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The Relevance of Ultrasound Imaging of Suspicious Axillary Lymph Nodes and Fine-needle Aspiration Biopsy in the Post-ACOSOG Z11 Era in Early Breast Cancer

Posted Feb 28, 2017 Updated Apr 10, 2023
By Gopal R. Vijayaraghavan MD MPH , Srinivasan Vedantham PhD , Milliam Kataoka MD PhD , Carolynn DeBenedectis MD , Robert M. Quinlan MD
12 min read

Rationale and Objectives

Evaluation of nodal involvement in early-stage breast cancers (T1 or T2) changed following the Z11 trial; however, not all patients meet the Z11 inclusion criteria. Hence, the relevance of ultrasound imaging of the axilla and fine-needle aspiration biopsy (FNA) in early-stage breast cancers was investigated.

Materials and Methods

In this single-center, retrospective study, 758 subjects had pathology-verified breast cancer diagnosis over a 3-year period, of which 128 subjects with T1 or T2 breast tumors had abnormal axillary lymph nodes on ultrasound, had FNA, and proceeded to axillary surgery. Ultrasound images were reviewed and analyzed using multivariable logistic regression to identify the features predictive of positive FNA. Accuracy of FNA was quantified as the area under the receiver operating characteristic curve with axillary surgery as reference standard.

Results

Of 128 subjects, 61 were positive on FNA and 65 were positive on axillary surgery. Sensitivity, specificity, positive predictive value, and negative predictive value of FNA were 52 of 65 (80%), 54 of 63 (85.7%), 52 of 61(85.2%), and 54 of 67 (80.5%), respectively. After adjusting for neoadjuvant chemotherapy between FNA and surgery, a positive FNA was associated with higher likelihood for positive axillary surgery (odds ratio: 22.7; 95% confidence interval [CI]: 7.2–71.3, P < .0001), and the accuracy of FNA was 0.801 (95% CI: 0.727–0.876). Among ultrasound imaging features, cortical thickness and abnormal hilum were predictive ( P < .017) of positive FNA with accuracy of 0.817 (95% CI: 0.741–0.893).

Conclusions

Ultrasound imaging and FNA can play an important role in the management of early breast cancers even in the post-Z11 era. Higher weightage can be accorded to cortical thickness and hilum during ultrasound evaluation.

Introduction

Management of breast cancer has been evolving over the last few decades. Less invasive procedures with lower morbidity have been shown to be equally effective with no adverse impact on outcomes . Metastatic involvement of the axilla is an important prognostic indicator on the outcome in patients with breast cancer. In stage I-II breast cancers, tumor grade, size, receptor status, and lymphovascular invasion of the tumor increase the odds for involvement of the axilla . The imaging modality of choice for evaluation of the axilla is ultrasound (US). When suspicious lymph nodes are identified on US, fine-needle aspiration biopsy (FNA) or core-needle biopsy typically follows, both to establish a histological diagnosis and to guide further management. A number of studies have outlined the benefits of US and FNA in the evaluation of axillary lymph nodes .

The publication of the American College of Surgeons Oncology Group Z11 trial, however, resulted in a paradigm shift in the way early T1 and T2 breast cancers are managed at most institutions . The study showed no benefit for axillary lymph node dissection (ALND) over surgical sentinel node biopsy (SNB) for patients with low burden of axillary disease who underwent breast conserving therapy and received whole breast irradiation. It established SNB as the standard of care . As a consequence, the value of imaging and interventional procedures of axillary lymph nodes has been questioned . To remain relevant and continue to contribute meaningfully to patient care, it is important for breast imagers to adapt to these changes.

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Methods and Materials

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Human Subjects

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Table 1

Distribution of Tumor Stage, Grade, and the Axillary Surgery Following FNA in Subjects with Stage T2 or Lower Cancers

n__Tumor stage T1a 7 T1b 14 T1c 48 T2 59Tumor grade I 17 II 58 III 53Axillary surgery SNB 54 ALND 65 SNB followed by ALND 9

ALND, axillary lymph node dissection; FNA, fine-needle aspiration biopsy; SNB, sentinel node biopsy.

