Study of Radiation Fractionation on Patient Outcomes After Breast REConstruction (FABREC) for Invasive Breast Carcinoma

Over 180,000 diagnoses of invasive breast cancer are made in the US each year. Over one‐third
of women with early stage and over half with late‐stage breast cancer are treated with
mastectomy (removal of the entire breast) due to tumor size, multiple cancers within the
breast, genetic cancer predisposition, and/or patient preference. Following treatment with
mastectomy, women who receive breast reconstructive surgery may experience better quality of
life as they do not have to leave surgery with a bare chest wall. However, large randomized
trials of post-mastectomy radiation therapy reveal a survival benefit with the addition of
radiation after mastectomy in women who have cancer present in the axillary lymph nodes (6).
The delivery of radiation therapy in the presence of a breast reconstruction is challenging
and often leads to undesirable consequences including reconstruction loss, need for major
surgical revision, or poor cosmetic outcomes. Therefore, oncologists and patients are forced
to decide between the potential for improved oncologic outcomes with radiation therapy versus
increased likelihood of complications and suboptimal cosmetic results. Because of this, some
patients may be foregoing reconstruction if radiation therapy after mastectomy is needed; or
foregoing radiation therapy if they have had breast reconstructive surgery (28).

Hypofractionation enhances patient convenience and decreases treatment burden. This regimen
has been shown in randomized trials largely in the breast‐conservation setting to reduce
acute radiation therapy side‐effects, decrease fatigue at six months and improve cosmetic
results (21, 22). Despite these results, adoption of hypofractionation has been slow among
women with breast cancer treated with breast‐conserving surgery (24, 25) likely due to
familiarity and experience of conventional long‐course radiation therapy.

While hypofractionation is used commonly in the UK for patients with mastectomy, there are no
randomized studies particularly studying outcomes following shorter course radiation therapy
in women who undergo mastectomy with breast reconstruction. Therefore, there is an even
greater barrier to the use of hypofractionation in this setting in the US. With improved
cosmetic results found with hypofractionation, this shorter regimen may have the potential to
improve reconstruction success rates which are unfortunately modest overall, for patients who
require post-mastectomy radiation. Especially in contrast to financial disincentives to
reduce number of radiation treatments, Level I randomized evidence is needed in this
population to change practice patterns regarding radiation regimen.

Our study of radiation fractionation regimens has the potential to increase use of
hypofractionation among women treated with mastectomy, thereby decreasing treatment burden.
Our team of patient stakeholders ensures that our outcomes measures encompass all domains of
survivorship after breast cancer (physical and mental health as well as satisfaction with the
decision‐making process). Despite the large numbers of breast cancer survivors who undergo
mastectomy, reconstruction and radiation therapy, little is known about which domains of
quality of life are affected and their importance to these patients. This study uses
previously validated tools for measuring patient outcomes, and have added questions for areas
which are important to patients that may not have been captured adequately by previous tools.
In concert with the increasing awareness of the importance of survivorship care to cancer
care, identifying a comprehensive set of outcomes measurement tools following treatment with
radiation therapy, mastectomy, and reconstruction is an important asset for future treatment
evaluation in these women.

Inclusion Criteria:

1. Diagnosed with clinical or pathologic stage I‐III invasive breast cancer with TX‐T3
tumor

2. Has been treated with mastectomy

3. Has undergone immediate reconstructive surgery with placement of a tissue expander or
permanent implant at time of mastectomy

4. Is a candidate for unilateral post‐mastectomy radiation therapy as per National
Comprehensive Cancer Network (NCCN) guidelines (post‐mastectomy radiation therapy is
indicated for most patients with positive lymph nodes at time of surgery and
infrequently for selected node‐negative patients)

5. Use of bolus is permitted, but not required

6. Age ≥18

Exclusion Criteria:

1. T4 cancer

2. Recurrent breast cancer or history of prior breast radiation therapy

3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, and/or
mental health illness that the consenting investigator feels would affect patient's
ability to participate in this study

4. Pregnant or nursing

5. History of a different malignancy except for the following circumstances:

- Disease‐free for at least five years and deemed by the investigator to be at low
risk for recurrence of that malignancy (<5 %).

- Cervical cancer in situ and basal cell or squamous cell carcinoma of the skin

6. Breast cancer requiring bilateral breast/chest wall radiation therapy.