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Page 2 of 15 Friedman et al. Plast Aesthet Res 2023;10:23 https://dx.doi.org/10.20517/2347-9264.2022.100

Keywords: Lymphatic anatomy, immediate lymphatic reconstruction, lymphedema

INTRODUCTION
A significant survivorship issue following breast cancer treatment is breast cancer-related lymphedema
(BCRL). BCRL arises due to the accumulation of lymphatic fluid in the upper extremity as a result of
damage to the lymphatic system during axillary lymph node dissection (ALND) . The fluid accumulation
[1]
can result in disfiguring edema, erythema, pain, tightness, heaviness, and diminished function of the
affected extremity . If left untreated, BCRL is typically progressive and can be complicated by life-
[2,3]
threatening infections. In addition to distressing physical symptoms, patients may face psychosocial
burdens secondary to BCRL [4,5,6] . Additionally, patients with BCRL face considerable out-of-pocket costs
[7,8]
irrespective of treatment modality .

The incidence of BCRL following axillary lymph node dissection is reported to be between 21% to 34% [9-14] .
Variation in reported incidence may be due to the lack of standardization in methods of assessment and
diagnostic criteria. Notably, the incidence of lymphedema is disproportionately higher among Black and
Hispanic patient populations, highlighting a healthcare disparity among breast cancer survivors . Breast
[15]
cancer mortality rates have declined due to advancements in diagnostic modalities and clinical
management . Therefore, the rates of BCRL can be expected to increase in the coming decades and there
[16]
remains an unmet need for physicians and researchers dedicated to the prevention and treatment of this
disease .
[17]
The pathophysiology of BCRL occurs through three stages: fluid accumulation, fibrosis, and fatty tissue
deposition. In the initial stages, interstitial fluid stasis takes place and proliferation of inflammatory cells
ensues . This inflammatory response leads to lymphatic vessel deterioration, fibrosis, and inhibition of
[18]
lymphangiogenesis [19-22] . Lastly, subcutaneous adipose tissue is deposited [23,24] . Notably, multiple genes have
been implicated in the development of BCRL, including HGF and GJC2 genes [25-28] . This knowledge has been
utilized clinically by recommending genetic testing for patients for earlier detection of lymphedema, though
[29]
further research is warranted .

As the underlying inciting event of BCRL development is the disruption of lymphatic vessels during
oncologic surgery, our team has focused on the operative prevention of BCRL. The purpose of this review is
to highlight ways in which variations in lymphatic anatomy can inform the application and improve the
accessibility of the surgical prevention of lymphedema. In order to adequately discuss surgical prevention, it
is important to first understand identifiable preoperative risk factors.

RISK FACTORS FOR DEVELOPING BCRL
The single greatest risk factor is ALND. Patients who undergo ALND are at a substantially higher risk of
developing BCRL, with a relative risk of 3.47 in comparison to those who do not require ALND for
oncologic treatment [11,30,31] . Findings from Yusof et al. determined that ten or more excised lymph nodes was
associated with a three-fold increased risk of BCRL, due to more extensive damage to the lymphatic
vessels . Furthermore, patients with a larger burden of oncologic disease within the lymph nodes may be at
[32]
higher risk of BCRL development, as the invasion of cancer cells within the lymph nodes may overcrowd
and disrupt normal lymphatic architecture, thereby impairing lymphatic flow [30,33] .