NCCN Guidelines Insights: Breast Cancer, Version 3.2018

Featured Updates to the NCCN Guidelines

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor–positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

Abstract

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor–positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

NCCN: Continuing Education

Target Audience: This activity is designed to meet the educational needs of physicians, nurses, pharmacists, and other healthcare professionals who manage patients with cancer.

Accreditation Statements

In support of improving patient care, National Comprehensive Cancer Network (NCCN) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Medicine (ACCME): NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nursing (ANCC): NCCN designates this educational activity for a maximum of 1.0 contact hour.

Pharmacy (ACPE): NCCN designates this knowledge-based continuing education activity for 1.0 contact hour (0.1 CEUs) of continuing education credit. UAN: 0836-0000-19-010-H01-P

All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: (1) review the educational content; (2) take the posttest with a 66% minimum passing score and complete the evaluation at https://education.nccn.org/node/84931; and (3) view/print certificate.

Pharmacists: You must complete the posttest and evaluation within 30 days of the activity. Continuing pharmacy education credit is reported to the CPE Monitor once you have completed the posttest and evaluation and claimed your credits. Before completing these requirements, be sure your NCCN profile has been updated with your NAPB e-profile ID and date of birth. Your credit cannot be reported without this information. If you have any questions, please e-mail education@nccn.org.

Release date: February 10, 2019; Expiration date: February 10, 2020

Learning Objectives:

Upon completion of this activity, participants will be able to:

  • Integrate into professional practice the updates to the NCCN Guidelines for Breast Cancer

  • Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Breast Cancer

Disclosure of Relevant Financial Relationships

The NCCN staff listed below discloses no relevant financial relationships:

Kerrin M. Rosenthal, MA; Kimberly Callan, MS; Genevieve Emberger Hartzman, MA; Erin Hesler; Kristina M. Gregory, RN, MSN, OCN; Rashmi Kumar, PhD; Karen Kanefield; and Kathy Smith.

Individuals Who Provided Content Development and/or Authorship Assistance:

Matthew P. Goetz, MD, Panel Member, has disclosed that he has served as a scientific advisor for Biotheranostics, Eli Lilly and Company, and Sermonix Pharmaceuticals; has received grant/research support from Eli Lilly and Company and Pfizer Inc.; and has received consulting fees/honoraria from Genomic Health, Inc., Biovica International AB, and Sermonix Pharmaceuticals.

William J. Gradishar, MD, Panel Chair, has disclosed that he has no relevant financial relationships.

Jame Abraham, MD, Panel Member, has disclosed that he has no relevant financial relationships.

Harold J. Burstein, MD, PhD, Panel Member, has disclosed that he has no relevant financial relationships.

Chau Dang, MD, Panel Member, has disclosed that she has received grant/research support from Roche/Genentech and Puma Biotechnology, Inc.

Lori J. Goldstein, MD, Panel Member, has disclosed that she has served as a scientific advisor for Amgen Inc., AstraZeneca Pharmaceuticals LP, Daiichi Sankyo, Inc., Eisai Inc., Genomic Health, Inc., and Merck & Co., Inc.

Steven J. Isakoff, MD, PhD, Panel Member, has disclosed that he receives grant/research support from AbbVie, Inc., AstraZeneca Pharmaceuticals LP, Genentech, Inc., Merck & Co., Inc., OncoPep, Inc., and PharmaMar. He also has received consulting fees/honoraria from Genentech, Inc., Immunomedics, Inc., Myriad Genetic Laboratories, Inc., Hengrui Therapeutics, Inc., Mylan, and Puma Biotechnology, Inc.

Meena S. Moran, MD, Panel Member, has disclosed that she has no relevant financial relationships.

Hope S. Rugo, MD, Panel Member, has disclosed that she receives grant/research support from Pfizer Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals; Eli Lilly and Company; OBI Pharma; Genentech, Inc.; Odonate Therapeutics, Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Seattle Genetics, Inc.; and MacroGenics, Inc. She also receives consulting fees/honoraria from Eli Lilly and Company, Mylan, Pfizer Inc., Amgen Inc., Merck & Co., Inc., and Puma Biotechnology, Inc.

Karen Lisa Smith, MD, MPH, Panel Member, has disclosed that she has received grant/research support from Pfizer Inc. and Puma Biotechnology, Inc., and that her spouse has equity interest/stock options in AbbVie Inc. and Abbott Laboratories.

Hatem Soliman, MD, Panel Member, has disclosed that he has served as a consultant for Eli Lilly and Company, Pfizer Inc., AstraZeneca Pharmaceuticals LP, Novartis AG, Puma Biotechnology, Inc., and Celgene Corporation.

