Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02159274 |
| Other study ID # |
KRH-2014 |
| Secondary ID |
1-10-72-335-1320 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 2014 |
| Est. completion date |
October 2018 |
Study information
| Verified date |
October 2018 |
| Source |
University of Aarhus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Breast cancer affects a large proportion of Danish women and late morbidity following breast
cancer treatment including pain, reduced motility and force of the arm and shoulder,
disturbed sensitivity, and lymph edema affects many patients. The risk for such late
complications have previously been carefully described by us and others in patients operated
by traditional methods, but the follow-up in most of these studies have been rather short ,
and long time follow-up results are not available. The impact of the new oncoplastic
techniques that allows more women to have breast conserving surgery is not known yet. These
operations are more extensive and therefore might be accompanied by more complications. The
purpose of this study is to give answer to that question.The study includes three parts.
First a questionnaire to patients who have breast conserving surgery performed in one of the
three breast units in Central Region Denmark. It contains questions regarding arm morbidity,
quality of life, comorbidity, and body image. The questionnaire should be filled in
preoperatively and 18 months after surgery. The second part consists of an objective
evaluation of shoulder and arm function and cosmesis before and after breast conserving
surgery with and without oncoplastic techniques. This should be performed at baseline before
surgery and 18 months later. The third part is a long time follow-up of patients after breast
conserving surgery without oncoplastic techniques. This group of patients is recruited from
three breast units in Central Region Denmark. It contains questions regarding arm morbidity,
quality of life, comorbidity, and body image. The questionnaire should be filled in
preoperatively and 18 months after surgery. The second part consists of an objective
evaluation of shoulder and arm function and cosmesis before and after breast conserving
surgery with and without oncoplastic techniques. This should be performed at baseline before
surgery and 18 months later. The third part is a long time follow-up of patients after breast
conserving surgery without oncoplastic techniques. This group of patients is recruited from
the cohort in a previous study with 18 months follow-up following breast conserving surgery
without oncoplastic technique.
Description:
Aims and perspectives:
During the last 20 years there has been increasing focus on the morbidity following breast
cancer treatment. This has lead to new and less mutilating surgical techniques to replace the
traditional operations: Breast conserving surgery (BCS) instead of mastectomy and sentinel
lymph node dissection (SLND) instead of axillary lymph node dissection (ALND). Lately,
oncoplastic techniques have been introduced. These techniques further increase the ability to
preserve the breast in breast cancer and are expected to increase the cosmetic results
compared with traditional techniques, but they are somewhat larger procedures and might
therefore lead to increased morbidity after treatment. Hitherto this has not been evaluated
in clinical research trials.
The aim of the present study is to examine if oncoplastic techniques in relation to breast
cancer treatment have an independent influence on morbidity and quality of life compared to
traditional BCS.
In addition, a group of breast cancer patients treated with BCS 10 years ago and who
underwent a similar study back then, will be invited to a reevaluation of shoulder function
and morbidity.
Background:
Previously, mastectomy was the most applied surgical procedure related to breast cancer.
Until the beginning of 1990's it was, by DBCG (Danish Breast Cancer Cooperative Group),
recommended as a standard treatment. During the transition towards a more gentle surgical
procedure, the use of oncoplastic techniques has been incorporated1,2.
The definition of oncoplastic breast surgery is defined by DBCG as: "a breast conserving
procedure, including techniques of plastic surgery, where traditional breast conserving
surgery would have lead to a cosmetic unsatisfactory result, and mastectomy would have been
the alternative. The requirement for classifying a procedure as oncoplastic is 'the transfer
of tissue that requires further skin incision than the breast conserving surgery in its
own'3.
The oncoplastic techniques in breast cancer surgery are divided into 3 groups: volume
displacement, volume reduction and volume replacement3-5. The oncological results of
oncoplastic breast surgery has been evaluated in other studies and found comparable to the
oncological results of traditional BCS and mastectomy6.
