Delayed-immediate Versus Delayed Breast Reconstruction in Breast Cancer Patients With Mastectomy and Radiation Therapy

Not Applicable

Recruiting

• Conditions: Complication of Radiation Therapy; Breast Implant; Complications; Breast Neoplasm Female
• Interventions: Procedure: Delayed-immediate reconstruction; Procedure: Delayed reconstruction

• Registration Number: NCT03730922
• Lead Sponsor: Danish Breast Cancer Cooperative Group

Brief Summary

In breast cancer patients treated by mastectomy and adjuvant post-mastectomy radiation therapy (PMRT) reconstruction is often delayed until 6 - 12 month after completion of chemotherapy and PMRT, due to high risk of complication. In this trial the safety of the delayed-immediate reconstruction method is tested, where a skin sparing mastectomy and reconstruction with silicone implant is performed at primary surgery to save the native skin for the final delayed reconstruction.

Detailed Description

An increasing proportion of breast cancer patients treated by mastectomy wish for a breast reconstruction. If post-mastectomy radiation therapy is recommended, the reconstruction is often delayed until 6 - 12 months after completion of chemotherapy and radiation therapy due to risk of complication that might delay adjuvant treatment. At this time the native skin over the removed breast cannot be used in the reconstruction, resulting in a suboptimal aesthetic outcome. In the delayed-immediate reconstruction method, a skin sparing mastectomy and reconstruction with implant is performed at primary surgery, to save the native skin under radiation therapy, thereby improving the chance for a good aesthetic outcome at the final delayed reconstruction. In this trial breast cancer patients treated by mastectomy and loco-regional radiation therapy is randomized to either delayed reconstruction or delayed-immediate reconstruction. The complication rate as well as morbidity, aesthetic outcome and psychological well-being after delayed-immediate reconstruction will be compared with delayed reconstruction

Study Timeline

• Study First Submitted: 2018-10-02
• Study First Submitted QC: 2018-11-02
• Study First Posted: 2018-11-05
• Study Start: 2020-01-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-06
• Primary Completion: 2025-11
• Study Completion: 2035-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 590

Inclusion Criteria

• Woman >18 years who are offered a mastectomy for invasive breast can-cer pT1-3, pN0-N3, M0 and wish reconstruction. The patient can be inclu-ded no matter the status of estrogen receptor, progesterone receptor, malignancy grade, and HER2 status.
• The patient is a candidate for loco-regional radiation therapy according to national or institutional guidelines.
• Highly selected patients with inflammatory breast cancer, namely those with complete or near complete response to neoadjuvant systemic thera-py judged by imaging and clinical examination before surgery. Any skin edema and clinical signs of skin involvement must have disappeared during systemic therapy. It is highly recommended that the decision to offer an inflammatory breast cancer patient inclusion in the DBCG RT Recon trial is made during a multidisciplinary team conference.
• Adjuvant systemic therapy with chemotherapy, endocrine therapy, anti-HER2 treatment and other targeted therapies used in the adjuvant setting either as new standard or as part of a trial during the course of the trial is accepted.
• Neoadjuvant chemotherapy and primary systemic therapy of an operable breast cancer is accepted.
• Patient with previous non-breast malignancy is accepted if the patient has been without disease minimum 5 years, and the treating oncologist esti-mates a low risk of recurrence. Patients with the following diseases can be accepted despite less than 5 years disease free interval: carcinoma in situ cervicis, carcinoma in situ coli, melanoma in situ, basal cell carcino-ma of the skin, squamous cell carcinoma of the skin.
• Life expectancy minimum 10 years.

