Axillary lymph node dissection is not required for breast cancer patients with minimal axillary residual disease after neoadjuvant chemotherapy

doi:10.21203/rs.3.rs-4712847/v1

Download PDF

Research Article

Axillary lymph node dissection is not required for breast cancer patients with minimal axillary residual disease after neoadjuvant chemotherapy

https://doi.org/10.21203/rs.3.rs-4712847/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Sentinel lymph node biopsy(SLNB) is widely used in patients who receive neoadjuvant chemotherapy(NAC). Still, axillary lymph node dissection(ALND) is recommended for patients with any axillary residual disease after NAC. The necessity of ALND in patients with minimal axillary disease is unclear. We aim to investigate regional recurrence rates in patients with limited axillary residual disease after NAC underwent SLNB + image-tailored axillary surgery and adjuvant radiotherapy (RT).

Methods

Patients with clinical stages were T1-3 and N1 at the time of diagnosis, clinically good or complete axillary response after NAC, and limited axillary residue (≤ 3 pathological lymph nodes) with favorable response to NAC in the final pathological examination were included in the study. All patients underwent SLNB + image-tailored axillary surgery. Peripheral lymphatic radiotherapy was applied, and no further surgery was performed in patients with compatible radiology and pathology results.

Results

Our study, which evaluated 139 patients with a median age of 47 years, found that the median number of excised lymph nodes was 4. Notably, 46% of patients had between 1 and 3 lymph nodes excised, while 45% had between 4 and 6. Only 9% of patients had ≥ 7 lymph nodes. 83(60%) of the patients underwent breast-conserving surgery (BCS), and 56(40%) underwent mastectomy. The study's median follow-up period was 44 months. During this duration, one breast recurrence (0.7%), one supraclavicular recurrence (0.7%), and six systemic recurrences (4.3%) were observed. No axillary recurrence occurred within the follow-up period.

Conclusions

Patients presenting with pathological-suspicious ≤ 3 lymph nodes on imaging and showing a good response to NAC can be considered suitable candidates for SLNB + image-tailored axillary surgery, followed by adjuvant RT instead of ALND.

Breast Cancer

Breast surgery

Neoadjuvant chemotherapy

axillary lymph node dissection

sentinel lymph node biopsy

In recent decades, there has been a shift towards personalized treatment approaches for breast cancer patients. The traditional one-size-fits-all surgical methods are being reconsidered, and more tailored minimally invasive interventions are being developed. In the 1990s, Giuliano et al. first described sentinel lymph node biopsy (SLNB), demonstrating that axillary lymph node dissection (ALND) is unnecessary for SLNB-negative breast cancer patients (1). Landmark trials such as NSABP B-04 and NSABP B-32 have shown that the extent of axillary surgery does not improve survival for clinically node-negative patients (2)(3).

The evidence overwhelmingly supports SLNB as the preferred treatment for axillary surgery in early breast cancer, considering its proven benefits in terms of morbidity, quality of life, and oncological safety (4). Notably, clinical studies like ACOSOG Z0011 and AMAROS have shown that even in cases of limited axillary involvement with a positive SLNB, axillary dissection does not offer lower axillary recurrence and survival benefit when axillary radiotherapy (RT) is applied (5, 6).

The extensive use of neoadjuvant chemotherapy (NAC) in locally advanced breast cancer and the remarkable rates of pathological complete response (pCR) have sparked a new debate on how to approach the axilla after NAC. While SLNB is commonly used in patients who initially present with no signs of cancer in the lymph nodes and are treated with NAC, its use in patients with positive axillary nodes before NAC is controversial (7). Prospective studies have been conducted to resolve this controversy. With current chemotherapy treatments, axillary pCR rates have reached 50%, making ALND unnecessary in almost half of the patients. Consequently, the option of SLNB has become more prominent in patients with a positive axillary status before NAC (8, 9).

In light of current guidelines, ALND is recommended for axillary residual disease after NAC, irrespective of disease burden, due to insufficient evidence. Nonetheless, there is growing scrutiny around the necessity of ALND, particularly in cases of limited axillary residue (10). Magnetic resonance imaging (MRI) and ultrasound (USG) are widely used to evaluate response to neoadjuvant therapy, with an approximately 60% success rate in predicting complete pathological response. However, the accuracy improves when comparing the presence of axillary response (shrinking) to baseline images (11, 12).

