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Page 2 of 15 Ewing et al. Plast Aesthet Res 2024;11:22 https://dx.doi.org/10.20517/2347-9264.2024.11

INTRODUCTION
Despite advancements in research and technology, breast cancer remains the second leading cause of
cancer-related mortality affecting women worldwide. About 1 in 8 women in the US are diagnosed during
their lifetime . The primary goal for breast cancer management is eradication of cancer, prevention of
[1]
metastasis, and reduction of local recurrence. Surgery, sometimes combined with radiotherapy, effectively
manages localized cancer, whereas systemic therapy (i.e., hormonal therapy, chemotherapy, targeted
therapy, combined therapy) controls for metastatic relapse. Over time, breast conservation therapy (BCT)
and, more recently, oncoplastic surgery have evolved to the forefront of management. With recent emphasis
on cosmetic outcomes, BCT combined with postoperative radiotherapy has emerged as the preferred
standard of care for early-stage breast cancer (stage I and II), replacing highly invasive surgeries such as
simple and modified radical mastectomy .
[2]

Radiation therapy is a widely recommended adjunct to surgery due to its significant role in reducing loco-
regional recurrence . Radiation reduces the 10-year risk of local cancer recurrence by approximately 50%
[3]
[1]
and the 15-year risk of mortality by approximately 20% when combined with breast-conserving therapy . It
is indicated for large tumors (> 5 cm), chest wall invasion, involvement of the lymph nodes, patients with
partial or incomplete resection, and relief of widespread metastasis in palliative patients . Furthermore,
[1,4]
postmastectomy radiation therapy (PMRT) has been employed for decades in patients with locally advanced
disease with a high risk of recurrence. Relative contraindications to radiation therapy include small tumors,
absence of nodal involvement, age > 70 years old, and hormone receptor-positive (HR+) cancers that lack
evidence for improved survival with radiotherapy.

Radiation is commonly delivered by standard external beams for whole breast and nodal irradiation,
[5]
brachytherapy for internal radiation, or a combination of both . The conventional radiation dosage of
45-50 Gray (Gy) is applied to the breast, with a boost treatment of 10-16 Gy for the lumpectomy site . An
[6]
additional 45-50 Gy dose, dependent on recurrence risk, is applied to the regional node. Administration
may take about six weeks, while hypofractionation, or lower doses of smaller fractionations, is reserved for
low-risk individuals.

Radiation induces the production of reactive oxygen species (ROS) , ultimately leading to a cancer cell’s
[7,8]
destruction. However, surrounding healthy tissues are at risk for damage. Radiation triggers a series of
pathophysiologic events leading to tissue injury; ROS cause (1) vascular damage and chronic hypoxia ; (2)
[9]
[10]
an inflammatory response ; and (3) activation of myofibroblasts to induce fibrosis . As a result, radiation
[11]
interferes with wound healing and negatively impacts the quality of the skin. Patients may present with skin
breakdown, hair and gland loss, ischemia, and ulcer formation.

Fibrosis-related complications are categorized as acute or chronic. Acute radiodermatitis (i.e., erythema,
edema, desquamation, and ulceration) occurs within three months of radiotherapy . Chronic
[12]
[13]
radiation-induced fibrosis occurs 4-6 months post-radiotherapy and can be irreversible . Radiation-
induced fibrosis complicates the sequence of breast reconstruction and forces surgeons to consider the
timing of radiation and the type of reconstruction (autologous vs. implant) to improve patient outcome, as
elaborated later [14-16] .

The types of breast reconstruction to consider include implant-based (direct-to-implant/immediate or
delayed with tissue expanders) and autologous reconstruction. In contrast to the immediate approach (i.e.,
reconstruction at the time of mastectomy), the delayed approach may take months to years. Autologous
breast reconstruction involves taking tissue from a donor site and transferring it to a recipient site.