Increasing evidence have shown that among breast cancer patients a substantial fraction
suffer from late symptoms including impairment of shoulder function, pain, disturbance in
sensibility, and lymph edema7-9. The sequels are attributable to treatment related factors,
including the breast surgical procedure10, axillary dissection11, and radiation therapy12.
Studies indicate that sentinel lymph node biopsy (SNLB) reduces shoulder morbidity as
compared to ALND11,13, but shoulder impairment also occur after this procedure14.
Recently, the occurrence of late symptoms has been addressed in two Danish publications based
on questionnaires7,8 with 2-3 years8 and more than 5 years7 observation, respectively. These
studies showed that chronic pain 2-3 years after surgery is a problem in up to 47% of
patients of whom 13% suffered from severe and 39% from moderate pain8. More than five years
after treatment, chronic pain was recorded in 29% of patients7, and this was associated with
poorer quality of life and a higher medicine consumption. Furthermore, a large part of long
time survivors reported arm swelling (25%), phantom symptoms (19%), paresthesia (47%), and
allodynia (15%)7.
The reported frequency of Lymph oedema following breast cancer treatment vary considerably,
probably depending on different definitions and different methods for measurement. As stated
earlier, many patients report a subjective feeling of swelling, though the proportion of
affected patients seems lower in studies, where objective measures are applied. In a study on
node negative patients comparing the results of sentinel node biopsy (SNB) with axillary
dissection (ALND)11 up to 18 months after surgery, arm swelling was reported in 7% and 44%,
respectively, emphasizing the advantage of the more limited procedure. Using the water
displacement method the difference in arm volume between these groups was very modest,
although statistically significant. At 18 months, the arm volume on the operated side was 10
ml less than on the non-affected arm in the SNB group, compared with an increase of 28 ml in
the ALND group. The water displacement method has been simplified and validated since15,16.
Shoulder morbidity median three years after surgery including ALND was measured in a study on
132 patients (mastectomy 67%, BCT 33%)10. The shoulder function was assessed by the Constant
Shoulder Score (CSS), combining subjective symptoms with objective measures of range of
motion (ROM) and strengths. Thirty-five percent of the patients had reductions in ROM, in
most cases it was flexion and abduction that were most affected. Among these patients CSS was
reduced by 12% on the treated side compared with the non-treated shoulder. Patients with
normal ROM had comparable CSS on the two sides. In comparison with BCS and radiotherapy,
mastectomy combined with postoperative radiation, more often lead to reduced ROM (OR 8.5). In
the study by Husted Madsen et al.11 on more recently operated node negative patients, ALND
turned out to be significantly associated with a poorer outcome when the dependent variable
was the absence or presence of subjective arm and shoulder complaints.
Most studies concerning morbidity, especially those with objective evaluation of patients,
have a short follow-up period typically only a few years. No such studies with long-term
follow-up up to 5-10 years are available.
A few studies have aimed at describing the effect of physiotherapy on shoulder-arm
morbidity13,17, and they have confirmed a better outcome after physiotherapy including
general advice and recommendations about how to use and protect the affected arm and
instructions for exercises. In the randomized study by Lauridsen et al.13, team instructed
physiotherapy consisting of 12 sessions of 60 minutes twice a week instituted between the 6th
and 8th postoperative week was compared to the same treatment postponed until the 26th
postoperative week. The team instructed physiotherapy commenced early immediately improved
the shoulder function, but the same treatment could improve shoulder function significantly
even when instituted as long as six months postoperatively.
In a recently published randomized study, Veiga et al.18 have found indications of a better
quality of life and self-esteem in BCS including oncoplastic surgery than in patients
undergoing traditional BCS. On the other hand, in a study including 101 patients it was found
that breast symmetry after BCS had had no effect on quality of life19. In that study symmetry
was evaluated by a breast analyzing tool (BAT), one of more available objective measures.
Most often, symmetry has been evaluated subjectively by a panel of experts, which has been
considered the gold standard. Lately, Cardoso et al. have introduced another objective method
where the cosmetic outcome is evaluated semi-automatically from systematic clinical fotos20.