Our study sought to evaluate the efficacy and the safety of image-tailored axillary surgery in combination with SLNB as a substitute for ALND in patients exhibiting limited axillary involvement and demonstrating favorable responses to NAC.

In this prospectively designed study, we evaluated patients with clinical stages of T1-3 and N1 at the time of diagnosis, who showed good or complete response to NAC for both the breast and axilla and exhibited favorable changes (> 50% fibrotic) in the final pathological examination. The study was conducted at the Breast Surgery Unit, Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, between January 2011 and December 2023.

Patients with T4, cN2-3, and M1 stages at admission, no clinical axillary response to NAC, more than three pathological lymph nodes on imaging, and complete axillary pathological response as per the final pathology report were excluded from the study.

All patients underwent evaluation by a multidisciplinary team before and after NAC. The tumor stage, NAC response, and the number of pathological lymph nodes with their location were determined using USG, mammography (MMG), MRI, and positron emission tomography-computed tomography (PET-CT) by a breast specialist radiologist. Patients who showed a significant or complete response in their axillary lymph nodes after NAC were included in the study, while those who showed progression or no regression were excluded (Fig. 1). Before surgery, it is important to identify the locations of pathological lymph nodes. For instance, level 1 in the inferior axilla can be close to the breast tail or lateral to the pectoralis minor muscle. In the superior axilla, level 1 can be lateral to the pectoralis major muscle, close to the axillary vein, or near the latissimus dorsi muscle. This information helps surgeons to target and remove these nodes more effectively during the operation, which is referred to as image-tailored surgery.

All patients underwent neoadjuvant chemotherapy, including anthracycline and taxane. Patients with HER2-neu-positive disease received additional trastuzumab therapy. Adjuvant hormonal therapy was administered to all hormone-positive patients. Patients with triple-negative disease had capecitabine after surgery, and those with HER-2-positive disease had trastuzumab or trastuzumab emtansine.

Patients underwent SLNB in conjunction with image-tailored lymph node excision performed by dedicated breast specialist surgeons. In a minority of cases, dual mapping (lymphoscintigraphy + blue dye) was employed (17%) and targeted axillary dissection (TAD) was carried out as per surgeon preference (7%). Lymph nodes were meticulously dissected from the excision material by an experienced pathologist. The presence of blue dye was noted during macroscopic evaluation. At least four sections were obtained from each lymph node block at 250-m intervals and stained with hematoxylin and eosin (H&E). Sentinel lymph nodes containing tumor cells detected by H&E or cytokeratin immunohistochemistry staining were considered positive, according to the AJCC 8th edition. Pathologic findings regarding chemotherapy response were also recorded, including regressional fibrosis, fibrohyalinization, and reactive changes.

The study investigated the relationship between the number of radiologically suspicious or positive lymph nodes and the number of lymph nodes removed. The number of lymph nodes removed was at least equal to the number found to be suspicious or pathologic. The multidisciplinary council reviewed patients' final pathology results. Evaluation encompassed assessing the number of lymph nodes removed, the number of pathological lymph nodes identified radiologically before NAC, and the number of nodes with residual disease pathologically. No further axillary intervention was scheduled for patients with consistent radiology and pathology results.

Patients who had breast-conserving surgery (BCS) received RT to the entire breast, while those who had a mastectomy received RT to the chest wall. All patients also received RT to the axilla (level I-II-III), which includes the supraclavicular lymph node regions with or without the internal mammary lymph node region.

Patients with high-load axillary residual disease, unable to undergo adjuvant RT, and having inconsistent radiologic and pathological findings regarding the number of positive nodes underwent ALND. This group of patients was also excluded from the study (Fig. 1).

Demographic, clinicopathological, and radiological data of the patients were analyzed. According to the current guidelines, patients were regularly examined and evaluated for local recurrence or systemic disease.

Statistical analysis

The assumption of normality of continuous variables was tested with the Shapiro-Wilk test. Categorical variables were presented as frequency(%), continuous variables as mean ± SD, median (IQR: P25-P75), and range. Comparisons between groups in continuous variables were made with the Mann-Whitney U test, and comparisons between groups in categorical variables were made with Chi-Square tests (Pearson Chi-Square Test, Continuity Correction Test, and Fisher's Exact Test). Diagnostic tests (sensitivity, specificity, PPV, NPV, and accuracy) were used to compare clinical findings and pathological results. Statistical analyses were made with SPSS software version 25 (IBM Corp., Armonk, NY, USA). Results were evaluated in the 95% confidence interval, and p < 0.05 was considered significant.

