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Published in: Annals of Surgical Oncology 13/2023

Open Access 01-09-2023 | Breast Cancer | Breast Oncology

The Predictive Utility of MammaPrint and BluePrint in Identifying Patients with Locally Advanced Breast Cancer Who are Most Likely to Have Nodal Downstaging and a Pathologic Complete Response After Neoadjuvant Chemotherapy

Authors: Peter Blumencranz, MD, FACS, Mehran Habibi, MD, Steve Shivers, PhD, Geza Acs, MD, Lisa E. Blumencranz, PhD, Erin B. Yoder, MS, Bastiaan van der Baan, MS, Andrea R. Menicucci, PhD, Patricia Dauer, PhD, William Audeh, MD, Charles E. Cox, MD

Published in: Annals of Surgical Oncology | Issue 13/2023

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Abstract

Background

Neoadjuvant chemotherapy (NCT) increases the feasibility of surgical resection by downstaging large primary breast tumors and nodal involvement, which may result in surgical de-escalation and improved outcomes. This subanalysis from the Multi-Institutional Neo-adjuvant Therapy MammaPrint Project I (MINT) trial evaluated the association between MammaPrint and BluePrint with nodal downstaging.

Patients and Methods

The prospective MINT trial (NCT01501487) enrolled 387 patients between 2011 and 2016 aged ≥ 18 years with invasive breast cancer (T2–T4). This subanalysis includes 146 patients with stage II–III, lymph node positive, who received NCT. MammaPrint stratifies tumors as having a Low Risk or High Risk of distant metastasis. Together with MammaPrint, BluePrint genomically (g) categorizes tumors as gLuminal A, gLuminal B, gHER2, or gBasal.

Results

Overall, 45.2% (n = 66/146) of patients had complete nodal downstaging, of whom 60.6% (n = 40/66) achieved a pathologic complete response. MammaPrint and combined MammaPrint and BluePrint were significantly associated with nodal downstaging (p = 0.007 and p < 0.001, respectively). A greater proportion of patients with MammaPrint High Risk tumors had nodal downstaging compared with Low Risk (p = 0.007). When classified with MammaPrint and BluePrint, more patients with gLuminal B, gHER2, and gBasal tumors had nodal downstaging compared with HR+HER2−, gLuminal A tumors (p = 0.538, p < 0.001, and p = 0.013, respectively).