Melinda L. Telli, MD, Panel Member, has disclosed that she has served as a scientific advisor for Celldex Therapeutics; Genentech, Inc.; Immunomedics, Inc.; Merck & Co., Inc.; Aduro BioTech, Inc.; Pfizer Inc.; and Tesaro, Inc.

John H. Ward, MD, Panel Member, has disclosed that he has no relevant financial relationships.

Dorothy A. Shead, MS, Director, Patient Information Operations, NCCN, has disclosed that she has no relevant financial relationships.

This activity is supported by educational grants from AstraZeneca, Celgene Corporation, Clovis Oncology, Eisai, Genentech, Genomic Health, Inc., Novartis, Taiho Oncology, Inc., and TESARO. This activity is supported by an independent educational grant from AbbVie. This activity is supported by educational funding provided by Amgen. This activity is supported by an unrestricted educational grant from Gilead Sciences, Medical Affairs.

Overview

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The American Cancer Society has estimated that 271,270 Americans will be diagnosed with breast cancer and 42,260 will die of disease in the United States in 2019.1 The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include up-to-date guidelines for the clinical management of patients with carcinoma in situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer–focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy.

In a recent version of these guidelines, the NCCN Breast Cancer Panel included updated recommendations for the use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor (HR)–positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

Adjuvant Systemic Therapy for HR-Positive/HER2-Negative Tumors

In patients with early-stage breast cancer, systemic adjuvant therapy is administered to reduce risk of cancer recurrence. Women with HR-positive, HER2-negative tumors receive adjuvant endocrine therapy to reduce the risk of recurrence, and those deemed at high risk for distant recurrence despite adjuvant endocrine therapy receive adjuvant chemotherapy. The incremental benefit of adding adjuvant chemotherapy to endocrine therapy in patients with a low clinical risk of recurrence, such as those with very small, low-grade, lymph node–negative tumors, is relatively small.2 The decision whether to administer adjuvant chemotherapy in patients with HR-positive, HER2-negative tumors is based on many factors, including lymph node status, tumor size and grade, lymphovascular invasion, age, comorbid conditions, and/or results of a gene expression profile test using multigene assays.

Multigene Assays

Several commercially available gene-based assays are useful in determining prognosis through predicting distant recurrence, local recurrence, or survival. Of these, only one, the 21-gene assay (Oncotype Dx, Genomic Health, Inc.) has been clinically validated for predicting the benefit of adding adjuvant chemotherapy to further reduce the risk of recurrence.

21-Gene Assay

Node-Negative, HR-Positive, HER2-Negative Breast Cancer

The 21-gene recurrence score (RS) is one of the most validated multigene assays. The RS is helpful in determining the prognosis in women with HR-positive, HER2-negative tumors treated with endocrine therapy alone by predicting locoregional and distant recurrence.35 This assay has also been validated to predict the benefit from adding adjuvant chemotherapy to adjuvant endocrine therapy for women with HR-positive, HER2-negative, node-negative breast cancer.68

Among patients with T1b/T1c and T2, lymph node–negative, HR-positive, HER2-negative tumors with RS between 0 and 10, the risk of distant recurrence is low, and these patients derive no incremental benefit from the addition of adjuvant chemotherapy to endocrine therapy.7,9 At the other end of the spectrum, patients with node-negative, HR-positive, HER2-negative cancers with high RS (≥31) have a higher risk of distant recurrence, and secondary analyses of prospective studies show that these patients derive a clear benefit from adjuvant chemotherapy.7,9

For patients with an intermediate RS (11–25), the recently reported TAILORx trial of postmenopausal women (N=6,711) with node-negative, HR-positive, HER2-negative breast cancer showed similar disease-free survival rates at 9 years in those who received adjuvant chemotherapy followed by endocrine therapy compared with endocrine therapy alone.9 However, a subset analysis of women aged ≤50 years with RS of 16 to 25 showed significantly lower rates of distance recurrence with the addition of adjuvant chemotherapy to endocrine therapy.9 The cutoff for low, intermediate, and high RS was different in TAILORx versus NSABP B-20. The NSABP-B20 was the first trial to validate the 21-gene assay as both a prognostic and a predictive tool, and identified RS cutoffs to predict the magnitude of chemotherapy benefit in patients with node-negative, HR-positive breast cancer.7