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Ultrasound Imaging and FNA

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Retrospective Review

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Reference Standard

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Statistical Analysis

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Results

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Ultrasound Imaging Features

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Table 2

Odds Ratio and 95% Confidence Intervals of Ultrasound Imaging Features Predictive of a Positive Result From Ultrasound-guided Fine-needle Aspiration Biopsy (FNA)

Ultrasound Imaging Feature Odds Ratio Estimate 95% Confidence Intervals_P_ Value_All breast cancer stages_ ( n = 150) Cortical thickness in mm 1.268 1.075 1.496 .0048 Hilum (abnormal vs. normal) 5.271 2.217 12.530 .0002Stage T2 or lower ( n = 128) Cortical thickness in mm 1.258 1.042 1.520 .0172 Hilum (abnormal vs. normal) 4.509 1.735 11.718 .0020

Other than cortical thickness in mm and hilum status categorized as normal or abnormal, none of the other ultrasound imaging features and measurements were significantly ( P > .3769) associated with a positive FNA.

Figure 1, Receiver operating characteristic curve indicating that cortical thickness in millimeter and hilum status were predictive of a positive result from ultrasound-guided fine-needle aspiration biopsy.

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Axillary Surgery

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Table 3

Odds Ratio and 95% Confidence Intervals of the Predictor(s) Associated with Axillary Lymph Node Metastasis From Pathology Analysis of Sentinel Node Biopsy (SNB) or Axillary Lymph Node Dissection (ALND)

Predictor Odds Ratio Estimate 95% Confidence Intervals_P_ Value Cohort: Excludes Subjects Who Underwent NCT (Univariate Analysis)All breast cancer stages (n = 101) FNA (positive vs. negative) 116.646 14.724 924.084 <.0001Stage T2 or lower (n = 93) FNA (positive vs. negative) 105.133 13.158 840.046 <.0001

Cohort: Includes Subjects Who Underwent NCT (Multivariable Analysis)All breast cancer stages ( n = 150) FNA (positive vs. negative) 25.533 8.209 79.418 <.0001 NCT (yes vs. no) 0.224 0.07 0.722 .0122Stage T2 or lower ( n = 128) FNA (positive vs. negative) 22.672 7.205 71.342 <.0001 NCT (yes vs. no) 0.226 0.066 0.768 .0172

Some of the subjects underwent interim neoadjuvant chemotherapy (NCT) between the time of ultrasound-guided fine-needle aspiration biopsy (FNA) and the surgical procedure, and was included in the model. Hence, the results are presented for the cohort of subjects who did not undergo NCT, and for the entire study sample that includes subjects who underwent NCT.

Figure 2, Receiver operating characteristic curves showing that a positive fine-needle aspiration biopsy is predictive of axillary lymph node metastasis from surgical procedure (a) for the cohort of subjects who did not undergo interim neoadjuvant chemotherapy (NCT), and (b) for the entire study sample that included subjects who underwent NCT.

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Discussion

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Figure 3, 48-year-old female with a lower inner quadrant invasive ductal carcinoma (T2 tumor: 2.1 × 1.6 cm mass, grade 3) ( top row ). Right axilla demonstrates an oval heterogeneous anechoic lymph node ( left bottom ), without fatty hila, cortical thickening, and abnormal vascularity (image not shown). Fine-needle aspiration biopsy (needle in appropriate position, bottom right ) was positive.

Figure 4, 75-year-old woman, with a left breast primary tumor (T1: 1.4 × 1 cm at 12 o'clock) that was pathology verified as invasive ductal carcinoma. Evaluation of the axilla demonstrated a round lymph node, with eccentric displacement of central fatty hila, focal cortical thickness of 5 mm, and non-hilar blood flow. Fine-needle aspiration biopsy was positive for malignant cells of ductal origin.

Figure 5, 31-year-old woman presenting with a palpable right axillary mass. Baseline mammogram was negative (not shown). Ultrasound evaluation of the right axilla demonstrated an enlarged lymph node with eccentric displacement of fatty hila, diffuse cortical thickness exceeding 3 mm, and non-hilar abnormal blood flow on color imaging ( left and middle ). Fine-needle aspiration biopsy showing the needle in the abnormal cortex ( right ). Histology: Focal necrosis and inflammation, no evidence of malignancy (Kikuchi disease was a suggested possibility). Distinction between a reactive, inflamed node from any cause and metastatic disease is difficult on imaging.

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Conclusion

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Acknowledgments

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Academic Radiology, Volume 24, Issue 3
Journals General Radiology
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