Background

Breast cancer is the most common new cancer diagnosis among women in the United States and the second most common cause of cancer death.¹ Approximately 268,600 new breast cancer diagnoses and 41,760 cancer-related deaths in the U.S. were estimated for 2019.² Surgery is a standard component of the treatment strategy for most patients with breast cancer. Surgical options include mastectomy (where the entire breast is removed) and lumpectomy or segmental mastectomy (where a portion of the breast is removed). Radiation is generally recommended following lumpectomy, but less frequently following mastectomy. The indications for post mastectomy radiation therapy (PMRT) include four or more positive axillary lymph nodes, axillary nodal involvement that persists after systemic therapy, and stage T3 breast tumors.³ The evidence to support PMRT in patients with one to three positive lymph nodes, younger age, tumor margins less than 1 mm, lymphovascular tumor invasion, and high nuclear grade or negative nodal disease is less clear. Mastectomy is chosen or recommended for approximately 50 percent of women in the U.S. with breast cancer.⁴ Nonsurgical treatments that are used in conjunction with surgery include radiation therapy as well as chemotherapy and endocrine (hormonal) therapy with a range of pharmacologic agents.

Breast reconstruction is commonly offered to women receiving mastectomy for breast cancer. (In this report, we use the term “women” to refer to phenotypic females, regardless of gender.) Women are increasingly choosing to undergo breast reconstruction, although some women are not considered candidates and some choose to avoid reconstruction.^{5, 6} As of 2016, more than 40 percent of women in the U.S. who underwent mastectomy for breast cancer had reconstruction.⁴ According to the American Society of Plastic Surgeons/Plastic Surgery Foundation, approximately 107,200 women in the U.S. underwent breast reconstruction in 2019.⁷ Federal regulations require that health insurance policies that cover mastectomy also cover breast reconstruction.⁸ Breast reconstruction is also offered to women who undergo mastectomy for prophylaxis against breast cancer, such as women with high-risk gene mutations such as BRCA1 and BRCA2.^9–11

For women who choose breast reconstruction surgery, two main considerations must be made: timing and type of reconstruction. Breast reconstruction can be initiated either at the time of mastectomy (immediate reconstruction) or at a later date (delayed reconstruction). Immediate reconstruction is the most common practice in the U.S., selected for approximately 75 percent of patients.⁷ Immediate reconstruction is believed to be associated with better aesthetic results, lower overall costs, and better patient psychological well-being than delayed reconstruction.¹² This is at least in part related to the fact that both mastectomy and reconstruction are done during the same surgery, thus reducing the number of surgeries and exposures to anesthesia. Although immediate reconstruction has traditionally been thought to be associated with more postoperative complications than delayed reconstruction in the setting of PMRT, a recent systematic review suggested found that complication rates were comparable.¹³ Immediate reconstruction may impact the planning and delivery of radiation therapy in a negative fashion, particularly in regard to chest wall and/or nodal coverage and heart/lung minimization.^{14, 15}

Based on the type of procedure and composition of the newly reconstructed breast, reconstruction can be categorized into either implant-based reconstruction (IBR) or autologous reconstruction (AR). Most reconstruction procedures in the U.S. (81%) are implant-based. Implants are prosthetic devices that replace the surgically removed breast tissue or, in the case of breast augmentation, are intended to increase the size of the intact breast. IBR can occur in either one or two stages. In planned single-stage implant placement, also known as direct-to-implant placement, IBR is accomplished through a single implantation procedure. In planned two-stage implant placement, a tissue expander is placed as a first procedure, followed by permanent implant placement at a later date. Direct-to-implant placements comprise 16 percent and tissue expander-based reconstructions 84 percent of IBR procedures.⁷ IBR can be further divided based on the physical design of the implant (silicone, saline, or double lumen [e.g., may contain both silicone and saline¹⁶]), the anatomic plane in which the device is placed (prepectoral, partial submuscular, or total submuscular), and whether or not an adjunctive human acellular dermal matrix (ADM) is incorporated into the reconstruction. Regardless of these factors, IBR poses potential risks, such as infection, rupture, deflation, and malposition.¹⁷

Approximately 95 percent of implants for breast reconstruction used in the U.S. are silicone-filled because of the more natural feel and appearance and greater patient satisfaction than with saline implants.^{7, 18} A 2015 systematic review concluded that the evidence remained inconclusive about any association between silicone implants and long-term cancer or rheumatologic health outcomes.¹⁹ However, there have been continued reports of systemic symptoms, such as joint pains, muscle aches, and chronic fatigue. Additionally, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a rare type of non-Hodgkin’s lymphoma, may occur, especially with textured implants (regardless of fill type). The risk of BIA-ALCL led the U.S. Food and Drug Administration to request a recall of one manufacturer’s textured implant and tissue expander in 2019²⁰ and to recommend a boxed warning for all breast implants in 2020.²¹

