Study of Preoperative Boost Radiotherapy

The study team proposes in this trial to build on the favorable results of the intraoperative
boost trials but using a preoperative delivery approach. The PI has demonstrated the
feasibility of the preoperative approach and successfully completed a Phase I dose-finding
partial breast trial. The preoperative approach has several advantages: 1) expensive
intra-operative equipment is unnecessary, 2) a small intact breast tumor results in
significantly less uninvolved breast tissue receiving high radiation doses which likely
decreases toxicity; 3) more accurate targeting of the high-risk areas of subclinical disease
surrounding the tumor is possible, 4) smaller treatment volumes are amenable to dose
escalation which can further accelerate treatment and improve accessibility for subjects, and
5) the pre-operative approach provides a novel opportunity to study breast cancer radiation
response.

Radiotherapy to the intact tumor is a relatively rare event in breast cancer irradiation,
particularly in the setting of early stage breast cancer. Tumor and normal tissue radiation
response remain relatively poorly understood. Markers capable of predicting radiation
response are rare indeed. Therefore, paired pre- and post-radiation tissue will be examined
for FAS gene expression and compared among the breast cancer subtypes. FAS is the name of a
gene ( not an acronym) that is known to play a critical role in the induction of programmed
cell death and is an established prognostic marker in breast cancer. Previous study team
findings that FAS induction appears to be breast cancer subtype-specific has not been
previously observed and provides a possible explanation for the differential rates of tumor
response observed clinically in distinct breast tumor subtypes. The study team's preclinical
work with FAS suggests a potential role as a radiation response biomarker. The study goal is
to validate those findings in this large cohort of diverse breast cancer subjects. However,
because preoperative delivery of the boost to the intact tumor is unique, this study will
include a secondary cosmetic outcome that includes predefined stopping boundaries for early
indications of suboptimal cosmetic outcomes with this novel approach

Inclusion Criteria:

1. Women with a biopsy proven diagnosis of ductal carcinoma in situ or invasive carcinoma
of the breast. Biopsy tissue (either slides or block) from outside institutions will
be reviewed to confirm diagnosis.

2. Breast preservation candidates (no prior breast or nodal radiotherapy, no imaging
evidence of multicentric disease preventing resection through a single incision, no
pregnant women, and no comorbid conditions precluding surgery)

3. cTis-T3 cancer judged to benefit (by treating radiation oncologist) from a tumor bed
boost

4. Women of child-bearing potential must consent to use adequate contraception during the
course of the study: (1) surgical sterilization (such as a tubal ligation or
hysterectomy), (2) approved hormonal contraceptives (such as birth control pills,
patches, implants or injections), (3) barrier methods (such as a condom or diaphragm)
used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures
such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable
methods for routine use.

5. White blood cell (WBC) > 3000, Hgb > 10, platelets >100000 within 30 days of consent

6. Eligible for contrasted magnetic resonance imaging( MRI) on initial evaluation with
glomerular filtration rate (GFR) ≥ 60 ml/min. A diagnostic MRI ordered within 60 days
of diagnosis will be considered an acceptable alternative and will not be repeated.

7. Outside breast imaging will be reviewed at Duke to confirm that findings are
consistent with trial eligibility

Exclusion Criteria:

1. Breast implant in the breast to be treated (contralateral breast implant is
acceptable)

2. Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus,
rheumatoid arthritis, scleroderma)

3. Subjects unable to receive study treatment planning secondary to body habitus or
inability to lie flat on the stomach for at least 1 hour

4. Positive serum pregnancy test

5. Insufficient breast imaging to judge clinical stage

6. Subjects without placement of a biopsy clip at the diagnostic procedure who are
unwilling to undergo clip placement.

7. Subjects in whom treatment planning constraints cannot be met