Out of the 308 patients assessed for eligibility, 28 patients with four or more pathological lymph nodes in the preoperative evaluation were excluded. Additionally, three patients declined to participate, and nine patients were excluded due to disease progression during treatment. Breast surgery with SLNB + image tailored axillary surgery was performed on the remaining patients. Furthermore, 85 patients with pathological complete response, three with incompatible pathology and radiology results, 28 with high-load axillary residual disease (four or more metastatic lymph nodes) in pathological evaluation, and one with contraindication for adjuvant radiotherapy were also excluded from the study (Fig. 2). A total of 139 patients with a median age of 47 years (IQR, 39–54; range, 21–73) were included in the study. Of these, 128 patients had T1-2 stage tumors, while 11 had T3 stage tumors. Breast-conserving surgery was performed on 83 patients (59.7%), while 56 patients (40.3%) underwent mastectomy. Non-luminal subtype was found in 30 patients (21.6%), whereas 109 patients (78.4%) had luminal subtype. Prior to neoadjuvant chemotherapy (NAC), MRI and USG imaging of all patients were examined by a breast radiologist. The imaging revealed a single pathological lymph node in 76 patients, 2 in 41 patients, and 3 in 22 patients. Pathological features of the lymph nodes were confirmed through fine-needle aspiration biopsy (FNAB).

During the study, sentinel lymph node biopsy (SLNB) was carried out using blue dye in 115 cases (82.7%) and with the combined method of blue dye and lymphoscintigraphy in 24 cases (17.3%) (Table 1). The identification rate of SLNB was 97.3% when using the single tracer (blue dye) and 100% when using the dual tracer. In only three patients, no blue dye was observed in the axilla. In these cases, lymph node excision was conducted based on palpation findings and radiological imaging.

Table 1 Patient characteristics

Characteristics(N = 139)	Category	n(%)
Median age(IQR)	All	47(39–54)
Age, minimum-maximum	All	21–73
Age	≤ 50	89(64)
	> 50	50(36)
Clinical T stage	cT1/2	128(92.1)
	cT3	11(7.9)
Type of Breast Surgery	BCS	83(59.7)
	Mastectomy	56(40.3)
Histopathology of core biopsy and surgical specimen	Invasive ductal carcinoma	123(88.5)
	Invasive Lobular carcinoma	2(1.4)
	Invasive ductal&lobular carcinoma	11(7.9)
	Other	3(2.2)
pCR (breast)	Complete	28(20.1)
	Near complete(> 90%)	30(21.6)
	80–90%	24(17.3)
	50–80%	34(24.5)
	< 50%	23(16.5)
HER2- neu	Negative	108(77.4)
	Positive	31(22.3)
Tumor Subtype (IHC)	Luminal A	13(9.4)
	Luminal B/HER2(-)	76(55.1)
	Luminal B/HER2(+)	19(13.8)
	Non luminal B/HER2(+)	12(8.7)
	Triple-negative	18(13)
Tumor Subtype (IHC)	Luminal	109(78.4)
	Non-luminal	30(21.6)
Sentinel Lymph Node Methodology	Blue Dye	115(82.7)
	Combined (Blue dye and radioisotope)	24(17.3)
Radiologic lymph node involvement^#	1ln	77(55.4)
	2ln	40(28.8)
	3ln	22(15.8)
TAD	Yes	10(7.2)
	No	129(92.8)
Number of sentinel lymph nodes	1–3	92(66.2)
	≥ 4	47(33.8)
Number of metastatic sentinel lymph nodes	1	112(80.6)
	≥ 2	27(19.4)
Number of total LN (Median:4, range:1–9)	1–3	64(46)
	≥ 4	75(54)
Number of total metastatic LN	1	101(72.7)
	≥ 2	38(27.3)
Characteristics of metastatic lymph nodes (LNs) removed	Macrometastasis	80(57.6)
Characteristics of metastatic lymph nodes (LNs) removed	Micrometastasis	43(30.9)
	Isolated tumor cells	16(11.5)
Presence of extracapsular extension	Yes	23(16.5)
	No	116(83.5)
Non sentinel lymph node positivity (n = 52)*	Yes	12(23.1)
	No	40(76.9)
Lymph Node Ratio(LNR)	≤ 0.33	91(65.5)
	> 0.33	48(34.5)
IQR : Interquartile Range(P₂₅- P₇₅), BCS: Breast breast-conserving surgery

^# It refers to the number of lymph nodes that appear suspicious or pathological in radiological evaluation before NAC.

