Faculty Bibliography

BACKGROUND: Accelerated whole-breast radiotherapy (RT) with tumor bed boost in the treatment of early invasive breast cancer has demonstrated equivalent local control and cosmesis when compared with standard RT. Its efficacy in the treatment of ductal carcinoma in situ (DCIS) remains unknown. METHODS AND MATERIALS: Patients treated for DCIS with lumpectomy and negative margins were eligible for 2 consecutive hypofractionated whole-breast RT clinical trials. The first trial (New York University [NYU] 01-51) prescribed to the whole breast 42 Gy (2.8 Gy in 15 fractions) and the second trial (NYU 05-181) 40.5 Gy (2.7 Gy in 15 fractions) with an additional daily boost of 0.5 Gy to the surgical cavity. RESULTS: Between 2002 and 2009, 145 DCIS patients accrued, 59 to the first protocol and 86 to the second trial. Median age was 56 years and 65% were postmenopausal at the time of treatment. Based on optimal sparing of normal tissue, 79% of the patients were planned and treated prone and 21% supine. At 5 years' median follow-up (60 months; range 2.6-105.5 months), 6 patients (4.1%) experienced an ipsilateral breast recurrence in all cases of DCIS histology. In 3/6 patients, recurrence occurred at the original site of DCIS and in the remaining 3 cases outside the original tumor bed. New contralateral breast cancers arose in 3 cases (1 DCIS and 2 invasive carcinomas). Cosmetic self-assessment at least 2 years after treatment is available in 125 patients: 91% reported good-to-excellent and 9% reported fair-to-poor outcomes. CONCLUSIONS: With a median follow-up of 5 years, the ipsilateral local recurrence rate is 4.1%, comparable to that reported from the NSABP (National Surgical Adjuvant Breast and Bowel Project) trials that employed 50 Gy in 25 fractions of radiotherapy for DCIS. There were no invasive recurrences. These results provide preliminary evidence that accelerated hypofractionated external beam radiotherapy is a viable option for DCIS.

Objective: Locally advanced breast cancer (LABC) is the most common presentation of breast cancer worldwide. In the United States, neoadjuvant therapy has become the standard of care for LABC. Recently, Adams et al reported a 34% pathologic response rate among 105 patients with LABC treated with taxanebased, preoperative chemo-radiation: 5-year DFS and OS results were comparable to those of much more aggressive chemotherapy regimens in the neoadjuvant setting. As is reported for patients treated by neoadjuvant chemotherapy, the achievement of a pathological response to chemo-radiation reflected better DFS and OS. Importantly, a pathological response occurred in 54% of patients with hormone-negative tumors. Since this approach is simple and cost-effective, it has attracted interest from several international centers. We report the surgical outcomes after taxane-radiation in 63 LABC patients treated in a multiinstitutional clinical trial in India, South Africa, and the United States. Methods: Women with LABC (stages IIB-IIIC), ECOG performance status of 0 to 1, were eligible. Patients were treated with paclitaxel (30 mg/m(2) intravenously twice a week) for 6-12 weeks. Daily radiotherapy was delivered to breast, axillary, and supraclavicular lymph nodes during weeks 2-7 of paclitaxel treatment, at 1.8 Gy per fraction to a total dose of 45 Gy with a tumor boost of 14 Gy at 2 Gy/fraction. Seventeen of 63 patients received four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 prior to the paclitaxel -RT regimen. Mastectomy or lumpectomy, as decided by each surgeon, was performed 4 weeks after completion of preoperative therapy or upon recovery of chemoradiationinduced dermatitis. All patients had a level I/II axillary lymph node dissection. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan. Surgical complications were recorded. Results: Forty-three patients underwent modified radical mastectomyand 20 underwent lumpectomy. Of mastectomy patients, 17 (39.5%) underwent immediate breast reconstruction: free flap reconstruction (8), pedicle flaps (3), advancement flaps(2), tissue expander placement (2), and major chest wall and sternum reconstruction (1). Of lumpectomy patients, five (25%) had further surgery for positive margins; a second lumpectomy (3), and a mastectomy (2). All revealed residual disease and negative margins were achieved. Twenty-one patients had at least 1 complication of whom 17 were treated as outpatients. Eleven (17.4%) had a recurrent seroma, 8 (12.7%) had delayed healing, and 7 (11.1%) developed a postoperative infection. Of the 17 who underwent reconstruction, 3 (17.6%) developed flap necrosis, requiring surgical debridement. The degree of acute chemo-radiation dermatitis was analyzed to explore correlation with the surgical complications. Dermatitis was grade 1 in 21 patients, grade 2 in 29 patients, grade 3 in 11 patients, and 2 had none. The grade of dermatitis did not correlate with risk of complications. Conclusions: Preoperative paclitaxel with radiotherapy is relatively well tolerated. Risk of complication is similar to that reported in the literature for patients treated with neoadjuvant therapy. The highest morbidity was associated with immediate free flap reconstruction. Delayed reconstruction may be advisable for patients treated with neoadjuvant chemo-radiation. (Table presented)