Critical review of axillary recurrence in early breast cancer

https://doi.org/10.1016/j.critrevonc.2018.06.013Get rights and content

Highlights

  • Axillary Recurrence (AR) rate after an appropriated treatment in early breast cancer is less than 1%.

  • Predictive factors for AR are patient age, HR status, tumor size and histologic grade.

  • SLNB is not associated with an increase of AR in SNL-negative and SLN-positive (1–2 nodes) in cT1-2, no palpable nodes cases.

  • Prognosis after AR depends on the ER status and the initial systemic treatment.

  • Treatment of AR should include systemic therapy for a limited-period.

Abstract

Around 2% of early breast cancer cases treated with axillary lymph node dissection (ALND) underwent axillary recurrence (AR) and it has a deleterious effect in prognosis. Different scenarios have incorporated Sentinel Lymph Node (SLN) Biopsy (SLNB) instead of ALND as part of the standard treatment and more effective systemic treatment has also been incorporated in routine management after first curative surgery and after regional recurrence. However, there is concern about the effect of SLNB alone over AR risk and how to predict and treat AR. SLN biopsy (SLNB) has been largely accepted as a valid option for SLN-negative cases, and recent prospective studies have demonstrated that it is also safe for some SLN-positive cases and both scenarios carry low AR rates. Different studies have identified clinicopathological factors related to aggressiveness as well as high-risk molecular signatures can predict the development of locoregional recurrence. Other publications have evaluated factors affecting prognosis after AR and find that time between initial treatment and AR as well as tumor aggressive behavior influence patient survival. Retrospective and prospective studies indicate that treatment of AR should include local and systemic treatment for a limited time.

Introduction

Recurrences after curative treatment in early breast cancer are usually divided into distant and loco-regional recurrence (LRR). Definition of regional recurrence (RR) after surgery includes locations in internal mammary, supraclavicular or infraclavicular lymph nodes, as well as axillary recurrence (AR). Although it had been assumed that AR reflects only insufficient control of the axilla (Smidt et al., 2005; van der Ploeg et al., 2008), the low AR rate even in cases without axilla management suggests that it reflects the absence of an effective immune system activity against remaining involved nodes and an insufficient response to the administered radiation and systemic treatment (International Breast Cancer Study G et al., 2006; Martelli et al., 2008; Hughes et al., 2004; Agresti et al., 2014; Lyman et al., 2005; Tvedskov et al., 2014, Tvedskov et al., 2012; Haffty et al., 2011; de Boer et al., 2009).

Axillary recurrences usually happen between 24 and 48 months after initial treatment, are associated with a deleterious effect on patient outcome and require a treatment that includes surgery rescue (Smidt et al., 2005; van der Ploeg et al., 2008; Houvenaeghel et al., 2016). Prevalence of AR and its management depends on the initial treatment of axilla and because standard treatment of the axilla in breast cancer has been changing over time, there has appeared some controversial issues in the field (Mamounas, 2003; Wang et al., 2011).

During the last decades, there has been a change in surgical management from radical resection to increasing levels of tissue preservation. Axillary lymph node dissection (ALND) has been part of the treatment in early breast cancer, but several morbidities like motion defects, edema, pain, and sensory neuropathies have been related to this procedure.

The NSABP-32 trial showed that Sentinel Lymph Node Biopsy (SLNB) minimize side effects with equivalent survival and regional control than ALND in the SLNB-negative scenario in 2010 and SNLB quickly became the standard of care in early breast cancer with clinically node-negative breast cancer (Mamounas, 2003). In 2011, the Z0011 trial by Giuliano et al. found that SLNB without ALND offers similar survival and regional control as ALND in some early breast cancer cases with axilla involvement (Giuliano et al., 2011).

The purpose of this review is to evaluate the incidence of AR in scenarios of negative or positive SLN that goes or not to ALND. Also, identify the variables associated with the risk and to the prognosis after this type of RR. Finally, analyze information about current concepts in AR treatment.

Section snippets

Methods

The aim was to select original studies in terms of information for AR: incidence after different initial axillary management, predictor features for AR development, prognostic features after AR, and AR management.

Three members of the study team (CAC, MC and LPR) performed a publication analysis through the PubMed search engine of MEDLINE-indexed literature from the National Center for Biotechnology Information (http://www.pubmed.gov) and EMBASE databases for English language articles published

Axillary recurrence rate after axillary lymph node dissection in breast cancer

The standard management of axillary lymph node has traditionally included ALND, and different retrospective and prospective series with follow-up of 5–10 years indicate that around 5–15% of breast cancer patients who went to ALND develop LRR (McBride et al., 2014). Initial studies found AR rates as high as 15%, however, studies performed in the last two decades have described rates lower than 2%, this decrease is the result of the development of more effective systemic therapy and the regular

Conclusions

After reviewing the evidence, we can conclude that prevalence of AR is low despite the extension of the surgery performed in the axilla. Sentinel Lymph Node Biopsy has not been associated with a larger AR rate in negative pathological axilla, nor in SLN-positive (1–2 nodes) in the scenario of cT 1-2 without palpable lymph nodes. The most important factors predicting axillary recurrence are ER-negative status, younger age, larger tumor size and high histologic grade.

Axillary recurrence is

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

To our knowledge, no conflict of interest exists.

Carlos A. Castaneda graduated in Medicine at the University of San Marcos, Peru in 1999 and four years later obtained Board Certification in Medical Oncology at the Cayetano Heredia University. After spending a research period in the USA and completing his training with Science Master in Spain and Germany Universities, returned in Peru, where became faculty at medical department of Instituto Nacional de Enfermedades Neoplasicas (Peruvian Cancer Institute) and professor at Peruvian Universities.

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  • Carlos A. Castaneda graduated in Medicine at the University of San Marcos, Peru in 1999 and four years later obtained Board Certification in Medical Oncology at the Cayetano Heredia University. After spending a research period in the USA and completing his training with Science Master in Spain and Germany Universities, returned in Peru, where became faculty at medical department of Instituto Nacional de Enfermedades Neoplasicas (Peruvian Cancer Institute) and professor at Peruvian Universities. From December 2012, Dr. Castaneda is serving as Executive Director of Research Department at Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru. His clinical and research interests involve Breast Cancer and translational research.

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