Breast Reconstruction in the Setting of Postmastectomy Radiotherapy: Controversies and Disparities

ABSTRACT: The complex decision of breast reconstruction in the setting of postmastectomy radiotherapy (PMRT) involves an understanding of the indications of PMRT and weighing the risks and benefits of various reconstruction options suitable for each patient. Classic indications for PMRT include patients with at least T3 tumors, 4 or more positive lymph nodes, and/or positive surgical margins. The benefit of PMRT in patients with T1-T2 tumors with 1 to 3 positive lymph nodes, however, remains unclear. Breast reconstruction is known to improve quality of life in breast cancer patients. Reconstruction rates have continued to increase despite the lack of medical consensus in these patients with early cancers and limited nodal burden. A collaborative effort among providers is therefore of utmost importance in selecting an optimal approach of reconstruction in the setting of PMRT to minimize postoperative complications. In this review, we discuss the advantages and disadvantages of each reconstruction method with PMRT and highlight the practice patterns at different types of institutions, especially noting the disparities seen at safety net institutions. By refocusing on this important topic, we hope to encourage a multidisciplinary effort to reduce disparities and find innovative algorithms that can be applied to patients at diverse institutions.

Introduction

Breast reconstruction in the setting of postmastectomy radiotherapy (PMRT) is a complex topic that requires an understanding of the risks and benefits of each reconstruction option and the indications of PMRT. The 2001 American Society of Clinical Oncology guidelines for PMRT established indications for its use in patients with at least T3 tumors, 4 or more positive lymph nodes, and/or positive surgical margins, and these indications remain undisputed today.[1] The benefit of PMRT in women with T1-T2 tumors with 1 to 3 positive lymph nodes has remained unclear, however, and continues to be an area of clinical ambiguity. In 2016, a consensus panel addressing this subset of patients was convened and included representation from the American Society for Radiation Oncology and the Society of Surgical Oncology.[2] Although they reached a consensus that PMRT resulted in a reduction of breast cancer recurrence and mortality, they noted that those with small tumors and limited nodal disease still constituted a group of patients whose risks from PMRT might outweigh the benefits.[2] The lack of consensus among physicians for this remaining group of women has added to the complexity of management when breast reconstruction is considered.

Breast reconstruction rates have continued to increase over time, despite the lack of consensus for the management of patients receiving both reconstruction and PMRT.[3–5] In a SEER database from 2000 to 2011, reconstruction rates continued to increase in the subset of mastectomy patients with 1 to 3 positive lymph nodes.[5] The optimal timing of each therapy as well as practice patterns vary among providers and across different institutions.[5,6] The dynamics become even more complex in safety net hospitals, in which socioeconomic variables play a larger role in the consideration for reconstruction.[7] For this reason, we aim to provide an overview of the current practices of breast reconstruction and PMRT. We provide a review of the advantages and disadvantages of each method of reconstruction. We also discuss the controversies in reconstruction and PMRT, including the variations in practice patterns as well as the paucity of data applicable to diverse institutions. In doing so, we hope to draw further attention and investigation into developing algorithms that help providers improve outcomes for these patients.

Implant-based breast reconstruction and radiotherapy: advantages and disadvantages

Implant-based breast reconstruction represents 80% of the reconstruction performed after a mastectomy.[9,10] The implant can be composed of saline or silicone. Anatomically, it can be placed in the subpectoral space, under the pectoralis muscle, or prepectoral space, above the pectoralis muscle. Implant-based breast reconstruction can be performed in conjunction with a mastectomy as an immediate, one-stage, direct-to-implant procedure, or in a delayed fashion as a separate procedure several months after both the mastectomy and radiation have been completed.

A delayed-immediate reconstruction is a two-stage procedure in which a tissue expander is first placed during the mastectomy. The timing varies with regard to when a tissue expander is inflated relative to when radiation is delivered. Radiation can precede or be delivered after placement of the tissue expander. The tissue expander may be fully inflated during surgery or undergo rapid inflation in the weeks following surgery. In either of these cases, the second stage occurs after PMRT is completed and the tissue expander is then exchanged for a permanent implant.