Node-Positive, HR-Positive, HER2-Negative Breast Cancer

In the West German Study Group PlanB trial, women (N=110) with node-positive, HR-positive, HER2-negative tumors and RS <11 were found to have a 5-year disease-free survival of 94.4% when treated with endocrine therapy alone.10 In a secondary analysis of a prospective registry of women with node-positive, and HR-positive, HER2-negative tumors, the 5-year risk of distant recurrence in patients with RS <18 who were treated with endocrine therapy alone was 2.7%.11 These results suggest that in patients with limited nodal disease (1–3 positive lymph nodes) and a low RS, the absolute benefit from chemotherapy is likely to be very small.10,11

There is a clear benefit from adjuvant chemotherapy in patients with node-positive, HR-positive, HER2-negative tumors if they have a high RS (≥31). In a secondary analysis of the SWOG-8814 trial of women with node-positive, HR-positive tumors, high RS (≥31) was predictive of chemotherapy benefit. This study evaluated breast cancer specimens from node-positive, HR-positive postmenopausal women (N=367) randomized to endocrine therapy with tamoxifen alone or chemotherapy with CAF (cyclophosphamide/doxorubicin/fluorouracil) followed by tamoxifen.6 Compared with tamoxifen alone, treatment with CAF among women with high RS (≥31) resulted in improved 10-year disease-free survival (55% vs 43%; hazard ratio [HR], 0.59; 95% CI, 0.35–1.01) and overall survival (73% vs 54%; HR, 0.56; 95% CI, 0.31–1.02).6

The absolute benefit of chemotherapy in patients with limited lymph node involvement and RS ≤25 remains to be determined. The ongoing SWOG-S1007 RxPONDER trial (ClinicalTrials.gov identifier: NCT01272037) assigned women with 1 to 3 positive lymph nodes and HR-positive, HER2-negative breast cancer and RS ≤25 to standard endocrine therapy either with or without adjuvant chemotherapy. The results of this trial are expected to determine the benefit (if any) for chemotherapy in this group of patients.

70-Gene Assay

Results from the randomized MINDACT trial12 demonstrated that the 70-gene assay (MammaPrint, Agendia) can identify a subset of patients who have a low likelihood of distant recurrence despite high-risk clinical features (based on tumor size, tumor grade, nodal status). In this trial, 79% of patients had node-negative disease and 21% had 1 to 3 positive lymph nodes, and all patients underwent risk assessment using clinical criteria (using Adjuvant!Online) and genomic risk assessment using the 70-gene assay.

Patients with low-risk disease according to both clinical criteria and genomic assay results did not receive adjuvant chemotherapy, whereas those categorized as high risk by both assessments received chemotherapy. Patients with discordant results (ie, either high clinical risk/low genomic risk or low clinical risk/high genomic risk) were randomized to the chemotherapy group or the no-chemotherapy group based on either the clinical or the genomic result. The primary outcome of the study was met with the demonstration that among those with high clinical risk/low genomic risk, the 5-year rate of survival with no distant metastasis in those did not receive adjuvant chemotherapy was 94.7% (95% CI, 92.5–96.2).12

In the intention-to-treat population, among patients at high clinical risk/low genomic risk using the 70-gene assay, the 5-year rate of survival with no distant metastasis in those who received chemotherapy was 95.9% (95% CI, 94.0–97.2) versus 94.4% (95% CI, 92.3–95.9) in those who did not receive chemotherapy (adjusted HR for distant metastasis or death with chemotherapy vs no chemotherapy, 0.78; 95% CI, 0.50–1.21).12 Among patients at low clinical risk/high genomic risk, the 5-year rate of survival with no distant metastasis was 95.8% with chemotherapy (95% CI, 92.9–97.6) versus 95.0% (95% CI, 91.8%–97.0%) without chemotherapy (adjusted HR for distant metastasis or death with chemotherapy vs no chemotherapy, 1.17; 95% CI, 0.59–2.28). These data suggest that the results of the 70-gene signature do not provide evidence for making recommendations regarding chemotherapy for patients at low clinical risk.12

In a subgroup analysis by nodal status, among node-negative patients with high clinical risk/low genomic risk, the 5-year rate of survival with no distant metastasis was 95.7% (95% CI, 93.0–97.4) in those who received adjuvant chemotherapy compared with 93.2% (95% CI, 90.1–95.4) in those who did not receive chemotherapy.12 Among patients with 1 to 3 positive lymph nodes, the rates of survival without distant metastases were 96.3% (95% CI, 93.1–98.1) in those who received adjuvant chemotherapy versus 95.6 (95% CI, 92.7–97.4) in those who did not receive adjuvant chemotherapy.12 These data suggest that the additional benefit of adjuvant chemotherapy in patients with high-clinical risk/low genomic risk is likely to be small.

