Expert Explores the Optimal Approach of Radiation Therapy and Breast Reconstruction During Breast Cancer Conference

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The use of radiation therapy has become a staple in breast cancer treatment, with benefits seen in node-positive patients, those with locally advanced disease, and those with large-sized tumors. Similarly, breast reconstructive surgery has made its way into the treatment algorithm.

Although representing separate arms of breast cancer treatment, when combined, these 2 modalities can pose sequencing challenges to patients and their clinicians, in particular because radiation therapy can lead to infections, cosmesis, and ultimately failure of the reconstruction.¹ In addition, evidence of the combined use of these treatments has been largely anecdotal and driven by the clinician’s training institution.

“Historically, the combination of these treatments has been guided by the individual’s institutional experience,” Reshma Jagsi, MD, DPhil, the Lawrence W. Davis Professor and Chair, Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute in Atlanta, Georgia, told Targeted Therapies in Oncology in an interview.

“In the past, if you trained at institution X, you did it a particular way; if you trained at institution Y, you did it a different way,” Jagsi said. “Your experience was driven by single-institution retrospective analyses of outcomes that involved heterogenous groups of patients,” she continued.

Jagsi explained that retrospective analysis might include patients who received radiation treatment years ago but then underwent a mastectomy and breast reconstruction later on at disease recurrence. These patients might also have been included with other patients who received radiation therapy immediately after undergoing a mastectomy but underwent reconstruction later. Or they may have been included with patients who underwent reconstruction immediately at the time of mastectomy and who received radiation therapy later. “What you have is a mess of heterogeneity making it difficult to draw rigorous conclusions.”

Conducting retrospective chart reviews is also fraught with challenges, Jagsi emphasized. “Some charts didn’t even have patient outcomes, adding to the confusion,” she said.

At the 42nd Annual Miami Breast Cancer Conference®, from March 6 to 9, 2025, Jagsi, who is a conference cochair, will address the evidence for combining the 2 modalities. Patrick I. Borgen, MD; and Hope S. Rugo, MD, FASCO, are the other cochairs.

Jagsi has noted a fundamental shift in the last 15 years in the combined approach. “We have seen a thoughtful collection of prospective data from patients who were receiving various types and approaches of breast reconstruction and various timing of breast reconstruction, vis-à-vis radiation therapy,” Jagsi said.

Mastectomy Reconstruction Outcomes Consortium (MROC) Study

The prospective Mastectomy Reconstruction Outcomes Consortium (MROC) Study compared outcomes for the 5 commonly used options for breast reconstruction: expander/implant, latissimus dorsi/implant, pedicle transverse rectus abdominis musculocutaneous (TRAM), free TRAM, and deep inferior epigastric perforator techniques.²

These outcomes included complications, postoperative pain, psychosocial well-being, physical functioning, patient satisfaction, and costs. The effect of race and ethnicity on reconstruction outcomes were also evaluated.² This project involved 57 plastic surgeons at 11 academic and private practice sites across the US and Canada. Nine of 11 centers were academic institutions; 2 were private practices.²

A substudy of MROC, conducted by Pusic AL et al,³ evaluated patient-reported outcomes in women undergoing immediate implant-based or autologous reconstruction. In the study, only patients with a cancer diagnosis (ie, not patients undergoing prophylactic mastectomy) and those undergoing immediate reconstruction were included.

According to the investigators, at 1 year after mastectomy, patients who underwent autologous reconstruction were more satisfied with their breasts and had greater psychosocial and sexual well-being than those who underwent implant reconstruction.

“Back then, we would give 5 weeks of daily radiation treatment, but there has been interest in moderate hypofractionation––treating patients for 3 weeks with 42 or 42.5 Gy and 16 fractions or 40 Gy and 15 fractions,” Jagsi said.

Data from the UK Standardisation of Breast Radiotherapy (START) trials⁴ suggested that lower total doses of radiotherapy delivered in fewer, larger doses (fractions) are at least as safe and effective as the historical standard regimen (50 Gy in 25 fractions) for women after primary surgery for early-stage breast cancer.

The investigators concluded that a lower total dose in a smaller number of fractions could offer similar rates of tumor control and normal tissue damage to those of the international standard fractionation schedule of 50 Gy in 25 fractions.

