Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature

Pat W. Whitworth; Peter D. Beitsch; James V. Pellicane; Paul L. Baron; Laura A. Lee; Carrie L. Dul; Mary K. Murray; Mark A. Gittleman; Raye J. Budway; Rakhshanda Layeequr Rahman; Pond R. Kelemen; William C. Dooley; David T. Rock; Kenneth H. Cowan; Beth Ann Lesnikoski; Julie L. Barone; Andrew Y. Ashikari; Beth B. Dupree; Shiyu Wang; Andrea R. Menicucci; Erin B. Yoder; Christine Finn; Kate Corcoran; Lisa E. Blumencranz; William Audeh

doi:10.1200/PO.21.00463

Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature

Pat W. Whitworth, Peter D. Beitsch, James V. Pellicane, Paul L. Baron, Laura A. Lee, Carrie L. Dul, Mary K. Murray, Mark A. Gittleman, Raye J. Budway, Rakhshanda Layeequr Rahman, Pond R. Kelemen, William C. Dooley, David T. Rock, Kenneth H. Cowan, Beth Ann Lesnikoski, Julie L. Barone, Andrew Y. Ashikari, Beth B. Dupree, Shiyu Wang, Andrea R. MenicucciErin B. Yoder, Christine Finn, Kate Corcoran, Lisa E. Blumencranz, William Audeh

Research output: Contribution to journal › Article › peer-review

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Abstract

PURPOSEThe 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.METHODSNeoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC).RESULTS80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34% v 38%; P =.52), and significantly higher pCR than ER+/Luminal A (2%; P <.001) and ER+/Luminal B (6%; P <.001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR.CONCLUSIONSignificant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.

Original language	English (US)
Journal	JCO Precision Oncology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1200/PO.21.00463
State	Published - Apr 1 2022

ASJC Scopus subject areas

Oncology
Cancer Research

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Whitworth, P. W., Beitsch, P. D., Pellicane, J. V., Baron, P. L., Lee, L. A., Dul, C. L., Murray, M. K., Gittleman, M. A., Budway, R. J., Rahman, R. L., Kelemen, P. R., Dooley, W. C., Rock, D. T., Cowan, K. H., Lesnikoski, B. A., Barone, J. L., Ashikari, A. Y., Dupree, B. B., Wang, S., ... Audeh, W. (2022). Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature. JCO Precision Oncology, 6(1). https://doi.org/10.1200/PO.21.00463

Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature. / Whitworth, Pat W.; Beitsch, Peter D.; Pellicane, James V. et al.
In: JCO Precision Oncology, Vol. 6, No. 1, 01.04.2022.

Research output: Contribution to journal › Article › peer-review

Whitworth, PW, Beitsch, PD, Pellicane, JV, Baron, PL, Lee, LA, Dul, CL, Murray, MK, Gittleman, MA, Budway, RJ, Rahman, RL, Kelemen, PR, Dooley, WC, Rock, DT, Cowan, KH, Lesnikoski, BA, Barone, JL, Ashikari, AY, Dupree, BB, Wang, S, Menicucci, AR, Yoder, EB, Finn, C, Corcoran, K, Blumencranz, LE & Audeh, W 2022, 'Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature', JCO Precision Oncology, vol. 6, no. 1. https://doi.org/10.1200/PO.21.00463

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title = "Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature",

abstract = "PURPOSEThe 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.METHODSNeoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC).RESULTS80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34% v 38%; P =.52), and significantly higher pCR than ER+/Luminal A (2%; P <.001) and ER+/Luminal B (6%; P <.001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR.CONCLUSIONSignificant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.",

author = "Whitworth, {Pat W.} and Beitsch, {Peter D.} and Pellicane, {James V.} and Baron, {Paul L.} and Lee, {Laura A.} and Dul, {Carrie L.} and Murray, {Mary K.} and Gittleman, {Mark A.} and Budway, {Raye J.} and Rahman, {Rakhshanda Layeequr} and Kelemen, {Pond R.} and Dooley, {William C.} and Rock, {David T.} and Cowan, {Kenneth H.} and Lesnikoski, {Beth Ann} and Barone, {Julie L.} and Ashikari, {Andrew Y.} and Dupree, {Beth B.} and Shiyu Wang and Menicucci, {Andrea R.} and Yoder, {Erin B.} and Christine Finn and Kate Corcoran and Blumencranz, {Lisa E.} and William Audeh",

note = "Publisher Copyright: {\textcopyright} American Society of Clinical Oncology.",

year = "2022",

month = apr,

day = "1",

doi = "10.1200/PO.21.00463",

language = "English (US)",

volume = "6",

journal = "JCO Precision Oncology",

issn = "2473-4284",

publisher = "Lippincott Williams and Wilkins",

number = "1",

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TY - JOUR

T1 - Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature

AU - Whitworth, Pat W.

AU - Beitsch, Peter D.

AU - Pellicane, James V.

AU - Baron, Paul L.

AU - Lee, Laura A.

AU - Dul, Carrie L.

AU - Murray, Mary K.

AU - Gittleman, Mark A.

AU - Budway, Raye J.

AU - Rahman, Rakhshanda Layeequr

AU - Kelemen, Pond R.

AU - Dooley, William C.

AU - Rock, David T.

AU - Cowan, Kenneth H.

AU - Lesnikoski, Beth Ann

AU - Barone, Julie L.

AU - Ashikari, Andrew Y.

AU - Dupree, Beth B.

AU - Wang, Shiyu

AU - Menicucci, Andrea R.

AU - Yoder, Erin B.

AU - Finn, Christine

AU - Corcoran, Kate

AU - Blumencranz, Lisa E.

AU - Audeh, William

PY - 2022/4/1

Y1 - 2022/4/1

N2 - PURPOSEThe 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.METHODSNeoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC).RESULTS80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34% v 38%; P =.52), and significantly higher pCR than ER+/Luminal A (2%; P <.001) and ER+/Luminal B (6%; P <.001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR.CONCLUSIONSignificant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.

AB - PURPOSEThe 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.METHODSNeoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC).RESULTS80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34% v 38%; P =.52), and significantly higher pCR than ER+/Luminal A (2%; P <.001) and ER+/Luminal B (6%; P <.001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR.CONCLUSIONSignificant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.

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Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature

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