Axillary ultrasound examination is useful for selecting patients optimally suited for sentinel lymph node biopsy after primary systemic chemotherapy

doi:10.1016/j.amjsurg.2011.09.026

The American Journal of Surgery

Volume 204, Issue 4, October 2012, Pages 487-493

https://doi.org/10.1016/j.amjsurg.2011.09.026 Get rights and content

Abstract

Background

Controversy surrounds the reliability of sentinel lymph node biopsy after primary systemic chemotherapy. In this study, we assessed axillary ultrasound for selecting patients most likely to optimally benefit from biopsy.

Methods

The study included 87 patients who received primary systemic chemotherapy and underwent a sentinel lymph node biopsy followed by axillary lymph node dissection. Lymph nodes >10 mm in diameter, irregularly swollen, round, and homogeneously hypoechoic without an echo-rich center were considered axillary ultrasound positive.

Results

In axillary ultrasound–negative patients before and after primary systemic chemotherapy, identification, sensitivity, and false-negative rates were 81%, 100%, and 0%, respectively. However, in patients whose lymph nodes converted from positive to negative after primary systemic chemotherapy, these values were 83%, 70.8%, and 29.2%, respectively.

Conclusions

Axillary ultrasound–negative patients before and after primary systemic chemotherapy were suitable for sentinel lymph node biopsy. Axillary ultrasound should be used during primary systemic chemotherapy and before surgery.

Section snippets

Patients

This study was performed in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Saitama Medical University International Center Review Board. Informed consent was obtained from all patients for primary systemic chemotherapy, sentinel lymph node biopsy, and surgical procedures. The study included 87 patients whose symptoms corresponded to the American Joint Committee on Cancer stage II or III breast cancer and who were treated between June 2007 and June

Response to primary systemic chemotherapy

Responses to primary systemic chemotherapy were evaluated clinically and pathologically only in breast tumors. According to the Response Evaluation Criteria in Solid Tumors guidelines, 7 patients (8%) experienced a complete clinical response, and 58 (66.7%) experienced a partial clinical response. Therefore, the clinical response rate to primary systemic chemotherapy was 74.7% (Table 2). A pathologically complete response, which was defined as no residual cancer cells including either invasive

Comments

Because of its accuracy, easy availability, and safety (no radiation exposure), axillary ultrasound should be included in the patient assessment during primary systemic chemotherapy and before surgery for selecting patients optimally suited for sentinel lymph node biopsy after primary systemic chemotherapy. Sentinel lymph node biopsy has been widely performed as an accurate alternative to axillary lymph node dissection in patients with clinically node-negative early-stage breast cancer.1, 2

References (18)

U. Veronesi et al.
Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes
Lancet
(1997)
N. Klauber-Demore et al.
High-resolution axillary ultrasound is a poor prognostic test for determining pathologic lymph node status in patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer
Am J Surg
(2004)
D. Krag et al.
The sentinel node in breast cancer—a multicenter validation study
N Engl J Med
(1998)
A. Lucci et al.
Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group trial
J Clin Oncol
(2007)
I. Langer et al.
Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion axillary lymph node dissection after breast cancer surgery: a prospective Swiss multicenter study on 659 patient
Ann Surg
(2007)
M. Kaufmann et al.
Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives
Ann Oncol
(2006)
B. Fisher et al.
Effect of preoperative chemotherapy on local-regional disease in woman with operable breast cancer: finding from national surgical adjuvant breast and bowel project B-18
J Clin Oncol
(1997)
K. Sato et al.
Clinically useful detection criteria for sentinel nodes in patients with breast cancer using radioisotope technique
Jpn J Clin Oncol
(2002)
Y. Xing et al.
Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer
Br J Surg
(2006)

There are more references available in the full text version of this article.