50-Gene Assay

The 50-gene assay (PAM50; NanoString) risk of recurrence (ROR) score stratifies patients with HR-positive disease into high-, medium-, and low-risk groups. Several studies have demonstrated the prognostic value of ROR score in estimating risk of disease recurrence.1315

In a study using the Danish Breast Cancer Cooperative Group database, patients with node-negative tumors and low ROR had a distant recurrence risk of 5.0% (95% CI, 2.9%–8.0%) compared with 17.8% (95% CI, 14.0%–22.0%) in those with high ROR.14 Based on these analyses, patients with T1 and T2 node-negative HR-positive, HER2-negative tumors and an ROR score in the low range, regardless of tumor size, places the individual in the same prognostic category as those with T1a/T1bN0M0 tumors.14

In patients with 1 to 3 positive lymph nodes and HR-positive, HER2-negative disease with a low RS, the distant recurrence risk was <3.5% at 10 years with endocrine therapy alone.14 In the TransATAC study, no distant recurrence was seen at 10 years in a similar group.15

12-Gene Assay

The EndoPredict assay (Myriad Genetics) uses 12 genes to calculate a prognostic score. This assay appears to be useful in identifying a subgroup of patients with estrogen receptor–positive, HER2-negative tumors at very low risk of recurrence without adjuvant chemotherapy and helpful in identifying patients at low risk for a late recurrence.16 Based on results of 2 Austrian Breast and Colorectal Cancer Study Group trials, ABCSG-6 and ABCSG-8, patients with node-negative, HR-positive, HER2-negative disease with a low risk score by the 12-gene assay had a 4% risk of distant recurrence at 10 years.16 The prognostic value of the risk score from the 12-gene assay was found to be independent of conventional clinicopathologic factors. In patients with T1 and T2 node-negative, HR-positive, HER2-negative tumors, a 12-gene low-risk score, regardless of T size, places the tumor into the same prognostic category as T1a–T1bN0M0.

In the TransATAC study, patients with 1 to 3 positive nodes in the low-risk group had a 5.6% risk of distant recurrence at 10 years,15 suggesting that chemotherapy would be of limited benefit in these women.

Breast Cancer Index

The Breast Cancer Index (BCI) is a combination of 2 profiles, the HOXB13-to-IL17BR expression ratio (H:I ratio) and the Molecular Grade Index (MGI). Compared with clinical prognostic factors (eg, age, tumor size, tumor grade, lymph node status), the H:I ratio has been shown to be prognostic in the setting of adjuvant tamoxifen monotherapy.1720 The addition of MGI to H:I was determined to provide additional prognostic discrimination, leading to the BCI assay.21 In a secondary analysis of the TransATAC trial, BCI was prognostic in node-negative breast cancer for both early (years 0–5) and late (years 5–10) distant recurrence.22 For patients with T1 and T2 node-negative, HR-positive, HER2-negative tumors, a BCI in the low-risk range, regardless of T size, places the tumor into the same prognostic category as T1a/T1bN0M0.

There are limited data regarding the role of BCI in node-positive, HR-positive, HER2-negative breast cancer.

NCCN Recommendations

Use of Multigene Assays

The panel extensively reviewed the available multigene assays, their ability to predict benefit of adjuvant systemic chemotherapy, and their ability to determine prognosis by predicting risk of distant recurrence, and has summarized the treatment implications based on risk scores and nodal status (see table BINV-M, page 122). The panel notes that the multigene assays provide prognostic and therapy-predictive information that complements TNM and biomarker information.

Axillary Lymph Node–Negative, HR-Positive, HER2-Negative Tumors

Small tumors (up to 0.5 cm in greatest diameter) that do not involve the lymph nodes have a favorable prognosis, and therefore adjuvant chemotherapy is not recommended. According to the NCCN Breast Cancer Panel, adjuvant endocrine therapy may be considered in this group of patients to reduce the risk of a second contralateral breast cancer, and due to the small benefit in reducing the risk of local/regional and distant recurrence (category 2B) (see BINV-6, page 120).

For patients with invasive ductal or lobular tumors >0.5 cm in diameter and no lymph node involvement (node-negative), the NCCN panel recommends strongly considering the 21-gene RT-PCR assay to help estimate likelihood of recurrence and benefit from chemotherapy (category 1). The panel has noted that, based on an exploratory analysis from the TAILORx study,9 adjuvant chemotherapy may be considered in women aged ≤50 years with a 21-gene RS of 16 to 25. Also, patients with T1b tumors with low-grade histology should be considered for endocrine monotherapy, because the TAILORx study9 did not include patients with such tumors (see BINV-6, page 120).