* It refers to lymph nodes that are considered suspicious with intraoperative palpation findings and lymph nodes removed through image-tailored axillary surgery except for SLNB

A total of 64 patients (46%) had 1–3 excised lymph nodes, while 62 patients (45%) had 4–6 excised lymph nodes. Thirteen patients (9%) had seven or more lymph nodes removed (Table 2). The median number of excised lymph nodes was 4 (IQR, 3–5). Five patients had only one lymph node excised, as radiological findings suggested only one pathological node and no other palpable or suspicious node was found during the operation. Pathological examination revealed that 101 patients had a single metastatic lymph node, 32 patients had 2 metastatic lymph nodes, and 6 patients had 3 metastatic lymph nodes. Macrometastasis was observed in 80 nodes, micrometastasis in 43, and isolated tumor cells in 16. pCR was detected in the breast in 26 patients (18.7%).

Table 2

Comparison of radiological lymph node involvement with the number of excised lymph nodes
	Radiologic lymph node involvement
	1LN(n = 77)	2LN(n = 40)	3LN(n = 22)	Total(n = 139)
Quantitative variables	Median(IQR)/ Range	Median(IQR)/ Range	Median(IQR)/ Range	Median(IQR)/ Range
Number of total LN	4(3–5)/1–9	3(3–5)/2–9	5(3–6)/3–9	4(3–5)/1–9
Number of total metastatic LN	1(1–1)/1–1	2(1–2)/1–3	2(1–2)/1–3	1(1–2)/1–3
Total excised LN	n(%)	n(%)	n(%)	n(%)
1–3	37(48)	21(52.5)	6(27.3)	64(46)
4–6	36(46.8)	14(35)	12(54.5)	62(44.6)
≥ 7	4(5.2)	5(12.5)	4(18.2)	13(9.4)
N/A: Not available

The study compared the number of radiologically positive lymph nodes, pathologically positive lymph nodes, and positive sentinel lymph nodes, as shown in Table 2. All patients with one radiologically positive lymph node were found to have one metastatic lymph node. In this group, all patients had metastasis in the sentinel nodes and no metastasis was detected in non-sentinel lymph nodes. Among 41 patients with two radiologically positive lymph nodes, 17 (41%) had one metastatic lymph node, 22 (53%) had two metastatic lymph nodes, and 2 (5%) had three metastatic lymph nodes. Two patients with inconsistent pathology and radiology results were re-evaluated in a multidisciplinary council, and it was determined that axillary lymph node dissection (ALND) was not necessary. Radiology revealed three positive lymph nodes in 22 patients, of which 8 (36%) had one metastatic lymph node, 10 (45%) had two metastatic lymph nodes, and 4 (18%) had three metastatic lymph nodes (Additional file 1).

The median follow-up period was 44 months (IQR, 29–56). One patient experienced breast recurrence in the 31st month, and another patient had lymphatic recurrence in the supraclavicular area in the 39th month (Table 3). Systemic recurrence was observed in 6 (4.3%) patients. No axillary recurrence occurred during the follow-up period (Additional file 2).

Table 3

Characteristics of patients with local or regional recurrence
	Age	cT/N	ypSLN	LN ratio	pCR (breast)	Molecular subtype	Extracapsular invasion	LVI	Breast Surgery	Recurrence time(month)	Site of recurrence
Case 1	31	2/1	macromet	3/5	no	TN	yes	no	BCT	31	breast
Case 2	54	2/1	macromet	1/5	no	Lum-B	yes	no	mastectomy	39	supra
LN: lymph node, LVI: lymphovascular invasion

The efficacy of chemotherapeutic agents in the treatment of breast cancer is progressively on the rise. Following NAC, the incidence of axillary pCR may escalate to 50%. Notably, rates of pCR are even more pronounced in HER-2-positive and triple-negative patients (13). The notable efficacy of NAC warrants deliberation on the necessity of ALND in cases of limited axillary residual disease, thereby advocating for the adoption of less invasive techniques in axillary surgery. Particularly, SLNB is the preferred approach for patients who are converted from cN + to cN0 post-NAC.

