Prevention Is Key: Importance of Early Recognition and Referral in Combating Breast Cancer–Related Lymphedema

Breast Cancer–Related Lymphedema: A Byproduct of Breast Cancer Treatment and Survival

In the article that accompanies this commentary, Tandra and colleagues present a comprehensive review of the pathophysiology, diagnosis, and management of breast cancer–related lymphedema (BCRL), which affects roughly one in five patients with breast cancer.¹ The topic is timely and critical. As the arsenal of multimodal cancer treatment expands, oncologists face the unique challenge of how to manage enduring the adverse effects of the life-saving treatments they dispense.

Lymphedema is one of the most common and well-known complications of breast cancer. Even as Halstead’s radical mastectomy devolved during the 20th century with emerging muscle- and skin-sparing techniques, and with recent movement away from complete axillary nodal dissection, BCRL still affects a surprisingly high proportion of patients. Tandra et al and others^1-3 have described the burden this disease places on patients who contend with physical and psychosocial pain, restricted mobility, out-of-pocket costs, and lost productivity.

In the era of conservative breast surgery, how can we further reduce the burden of BCRL? Prevention and early detection are key. In each phase of patient care, from surgery onward, there are opportunities for preventing or promptly diagnosing BCRL before it progresses.

Prevention and Early Detection

Limiting axillary surgery and radiation.

The Z0011 study represented a tectonic shift away from complete axillary lymph node dissection by establishing criteria for definitive sentinel lymph node biopsy. The practice-changing study demonstrated that patients with small, clinically node-negative tumors who underwent breast-conserving surgery, sentinel node biopsy with up to two positive nodes on pathologic review, and adjuvant radiotherapy experienced similar locoregional recurrence and overall survival whether they also underwent complete axillary dissection. Recently, 10-year data from the After Mapping of the Axilla: Radiotherapy Or Surgery (AMAROS) trial demonstrated the safety and noninferiority of axillary radiotherapy compared with complete nodal dissection in select patients with positive sentinel lymph nodes. Implications from these two studies for BCRL are considerable. Compared with axillary dissection, sentinel lymph node biopsy poses roughly one quarter the risk, and radiotherapy roughly one half.^4,5 Thus, a first step in reducing BCRL requires clinicians to fully integrate evidence-based recommendations that limit axillary surgery when appropriate. Furthermore, as data emerge on the variable mortality risk across histologic subtypes and patient populations, researchers must continue refining selection criteria for axillary surgery. For example, multiple studies now postulate that elderly patients with early-stage, clinically node-negative disease are unlikely to benefit from, and may safely forgo, sentinel lymph node biopsy.^6,7

Secondary prevention through prehabilitation.

For patients who continue to meet criteria for axillary surgery and radiotherapy, secondary prevention through formalized rehabilitation programs may further reduce the burden of BCRL. Prospective studies have demonstrated that standard referral of at-risk patients for preemptive treatment by lymphedema specialists is more effective for preventing BCRL than patient education and surveillance.^8,9 A number of therapeutic approaches are supported, including physical therapy, progressive resistance training, manual lymphatic drainage, and compression garments; however, specific recommendations for “prehabilitation” programs, including optimal patient selection, treatment modality, and length of treatment, have not been established. Furthermore, a single approach may not befit all patients. At this time, ensuring the feasibility, suitability, and cost effectiveness of prehabilitation programs is paramount. We recommend that oncologists partner with institutional or regional lymphedema specialists to establish programs that work for their populations of patients and practitioners.

Screening to secure an early diagnosis.

Even with BCRL risk reduction through primary and secondary prevention, a percentage of patients will inevitably develop lymphedema. The natural history of the disease, which includes a subclinical latent stage followed by a symptomatic reversible stage, potentiates screening and early diagnosis. Prompt treatment of BCRL has been demonstrated to halt disease progression, limit morbidity, and even reverse the disease process in some patients.^1-3,8,9

Like preventive therapies for BCRL, there is no consensus on the optimal screening regimen. Diagnostic tools range from simple and inexpensive, such as measurement of arm circumference and water displacement, to risk carrying and costly, such as dual-energy X‐ray absorptiometry and lymphoscintigraphy. Less-sophisticated tools, although excellent for long-term use, are generally less effective at diagnosing subclinical lymphedema.^1,8,9 Fortunately, patient reporting of symptoms can aid in making the diagnosis when technology falls short. A patient’s individual experience can also help guide the modality and aggressiveness of BCRL management. Many validated questionnaires on lymphedema-related symptoms are available.¹⁰ We believe that, regardless of the specific screening regimen chosen, the key to its success and sustainability is coupling an accurate, practical diagnostic test with a validated patient-reported outcome tool.

Integrating BCRL Management With Cancer Care

Patients contend with myriad worries and responsibilities during the course of breast cancer care. Lymphedema is just one adverse effect the management of which should not place additional burden on patients and caregivers. As we learn more about the influence of exercise, nutrition, and psychosocial wellbeing on cancer outcomes and care satisfaction, our multidisciplinary treatment models must become less fragmented and more assimilated. Physical therapy and resistance training might be folded into a generalized exercise program prescribed at diagnosis. Routine skin care, lymphedema education, arm measurements, and screening questionnaires could be incorporated at regular intervals into the longitudinal oncologic care plan. As we continue achieving new feats in cancer treatment and survival, we should work toward developing more holistic, integrated models of care.

AUTHOR CONTRIBUTIONS

Conception and design: Danielle R. Heller, Tara Sanft

Collection and assembly of data: Danielle R. Heller, Tara Sanft

Data analysis and interpretation: All authors

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Prevention Is Key: Importance of Early Recognition and Referral in Combating Breast Cancer–Related Lymphedema

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jop/site/ifc/journal-policies.htm.

Brigid K. Killelea

Consulting or Advisory Role: Genentech

Travel, Accommodations, Expenses: Genentech

Tara Sanft

Honoraria: bioTheranostics

Consulting or Advisory Role: bioTheranostics

Research Funding: bioTheranostics (Inst)

No other potential conflicts of interest were reported.