Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer

The study team hypothesizes that a single fraction of 21Gy can be delivered preoperatively to the intact breast tumor with acceptable cosmetic outcomes. Furthermore, the investigators anticipate that pre- and post-radiation breast tumor samples will provide an avenue for understanding breast cancer radiation response

Rationale for single-fraction preoperative technique

This trial is proposed to build on the favorable results of the investigators' phase I trial by extending the findings to a larger cohort of subjects. The preoperative approach has several advantages:

• a small intact breast tumor results in significantly less uninvolved breast tissue receiving high radiation doses which likely decreases toxicity;
• more accurate targeting of the high-risk areas of subclinical disease surrounding the tumor is possible,
• smaller treatment volumes are amenable to dose escalation which can further accelerate treatment and improve accessibility for subjects,
• this technical approach is widely utilized in other tumor sites and can be delivered at most radiation facilities
• the pre-operative approach provides a novel opportunity to study breast cancer radiation response.

Inclusion criteria

• Women with a biopsy proven diagnosis of ductal carcinoma in situ or invasive carcinoma of the breast

a. Biopsy tissue (either slides or block) from outside institutions will be reviewed to confirm diagnosis.

• Breast preservation candidates (no prior breast or nodal radiotherapy, no imaging evidence of multicentric or multifocal disease, no pregnant women, and no comorbid conditions precluding surgery)
• Clinical T1N0M0 invasive carcinoma or Ductal carcinoma in situ (DCIS) < or equal to 2cm
• 60 years of age or older or 50-59 with a low Oncotype score (0-17) Oncotype is not required for women diagnosed with DCIS.
• Estrogen receptor positive (ER+), Human epidermal growth factor 2 negative (HER2-) HER-2 status is not required for women diagnosed with DCIS.
• Women of child-bearing potential must consent to use adequate contraception during the course of the study. Female subjects must agree to use a medically acceptable contraceptives including: (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.
• White blood cells (WBC) > 3000, Hemoglobin ( Hgb) > 9, platelets >100000 within 30 days of consent
• Eligible for contrasted magnetic resonance imaging (MRI) on initial evaluation with glomerular filtration rate (GFR) ≥ 60 ml/min. A diagnostic MRI ordered within one month will be considered an acceptable alternative and will not be repeated.
• Outside breast imaging will be reviewed at Duke to confirm findings are consistent with trial eligibility.

Exclusion criteria

• Neoadjuvant chemotherapy
• Breast implant in the breast to be treated with SBRT
• Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus, rheumatoid arthritis, scleroderma)
• Subjects unable to receive study treatment planning secondary to body habitus or inability to lie flat on the stomach at length
• HER2 positive
• Positive serum pregnancy test
• Insufficient breast imaging to judge clinical stage
• Subjects without placement of a biopsy clip at the diagnostic procedure who are unwilling to undergo clip placement.
• Subjects in whom treatment planning constraints cannot be met