Predictive factors for omitting lymphadenectomy in patients with node‐positive breast cancer treated with neo‐adjuvant systemic therapy

LBA1003 Background: Randomized trials have demonstrated that locoregional radiation after mastectomy reduces locoregional recurrence and improves overall survival (OS) in women with node positive breast cancer treated with adjuvant systemic therapy. MA.20 evaluated the addition of regional nodal irradiation (RNI) to whole breast irradiation (WBI) following breast conserving surgery (BCS). Methods: Women with high risk node-negative or node-positive breast cancer treated with BCS and adjuvant chemotherapy and/or endocrine therapy were stratified by positive nodes, axillary nodes removed, chemo- and endocrine therapy and randomized to WBI (50Gy in 25 fractions +/- boost irradiation) or WBI plus RNI (45Gy in 25 fractions) to the internal mammary, supraclavicular, and high axillary lymph nodes. The primary outcome was OS. The Data Safety Monitoring Committee approved the analysis plan for the protocol specified interim analysis of relapse patterns, survival and toxicity at 5 years. Upon review of the data, they recommended release of the results. Results: Between March 2000 to March 2007, 1,832 women were randomly assigned to WBI+RNI (916) or WBI (916). Median follow-up was 62 months. Characteristics of the study population were: mean age, 53.3 years; node negative, 10%; 1-3 positive nodes, 85%; > 4 positive nodes, 5%; adjuvant chemotherapy, 91%; and adjuvant endocrine therapy, 71%. WBI+RNI in comparison to WBI alone was associated with an improvement in isolated locoregional disease free survival (DFS; HR=.59, p=.02, 5 year risk: 96.8% and 94.5% respectively), distant DFS (HR=.64, p=.002, 5 year risk: 92.4% and 87.0% respectively), DFS (HR=.68, p=.003, 5 year risk: 89.7% and 84.0% respectively) and OS (HR=.76, p=.07, 5 year risk: 92.3% and 90.7% respectively). WBI+RNI in comparison to WBI was associated with an increase in grade 2 or greater pneumonitis (1.3% and 0.2% respectively, p=.01), and lymphedema (7.3% and 4.1% respectively, p=.004). Conclusions: The majority of women with node positive breast cancer are now managed by BCS followed by WBI and adjuvant systemic therapy. Results from MA.20 demonstrate that additional RNI reduces the risk of locoregional and distant recurrence, and improves DFS with a trend in improved OS.

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305Longterm follow-up of axillary node positive breast cancer patients receiving adjuvant systemic therapy alone: Patterns of recurrence

Radiotherapy and Oncology ◽

10.1016/s0167-8140(96)80314-8 ◽

1996 ◽

Vol 40 ◽

pp. S79

Author(s):

B.J. Fisher ◽

F.E. Perera ◽

A.L. Cooke ◽

A. Opeitum

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Systemic Therapy ◽

Axillary Node ◽

Adjuvant Systemic Therapy ◽

Breast Cancer Patients ◽

Node Positive ◽

Patterns Of Recurrence ◽

Positive Breast Cancer

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Trastuzumab as adjuvant systemic therapy for HER2-positive breast cancer

Nature Clinical Practice Oncology ◽

10.1038/ncponc1298 ◽

2008 ◽

Vol 6 (2) ◽

pp. 93-104 ◽

Cited By ~ 59

Author(s):

Gabriella Mariani ◽

Angelica Fasolo ◽

Elena De Benedictis ◽

Luca Gianni

Keyword(s):

Breast Cancer ◽

Systemic Therapy ◽

Adjuvant Systemic Therapy ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

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Does Locoregional Radiation Therapy Improve Survival in Breast Cancer? A Meta-Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.6.1220 ◽

2000 ◽

Vol 18 (6) ◽

pp. 1220-1229 ◽

Cited By ~ 381

Author(s):

Timothy J. Whelan ◽

Jim Julian ◽

Jim Wright ◽

Alejandro R. Jadad ◽

Mark L. Levine

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Systemic Therapy ◽

Odds Ratio ◽

Randomized Trials ◽

Meta Analysis ◽

Radical Mastectomy ◽

Node Positive ◽

Meta Analyses ◽

Positive Breast Cancer

PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.

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Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update

Journal of Clinical Oncology ◽

10.1200/jco.2017.74.0472 ◽

2017 ◽

Vol 35 (24) ◽

pp. 2838-2847 ◽

Cited By ~ 137

Author(s):

Ian Krop ◽

Nofisat Ismaila ◽

Fabrice Andre ◽

Robert C. Bast ◽

William Barlow ◽

...

Keyword(s):

Breast Cancer ◽

Systemic Therapy ◽

Hormone Receptor ◽

Early Stage ◽

Adjuvant Systemic Therapy ◽

Node Negative ◽

Clinical Risk ◽

Hormone Receptor Positive ◽

High Clinical Risk ◽

Positive Breast Cancer

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor–positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .

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