The approach to treating breast cancer has undergone significant evolution in recent decades. Management has moved from broadly applied therapies to more tailored, patient-specific treatments, greatly improving outcomes. However, like all therapeutic interventions, they come with potential side effects.
One particularly concerning sequela associated with breast cancer surgery is lymphedema. Lymphedema often results from an axillary lymph node dissection (ALND). It can be a debilitating condition characterized by arm swelling, discomfort, limited function and recurrent infections. Some women have stated that getting lymphedema was worse than the breast cancer. Therefore, lymphedema prevention is paramount, not only for the patient's quality of life but also for their overall health and well-being.
Shifting the Paradigm: Less Can Be More
The best way to avoid lymphedema is to prevent excessive lymph node removal. Sentinel lymph node biopsy (SLNB) has been the standard of care for axillary staging in early-stage invasive breast cancer, providing accurate nodal assessment with reduced morbidity compared to an ALND. Traditionally, patients with positive sentinel nodes underwent ALND. However, there has been a shift toward a more conservative strategy. Key studies like the ACOSOG Z0011 trial and AMAROS have shown that for select patients with early-stage breast cancer and limited nodal involvement, sentinel lymph node biopsy (SLNB) alone, without a subsequent ALND, is sufficient without compromising survival.
Similarly, a clinically node-positive breast cancer diagnosis once led directly to an ALND. However, findings from trials such as ACOSOG Z1071 and SENTINA have demonstrated the potential of neoadjuvant chemotherapy to downstage the axilla. Patients who respond to systemic treatment and no longer have clinically positive nodes may undergo an SLNB or targeted axillary node dissection to assess for residual nodal disease. If the sampled nodes show no signs of residual disease, a full ALND becomes unnecessary. This progression towards de-escalating axillary surgery spares patients from unnecessary extensive nodal clearance, particularly when chemotherapy has effectively eradicated nodal metastasis. In these cases, radiation alone may be adequate treatment and is associated with lower rates of lymphedema.
Numerous research initiatives, including those from our team, have been directed toward refining clinical assessment tools for axillary de-escalation. Using large cancer datasets for predictive modeling and employing genomic analyses can help determine which patients are prime candidates for more conservative axillary strategies.
Improving Axillary Decision-Making: Delayed Sentinel Node Biopsy
Another relatively novel approach to conserving lymph nodes is the implementation of delayed SLNB. Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer and, as such, typically does not require axillary staging procedures. However, patients undergoing a mastectomy for DCIS may have occult invasive carcinoma identified on final pathology. This situation can present a dilemma, as performing an SLNB may not be feasible following a mastectomy due to the absence of breast tissue for tracer injection.
Recognizing the possibility of an upgrade and the associated staging difficulties that could be introduced, surgeons frequently conduct an SLNB preemptively during mastectomy for DCIS. However, given that only approximately 20% of DCIS cases upgrade to invasive carcinoma, this preemptive strategy exposes the majority of patients to unnecessary potential complications, including pain, surgical site infection, arm mobility issues and potential lymphedema.
Delayed sentinel lymph node biopsy offers an alternative approach. In contrast to traditional sentinel node tracers, which dissipate within 24 hours, delayed SLNB uses Superparamagnetic Iron Oxide (SPIO) during the mastectomy to mark sentinel nodes for up to 30 days. This extended window allows clinicians to review the final pathology following mastectomy and make informed decisions regarding the need for axillary staging based on conclusive results. If invasive carcinoma is identified, a delayed sentinel lymph node biopsy focusing on the SPIO-marked nodes can be performed within the 30-day window. However, in the majority of cases where there is no invasive upgrade, the nodes are left intact, avoiding unnecessary surgical complications.
A Preventive Approach: Immediate Lymphatic Reconstruction
There are still cases where an ALND remains necessary, particularly with inflammatory breast cancer or locally advanced disease unresponsive to neoadjuvant chemotherapy. Immediate Lymphatic Reconstruction (ILR) offers a notable preventive measure against lymphedema in these scenarios.
This innovative technique, performed with an ALND, is designed to restore lymphatic continuity and flow, thereby mitigating lymphedema. Mounting data demonstrate a significant reduction in lymphedema rates with this technique. Given these results, ILR has been integrated into the standard ALND protocol at Beth Israel Deaconess Medical Center.
Despite its potential, it is noteworthy that this advanced procedure is available in only a few centers globally, underscoring the need for broader accessibility and awareness. The ILR procedure reflects the continuous advancements in breast cancer surgery — with patient outcomes and quality of life consistently prioritized.
The Horizon: A Call for More Research
While these advances in axillary management are groundbreaking, further research and exploration remain imperative. A future where nodal status can be determined without surgical intervention is exciting. Non-invasive techniques would significantly reduce post-operative complications and accelerate patient recovery.
There is a need for additional clinical trials to provide data to refine treatment methodologies further, personalize care, and judiciously adopt conservative strategies, optimizing efficacy and patient well-being.
There are also opportunities for research to delve deeper into the intricacies of nodal metastasis. Ongoing investigations in this domain may pave the way for novel strategies that limit or potentially prevent the spread of breast cancer.
The landscape of axillary management in breast cancer has transformed, driven by clinical research and surgical innovation. Staying updated on these changes ensures the best possible care for our patients. Moreover, the path ahead promises to bring even greater advancements.
- Consensus Statement on Axillary Management for Patients With In-Situ and Invasive Breast Cancer: A Concise Overview. American Society of Breast Surgeons. https://www.breastsurgeons.org/docs/statements/management-of-the-axilla.pdf
- Kantor O, Sipsy LM, Yao K, James TA. A Predictive Model for Axillary Node Pathologic Complete Response after Neoadjuvant Chemotherapy for Breast Cancer. Ann Surg Oncol. 2018 May;25(5):1304-1311. doi: 10.1245/s10434-018-6345-5. Epub 2018 Jan 24. PMID: 29368152.
- Pease AM, Riba LA, Gruner RA, Tung NM, James TA. Oncotype DX® Recurrence Score as a Predictor of Response to Neoadjuvant Chemotherapy. Ann Surg Oncol. 2019 Feb;26(2):366-371. doi: 10.1245/s10434-018-07107-8. Epub 2018 Dec 12. PMID: 30542840.
- Granoff MD, Fleishman A, Shillue K, Johnson AR, Ross J, Lee BT, Teller P, James TA, Singhal D. A Four-Year Institutional Experience of Immediate Lymphatic Reconstruction. Plast Reconstr Surg. 2023 Mar 8. doi: 10.1097/PRS.0000000000010381. Epub ahead of print. PMID: 36877759.
- Karakatsanis A, Eriksson S, Pistiolis L, et al. Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study [published online ahead of print, 2023 Jan 31]. Ann Surg Oncol. 2023;10.1245/s10434-022-13064-0. doi:10.1245/s10434-022-13064-0.