There are some advantages to a direct-to-implant procedure, particularly in the short-term period as well as if the patient does not require PMRT. The first advantage is the immediate creation of a breast mound that lends itself to an immediate psychosocial benefit.[6,8] Also, it is well-tolerated and can mostly be completed in a single procedure, which reduces the overall operative and anesthesia time as well as duration of hospital stay.[8] Although there is an operative advantage to a one-stage procedure, patients who receive immediate implant reconstruction are at risk for long-term complications, especially in the setting of PMRT. These patients have a higher incidence of capsular contracture and return to surgery for subsequent revisions compared to patients who receive autologous reconstruction or tissue expander placement.[6,11,12]

Although delayed-immediate reconstruction is a two-stage procedure, it allows for revisions that may arise after the completion of radiation, such as capsulotomy and other procedures for symmetry.[6] A review of several studies examining immediate and delayed-immediate implant reconstruction found that risks of capsular contracture, infection, or implant exposure could be as high as 37% in patients who received PMRT compared to those who did not receive it.[6] Although multiple office visits may be required for tissue expansion, delayed-immediate reconstruction affords patients a choice between either a permanent implant or an opportunity for autologous reconstruction during the second-stage procedure.[6,8]

Autologous breast reconstruction and radiotherapy: advantages and disadvantages

Autologous breast reconstruction involves using a tissue flap that is transplanted from another site in the patient’s body to reconstruct the breast. The transplanted tissue can be rotated into the breast by maintaining its original blood supply as a pedicled flap or it can be transplanted as a free flap with the blood vessels being distantly anastomosed with those in the breast.[8] Different flaps include the transverse rectus abdominis myocutaneous (TRAM) flap, deep inferior epigastric perforator (DIEP) flap, latissimus dorsi flap, transverse upper gracilis (TUG) or thigh flaps, or gluteal flaps. Similar to implant-based reconstruction, autologous reconstruction can be performed in an immediate or delayed fashion. A breast implant can also be placed along with an autologous flap if the volume provided by the flap alone is inadequate.

Autologous reconstruction can be advantageous due to its natural cosmetic outcome as the tissue settles over time, and it can be used in patients who do not desire implants.[8] The time needed for tissue harvesting and microvascular anastomoses leads to a longer operation and recovery time compared to implant-based reconstruction, eliminating this option in patients who are poor surgical candidates. Autologous reconstruction in the setting of PMRT can lead to fat necrosis, contracture, and wound issues, although the incidence of these complications may be higher in immediate versus delayed autologous breast reconstruction.[6,8,13] The 2018 National Comprehensive Cancer Network guidelines recommend autologous reconstruction as the preferred reconstruction option in patients undergoing PMRT.[14]

Controversies and disparities

Data on the preferred method and timing of reconstruction with adjuvant radiation have been conflicting. A literature review showed less postoperative complications, failure, and morbidity in patients receiving radiation with autologous reconstruction versus implant-based reconstruction.[6] A meta-analysis found a similar trend of reconstructive complications and failures in patients receiving immediate implant reconstruction and PMRT.[15] When comparing immediate to delayed-immediate implant-based reconstruction, a prospective multicenter study revealed similar complication rates in patients receiving radiation with a tissue expander versus those with an implant.[16]

Reported complications vary depending on the location of the implant as well. Several early studies have compared outcomes in prepectoral versus subpectoral prosthetic reconstruction after PMRT.[9,10] One study found that patients with prepectoral implants who received PMRT had lower rates of capsular contracture versus patients with subpectoral implants.[10] As implant coverage by the acellular dermal matrix (ADM) scaffold is larger in the prepectoral technique, surgeons have postulated that ADM may play a role in resisting contracture after radiation.[9,10]

Reasons for choosing different reconstructive and radiation algorithms include consideration of not only patient preference and comorbidities but also physician or institution preferences.[17] Investigators reported higher volumes of reconstruction being offered and performed at academic centers even when accounting for patient-related factors, reflecting institutional differences in offering reconstruction.[18] Furthermore, many studies of PMRT in women with T1-T2 tumors with 1 to 3 positive lymph nodes originate from these academic centers where practice patterns may not reflect those at other community centers.[19] More research is required to investigate why academic centers offer reconstruction at differing rates compared with nonacademic institutions.