Exclusion Criteria

• Pregnant or lactating.
• Previous breast cancer or Ductal carcinoma in Situ (DCIS).
• Bilateral breast cancer.
• Previous radiation therapy to the chest region.
• Previous non-breast malignancy (not including carcinoma in situ of the cervix or colon, melanoma in situ, basal cell carcinoma of the skin, and squamous cell carcinoma of the skin) within 5 years.
• Conditions indicating that the patient cannot go through breast reconstruction, the radiation therapy or follow up.
• Not being able to participate due to language or other personal issues.
• Life expectancy less than 10 years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
A: Delayed-immediate reconstruction	Delayed-immediate reconstruction	Primary Surgery: Skin sparing mastectomy (nipple sparing if appropriate) and axillary surgery according to guidelines or protocol. Reconstruction with silicone implant or expander covered by pectoral muscle and mesh or matrix. Delayed reconstruction: Final reconstruction with any reconstructive procedure - being it autologous or implant-based (one- or two-stage, +/- acellular dermal matrix (ADM)) - is performed 6-12 months after completion of chemotherapy and PMRT. Any contralateral procedure is allowed when doing the delayed surgery, but not in relation to the initial cancer surgery.
B: Delayed reconstruction	Delayed reconstruction	Primary surgery: Total mastectomy and axillary surgery according to guidelines or protocol. Delayed reconstruction: 6-12 months after completion of PMRT: final recon-struction with any reconstructive procedure - being it autologous or implant-based (one-or two-stage, +/- ADM). Any contralateral procedure is allowed at any time point after PMRT has been delivered This arm has been closed nov 2023

Primary Outcome Measures

Name	Time	Method
Number of patients with complications with surgical intervention	1 year after final reconstruction	Number of patients with complication deeming surgical intervention necessary (excluding percutaneous drainage and antibiotic treatment for inflammation in cases without need for open drainage): * Infection; * Hematoma; * Loss of implant/expander; * Necrosis; * Seroma

Secondary Outcome Measures

Name	Time	Method
Fear of cancer recurrence	10 years post-final reconstruction	Fear of cancer recurrence measured by Concerns About Recurrence Questionnaire-3 (CARQ-3 ) on a scale from 1 to 10, 10 worst (fear all the time)
Number of patients with complications without surgical intervention	1 year after final reconstruction	Number of patients with complication (Infection with need for antibiotics and/or necrosis) without intervention necessary
Number of patients with lymphoedema	10 years post-final reconstruction	Difference in arm circumference between arms 15 cm/10 cm proximal/distal to the olecranon bilaterally. Any difference ≥10% defines lymhoedema.
Aesthetic outcome	10 years post-final reconstruction	Aesthetic outcome scored bt the physician using breast Photo, on a scale from 0 to 3, 3 being worst
Depression	10 years post-final reconstruction	Degree of Depression measured by Becks Depression Inventory, BDII using a scale from 1 to 4, 4 being the worst
Patient´s satisfaction and quality of life (QoL)	10 years post-final reconstruction	Patient satisfaction and QoL measures by the BREAST-Q-instruments on a scale from 1 to 5, 5 being worst
Timely initiation of adjuvant therapy	1 year	Time from primary surgery to start of adjuvant therapy
Degree of patient reported morbidity regarding body image, painsensory disturbanses and feeling og lymphoedema	10 years post-final reconstruction	Patient reported morbidity measured by a questionnaire. The prevalence of pain will be assessed on a 0-10 numerical rating scale (NRS) and reported as: 'light pain' NRS 1-3; 'moderate pain' NRS 4-6; and 'severe pain' NRS 7-10. Sensory disturbances will be assessed by a dichotomous 'yes/no' question,. Lymphoedema will be assessed on a 0-10 numerical rating scale, 10 being worst. Body image will be assessed on a 0-7 numerical rating scale, 7 being best.
Number of patients with restricted range of motion of the shoulder	10 years post-final reconstruction	Differences between arms in range of motion of the shoulder measured at abduction/flexion with the patient sitting in front of a poster with a circle with degrees 0-180˚.Any difference ≥10 degrees defines defines restricted motion
Number of patients with capsular contracture	10 years post-final reconstruction	Degree of capsular Contracture using Baker grading

Trial Locations

Locations (8)

Ålborg Universitetshospital; 🇩🇰 Aalborg, Denmark

Esbjerg Sygehus; 🇩🇰 Esbjerg, Denmark

Gentofte Hospital/Herlev Hospital; 🇩🇰 Copenhagen, Denmark

Sjællands Universitetshospital; 🇩🇰 Roskilde, Denmark

Vejle Sygehus; 🇩🇰 Vejle, Denmark

Åbenrå Sygehus; 🇩🇰 Åbenrå, Denmark

Viborg Sygehus; 🇩🇰 Viborg, Denmark

Århus Universitets Hospital; 🇩🇰 Århus, Denmark