Although SLNB is often performed in patients who have converted to cN0 after NAC, some surgeons are concerned about the potential for false-negative results of SLNB. Caudle et al. suggested targeted axillary dissection for this concern (14). Boughey et al. also showed that the false negative rate (FNR) can be reduced to less than 10% with TAD(15). In clinically node-positive (cN+) patients who were converted to clinically node-negative (cN0), various prospective studies have demonstrated that FNR of the SLNB was higher than 10%, and if the dual mapping is used and ≥ 3 Lymph nodes are excised, and FNR can be reduced to acceptable rates of < 10% (4.9%-9.1%) regardless of TAD (16–18). In the SENTINA trial, the FNR was 24.3% for patients with one sentinel node removed and 18.5% for patients with two sentinel nodes removed (17). Three or more lymph node excisions and dual methods are recommended to reduce FNR (19).

In contrast, Galimberti et al. published 10-year follow-up results of patients who were initially cN + and became cN0 after NAC. Inclusion criteria were SLNB alone (one node is enough) without TAD, single tracer (no dual mapping), and nodal radiotherapy was not mandatory. Axillary failure occurred in 1.8% of the initially cN1/2 patients and 1.5% of the initially cN0 patients (20). Although there is a risk of false negativity of SLNB, nodal recurrence rates are not increased in patients with negative SLNB who do not undergo ALND (21, 22). Despite the lack of evidence regarding the negative impact of FNR on axillary recurrence and survival, the surgical community is actively pursuing strategies such as dual mapping and targeted axillary dissection to reduce FNR. It is recognized that despite diligent efforts, the FNR of SLNB cannot be reduced to zero, resulting in the presence of minimal residue in the axilla of a subset of patients. For patients undergoing upfront surgery, we have substantial evidence from prospective trials with 10 years of follow-up, such as ACOSOG Z0011 and AMAROS (5, 23). It is established that even if there is a limited residual disease in the axilla, ALND does not decrease axillary recurrence rates or extend overall survival as long as adjuvant RT is administered.

Now is the time to discuss avoiding ALND for N + disease following NAC. Reports of ongoing prospective trials, such as Alliance 11202 and NSABP B-51/RTOG 1304, are expected to clarify this topic (24, 25). A trial including SLNB + patients after NAC was presented in ASCO 2023. The study evaluated cN1 breast cancer that became ycN0 but remained node positive following NAC, according to findings from a retrospective analysis of patients treated in phase 3 prospective NSABP B-40 and B-41 trials. Results showed that more intense axillary surgery (ALND) was not associated with better cancer outcomes when compared with SLNB. 5-year loco-regional recurrence was 9% in the ALND group, compared with 12% for those who underwent SLNB (p = 0.790) in unselected patients. 5-year risk of metastasis was 31% and 26%, respectively, and 5-year risk of any recurrence was 33% and 32%, respectively (26). Similarly, in a few recently published studies, the superiority of ALND in oncological terms could not be demonstrated for neoadjuvant breast cancer patients with limited axillary residual disease (27–29). In a multicentric registry trial, Cabioglu et al. showed that ALND could be avoided in selected cN (+) patients who underwent SLNB after NAC having low-volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided (29). Almaharic et al. analyzed a total of 1617 patients from the National Cancer Database to compare survival following SLND and ALND in breast cancer patients with residual LN disease. Subgroup analysis demonstrated that SLNB was comparable with ALND in patients with luminal A or B tumors with a single metastatic lymph node (28). Unlike these studies, Our study showed no difference in local recurrence rates between luminal and non-luminal subtypes. In the database study of Kantor et al., 6554 HR+/her- cN0 patients receiving neoadjuvant endocrine therapy were evaluated, and > 90% of patients had less than three positive lymph nodes. No survival difference was found between SLNB and ALND in these patients (30).