Conclusions

Patients with genomically High Risk tumors, defined by MammaPrint with or without BluePrint, respond better to NCT and have a higher likelihood of nodal downstaging compared with patients with gLuminal A tumors. These genomic signatures can be used to select node-positive patients who are more likely to have nodal downstaging and avoid invasive surgical procedures.
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Literature
1.
go back to reference Mougalian SS, Soulos PR, Killelea BK, et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015;121(15):2544–52.CrossRefPubMed Mougalian SS, Soulos PR, Killelea BK, et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015;121(15):2544–52.CrossRefPubMed
2.
go back to reference Fisher B, Brown A, Mamounas EP, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):10.CrossRef Fisher B, Brown A, Mamounas EP, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):10.CrossRef
3.
go back to reference von Minckwitz G, Untch M, Blohmer JU, 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(15):1796–804.CrossRef von Minckwitz G, Untch M, Blohmer JU, 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(15):1796–804.CrossRef
4.
go back to reference Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17(2):460–9.CrossRefPubMed Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17(2):460–9.CrossRefPubMed
5.
go back to reference Fayanju OM, Ren Y, Thomas SM, et al. The clinical significance of breast-only and node-only pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT): a review of 20,000 breast cancer patients in the National Cancer Data Base (NCDB). Ann Surg. 2018;268(4):591–601.CrossRefPubMed Fayanju OM, Ren Y, Thomas SM, et al. The clinical significance of breast-only and node-only pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT): a review of 20,000 breast cancer patients in the National Cancer Data Base (NCDB). Ann Surg. 2018;268(4):591–601.CrossRefPubMed
6.
go back to reference Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.CrossRefPubMed Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.CrossRefPubMed
7.
go back to reference Mougalian SS, Hernandez M, Lei X, et al. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2(4):508–16.CrossRefPubMedPubMedCentral Mougalian SS, Hernandez M, Lei X, et al. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2(4):508–16.CrossRefPubMedPubMedCentral
8.
go back to reference Rouzier R, Extra JM, Klijanienko J, et al. Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol. 2002;20(5):6.CrossRef Rouzier R, Extra JM, Klijanienko J, et al. Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol. 2002;20(5):6.CrossRef
9.
go back to reference Hayashi N, Takahashi Y, Matsuda N, et al. The prognostic effect of changes in tumor stage and nodal status after neoadjuvant chemotherapy in each primary breast cancer subtype. Clin Breast Cancer. 2018;18(2):e219–29.CrossRefPubMed Hayashi N, Takahashi Y, Matsuda N, et al. The prognostic effect of changes in tumor stage and nodal status after neoadjuvant chemotherapy in each primary breast cancer subtype. Clin Breast Cancer. 2018;18(2):e219–29.CrossRefPubMed
10.
go back to reference Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310(14):1455–61.CrossRefPubMedPubMedCentral Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310(14):1455–61.CrossRefPubMedPubMedCentral
11.
go back to reference Erdahl LM, Boughey JC. Use of sentinel lymph node biopsy to select patients for local-regional therapy after neoadjuvant chemotherapy. Curr Breast Cancer Rep. 2014;6(1):10–6.CrossRefPubMedPubMedCentral Erdahl LM, Boughey JC. Use of sentinel lymph node biopsy to select patients for local-regional therapy after neoadjuvant chemotherapy. Curr Breast Cancer Rep. 2014;6(1):10–6.CrossRefPubMedPubMedCentral
13.
go back to reference Simons JM, van Nijnatten TJA, van der Pol CC, Luiten EJT, Koppert LB, Smidt ML. Diagnostic accuracy of different surgical procedures for axillary staging after neoadjuvant systemic therapy in node-positive breast cancer: a systematic review and meta-analysis. Ann Surg. 2019;269(3):432–42.CrossRefPubMed Simons JM, van Nijnatten TJA, van der Pol CC, Luiten EJT, Koppert LB, Smidt ML. Diagnostic accuracy of different surgical procedures for axillary staging after neoadjuvant systemic therapy in node-positive breast cancer: a systematic review and meta-analysis. Ann Surg. 2019;269(3):432–42.CrossRefPubMed
14.
go back to reference Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg. 2015;261(2):378–82.CrossRefPubMed Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg. 2015;261(2):378–82.CrossRefPubMed
15.
go back to reference Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016;34(10):1072–8.CrossRefPubMedPubMedCentral Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016;34(10):1072–8.CrossRefPubMedPubMedCentral
16.
go back to reference Cardoso F, van't Veer LJ, Bogaerts J, et al. 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016; 375(8):717–729. Cardoso F, van't Veer LJ, Bogaerts J, et al. 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016; 375(8):717–729.
