Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Oct 1;19(19):5533-40.
doi: 10.1158/1078-0432.CCR-13-0799. Epub 2013 Aug 15.

Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes

Hiroko Masuda  1 , Keith A Baggerly, Ying Wang, Ya Zhang, Ana Maria Gonzalez-Angulo, Funda Meric-Bernstam, Vicente Valero, Brian D Lehmann, Jennifer A Pietenpol, Gabriel N Hortobagyi, W Fraser Symmans, Naoto T Ueno
Affiliations

Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes

Hiroko Masuda et al. Clin Cancer Res. .

Abstract

Purpose: The clinical relevancy of the 7-subtype classification of triple-negative breast cancer (TNBC) reported by Lehmann and colleagues is unknown. We investigated the clinical relevancy of TNBC heterogeneity by determining pathologic complete response (pCR) rates after neoadjuvant chemotherapy, based on TNBC subtypes.

Experimental design: We revalidated the Lehmann and colleagues experiments using Affymetrix CEL files from public datasets. We applied these methods to 146 patients with TNBC with gene expression microarrays obtained from June 2000 to March 2010 at our institution. Of those, 130 had received standard neoadjuvant chemotherapy and had evaluable pathologic response data. We classified the TNBC samples by subtype and then correlated subtype and pCR status using Fisher exact test and a logistic regression model. We also assessed survival and compared the subtypes with PAM50 intrinsic subtypes and residual cancer burden (RCB) index.

Results: TNBC subtype and pCR status were significantly associated (P = 0.04379). The basal-like 1 (BL1) subtype had the highest pCR rate (52%); basal-like 2 (BL2) and luminal androgen receptor had the lowest (0% and 10%, respectively). TNBC subtype was an independent predictor of pCR status (P = 0.022) by a likelihood ratio test. The subtypes better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like).

Conclusions: Classifying TNBC by 7 subtypes predicts high versus low pCR rate. We confirm the clinical relevancy of the 7 subtypes of TNBC. We need to prospectively validate whether the pCR rate differences translate into long-term outcome differences. The 7-subtype classification may spur innovative personalized medicine strategies for patients with TNBC.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: There is no conflict in our study.

Figures

Figure 1
Figure 1
Figure 1A. Distant metastasis-free survival by TNBC subtype Figure 1B. Overall survival by TNBC subtype
Figure 2
Figure 2
Figure 2A. The relationship between PAM50 subtypes and the 7 subtypes (basal-like subtype) Figure 2B. The relationship between PAM50 subtypes and the 7 subtypes (Non-basal like subtypes)
Figure 3
Figure 3
The relationship between RCB index and the 7 subtypes
See this image and copyright information in PMC

References

    1. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109:1721–8. - PubMed
    1. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34. - PubMed
    1. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011:121. - PMC - PubMed
    1. Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81. - PubMed
    1. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804. - PubMed

Publication types