Axillary involvement is generally defined as N0 and N + without considering the volume of nodal disease (number and size of pathological nodes). The absence of image-tailored localization of suspicious lymph nodes places all N + patients in the same category and prevents individual decision-making (one size fits all). Our aim should be to determine precise, tailored surgical (need for ALND) and medical treatment (need for additional systemic treatment) approaches for every patient. To achieve this, we need to determine the extent of axillary involvement before NAC and assess the response after NAC using imaging to identify cases with minimal axillary residual disease.

In our study, we observed no axillary recurrences in 4 years of follow-up, despite expecting a high recurrence rate in patients with axillary residual disease after NAC. This suggests that minimal axillary residual disease may not necessitate ALND as long as radiological and pathological findings are consistent. It's worth noting that current guidelines recommend ALND for patients with any axillary residual disease, regardless of tumor burden and NAC response (10).

Our practice is based on multidisciplinary councils where we evaluate the clinicopathological features of patients, pre- and post-neoadjuvant imaging, and pathological examination results. Based on this evaluation, we devise a personalized treatment plan that goes beyond the current guidelines. It's important to note that we focus on the compatibility of imaging findings and pathological examination results. This approach allows us to initiate a personalized treatment for patients with limited axillary involvement without compromising oncological safety.

Most patients had an average of 6 or fewer lymph nodes removed (95% of patients with one pathological lymph node, 87% with two, and 82% with three). The number of lymph nodes removed in our study appears to be higher than standard SLNB. This is because we also removed palpable and suspicious lymph nodes guided by imaging. Excising more lymph nodes helps obtain a better correlation between imaging and final pathology, leading to safer decisions to avoid ALND. The number of excised lymph nodes could be decreased, but this may cause an increase in second axillary surgery rates.

Radiological evaluation of post-neoadjuvant axilla can be challenging. While imaging techniques are effective in identifying axillary involvement, they may be insufficient, particularly in assessing the complete response to NAC (31, 32). Our study focused on differentiating between high-volume axillary disease and limited disease (< 3 lymph nodes). Our objective in evaluating post-neoadjuvant response was not to discern complete response, and we included patients with a good partial response, so the constraints of imaging methods did not impact our study.

The study's main limitation was the absence of a comparison group. Additionally, interpreting the palpation findings requires experience. Our team consists of breast specialist surgeons and radiologists, and our center deals with a high volume of breast cancer cases. A comprehensive multidisciplinary tumor board evaluated all patients and determined individualized treatments. Therefore, conducting this prospective study in a tertiary referral center is feasible.

In patients with minimal axillary residual disease, SLNB + image-tailored axillary surgery and adjuvant radiotherapy may be sufficient for local control of the axilla as long as radiological and pathological correlation is ensured. ALND may be considered in patients suspected of having a high-volume residual disease. This study also confirmed that the belief that “chemo-resistance is equal to radio-resistance” is not valid in patients with minimal axillary residual disease (3 or fewer nodes) who exhibit a favorable response to NAC.

SLNB

Sentinel lymph node biopsy

NAC

neoadjuvant chemotherapy

ALND

axillary lymph node dissection

pCR

pathological complete response

MRI

Magnetic resonance imaging

USG

ultrasound

MMG

mammography

PET

CT-positron emission tomography-computed tomography

TAD

targeted axillary dissection

H&E

hematoxylin and eosin

BCS

breast-conserving surgery

FNR

false negative rate

Ethics approval and consent to participate

The study was approved by the ethical committee of Istanbul University, Istanbul Faculty of Medicine (08.08.2023-1981986), by the ethical standards of the institutional and national research committee, and with the 1964 Helsinki Declaration. Informed consent was obtained from all individual participants included in the study.

Consent for publication

The authors have approved the publication of the final version of the manuscript.

Availability of data and materials

The datasets analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding

No funding was received for this study.

Authors' contributions

Design of the work: Muslumanoglu M., Cabioglu N., Tukenmez M., Emiroglu S., Mollavelioglu B.

Acquisition of data: Karanlık H., Ozmen T., Muslumanoglu M., Cabioglu N., Tukenmez M., Emiroglu S., Mollavelioglu B., Ibis K.

Analysis and interpretation of data: Yılmaz R., Gunoz Comert R., Onder S., Bayram A., Oflas M., Has Simsek D.,

Drafting: Yılmaz R., Gunoz Comert R., Onder S., Bayram A., Oflas M., Has Simsek D., Ibis K., Mollavelioglu B.

