Sentinel node mapping performed before preoperative chemotherapy may avoid axillary dissection in breast cancer patients with negative or micrometastatic sentinel nodes

doi:10.1016/j.amjsurg.2007.08.068

The American Journal of Surgery

Volume 196, Issue 2, August 2008, Pages 176-183

https://doi.org/10.1016/j.amjsurg.2007.08.068 Get rights and content

Abstract

Background

Sentinel node (SN) biopsy after preoperative chemotherapy (PC) in breast cancer patients is associated with a lower identification rate (IR) and an increased false-negative rate (FNR) compared with SN biopsy in untreated patients. Our aims were to examine the feasibility of SN mapping before PC and the possibility to assess the lymph node status after chemotherapy through a follow-up lymphatic mapping.

Methods

SN biopsy was performed in 45 clinically node-negative breast cancer patients before PC. A follow-up lymphatic mapping was done after completion of chemotherapy and irrespective of the lymph node status was followed by axillary lymph node dissection (ALND).

Results

SN mapping before chemotherapy identified a mean of 2.3 SNs in all patients (IR 100%). Nineteen patients revealed a negative SN; 26 patients had a positive SN (micrometastasis found in 6/26 patients). After PC follow-up lymphatic mapping was successful in 29 of 45 patients (IR 64%). IR for follow-up mapping was 80% for patients with a negative or micrometastatic SN before chemotherapy compared with 45% for patients with macrometastatic SNs (P = .027, Fisher exact test). None of the patients with a negative or micrometastatic SN before chemotherapy revealed positive lymph nodes after PC (P = .031, McNemar test) and the FNR for follow-up lymphatic mapping in these patients was 0%. Contrary to that, 15 of 20 patients with a macrometastasis before PC had positive nodes after chemotherapy, and the FNR of follow-up mapping in these patients was 50%.

Conclusions

Patients with a negative SN before PC may forego complete ALND after PC, whereas this may not be valid for patients with macrometastatic SNs. Follow-up lymphatic mapping in patients with positive nodal status before chemotherapy is associated with a low IR and a high FNR.

Section snippets

Patients and Methods

Forty-five patients with invasive breast cancer were scheduled to PC to render them operable for breast-conservation surgery in case of large tumor size. Table 1 shows the clinical and pathological parameters of these patients. Breast cancer was diagnosed by core needle biopsy. Clinical examination and ultrasonography of the axilla before SN mapping found negative axillary lymph nodes in all patients.

All patients received 1 to 6 cycles (mean 5.2 cycles) of chemotherapy. The chemotherapy regimen

Results of SN biopsy before PC

One to six SNs (mean [standard deviation] 2.3 [1.1] SNs) were found in all 45 patients (identification rate [IR] 100%). They were removed from level I of the axilla (n = 42), level I and II (n = 2), and level I and the ipsilateral internal mammary chain (n = 1). Nineteen patients revealed a negative SN, 26 patients had a positive SN, and micrometastasis was found in 6 of 26 patients (Table 3).

Results of follow-up lymph node mapping/biopsy after PC

Table 3 shows the results of the follow-up lymph node mapping and the final lymph node status after PC.

Comments

SN biopsy performed before PC is associated with a high IR.26, 27, 28, 29, 30, 31, 32 None of these studies, however, reported on the FNR because patients with a negative SN were not scheduled to ALND after chemotherapy. Although follow-up of SN negative patients in these studies was short, no local recurrences were seen.28, 30, 32

SN biopsy after PC as it is currently performed by most institutions is associated with a decreased IR ranging from 76% to 94%.14, 15, 16, 17, 18, 19, 20, 21, 22, 23

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Cited by (26)

