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Page 2 of 18 Laustsen-Kiel et al. Plast Aesthet Res 2024;11:17 https://dx.doi.org/10.20517/2347-9264.2024.32

INTRODUCTION
Nearly 2.3 million women were diagnosed with breast cancer in 2022 . As mortality rates have
[1]
[2,3]
decreased , a growing number of women suffer from the long-term effects of breast cancer and its
treatment. As an oncologist, plastic-, or breast surgeon treating women diagnosed with breast cancer, it is
crucial to understand the relationship between cancer treatment, patient-related outcomes, and pertinent
strategies to prevent or treat long-term effects, such as BCRL. This narrative review aims to provide insight
into BCRL following breast reconstruction, addressing current knowledge about the association between
breast reconstruction and BCRL. The scope is perspectives on the pathophysiological and clinical
implications of BCRL, including a discussion on how oncologic breast surgery and adjuvant treatment
impact the risk of developing BCRL. The review also highlights advancements in diagnostics and treatment
over the last decade. Literature was systematically searched from EMBASE, Pubmed, Cochrane, and BASE
databases from January 2017 to December 2023 for breast reconstruction and BCRL articles. Since no
international checklist is published for narrative reviews, we adhered to the Scale for the Assessment of
Narrative Review Articles (SANRA) .
[4]

BREAST CANCER-RELATED LYMPHEDEMA
Secondary lymphedema may arise from surgical procedures, radiation, trauma, or infection. Nevertheless,
[5]
the predominant cause is breast cancer . The incidence of BCRL exhibits considerable variability
[10]
throughout the literature . The most recent systematic review reports an incidence of 21.9% . Thus,
[6-9]
approximately half a million women diagnosed with breast cancer in 2022 may potentially be diagnosed
with lymphedema during their lifetime.

PATHOPHYSIOLOGY
Lymphedema is characterized by the accumulation of protein-rich fluid, resulting in swelling of the affected
body part. The lymphatic vessels return around 2-4 L of fluid to the venous system daily . An imbalance
[11]
occurs when the lymphatic load exceeds the transport capacity, resulting in lymphedema. However, the
pathophysiology of lymphedema is more complex than excess fluid in the interstitial space.

The collecting lymphatic vessels are located in the subcutaneous adipose layer. Thus, lymph fluid
[12]
accumulates between adipocytes, resulting in adipose hyperplasia or hypertrophia . The exact pathway
from increased lymph fluid to hyperplasia or hypertrophia of adipocytes is not fully understood , and
[13]
consensus on whether adipocytes increase in size due to lymphedema is absent [13-15] . Nevertheless,
[16]
lymphedema leads to the deposition of adipose tissue .

Non-linear lymphatic anatomy and early disturbance in lymphatic transport are risk factors for the
development of BCRL [17,18] . The role of growth factors, such as vascular endothelial growth factor (VEGF)-C,
has been debated [19,20] , and treatment with VEGF-C adenovirus was applied in a randomized clinical trial,
with ambiguous results [12,21] . The deposition and remodeling of adipose tissue in lymphedema patients may
contribute to increased low-grade local inflammation due to the secretion of pro-inflammatory
+
cytokines [22,23] . This chronic inflammation, in which CD4 cells play a crucial role [21,24,25] , has been
demonstrated to facilitate fibrosis during the progression to more advanced stages of lymphedema.
Pathohistological studies have identified hyperplasia of collagen fibers and smooth muscle cells, causing
thickening of the lymphatic vessels. This contributes to the hardening of the lymphatics, compromising
their peristaltic ability and [26-28] , lastly, exacerbating the accumulation of lymph. In summary, the
pathophysiology of lymphedema results from an inappropriate circle of stasis, causing an imbalance in the
interstitial fluids, lymphatic vessel remodeling and function, and adipose tissue deposition.

CLINICAL AND PSYCHOLOGICAL IMPLICATIONS OF BREAST CANCER-RELATED