The differences in practice patterns not only vary between academic and community centers but also extend to safety net institutions. In a study reviewing the Nationwide Inpatient Sample database between 2005 and 2011, researchers found that those treated at safety net institutions were significantly less likely to receive immediate reconstruction compared to those treated at non-safety net institutions.[20] When examining the method of immediate reconstruction that was performed at either type of facility, the percentage of autologous procedures was higher in safety net hospitals.[20] In fact, investigators in another study observed a similar 10-year trend toward autologous reconstruction at their safety net hospital.[7]

Disparities in reconstruction also exist when considering race and insurance status, because safety net hospitals often provide care to minorities as well as to the underserved and underinsured.[21] In a national retrospective cohort study, non-Caucasians were less likely to undergo immediate breast reconstruction or implant-based reconstruction compared to Caucasian patients.[22] In fact, 39.4% of Caucasians compared to 28% to 35.7% of non-Caucasians underwent immediate breast reconstruction.[22] Implant-based reconstruction was received by 85.5% of Caucasians compared to a lower frequency of 75.6% to 83.4% of patients receiving reconstruction depending on the minority group.[22] Furthermore, patients with no insurance were less likely to receive breast reconstruction overall.[18]

Researchers found minority race and lack of insurance to be associated with an increased use of PMRT, likely reflecting an advanced stage of presentation in this population.[19] Due to the increased use of radiation in this subset, physicians may be unwilling to offer immediate reconstruction in an effort to mitigate the increased complication rates seen with immediate implant-based reconstruction. Patients at safety net hospitals, however, often have other comorbid conditions that may not make them optimal surgical candidates for autologous reconstruction. In those who are more likely to receive PMRT and less likely to tolerate autologous reconstruction, patients are left with a choice between delayed autologous reconstruction and no reconstruction. As mentioned previously, immediate reconstruction of the breast leads to positive psychosocial benefits.[6,8] An analysis of several studies utilizing Breast-Q, a quality-of-life assessment tool, found a consistent trend toward improved well-being and satisfaction in breast cancer patients receiving reconstruction.[23] Therefore, providers should make an effort to find alternate methods to reduce complications so that immediate implant-based reconstruction is still an option for these patients and disparities are reduced.

Conclusions and future directions

Breast reconstruction improves quality of life, but providers must be aware of the risks and benefits of each reconstruction approach in the setting of PMRT. The 2016 PMRT guideline update has served as a reminder for providers to revisit this topic. The uptrend in the use of reconstruction continues to reinforce the importance of collaboration among surgical oncologists, plastic surgeons, and radiation oncologists in regard to selecting the optimal approach to minimize complications in each patient.

It is also important to recognize that there are limited data from nonacademic and safety net institutions on this topic. Further research and data collected from diverse institutions will help minimize disparities. With autologous reconstruction seemingly preferred at safety net hospitals and newer data showing less capsular contracture in prepectoral implant-based reconstruction, perhaps offering prepectoral implants in these patients is another method that can be used to minimize disparities in the type of reconstruction chosen at these institutions. As we move forward, a multidisciplinary discussion will continue to be at the forefront in finding ways to improve the quality of oncologic treatment delivered while minimizing associated complications in our breast cancer patients.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

FIVE KEY REFERENCES

1. Recht A, Edge SB, Solin LJ, et al. Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1539-69.

2. Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. Pract Radiat Oncol. 2016;6:e219-34.

3. Albornoz CR, Bach PB, Mehrara BJ, et al. A paradigm shift in U.S. breast reconstruction: increasing implant rates. Plast Reconstr Surg. 2013;131:15-23.

4. Razdan SN, Cordeiro PG, Albornoz CR, et al. National breast reconstruction utilization in the setting of postmastectomy radiotherapy. J Reconstr Microsurg. 2017;33:312-7.

5. Frasier LL, Holden S, Holden T, et al. Temporal trends in postmastectomy radiation therapy and breast reconstruction associated with changes in National Comprehensive Cancer Network guidelines. JAMA Oncol. 2016;2:95-101.

Dr. Wood Professor of Surgery, Winship Cancer Institute of Emory University

Dr. Ho Doctor of Osteopathic Medicine, Winship Cancer Institute of Emory University

Dr. Subhedar Assistant Professor, Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine

References:

1. Recht A, Edge SB, Solin LJ, et al. Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1539-69.

2. Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. Pract Radiat Oncol. 2016;6:e219-34.