The panel noted that other prognostic multigene assays (listed on BINV-M, pages 122 and 123) may be considered to help estimate recurrence risk, but these assays have not been validated to predict the benefit of systemic chemotherapy. Also, among the other assays, the panel listed the 70-gene assay as a category 1 option based on the results of the prospective MINDACT12 trial demonstrating its ability to identify patients with a low genomic risk despite a high clinical risk (see BINV-6, page 120), in whom chemotherapy may be omitted without a detrimental effect. High clinical risk in the MINDACT trial was defined as >3 cm N0 or T2N1 for grade 1 tumors, T2N0–1 for grade 2 tumors, and T1c–2N0–1 for grade 3 tumors.

Furthermore, given no difference in outcomes with or without chemotherapy in the discordant low clinical risk/high genomic risk group, the MINDACT study suggests that the 70-gene panel is not useful for guiding systemic chemotherapy decisions in this subgroup of patients.

Because results of different assays may not be concordant with each other and these assays have not been compared head-to-head prospectively, clinicians should only order one of the available assays for a specific patient and tumor.

Axillary Lymph Node–Positive, HR-Positive, HER2-Negative Tumors

For patients with ≥4 involved nodes, the panel recommends systemic adjuvant chemotherapy followed by endocrine therapy (category 1) (see BINV-7, page 121).

Patients with <4 involved nodes or with pN1mi and ≤2 mm axillary node metastasis are most often candidates for chemotherapy in addition to endocrine therapy. The panel recommends that clinical decision-making for adjuvant chemotherapy be based on elements of clinical risk stratification, such as clinical characteristics, tumor stage, pathology, and comorbid conditions. If the patient is not a candidate for chemotherapy, the panel recommends adjuvant endocrine therapy alone (category 2A) (see BINV-7, page 121).

For patients who are candidates for systemic adjuvant chemotherapy based on clinical characteristics, tumor stage, and pathology, the panel recommends consideration of multigene assays to assess prognosis as a tool to assist with treatment decision-making. The panel notes that in N1mi and N1 tumors, although multigene assays have yet to be proven as predictive for adjuvant chemotherapy benefit, they are prognostic and can be used to identify low-risk patients who are likely to derive little or no absolute benefit from addition of adjuvant chemotherapy to adjuvant endocrine therapy. Although a secondary analysis of the prospective SWOG-8814 trial showed no benefit for chemotherapy for women with 1 to 3 involved ipsilateral axillary lymph nodes and low RS, it did show benefit for the addition of adjuvant chemotherapy in those with high RS (≥31) based on results of the 21-gene assay.6 At this time, the optimal RS cutoff (<11 vs <18) to withhold chemotherapy in patients with 1 to 3 positive lymph nodes and HR-positive, HER2-negative breast cancer is still unknown. Results of the RxPONDER trial (ClinicalTrials.gov identifier: NCT01272037) are expected to determine the benefit (if any) of chemotherapy in patients with 1 to 3 positive lymph nodes; HR-positive, HER2-negative disease; and an intermediate risk score. In the MINDACT trial, among patients with 1 to 3 positive nodes who had a high clinical risk of recurrence but low risk based on results of the 70-gene assay, rates of survival were similar between those who received adjuvant chemotherapy in addition to adjuvant endocrine therapy and those received adjuvant endocrine therapy alone, suggesting that chemotherapy could be omitted in this group.12 Other multigene assays listed on page BINV-M have not proven to be predictive of benefit from chemotherapy (pages 122 and 123).

Among patients who are candidates for systemic adjuvant chemotherapy based on clinical characteristics, tumor stage, and pathology, if multigene assay is not available, the panel recommends systemic adjuvant chemotherapy followed by endocrine therapy (category 1) (see BINV-7, page 121).

Summary

The updated recommendations in the NCCN Guidelines for Breast Cancer provide guidance on the use of multigene assays to either recommend or withhold adjuvant systemic chemotherapy therapy in women with HR-positive, HER2-negative early-stage invasive breast cancer based on nodal status and other clinicopathologic characteristics.

References

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Article Sections

Figures

References

  • 1.

    Siegel RLMiller KDJemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:734.

  • 2.

    Berry DACirrincione CHenderson IC. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 2006;295:16581667.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Paik SShak STang G. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:28172826.

  • 4.

    Dowsett MCuzick JWale C. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol 2010;28:18291834.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Mamounas EPTang GFisher B. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol 2010;28:16771683.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Albain KSBarlow WEShak S. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010;11:5565.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Paik STang GShak S. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:37263734.

    • Crossref
    • PubMed
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