Review of Novel Sentinel Lymph Node Biopsy Techniques in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy
2018, Clinical Breast Cancer
Citation Excerpt :
Sever and colleagues64 studied CEUS in 54 patients with the periareolar injection of 0.2 to 0.5 mL SonoVue (Bracco SpA). The breast was massaged and lymphatic channels were visualized immediately resulting in SLN identification in 89% of patients, which was later repeated by Schrenk et al.65 Cox and colleagues66 did a larger study of 347 patients, but the technique could not visualize or successfully biopsy 13.3% of patients with the sensitivity and specificity of 61% and 100%, respectively.
Breast cancer patients who present with nodal metastasis receive neoadjuvant chemotherapy (NAC) with increasing frequency and can have complete pathologic response after treatment. In this clinical scenario, sentinel node mapping and biopsy are gaining acceptance instead of axillary dissection to avoid morbidity. Biopsy proven positive lymph nodes must be reliably excised and examined after NAC to further decrease the false negativity rate of sentinel lymph node (SLN) surgery. The standard method for axillary staging in breast cancer patients even after NAC is SLN biopsy (SLNB) with a radioisotope, blue dye, or both (dual technique). Currently, preoperative axillary staging with ultrasound and biopsy, along with placement of an image-detectable marker to be removed at the time of definitive surgery is recommended. In this study, we evaluated some methods of SLNB for patients treated with NAC like indocyanine green fluorescence, superparamagnetic iron oxide nanoparticles, indigocarmine blue dye, contrast-enhanced ultrasound using microbubbles, and tattooing. Some methods are also needed to ensure that the initially biopsy proven positive node is removed at the time of surgery to be carefully evaluated for residual disease after chemotherapy like clip placement to the suspected or involved nodes before NAC, and removing the clipped node with the guidance of 125I-labeled radioactive seed or guide wires.
Assessment of sentinel lymph node biopsy in patients receiving neoadjuvant chemotherapy in breast cancer: Before or after?
2016, Gynecologie Obstetrique et Fertilite
La chimiothérapie néoadjuvante (CNA) peut permettre une réduction de la taille de la tumeur en vue d’un traitement conservateur impossible initialement. Elle permet également une réponse ganglionnaire axillaire histologique complète dans un tiers des cas. La pertinence du curage axillaire (CA) systématique après CNA est remise en question, en faveur de la procédure du ganglion sentinelle (GS). Cependant, le moment optimal par rapport à la CNA est encore débattu dans la littérature pour les patientes n’ayant pas d’envahissement ganglionnaire évalué par échographie avant la chimiothérapie. Pour les patientes avec envahissement ganglionnaire prouvé avant CNA, la réalisation d’un GS après CNA paraît envisageable en cas de réponse radio-clinique.
The main goal of preoperative chemotherapy is to reduce the size of the tumor and allow conservative treatment. Neoadjuvant treatment can affect axillary status with a downstaging in one third of the cases. For these patients, the benefit of axillary node dissection is questioned and the sentinel node biopsy (SLNB) seems to be a relevant option. However, the timing of performing SLNB is still debated especially for clinical negative patients with negative axillary ultrasound before preoperative chemotherapy. For axillary positive nodes proved by biopsy/cytology before preoperative chemotherapy, SLNB can be an option if there is a good clinical and radiological response.
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.
Assessing the impact of neoadjuvant chemotherapy on the management of the breast and axilla in breast cancer
2014, Clinical Breast Cancer
Citation Excerpt :
However, in 1 case, although the sentinel node after chemotherapy was negative for metastatic disease, a high burden of axillary metastases was noted in nonsentinel nodes. This may represent aberrations in lymphatic flow as a consequence of the effects of NAC or a patchy lymphatic response to therapy, phenomena that have been well reported in the international literature.5,22-26 As the findings of the American College of Surgeons Oncology Group Z0011 trial15 (Lymph Node Removal in Treating Women Who Have Stage I or Stage IIA Breast Cancer) become more integrated into clinical practice, it may become necessary to interpret sentinel node results not in isolation but rather in light of other prognostic indicators such as molecular subtype and tumor grade.
Nodal status is a sensitive prognostic indicator in breast cancer. Axillary metastases may be an indication for neoadjuvant systemic therapy. The aims of this study were to compare pathologic response rates to neoadjuvant chemotherapy (NAC) in the breast and axilla across different molecular subtypes of breast cancer and to compare the predictive value of axillary assessment before and after chemotherapy in determining final nodal status in this cohort of patients.
The cohort comprised patients undergoing NAC from 2003 to November 2012. Data regarding patient and tumor characteristics, management, and outcomes were obtained from a prospectively maintained database and analyzed using PASW Statistics, version 18 (SPSS Inc, Chicago, IL).
Two hundred two cancers were identified in 196 patients. One hundred thirty-one (65%) diagnostic axillary procedures were performed, 105 (80%) before NAC, of which 93 (89%) were positive. In 28 (30%), downstaging was noted before NAC. Human epidermal growth factor receptor 2 (HER2) subtypes had the highest rate of complete pathologic response (n = 11 [61%]) and negative axillary clearance (AXCn) (n = 11 [69%]). Of 177 AXCns, 68 (38%) were negative before NAC.
AXCn in patients undergoing NAC remains controversial. HER2 subtypes are less likely to have axillary involvement after NAC and may demand different management.
Is optimal timing of sentinel lymph node biopsy before neoadjuvant chemotherapy in patients with breast cancer? A literature review
2012, Surgical Oncology
Twenty five percent of women with breast cancer who undergo preoperative chemotherapy do not have axillary metastases. These patients need to withstand sentinel lymph node biopsy (SLNB). The optimal timing of SLNB in patients with neoadjuvant chemotherapy has not yet been defined.
We systematically reviewed the literature for studies concerning the efficacy of sentinel lymph node biopsy before neoadjeuvant chemotherapy. A literature search was performed for the years 1993 through 2011 using the databases MEDLINE and EMBASE. Data that assessed the reliability of sentinel lymph node biopsy before chemotherapy were collected.
We identified 10 high-quality studies from 387 papers, which are analyzed further in this review. The identification rates reported ranged from 97% to 100%. The sensitivities of sentinel lymph node biopsy were 100%, and the false negative rates were 0%. Use an isotope combined with blue dye was associated with a higher probability of identification than that of using an isotope or blue dye alone (99.5% vs 98.5%). Only two studies compared data based on different timing for the sentinel lymph node biopsy. They achieved a lower false negative rate (0% vs 15.8%) and higher success rate (100% vs 81%) in patients with sentinel lymph node biopsy prior to neoadjuvant chemotherapy.
Sentinel lymph node biopsy prior to chemotherapy potentially gives a more accurate evaluation of axillary status, because it is unaffected by any previous therapeutic intervention.
Sentinel lymph node and neoadjuvant therapy in breast cancer
2010, Revista Espanola de Medicina Nuclear