3. Albornoz CR, Bach PB, Mehrara BJ, et al. A paradigm shift in U.S. breast reconstruction: increasing implant rates. Plast Reconstr Surg. 2013;131:15-23.

4. Razdan SN, Cordeiro PG, Albornoz CR, et al. National breast reconstruction utilization in the setting of postmastectomy radiotherapy. J Reconstr Microsurg. 2017;33:312-7.

5. Frasier LL, Holden S, Holden T, et al. Temporal trends in postmastectomy radiation therapy and breast reconstruction associated with changes in National Comprehensive Cancer Network guidelines. JAMA Oncol. 2016;2:95-101.

6. Yun JH, Diaz R, Orman AG. Breast reconstruction and radiation therapy. Cancer Control. 2018:25:1-7.

7. Chen VW, Lin A, Hoang D, Carey J. Trends in breast reconstruction techniques at a large safety net hospital: a 10-year institutional review. Ann Breast Surg. 2018;2:14.

8. Ho AY, Hu ZI, Mehrara BJ, Wilkins EG. Radiotherapy in the setting of breast reconstruction: types, techniques, and timing. Lancet Oncol. 2017;18:e742-53.

9. Nahabedian MY, Cocilovo C. Two-stage prosthetic breast reconstruction: a comparison between prepectoral and partial subpectoral techniques. Plast Reconstr Surg. 2017;140(6S):22S-30S.

10. Sinnott CJ, Persing SM, Pronovost M, et al. Impact of postmastectomy radiation therapy in prepectoral versus subpectoral implant-based breast reconstruction. Ann Surg Oncol. 2018;25:2899-908.

11. Hughes K, Brown C, Perez V, et al. The effect of radiotherapy on implant-based breast reconstruction in the setting of skin-sparing mastectomy: clinical series and review of complications. Anticancer Res. 2012;32:553-7.

12. Roostaeian J, Pavone L, Da Lio A, et al. Immediate placement of implants in breast reconstruction: patient selection and outcomes. Plast Reconstr Surg. 2011;127:1407-16.

13. Patel KM, Albino F, Fan KL, et al. Microvascular autologous breast reconstruction in the context of radiation therapy: comparing two reconstructive algorithms. Plast Reconstr Surg. 2013;132:251-7.

14. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer. Version 4. February 8, 2018. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed May 9, 2019.

15. Pu Y, Mao TC, Zhang YM, et al. The role of postmastectomy radiation therapy in patients with immediate prosthetic breast reconstruction: a meta-analysis. Medicine. 2018;97:1-6.

16. Santosa KB, Chen X, Qi J, et al. Postmastectomy radiation therapy and two-stage implant-based breast reconstruction: is there a better time to irradiate? Plast Reconstr Surg. 2016;138:761-9.

17. Shah C, Kundu N, Arthur D, Vicini F. Radiation therapy following postmastectomy reconstruction: a systematic review. Ann Surg Oncol. 2013;20:1313-22.

18. Sisco M, Du H, Warner JP, et al. Have we expanded the equitable delivery of postmastectomy breast reconstruction in the new millennium? Evidence from the National Cancer Data Base. J Am Coll Surg. 2012;215:658-66.

19. Jagsi R, Abrahamse P, Morrow M, et al. Postmastctomy radiotherapy for breast cancer: patterns, correlates, communication, and insights into the decision process. Cancer. 2009;115:1185-93.

20. Ballard TNS, Zhong L, Momoh AO, et al. Improved rates of immediate breast reconstruction at safety net hospitals. Plast Reconstr Surg. 2017;140:1-10.

21. Bradley CJ, Dahman B, Shickle LM, Lee W. Surgery wait times and specialty services for insured and uninsured breast cancer patients: does hospital safety net status matter? Health Serv Res. 2012;47:677-97.

22. Offodile AC 2nd, Tsai TC, Wenger JB, Guo L. Racial disparities in the type of postmastectomy reconstruction chosen. J Surg Res. 2015;195:368-76.

23. Mundy LR, Homa K, Klassen AF, et al. Breast cancer and reconstruction: normative data for interpreting the BREAST-Q. Plast Reconstr Surg. 2017;139:1046e-55e.