17.
go back to reference Piccart M, van't Veer LJ, Poncet C, et al. 70-Gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol. 2021; 22(4):476-488. Piccart M, van't Veer LJ, Poncet C, et al. 70-Gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol. 2021; 22(4):476-488.
18.
go back to reference Krijgsman O, Roepman P, Zwart W, et al. A diagnostic gene profile for molecular subtyping of breast cancer associated with treatment response. Breast Cancer Res Treat. 2012;133(1):37–47.CrossRefPubMed Krijgsman O, Roepman P, Zwart W, et al. A diagnostic gene profile for molecular subtyping of breast cancer associated with treatment response. Breast Cancer Res Treat. 2012;133(1):37–47.CrossRefPubMed
19.
go back to reference Whitworth P, Beitsch PD, Pellicane JV, et al. Age-independent preoperative chemosensitivity and 5-year outcome determined by combined 70- and 80-gene signature in a prospective trial in early-stage breast cancer. Ann Surg Oncol. 2022;29(7):4141–52.CrossRefPubMedPubMedCentral Whitworth P, Beitsch PD, Pellicane JV, et al. Age-independent preoperative chemosensitivity and 5-year outcome determined by combined 70- and 80-gene signature in a prospective trial in early-stage breast cancer. Ann Surg Oncol. 2022;29(7):4141–52.CrossRefPubMedPubMedCentral
20.
go back to reference Whitworth PW, Beitsch PD, Pellicane JV, et al. 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 Precis Oncol. 2022;6:e2100463.CrossRefPubMedPubMedCentral Whitworth PW, Beitsch PD, Pellicane JV, et al. 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 Precis Oncol. 2022;6:e2100463.CrossRefPubMedPubMedCentral
21.
go back to reference Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.CrossRefPubMed Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.CrossRefPubMed
22.
go back to reference Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25(1):118–45.CrossRefPubMed Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25(1):118–45.CrossRefPubMed
23.
go back to reference Van't Veer L, Dal H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:6. Van't Veer L, Dal H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:6.
24.
go back to reference Esserman LJ, Berry DA, DeMichele A, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30(26):3242–9.CrossRefPubMedPubMedCentral Esserman LJ, Berry DA, DeMichele A, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30(26):3242–9.CrossRefPubMedPubMedCentral
25.
go back to reference Göker E, Hendriks MP, van Tilburg M, et al. Treatment response and 5-year distant metastasis-free survival outcome in breast cancer patients after the use of MammaPrint and BluePrint to guide preoperative systemic treatment decisions. Eur J Cancer. 2022;167:92–102.CrossRefPubMed Göker E, Hendriks MP, van Tilburg M, et al. Treatment response and 5-year distant metastasis-free survival outcome in breast cancer patients after the use of MammaPrint and BluePrint to guide preoperative systemic treatment decisions. Eur J Cancer. 2022;167:92–102.CrossRefPubMed
26.
go back to reference Di Micco R, Zuber V, Fiacco E, et al. Sentinel node biopsy after primary systemic therapy in node positive breast cancer patients: Time trend, imaging staging power and nodal downstaging according to molecular subtype. Eur J Surg Oncol. 2019;45(6):969–75.CrossRefPubMed Di Micco R, Zuber V, Fiacco E, et al. Sentinel node biopsy after primary systemic therapy in node positive breast cancer patients: Time trend, imaging staging power and nodal downstaging according to molecular subtype. Eur J Surg Oncol. 2019;45(6):969–75.CrossRefPubMed
27.
go back to reference Barron AU, Hoskin TL, Day CN, Hwang ES, Kuerer HM, Boughey JC. Association of low nodal positivity rate among patients with ERBB2-positive or triple-negative breast cancer and breast pathologic complete response to neoadjuvant chemotherapy. JAMA Surg. 2018;153(12):1120–6.CrossRefPubMedPubMedCentral Barron AU, Hoskin TL, Day CN, Hwang ES, Kuerer HM, Boughey JC. Association of low nodal positivity rate among patients with ERBB2-positive or triple-negative breast cancer and breast pathologic complete response to neoadjuvant chemotherapy. JAMA Surg. 2018;153(12):1120–6.CrossRefPubMedPubMedCentral
Metadata
Title
The Predictive Utility of MammaPrint and BluePrint in Identifying Patients with Locally Advanced Breast Cancer Who are Most Likely to Have Nodal Downstaging and a Pathologic Complete Response After Neoadjuvant Chemotherapy
Authors
Peter Blumencranz, MD, FACS
Mehran Habibi, MD
Steve Shivers, PhD
Geza Acs, MD
Lisa E. Blumencranz, PhD
Erin B. Yoder, MS
Bastiaan van der Baan, MS
Andrea R. Menicucci, PhD
Patricia Dauer, PhD
William Audeh, MD
Charles E. Cox, MD
Publication date
01-09-2023
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2023
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-023-14027-9

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