The anatomic plane in which the implant is placed during breast reconstruction can have implications on complications, aesthetics, and cost. The most common anatomic plane has traditionally been total submuscular placement, where the implant is placed beneath the pectoralis major muscle. It provides vascularized soft tissue coverage of the implant. However, total submuscular placement has challenges, such as limits to the possible size of the breast reconstruction and incidence of “animation deformity” (i.e., distortion of the reconstructed breast during contraction of the pectoralis major muscle). Animation deformity is experienced by as many as 80 percent of patients who receive total submuscular placement of the implant.²² To overcome these challenges, another option is partial submuscular placement with ADM use (which creates a musculofascial pocket to leave the rib cage covered by a portion of the muscle²³) or prepectoral placement with ADM (in front of, or superficial to, the muscle). Prepectoral placement also obviates the need for pectoralis muscle dissection and may cause less pain.²⁴ However, the prepectoral technique currently used is relatively novel, and evidence regarding comparative effectiveness, aesthetics, and harms of the various anatomic planes of implant placement is lacking.

ADMs can be derived from human (allografts), animal (xenografts), or synthetic sources. They represent a heterogeneous group of biologic scaffolds that are used in reconstructive surgery to hold the implant in place. ADMs allow for repopulation, revascularization, and integration of the host’s cells into the implanted tissue.²⁵ Use of ADMs may reduce the incidence of capsular contracture and may improve the aesthetic definition of the inframammary fold (where the lower breast meets the chest wall) and the medial (i.e., midline) border of the breast. However, ADMs may lead to postoperative complications, such as infection and seroma.^26–29

In AR, breast reconstruction is done with the patient’s own tissue, thereby generally obviating the need for implants. In 2018, AR represented approximately 19 percent of breast reconstruction procedures performed in the U.S.⁷ AR is generally described by the anatomic region from which the tissue flap is sourced. These include deep inferior epigastric perforator (DIEP; 52% of ARs), latissimus dorsi (LD; 22%), transverse rectus abdominis myocutaneous (TRAM; 21%), and others (5%).⁷ DIEP flaps use fat and skin from the patient’s abdomen. LD flaps use muscle, fat, and/or skin from the patient’s back and are often accompanied by implant placement (“hybrid” reconstruction³⁰). TRAM flaps include muscle, fat, and skin from the patient’s abdomen. The options regarding source of the AR flap are limited by the patient’s body habitus, prior surgery, medical comorbidities, and preference. Different flap types vary in their associated types and frequencies of complications. In contrast to IBR, AR can have several advantages, including: (1) AR is intended to be completed in a single, albeit multi-site, surgery (as opposed to most IBRs, which require two-stage implant placements) and (2) AR is intended to be life-long although some patients require small revision surgeries of the breast and/or the donor site (implants, even when single-stage, are recommended to be replaced every 10 years). However, AR requires a larger operation and may have more major complications, such as deep vein thrombosis, abdominal bulge or hernias, wound dehiscence, delayed healing, and scarring. The long-term sequelae of AR, especially patient-reported clinical outcomes, such as satisfaction, psychosocial well-being, and sexual well-being, as well as long-term harms, e.g., harms to the area of flap harvest, remain unclear.

Purpose of the Review

This systematic review assesses the surgical breast reconstruction treatments for women who are undergoing (or have undergone) mastectomy for breast cancer (or breast cancer prophylaxis). The review does not address the choice of whether patients who have undergone mastectomy should undergo breast reconstruction.

Specifically, the review addresses the (comparative) benefits and harms of:

• IBR versus AR (Key Question [KQ] 1)
• Timing of IBR and AR in relation to chemotherapy and radiation therapy (KQ 2)
• Various options for IBR, including implant materials (KQ 3), implant placement planes (KQ 4), and use of human ADMs (KQ 5)
• Various flap types for AR (KQ 6).

The intended audience for this systematic review includes plastic surgeons, breast surgical oncologists, medical oncologists, radiation oncologists, other care providers for women undergoing mastectomy for breast cancer, guideline developers, healthcare policy makers, and patients. It is expected that the findings will inform clinical guidance for breast reconstruction after mastectomy.