Faculty Bibliography

BACKGROUND: Advances in cancer treatments continue to reduce the incidence of lymphedema. Yet, many breast cancer survivors still face long-term postoperative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate The Optimal Lymph Flow program, a patient-centered education and behavioral program focusing on self-care strategies to enhance lymphedema risk reduction by promoting lymph flow and optimize body mass index (BMI). METHODS: A prospective, longitudinal, quasi-experimental design with repeated-measures was used. The study outcomes included lymph volume changes by infrared perometer, and BMI by a bioimpedance device at pre-surgery baseline, 2-4 weeks after surgery, 6-month and 12-month follow-up. A total of 140 patients were recruited and participated in The Optimal Lymph Flow program; 134 patients completed the study with 4 % attrition rate. RESULTS: Fifty-eight percent of patients had axillary node dissection and 42 % had sentinel lymph node biopsy (SLNB). The majority (97 %) of patients maintained and improved their preoperative limb volume (LV) and BMI at the study endpoint of 12 months following cancer surgery. Cumulatively, two patients with SLNB and two patients with axillary lymph node dissection had measurable lymphedema (>10 % LV change). At the 12-month follow-up, among the four patients with measurable lymphedema, two patients' LV returned to preoperative level without compression therapy but by maintaining The Optimal Lymph Flow exercises to promote daily lymph flow. CONCLUSIONS: This educational and behavioral program is effective in enhancing lymphedema risk reduction. The study provided initial evidence for emerging change in lymphedema care from treatment-focus to proactive risk reduction.

BACKGROUND: Reconstruction in the setting of prior breast irradiation is conventionally considered a higher-risk procedure. Limited data exist regarding nipple-sparing mastectomy in irradiated breasts, a higher-risk procedure in higher-risk patients. METHODS: The authors identified and reviewed the records of 501 nipple-sparing mastectomy breasts at their institution from 2006 to 2013. RESULTS: Of 501 nipple-sparing mastectomy breasts, 26 were irradiated. The average time between radiation and mastectomy was 12 years. Reconstruction methods in the 26 breasts included tissue expander (n = 14), microvascular free flap (n = 8), direct implant (n = 2), latissimus dorsi flap with implant (n = 1), and rotational perforator flap (n = 1). Rate of return to the operating room for mastectomy flap necrosis was 11.5 percent (three of 26). Nipple-areola complex complications included one complete necrosis (3.8 percent) and one partial necrosis (3.8 percent). Complications were compared between this subset of previously irradiated patients and the larger nipple-sparing mastectomy cohort. There was no significant difference in body mass index, but the irradiated group was significantly older (51 years versus 47.2 years; p = 0.05). There was no statistically significant difference with regard to mastectomy flap necrosis (p = 0.46), partial nipple-areola complex necrosis (p = 1.00), complete nipple-areola complex necrosis (p = 0.47), implant explantation (p = 0.06), hematoma (p = 1.00), seroma (p = 1.00), or capsular contracture (p = 1.00). CONCLUSION: In the largest study to date of nipple-sparing mastectomy in irradiated breasts, the authors demonstrate that implant-based and autologous reconstruction can be performed with complications comparable to those of the rest of their nipple-sparing mastectomy patients.

PURPOSE: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. METHODS AND MATERIALS: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. RESULTS: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm(3), mean 19.65 cm(3). In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm(3), mean 1.59 cm(3). There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. CONCLUSIONS: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard 6-week radiation therapy with a sequential boost.

BACKGROUND: Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified. METHODS: One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role. RESULTS: We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-beta and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002). CONCLUSIONS: Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients.