Faculty Bibliography

BACKGROUND AND PURPOSE: We evaluated the effect of post-mastectomy radiation (PMRT) in 1-3 positive lymph nodes (LN) in patients who received uniform modern systemic therapy. MATERIALS AND METHODS: Cohort study using individual data collected for 1,649 node-positive women who received doxorubicin/cyclophosphamide with sequential docetaxel in 2000-2003 on the control arm of BCIRG-005. All women underwent mastectomy or lumpectomy and axillary LN dissection. PMRT was given at investigator's discretion. RESULTS: A total of 523 women with 1-3 positive LN underwent mastectomy and 39% (206/523) received PMRT. With a median follow-up of 10years, PMRT improved loco-regional control (LRC) from 91% to 98% (p=0.001) but had no effect on overall survival (OS) (84% vs. 86%, p=0.9). On multivariate analysis, PMRT improved local control (LC) (hazard ratio, 0.14; 95% CI, 0.03-0.62; p=0.01) and LRC (hazard ratio, 0.15; 95% CI, 0.04-0.50; p=0.002). PMRT did not significantly impact OS on multivariate analysis (hazard ratio, 0.91; 95% CI, 0.55-1.51; p=0.7). Results remained consistent with the use of propensity score analysis. CONCLUSIONS: In this cohort of patients with N1 disease treated with modern systemic therapy, PMRT improves LRC but has no effect on OS. The rates of OS were excellent, irrespective of adjuvant radiation.

PURPOSE: Cardiac toxicity due to conventional breast radiation therapy (RT) has been extensively reported, and it affects both the life expectancy and quality of life of affected women. Given the favorable oncologic outcomes in most women irradiated for breast cancer, it is increasingly paramount to minimize treatment side effects and improve survivorship for these patients. Proton RT offers promise in limiting heart dose, but the modality is costly and access is limited. Using cost-effectiveness analysis, we provide a decision-making tool to help determine which breast cancer patients may benefit from proton RT referral. METHODS AND MATERIALS: A Markov cohort model was constructed to compare the cost-effectiveness of proton versus photon RT for breast cancer management. The model was analyzed for different strata of women based on age (40 years, 50 years, and 60 years) and the presence or lack of cardiac risk factors (CRFs). Model entrants could have 1 of 3 health states: healthy, alive with coronary heart disease (CHD), or dead. Base-case analysis assumed CHD was managed medically. No difference in tumor control was assumed between arms. Probabilistic sensitivity analysis was performed to test model robustness and the influence of including catheterization as a downstream possibility within the health state of CHD. RESULTS: Proton RT was not cost-effective in women without CRFs or a mean heart dose (MHD) <5 Gy. Base-case analysis noted cost-effectiveness for proton RT in women with >/=1 CRF at an approximate minimum MHD of 6 Gy with a willingness-to-pay threshold of $100,000/quality-adjusted life-year. For women with >/=1 CRF, probabilistic sensitivity analysis noted the preference of proton RT for an MHD >/=5 Gy with a similar willingness-to-pay threshold. CONCLUSIONS: Despite the cost of treatment, scenarios do exist whereby proton therapy is cost-effective. Referral for proton therapy may be cost-effective for patients with >/=1 CRF in cases for which photon plans are unable to achieve an MHD <5 Gy.

Triple-negative breast cancer (TNBC) disproportionately affects black women. However, black race as a prognostic factor in TNBC has not been well studied. We evaluated the effect of race, among other variables, on outcomes in women with TNBC. A total of 704 patients with stages I-III TNBC treated with breast-conserving surgery +/- adjuvant radiation therapy (RT) and chemotherapy were identified from an institutional database. Competing risk analyses, Kaplan-Meier methods, and Cox proportional hazards models identified associations among clinicopathologic variables on locoregional recurrence (LRR), distant recurrence (DR), and overall survival (OS). LRR was defined as a biopsy proven, triple receptor-negative recurrence in the ipsilateral breast or regional lymph nodes. At a median follow-up of 51 months, there were 55 LRR, 61 DR, and 111 death events. Compared to non-black women, black women had higher disease stage and were more likely to receive axillary lymph node dissection, chemotherapy, and nodal irradiation (all P < 0.05). After adjustment for stage, age, lymphovascular invasion, chemotherapy, and RT on multivariate analysis, black race was prognostic for increased risk of LRR (hazard ratio [HR] = 3.17; 95 % confidence interval: 1.7-5.8; P = 0.0002). The 5-year risk of regional recurrence was higher in black women (10 vs. 2 %, P < 0.0001), but local failures were similar between groups (3.0 vs. 5.3 %, P = 0.15). RT was an independent predictor for decreased LRR and increased OS on multivariate analyses (P = 0.0006 and P = 0.0003, respectively). Black women with TNBC had equivalent local control, but higher risk of regional nodal failure, compared with non-black counterparts. The routine use of comprehensive nodal irradiation may be beneficial for black women with TNBC.

BACKGROUND: The authors evaluated the clinical characteristics, natural history, and outcomes of patients who had