“In the US, many of our patients underwent breast reconstruction together with mastectomy. We wanted evidence [of] whether hypofractionation in the setting of breast reconstruction would be safe and effective,” Jagsi said. “We worry that if we give radiation treatment in bigger doses per day, it could lead to late fibrosis and other toxicity. That’s problematic in the setting of breast reconstruction,” she continued.

Two Studies

Jagsi noted that findings from 2 important trials can inform the clinician’s decision.

The FABREC trial (NCT03422003)⁵ compared quality of life (QOL) and clinical outcomes of hypofractionated (HF) vs conventionally fractionated (CF) postmastectomy radiation therapy (PMRT) in 400 patients at 18 centers with stage 0-III breast cancer who had undergone immediate prosthetic reconstruction.

The investigators reported no difference in any oncologic outcomes, including distant recurrence, death, or local recurrence, and no difference in toxicity outcomes.

Further, they reported improvements in QOL domains with HF, especially in younger patients, as well as fewer treatment breaks and less financial toxicity.

“The investigators’ findings suggest that it is acceptable to use the shorter regimen of treatment, which is more convenient for patients,” Jagsi said.

Evidence from the second trial was presented at the 2024 American Society for Radiation Oncology Annual Meeting. Findings from the phase 3 RT CHARM trial (Alliance A221505; NCT03414970) demonstrated that a shorter course of postmastectomy radiation, combined with breast reconstruction, is safe and effective. Cutting treatment time nearly in half—from 25 to 16 treatment sessions—could make postmastectomy radiation a more accessible option for patients.⁶

In the trial, patients were randomly assigned to receive either conventional radiation of 25 fractions delivered across 5 weeks (50 Gy total; n = 449) or hypofractionated radiation consisting of 16 fractions delivered across roughly 3 weeks (42.56 Gy total; n = 449). Slightly more than half the patients (51%) received chemotherapy prior to their mastectomies, and 37% received chemotherapy following mastectomy.

“These results reassuringly suggest that when we use moderate hypofractionation that the outcomes are not worse than when we use conventional fractionation,” Jagsi said. “There are some nuances and some important points about those studies, including the fact that there are still substantial rates of complications that do exist, particularly when implant-based reconstruction is pursued in the context of postmastectomy radiation treatment.”

“For the conference in Miami, we’ll focus on these recent landmark trials that suggest we can safely use more efficient hypofractionated approaches in patients who have had breast reconstruction, along with prior observational studies that help also to inform what approaches to reconstruction type and timing are best suited to optimize long-term outcomes,” Jagsi concluded.

REFERENCES

• Sekiguchi K, Kawamori J, Yamauchi H. Breast reconstruction and postmastectomy radiotherapy: complications by type and timing and other problems in radiation oncology. Breast Cancer. 2017;24(4):511-520. doi:10.1007/s12282-017-0754-3

• Wilkins E. Grant 5R01CA152192-05. Mastectomy reconstruction outcome consortium (Mroc Study). National Cancer Institute. Accessed December 5, 2024. https://tinyurl.com/2u6svh2d

• Jagsi R, Momoh AO, Qi J, Hamill JB, Billig J, Kim HM, Pusic AL, Wilkins EG. Impact of Radiotherapy on Complications and Patient-Reported Outcomes After Breast Reconstruction. J Natl Cancer Inst. 2018;110(2):157–65. doi: 10.1093/jnci/djx148. PMID: 28954300; PMCID: PMC6059091.

• START Trialists’ Group; Bentzen SM, Agrawal RK, Aird EGA, et al. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008;9(4):331-341. doi:10.1016/S1470-2045(08)70077-9

• Wong JS, Uno H, Tramontano A, et al. Patient-reported and toxicity results from the FABREC study: a multicenter randomized trial of hypofractionated vs. conventionally-fractionated postmastectomy radiation therapy after implant-based reconstruction. Int J Radiat Oncol Biol Phys. 2023;117(4):E3-E4. doi:10.1016/j.ijrobp.2023.08.029

• Poppe MM, Le-Rademacher J, Haffty BG Jr, et al. A randomized trial of hypofractionated post-mastectomy radiation therapy (PMRT) in women with breast reconstruction (RT CHARM, Alliance A221505). Int J Radiat Oncol Biol Phys. 2024;120:(suppl 2):S11. doi:10.1016/j.ijrobp.2024.07.002