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Friedman et al. Plast Aesthet Res 2023;10:23 https://dx.doi.org/10.20517/2347-9264.2022.100 Page 3 of 15

Regional lymph node radiation (RLNR) substantially increases a patient’s risk of BCRL in a delayed manner,
as it can take months or years for radiation-related fibrosis to develop [34,35] . The development of fibrosis
within the lymph node can compress and distort the lymphatic tissue, resulting in increased fluid
accumulation in the distal lymphatics [36,37] . RLNR targeted at supraclavicular or axillary lymph nodes
presents the greatest risk of BCRL, whereas the risk after chest wall radiotherapy appears to be lower .
[37]
Body mass index (BMI) is recognized as the primary modifiable risk factor linked to the development of
BCRL [30,38-40] . A higher BMI has been positively correlated with the development of BCRL, with obese
patients having a greater risk of developing lymphedema compared to those who are overweight or within
the normal range . This correlation may be explained by underlying biochemical changes to the lymphatic
[39]
system in patients with higher BMI, including inflammatory processes and direct injury to lymphatic
[41]
endothelial cells, which likely induce baseline lymphatic disruption .
There are other important risk factors that remain controversial. Multiple studies have reported an
association between taxane-based chemotherapeutic administration and BCRL development [42-46] , while
other studies have not supported this finding . Cariati et al. demonstrated that the use of adjuvant taxane-
[47]
[45]
based chemotherapy conferred a threefold increase in the risk of BCRL development . In a large
prospective study, Swaroop et al. noted that adjuvant docetaxol increased the risk of mild swelling though
taxane-based chemotherapy was not a risk factor for BCRL development . Fewer studies have focused on
[47]
examining the effects of neoadjuvant taxane-based chemotherapy on the development of BCRL [48-50] .
Johnson et al. demonstrated that patients who received neoadjuvant taxane-based chemotherapy had a
reduction in lymphatic contractile function and demonstrated a possible association with the presence of
peripheral neuropathy in those who received neoadjuvant taxane-based chemotherapy .
[48]

Multiple prior studies have noted an association between increasing age and BCRL [51-53] . Shang et al.
demonstrated that aging results in loss of muscle cells, impairment of lymphatic contractile function, and
[54]
increased production of inflammatory cytokines . However, other studies offer contradictory findings,
with some reporting that the incidence of BCRL is higher in younger women [55-57] .

There is uncertainty as to how factors pertaining to oncologic breast surgery, such as the extent of breast
surgery and reconstruction, may modify individual risk of BCRL. A previous investigation reported that
[58]
modified radical mastectomy appeared to be an independent risk factor for BCRL . Other studies have
indicated that the rate of BCRL was higher in those who underwent a total mastectomy compared to those
who underwent partial mastectomy . Additionally, patients undergoing multiple surgeries including both
[59]
mastectomy and lumpectomy on the same breast are likely at higher risk of BCRL than those having only
one procedure alone . In addition, multiple studies have examined the relationship between breast
[32]
reconstruction and BCRL development. In a meta-analysis, Siotos et al. determined that breast
reconstruction was associated with a lower risk of lymphedema compared to mastectomy alone . In a
[60]
matched cohort study of over 400 patients, Basta et al. reported that immediate breast reconstruction did
[61]
seem to influence the risk of BCRL development . Though the influence of breast reconstruction on the
risk of BCRL development is not fully understood, breast reconstruction does not appear to adversely affect
the risk of BCRL .
[62]
IMMEDIATE LYMPHATIC RECONSTRUCTION
Lymphovenous bypass (LVB), as described by Yukio Yamada in 1969 as a surgical treatment for chronic
lymphedema, was the first successful surgical technique developed to restore lymphatic flow in an animal
[63]
model . In this study, a successful anastomosis of the thoracic duct into the venous system was created,