Faculty Bibliography

Many breast cancer survivors have coexistent chronic diseases or comorbidities at the time of their cancer diagnosis. The purpose of the study was to evaluate the association of comorbidities on breast cancer survivors' quality of life. A prospective design was used to recruit 140 women before cancer surgery, 134 women completed the study. Comorbidities were assessed using self-report and verified by medical record review and the Charlson Comorbidity Index (CCI) before and 12-month after cancer surgery. Quality of life was evaluated using Short-Form Health Survey (SF-36 v2). Descriptive statistics, chi-square tests, t-tests, Fisher's exact test, and correlations were performed for data analysis. A total of 28 comorbidities were identified. Among the 134 patients, 73.8% had at least one of the comorbidities, 54.7% had 2-4, and only 7.4% had 5-8. Comorbidities did not change at 12 months after surgery. Numbers of comorbidities by patients' self-report and weighted categorization of comorbidities by CCI had a similar negative correlation with overall quality of life scores as well as domains of general health, physical functioning, bodily pain, and vitality. Comorbidities, specifically hypertension, arthritis, and diabetes, were associated with poorer quality of life in multiple domains among breast cancer survivors. Future research should consider the combined influence of comorbidity and cancer on patients' quality of life.

IntroductionEstrogen inhibition is effective in preventing breast cancer in only up to 50% of women with precancerous lesions and many experience side effects that are poorly tolerated. As insulin-like growth factor I (IGF-I) underlies both estrogen and progesterone actions and has other direct effects on mammary development and carcinogenesis, we hypothesized that IGF-I inhibition might provide a novel approach for breast cancer chemoprevention.MethodsIn total, 13 women with core breast biopsies diagnostic of atypical hyperplasia (AH) were treated for 10 days with pasireotide, a somatostatin analog which uniquely inhibits IGF-I action in the mammary gland. They then had excision biopsies. 12 patients also had proliferative lesions and one a ductal carcinoma in situ (DCIS). Primary outcomes were changes in cell proliferation and apoptosis after treatment. Expression of estrogen receptor (ER), progesterone receptor (PR), and phosphorylated Insulin-like growth factor I receptor (IGF-1R), protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2) were also assessed. Core and excision biopsies from 14 untreated patients served as non-blinded controls. Hyperglycemia and other side effects were carefully monitored.ResultsPasireotide decreased proliferation and increased apoptosis in all AH (from 3.6 inverted question mark+/- inverted question mark2.6% to 1.3 inverted question mark+/- inverted question mark1.2% and from 0.3 inverted question mark+/- inverted question mark0.2% to 1.5 inverted question mark+/- inverted question mark1.6%, respectively) and proliferative lesions (from 3.8 inverted question mark+/- inverted question mark2.5% to 1.8 inverted question mark+/- inverted question mark1.8% and from 0.3 inverted question mark+/- inverted question mark0.2% to 1.3 inverted question mark+/- inverted question mark0.6%, respectively). The DCIS responded similarly. ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly. In contrast, tissue from untreated controls showed no change in cell proliferation or phosphorylation of IGF-1R, AKT or ERK 1/2. Mild to moderate hyperglycemia associated with reduced insulin levels was found. Glucose fell into the normal range after discontinuing treatment. Pasireotide was well tolerated and did not cause symptoms of estrogen deprivation.ConclusionsIGF-I inhibition by pasireotide, acting through the IGF-1R, was associated with decreased proliferation and increased apoptosis in pre-malignant breast lesions and one DCIS. Assuming hyperglycemia can be controlled, these data suggest that inhibiting the IGF-I pathway may prove an effective alternative for breast cancer chemoprevention.Trial registration NCT01372644 Trial date: July 1, 2007.

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.