Important intellectual content: Karanlık H., Ozmen T., Aydiner A., Ozmen V., Igci A., Muslumanoglu M., Cabioglu N., Tukenmez M.

Acknowledgments

The authors are grateful to Atilla Bozdogan, MSc, who helped with the preparation of the

statistical analysis

Veronesi U, Viale G, Paganelli G, Zurrida S, Luini A, Galimberti V, Veronesi P, Intra M, Maisonneuve P, Zucca F, Gatti G. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. 2010;251(4):595–600.
Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347(8):567–75.
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, Ashikaga T, Weaver DL, Mamounas EP, Jalovec LM, Frazier TG. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomized phase 3 trial. Lancet Oncol. 2010;11(10):927–33.
Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, Yiangou C, Horgan K, Bundred N, Monypenny I, England D. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006;98(9):599–609.
Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318(10):918–26.
Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981–22023 AMAROS): a randomized, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303–10.
Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, Goetz MP. Breast cancer, version 4.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16(3):310–20.
Al-Hilli Z, Hoskin TL, Day CN, Habermann EB, Boughey JC. Impact of neoadjuvant chemotherapy on nodal disease and nodal surgery by tumor subtype. Ann Surg Oncol. 2018;25:482–93.
Nguyen TT, Hoskin TL, Day CN, Degnim AC, Jakub JW, Hieken TJ, Boughey JC. Decreasing use of axillary dissection in node-positive breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2018;25:2596–602.
Dwyer M. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®) Breast Cancer NCCN.org NCCN Guidelines for Patients ® available at www.nccn.org/patients. 2023; https://www.nccn.
Panda SK, Goel A, Nayak V, Shaik Basha S, Pande PK, Kumar K. Can preoperative ultrasonography and MRI replace sentinel lymph node biopsy in management of axilla in early breast cancer—a prospective study from a tertiary cancer center. Indian J Surg Oncol. 2019;10(3):483–8.
Abe H, Schacht D, Kulkarni K, Shimauchi A, Yamaguchi K, Sennett CA, Jiang Y. Accuracy of axillary lymph node staging in breast cancer patients: an observer-performance study comparison of MRI and ultrasound. Acad Radiol. 2013;20(11):1399–404.
Boughey JC, McCall LM, Ballman KV, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Flippo-Morton T, Hunt KK. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg. 2014;260(4):608.
Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, Bedrosian I, Hobbs BP, DeSnyder SM, Hwang RF, Adrada BE. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016;34(10):1072.
Boughey JC, Ballman KV, Le-Petross HT, McCall LM, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Feliberti EC, Hunt KK. Identification and resection of the clipped node decreases the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy–results from ACOSOG Z1071 (Alliance). Ann Surg. 2016;263(4):802.
Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Kuerer HM, Bowling M, Flippo-Morton TS, Byrd DR. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310(14):1455–61.
Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, von Minckwitz G, Nekljudova V, Schmatloch S. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14(7):609–18.
Boileau JF, Poirier B, Basik M, Holloway CM, Gaboury L, Sideris L, Meterissian S, Arnaout A, Brackstone M, McCready DR, Karp SE. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;33(3):258–64.
Yan M, Abdi MA, Falkson C. Axillary management in breast cancer patients: a comprehensive review of the key trials. Clin Breast Cancer. 2018;18(6):e1251–9.
Galimberti V, Fontana SK, Vicini E, Morigi C, Sargenti M, Corso G, Magnoni F, Intra M, Veronesi P. This house believes that: Sentinel node biopsy alone is better than TAD after NACT for cN + patients. Breast. 2023;67:21–5.
Wong SM, Basik M, Florianova L, Margolese R, Dumitra S, Muanza T, Carbonneau A, Ferrario C, Boileau JF. Oncologic safety of sentinel lymph node biopsy alone after neoadjuvant chemotherapy for breast cancer. Ann Surg Oncol. 2021;28:2621–9.