Cited by (17)

Mannosylated engineered trichosanthin-legumain protein vaccine hydrogel for breast cancer immunotherapy
2022, International Journal of Biological Macromolecules
The development of cancer vaccines based on tumor-associated antigens is hurdled by lack of an efficient adjuvant and insufficient efficacy. To improve the efficacy of vaccines, a genetically-engineered method was employed in this work to achieve the codelivery of antigen and adjuvant to enhance immune responses. Trichosanthin is a plant-derived protein that possesses cancer immune stimulation function. A genetically engineered protein vaccine composed of trichosanthin (adjuvant) and legumain domain (a peptidic antigen) was constructed, which was further chemically modified with mannose for targeting dendritic cells (DCs). The method is facile and ready for scaling up for massive production. Such a “two-in-one” vaccine is advantageous for codelivery for augmenting the immune responses. The vaccine inhibited the tumors by triggering a robust cytotoxic T lymphocyte response in the orthotopic-breast-tumor mice. Furthermore, the vaccine was loaded into the temperature-sensitive hydrogel based on Pluronic F127 for implanting use in the post-surgical site. The sustained-released vaccine from the hydrogel inhibited not only the tumor recurrence but also the lung metastases of breast cancer. These findings demonstrated that it was a safe and effective vaccination for breast cancer immunotherapy in a prophylactical and therapeutical manner for remodeling the tumor immune microenvironment and arresting tumor growth.
The Loss of Lymph Node Metastases After Neoadjuvant Chemotherapy in Patients With Cytology-proven Axillary Node-positive Primary Breast Cancer
2019, Clinical Breast Cancer
Citation Excerpt :
Over 30% of patients with breast cancer and axillary lymph node (LN) metastases reportedly achieve axillary pathologic complete response (pCR) after NAC,3-9 whereas the rate of response to NAC depends on breast cancer subtype.10,11 However, assessment of LN status after NAC by physical examination or ultrasonography (US) is problematic because of the high false-negative rate (FNR) of over 40%.12-14 The FNR by sentinel lymph node biopsy (SNB) after NAC is also over 10%.13-16
Axillary lymph node (LN) dissection after neoadjuvant chemotherapy (NAC) still remains a standard treatment of initially LN-positive primary breast cancer because of the difficulty of assessment of LN status. The aim of this study was to assess the LN status after NAC in initially LN-positive primary breast cancer patients who were assessed as clinically LN-negative after NAC (ycN0) and identify factors associated with loss of LN metastasis.
The study cohort comprised 279 patients with cytology-proven LN-positivity before NAC. LN status was assessed by ultrasonography. Regional recurrence-free survival and overall survival according to pathologic LN after NAC (ypN) status were assessed in patients with ycN0.
Of the 279 patients, 179 patients (64.2%) had ycN0. High nuclear grade, estrogen receptor-negative (ER⁻), and human epidermal growth factor receptor 2-positive (HER2⁺), were significant predictors of ycN0/ypN0 (P < .001, .007, and .046, respectively). Metastases persisted in 1 or 2 LNs for 5 (20.0%) of 25 patients with ER⁻/HER2⁺ and for 4 (21.1%) of 19 patients with ER⁻/HER2⁻, and in 3 or more LNs for 0 (0%) of 25 patients with ER⁻/HER2⁺ and for 1 (5.3%) of 19 patients with ER⁻/HER2⁻. Patients with ER⁺ tumors had more numerous residual LN metastases than those with ER⁻ tumors (P < .001). Among patients with ycN0, ypN status was not associated with regional recurrence-free survival or overall survival.
Three or more residual LN metastases were rare in patients with ER⁻ tumors if assessed as ycN0 by ultrasonography. Prospective studies are needed to confirm the prognostic impact of not performing axillary lymph node dissection in such patients.
Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients
2016, American Journal of Surgery
Citation Excerpt :
Axillary ultrasound scanning (AUS) is commonly used at initial diagnosis of breast cancer to clinically stage the axillary nodes. Its role in post-NAC patients has been investigated in several studies, where it has been found to be better at detecting positive nodes rather than predicting pCR, with a sensitivity, specificity and positive predictive value (PPV) of 32% to 69.8%, 56% to 94%, and 59% to 89%, respectively.10,55–58 Boughey et al55 have suggested that using a strategy where patients with a normal AUS undergo SLNB may reduce the FNR from 12.6% to 9.8% when 2 or more nodes are removed while sparing many patients from ALND.
The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial.
