulation, low expression of the Ki-67 proliferation marker, enrichment for markers associated with EMT (the epithelial-mesenchymal transition), and, importantly, the expression of features associated with mammary cancer stem cells (CSCs), such as the CD44+CD24-/low phenotype, features NOT shared with MDA-MB-468. (As a final note, despite mistakenly being thought so, MDA-MB-435 is not a TNBC cell line, and indeed is not a breast cancer cell line at all, and is officially listed by all authoritative Cell Line Databanks/Registries (including ATCC among others) as a misidentified/misclassified melanoma cell line that should not be further used in the breast cancer context (see my paper: The Boundaries and Limitations of Preclinical Research: A Mini-Review [4]).

1. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010, 12:R68.

2. Neve RM, Chin K, Fridlyand J, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006, 10:515-527.

3. Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3:537-549.

4. Kaniklidis, C. The Boundaries and Limitations of Preclinical Research: A Mini-Review. (2013; publication pending: available from my ResearchGate Profile.

Constantine Kaniklidis

Director of Medical Research,

No Surrender Breast Cancer Foundation (NSBCF)

European Association for Cancer Research (EACR)

Thank you Constantin, and I agree with you that we still need more focusing on the identification and GE of TNBC.

Thank very much for the information. Do you know what is the current treatment for TNBC??

There are a lot of drug riegim used in TNBC treatment according to the subtype but the famous catigory which is basal like TNBC is very sensitive to Cisplatin therapy ... but there are a lot of other combination riegim used currently ... so, you need to categories the TNBC and then choose the best therapy