Barrio AV, Montagna G, Mamtani A, Sevilimedu V, Edelweiss M, Capko D, Cody HS, El-Tamer M, Gemignani ML, Heerdt A, Kirstein L. Nodal recurrence in patients with node-positive breast cancer treated with sentinel node biopsy alone after neoadjuvant chemotherapy—a rare event. JAMA Oncol. 2021;7(12):1851–5.
Bartels SAL, Donker M, Poncet C, Sauvé N, Straver ME, van de Velde CJH, Mansel RE, Blanken C, Orzalesi L, Klinkenbijl JHG, van der Mijle HCJ, Nieuwenhuijzen GAP, Veltkamp SC, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JWS, Belkacemi Y, Rutgers EJT. Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981–22023 AMAROS Trial. J Clin oncology: official J Am Soc Clin Oncol. 2023;41(12):2159–65. https://doi.org/10.1200/JCO.22.01565.
Mamounas EP, Bandos H, White JR, Julian TB, Khan AJ, Shaitelman SF, Torres MA, Vicini F, Ganz PA, McCloskey SA, Paik S. NRG Oncology/NSABP B-51/RTOG 1304: Phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to whole breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence-free interval (IBCR-FI) in patients (pts) with pathologically positive axillary (PPAx) nodes who are ypN0 after neoadjuvant chemotherapy (NC).
Comparison of Axillary Lymph Node Dissection With Axillary Radiation for Patients With. Node-Positive Breast Cancer Treated With Chemotherapy | ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT01901094.
Mailhot Vega R, Deladisma AM, Mobley EM, Wang S, Morris CG, Oladeru OT, Brooks E, Gharia BM, Spiguel LR, MacDonald SM, Mamounas EP. Axillary surgery efficacy for patients with breast cancer receiving neoadjuvant chemotherapy on NSABP B40 and B41.
van Loevezijn AA, van der Noordaa ME, Stokkel MP, van Werkhoven ED, Groen EJ, Loo CE, Elkhuizen PH, Sonke GS, Russell NS, van Duijnhoven FH, Vrancken Peeters MJ. Three-year follow-up of de-escalated axillary treatment after neoadjuvant systemic therapy in clinically node-positive breast cancer: the MARI-protocol. Breast Cancer Res Treat. 2022;193(1):37–48.
Almahariq MF, Levitin R, Quinn TJ, Chen PY, Dekhne N, Kiran S, Desai A, Benitez P, Jawad MS, Gustafson GS, Dilworth JT. Omission of axillary lymph node dissection is associated with inferior survival in breast cancer patients with residual N1 nodal disease following neoadjuvant chemotherapy. Ann Surg Oncol. 2021;28:930–40.
Cabıoğlu N, Karanlık H, Yıldırım N, Müslümanoğlu M, Karadeniz GÇ, Can DT, Tükenmez M, Ersoy YE, Uras C, Zengel B, Emiroğlu S. Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study. Eur J Surg Oncol. 2021;47(10):2506–14.
Kantor O, Wakeman M, Weiss A, Wong S, Laws A, Grossmith S, Mittendorf EA, King TA. Axillary management after neoadjuvant endocrine therapy for hormone receptor-positive breast cancer. Ann Surg Oncol. 2021;28:1358–67.
Ahmed M, Jozsa F, Baker R, Rubio IT, Benson J, Douek M. Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients. Breast Cancer Res Treat. 2017;166(2):329–336. 10.1007/s10549-017-4405-3. Epub 2017 Jul 28. Erratum in: Breast Cancer Res Treat. 2017;166(2):337. PMID: 28755147; PMCID: PMC5668351.
Kim R, Chang JM, Lee HB, Lee SH, Kim SY, Kim ES, Cho N, Moon WK. Predicting Axillary Response to Neoadjuvant Chemotherapy: Breast MRI and US in Patients with Node-Positive Breast Cancer. Radiology. 2019;293(1):49–57. 10.1148/radiol.2019190014. Epub 2019 Aug 13. PMID: 31407967.

No competing interests reported.

Download PDF

Editorial decision: Revision requested
31 Aug, 2024
Reviews received at journal
18 Aug, 2024
Reviewers agreed at journal
06 Aug, 2024
Reviews received at journal
29 Jul, 2024
Reviewers agreed at journal
27 Jul, 2024
Reviewers invited by journal
25 Jul, 2024
Editor assigned by journal
11 Jul, 2024
Submission checks completed at journal
09 Jul, 2024
First submitted to journal
09 Jul, 2024

You are reading this latest preprint version

Axillary lymph node dissection is not required for breast cancer patients with minimal axillary residual disease after neoadjuvant chemotherapy

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

INTRODUCTION

METHODS

Statistical analysis

RESULTS

DISCUSSION

CONCLUSİON

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1