A computer-aided search of the literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR).
Nineteen articles were used in the analysis yielding 3,398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased pCR rate when compared to N2 or N3 disease (P = .06).
SLNB after NAC in biopsy-proven node-positive patients results in reasonably acceptable FNR and IR, making it a valid alternative management strategy to axillary dissection. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population.
The diagnostic performance of sentinel lymph node biopsy in pathologically confirmed node positive breast cancer patients after neoadjuvant systemic therapy: A systematic review and meta-analysis
2015, European Journal of Surgical Oncology
Citation Excerpt :
In their study, the PPV for axillary ultrasound in breast cancer patients improved from 79.6 towards 100%, when fine-needle cytology was added to the general axillary ultrasound. As a consequence, several studies were excluded for this meta-analysis due to differences in defining clinically node positive patients, like the SENTINA trial.38–40 In the SENTINA trial, pathologically confirmed nodal disease was not required for inclusion, resulting in the definition of node positive disease based on ultrasound.
To provide a systematic review and meta-analysis of studies investigating sentinel lymph node biopsy after neoadjuvant systemic therapy in pathologically confirmed node positive breast cancer patients.
Pubmed and Embase databases were searched until June 19th, 2015. All abstracts were read and data extraction was performed by two independent readers. A random-effects model was used to pool the proportion for identification rate, false-negative rate (FNR) and axillary pCR with 95% confidence intervals. Subgroup analyses affirmed potential confounders for identification rate and FNR.
A total of 997 abstracts were identified and eventually eight studies were included. Pooled estimates were 92.3% (90.8–93.7%) for identification rate, 15.1% (12.7–17.6%) for FNR and 36.8% (34.2–39.5%) for axillary pCR. After subgroup analysis, FNR is significantly worse if one sentinel node was removed compared to two or more sentinel nodes (23.9% versus 10.4%, p = 0.026) and if studies contained clinically nodal stage 1–3, compared to studies with clinically nodal stage 1–2 patients (21.4 versus 13.1%, p = 0.049). Other factors, including single tracer mapping and the definition of axillary pCR, were not significantly different.
Based on current evidence it seems not justified to omit further axillary treatment in every clinically node positive breast cancer patients with a negative sentinel lymph node biopsy after neoadjuvant systemic therapy.
Delivery of Molecules to the Lymph Node via Lymphatic Vessels Using Ultrasound and Nano/Microbubbles
2015, Ultrasound in Medicine and Biology
Citation Excerpt :
The sentinel lymph node (LN) is defined as the first LN or group of LNs to which tumor cells are likely to spread from the primary lesion, and its status is regarded as an independent prognostic factor (Hirakawa et al. 2009; Tobler and Detmar 2006). Metastasis to the sentinel LN is typically diagnosed with imaging modalities such as ultrasound (US), computed tomography (CT), magnetic resonance imaging and positron emission tomography, and the metastasis is histologically confirmed by biopsy (Black et al. 2007; Shigekawa et al. 2012; Yamamoto et al. 2010). In cases of head and neck cancer, when the sentinel LN is positive, neck dissection is performed to improve the survival rate (Liauw et al. 2006).
Lymph node (LN) dissection is the primary option for head and neck cancer when imaging modalities and biopsy confirm metastasis to the sentinel LN. However, there are no effective alternative treatments to dissection for LN metastasis. Here, we describe a novel drug delivery system combining nano/microbubbles (NMBs) with ultrasound (US) that exhibits considerable potential for the delivery of exogenous molecules into LNs through the lymphatic vessels. A solution containing fluorophores (as a model of a therapeutic molecule) and NMBs was injected into the subiliac LNs of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LNs (up to 13 mm in diameter, similar to human LNs). It was found that the NMBs were delivered to the entire area of the proper axillary LN (proper-ALN) via the lymphatic channels and that these were retained there for more than 8 min. Furthermore, exposure to US in the presence of NMBs enhanced the delivery of fluorophores into the lymphocytes near the lymphatic channels, compared with exposure to US in the absence of NMBs. It is proposed that a system using US and NMBs to deliver therapeutic drugs via lymphatic vessels can serve as a new treatment method for LN metastasis.
