Clinical Summary: 

• Design/Population: The international phase 3 PREPEC trial randomized 380 women undergoing skin- or nipple-sparing mastectomy for breast cancer treatment or prevention to prepectoral or subpectoral implant-based breast reconstruction across 26 centers in 10 countries.
• Key Outcomes: Prepectoral reconstruction significantly improved long-term physical well-being and quality of life compared with subpectoral reconstruction, exceeding the predefined threshold for a clinically meaningful benefit. This advantage was accompanied by a higher risk of implant or expander loss, while overall complication rates were similar between groups.
• Clinical Relevance: These findings support prepectoral implant placement as a patient-centered reconstructive approach that improves long-term quality of life, although careful attention to surgical technique and patient selection remains important.

Walter Weber, MD, University Hospital, Basel, Switzerland, discusses results from the phase 3 PREPEC trial, a patient advocate–initiated study evaluating implant positioning strategies following mastectomy. The trial was designed to test whether muscle-sparing prepectoral reconstruction could improve patient-reported outcomes compared with traditional subpectoral reconstruction.

The study demonstrated clinically meaningful improvements in physical well-being, psychosocial well-being, sexual well-being, and overall satisfaction with prepectoral reconstruction. Although implant loss occurred more frequently with prepectoral placement, overall complication rates were comparable between groups, with early complications tending to occur more often after prepectoral reconstruction and late complications more commonly observed following subpectoral reconstruction. 

Dr Weber presented these results at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

Hello, my name is Walter Weber, and I’m presenting the results of the PREPEC trial. 

The PREPEC trial was designed to address an important question in implant-based breast reconstruction after skin-sparing mastectomy, or SSM, and nipple-sparing mastectomy, or NSM. Specifically, we wanted to determine the optimal position for implant-based breast reconstruction. 

Pre-pectoral reconstruction avoids dissection of the pectoralis major muscle, which may improve postoperative comfort and quality of life, but it also provides less soft tissue coverage over the implant. Sub-pectoral reconstruction, on the other hand, places the implant beneath the muscle but may be associated with more long-term chest symptoms.

PREPEC, also known as OPBC-02, was a pragmatic, international, randomized phase 3 superiority trial. Women aged 18 years or older undergoing skin-sparing or nipple-sparing mastectomy for treatment or prevention of breast cancer were randomized 1:1 to either pre-pectoral or sub-pectoral implant-based breast reconstruction. Apart from implant positioning, surgery followed standard local practice. The primary end point was patient-reported physical well-being of the chest at 24 months, measured using the BREAST-Q questionnaire. 

Between July 2020 and February 2023, 383 patients were randomized across 26 centers in 10 countries. The final analysis included 380 patients, with 191 assigned to pre-pectoral reconstruction and 189 assigned to sub-pectoral reconstruction. Approximately 73% of procedures were unilateral, and about 58% involved nipple-sparing mastectomy. Most patients, nearly 78%, underwent surgery for treatment of breast cancer, while smaller proportions underwent therapeutic plus preventive surgery or purely preventive surgery. Importantly, completion rates for the BREAST-Q questionnaires were very high, ranging from 83% to 95% across all follow-up time points.

Looking at the primary end point, pre-pectoral reconstruction significantly improved physical well-being of the chest at 24 months compared with sub-pectoral reconstruction. The adjusted BREAST-Q scores were 79.2 for pre-pectoral reconstruction and 74.3 for sub-pectoral reconstruction. This corresponded to a mean difference of 4.8 points, which was statistically significant and exceeded the predefined threshold for a clinically meaningful difference. The benefit was consistent across sensitivity analyses and subgroup analyses. 

We also looked carefully at safety. The primary safety end point was loss or replacement of the expander or implant within 24 months for any reason. This occurred in 21.1% of patients in the pre-pectoral group compared with 14.5% in the sub-pectoral group. After adjustment, the estimated increase in implant loss or replacement associated with pre-pectoral reconstruction was approximately 5.7%.

Overall complication rates were very similar between groups, occurring in about 54% to 56% of patients. However, there were some differences in the timing of complications. Early complications were somewhat more common after pre-pectoral reconstruction, whereas late complications were more common after sub-pectoral reconstruction.

In summary, the PREPEC trial demonstrated that pre-pectoral implant-based breast reconstruction significantly improved long-term patient-reported quality of life, particularly physical well-being of the chest, compared with sub-pectoral reconstruction. This benefit came at the cost of a somewhat higher risk of implant or expander loss or replacement.

These findings provide important information for patients and surgeons when discussing reconstruction options after mastectomy. 

Source:

Weber W, Shi R, Matrai Z, et al. Surgical de-escalation of implant-based breast reconstruction (IBBR) after mastectomy for breast cancer treatment or prevention: The international randomized phase III PREPEC trial (OPBC-02). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 504.