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Clinical surgery-InternationalSentinel node mapping performed before preoperative chemotherapy may avoid axillary dissection in breast cancer patients with negative or micrometastatic sentinel nodes

Abstract

Background

Methods

Results

Conclusions

Section snippets

Patients and Methods

Results of SN biopsy before PC

Results of follow-up lymph node mapping/biopsy after PC

Comments

Am J Surg

Eur J Cancer

Am J Surg

J Am Coll Surg

Am J Surg

Am J Surg

Am J Surg

Am J Surg

J Am Coll Surg

Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer

J Clin Oncol

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

The feasibility of minimally invasive surgery for stage IIA, IIB, and IIIA breast carcinoma patients after tumor downstaging with induction chemotherapy

Cancer

Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy

Ann Surg

Prognostic value of lymph node metastases after neoadjuvant chemotherapy for large-sized operable carcinoma of the breast

J Am Coll Surg

Prognostic value of persistent node involvement after neoadjuvant chemotherapy in patients with operable breast cancer

Br J Cancer

MRI vs. histologic measurement of breast cancer following chemotherapy: comparison with x-ray mammography and palpation

J Magn Reson Imaging

Axillary staging using positron emission tomography in breast cancer patients qualifying for sentinel lymph node biopsy

Breast J

Improved axillary staging of breast cancer with Sentinel lymphadenectomy

Ann Surg

Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer

Ann Surg

Lessons learned from 500 cases of lymphatic mapping for breast cancer

Ann Surg

Clinical surgery-International
Sentinel node mapping performed before preoperative chemotherapy may avoid axillary dissection in breast cancer patients with negative or micrometastatic sentinel nodes