Segunda biopsia del ganglio centinela después de quimioterapia neoadyuvante en pacientes con cáncer de mama, axila negativa y ganglio centinela metastásico al diagnóstico inicial. Resultados preliminares
2014, Revista de Senologia y Patologia Mamaria
Valorar la validez diagnóstica de una segunda biopsia del ganglio centinela (GC) en pacientes con cáncer de mama operable y axila negativa al diagnóstico, con GC metastásico, tratadas con quimioterapia neoadyuvante (QTN).
Estudio prospectivo realizado en 52 mujeres con cáncer de mama infiltrante (2 bilateral); estadio II-A (cT2N0M0): 50, II-B (cT3N0M0): 4. El estatus axilar se estableció por exploración física, ecografía y punción ecoguiada de los ganglios sospechosos. Pauta QTN: epirrubicina/ciclofosfamida × 4, y docetaxel × 4. El día antes de la cirugía se inyectó periareolarmente 74-111 MBq de nanocoloide de albúmina. El GC se analizó por amplificación de ácido nucleico de un solo paso. Se realizó linfadenectomía axilar en las pacientes con GC positivo al diagnóstico.
El GC axilar pre-QTN se identificó en el 96,3% de los casos; GC extirpados 1,8 ± 0,8 (rango 1-4). En el 55,8% el resultado del GC fue positivo. Actualmente, 44 pacientes (2 bilateral) han completado el tratamiento. Se ha realizado una segunda biopsia del GC posneoadyuvancia en 22 pacientes: 20 con GC pre-QTN positivo, 2 sin migración axilar preneoadyuvancia. Solo se identificó el GC en el 54,5% de las pacientes; GC resecados 1,5 ± 0,8 (rango 1-3). En 9 de las 10 mujeres sin migración la linfadenectomía axilar fue negativa. En 7 pacientes el GC fue un verdadero positivo, y en 4 de ellas los GC eran los únicos afectados de la axila. En 2 casos el resultado fue falso negativo (22,2%).
Los resultados de una segunda biopsia del GC post-QTN no son adecuados para su aplicación en la práctica clínica.
To evaluate the accuracy of a second sentinel lymph node (SLN) biopsy in patients with operable breast cancer and clinically negative axilla, with metastatic SLN at diagnosis, treated with neoadjuvant chemotherapy (NAC).
A prospective study was performed in 52 women with invasive ductal carcinoma (2 bilateral); stage IIA (cT2N0M0): 50, IIB (cT3N0M0): 4. Axillary evaluation included physical examination and axillary ultrasound, with ultrasound-guided core needle biopsy of any suspicious lymph node. The NAC scheme consisted of epirubicin/cyclophosphamide × 4, and docetaxel × 4. The day before surgery, 74-111 MBq albumin nanocolloid was injected periareolarly. The SLN was analyzed by one-step nucleic acid amplification. Axillary lymph node dissection was performed in patients with positive SLN at presentation.
Pre-NAC axillary SLN was identified in 96.3% of the patients. The mean number of extirpated SLN was 1.8 ± 0.8 (range 1-4). In 55.8% of the patients, the SLN was positive. Currently, 44 patients (2 bilateral) have completed NAC and surgical treatment. A second SLN biopsy was performed post-NAC in 22 patients: 20 with positive pre-NAC SLN and 2 without pre-NAC SLN identification. SLN was only identified in 54.5% of cases. The mean number of extirpated SLN was 1.5 ± 0.8 (range 1-3). Non migration occurred in 10 patients, 9 patients without axillary lymph node dissection involvement. In 7 patients, the post-NAC SLN was a true positive and was the only axillary lymph node affected in 4. The false negative rate was 22.2%.
A second SLN biopsy after NAC in women with a positive SLN at diagnosis is not a useful option.

View all citing articles on Scopus

View full text

Minimally invasive surgeryAxillary ultrasound examination is useful for selecting patients optimally suited for sentinel lymph node biopsy after primary systemic chemotherapy

Abstract

Background

Methods

Results

Conclusions

Section snippets

Patients

Response to primary systemic chemotherapy

Comments

Lancet

Am J Surg

The sentinel node in breast cancer—a multicenter validation study

N Engl J Med

Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group trial

J Clin Oncol

Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion axillary lymph node dissection after breast cancer surgery: a prospective Swiss multicenter study on 659 patient

Ann Surg

Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives

Ann Oncol

Effect of preoperative chemotherapy on local-regional disease in woman with operable breast cancer: finding from national surgical adjuvant breast and bowel project B-18

J Clin Oncol

Clinically useful detection criteria for sentinel nodes in patients with breast cancer using radioisotope technique

Jpn J Clin Oncol

Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer

Br J Surg

Minimally invasive surgery
Axillary ultrasound examination is useful for selecting patients optimally suited for sentinel lymph node biopsy after primary systemic chemotherapy