They reported a 70% agreement between the expert panel and their measurements. The cosmetic
outcome after BCS has been evaluated by Lyngholm et al.21 using the "breast retraction
assessment" (BAT) which estimates the symmetry based on measurements on clinical photos22.
The relation between the oncoplastic surgical techniques and shoulder disability, chronic
pain, and lymph edema has hitherto not been systematically investigated, but some attempts
have been made to describe the impact on shoulder function of post-mastectomy reconstructive
surgery. In a study from Sweden23, shoulder function after reconstructive procedures
involving the latissimus dorsi flap was examined. The main finding was that the
reconstruction lead to an insignificant increase in long-term shoulder morbidity, but it was
also noted that a small subset of patients developed long-term impairment.
Design and methods:
The study includes three parts:
1. A questionnaire describing the occurrence of loco-regional morbidity in patients who has
undergone breast conserving surgery with and without oncoplastic techniques.
2. Objective evaluation of shoulder and arm function and cosmesis before and after breast
conserving surgery with and without oncoplastic techniques.
3. Long time follow-up of patients after breast conserving surgery without oncoplastic
techniques.
Part 1
The questionnaire combines previous used and validated forms addressing shoulder and arm
function, pain, sensibility, cosmesis and body image, and QoL. The questionnaire should be
filled in preoperatively and 18 months after surgery. Patients included in the longtime
follow-up study described below are asked to answer the same questionnaire, which includes
questions about the following:
- Arm morbidity: Pain, sensibility, swelling, restriction of movements, force
- Quality of life (EORTC QLQ-C30 and QLQ-BR23)
- Comorbidity - Charlsons Comorbidity Index
- Body Image
- Physiotherapy Part 2
Cohort study with 18 months follow-up. Patients are evaluated at baseline before surgery and
after 18 months with the following methods:
- Passive Range of movement (pROM). The passive motion of both shoulders are measured in
supine position by use of a goniometer: flexion, extension, abduction, inner and outer
rotation
- Constant Shoulder Score (CSS). Including active Range of movement (aROM) in flexion,
abduction, rotation and strengths during shoulder abduction in upright standing position
with the IsoForceControl dynamometer
- Sensibility recording
- Arm circumference
- Arm volume - simplified water displacement method
- Cosmetic outcome - using clinical photos of the breast region (frontal- and side view)
and estimation of BRA (Breast Retraction Assessment) Re. part 1 and 2
Inclusion:
Patients, who are undergoing breast conserving surgery for invasive breast cancer or
carcinoma in situ by one of the three breast surgical units at hospitals in Central Denmark
Region (Viborg, Randers, and Aarhus). They will be divided in the two groups:
- BCS including oncoplastic surgical techniques
- BCS without oncoplastic surgical techniques
Exclusion:
- Patients who are unable to sign an informed consent form
- Patients above the age of 75 years and under the age of 18 years.
- Patients who have previously been operated in the same or the contralateral breast,
shoulder or arm Part 3 The study performed by Husted Madsen et al. in 2003-4 included in
all 395 patients. Surviving patients from this cohort are asked to e new evaluation of
shoulder and arm function following the same procedure as described in Part 1 and 2.
Statistics:
Based on previous experience and statistical calculations estimated that the investigators
need 495 to participate in the questionnaire (Part 1) and 220 patient for the objective
evaluation (Part 2) Further details can be added If requested.
Ethics:
Patients included in part 1 and 2 will be contacted in the breast units after confirmation of
the diagnosis and after decision about the treatment has been made. Before inclusion oral and
written information about the study are given and the patient is asked to sign an informed
consent form. For part 3 of these studies, patients receive a letter invitation and these
patients are also asked to sign an informed consent form before entering the study.
There is only minor discomfort associated with the objective evaluation and no major
complications or side effects are expected.
The protocol is submitted to The Local Research Ethics Committee for Central Region Denmark
for approval.
