Metaplastic Breast Cancer: Practice Patterns, Outcomes, and the Role of Radiotherapy.

PURPOSE: Metaplastic breast cancer (MBC) is a rare, aggressive form of breast cancer with limited data to guide management. This study of a large, contemporary US database described national practice patterns and addressed the impact of radiotherapy (RT) on survival. METHODS: The National Cancer Data Base was queried (2004-2013) for women with non-metastatic MBC. Multivariable logistic regression ascertained factors associated with RT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with either lumpectomy or mastectomy with or without RT, while substratifying patients into pT1-2N0 and pT3-4/N+ subcohorts. Cox proportional hazards modeling determined variables associated with OS. RESULTS: Of 5211 total patients, 447 (9%) had lumpectomy alone, 1831 (35%) had post-lumpectomy RT, 2020 (39%) had mastectomy alone, and 913 (18%) had post-mastectomy RT (PMRT). Most patients underwent chemotherapy (79%), and mastectomy was the most common surgical approach (56%). RT delivery was impacted by many factors, including higher nodal disease (p < 0.001), but not T classification or estrogen receptor status (p > 0.05 for both). Post-lumpectomy RT was associated with higher OS in both the pT1-2N0 and pT3-4/N+ subsets (p < 0.001 for both), while PMRT was associated with OS benefits in pT3-4/N+ cases (p < 0.001), but not in pT1-2N0 cases (p = 0.259). CONCLUSIONS: In the largest study to date evaluating MBC, practice patterns of surgery, systemic therapy, and RT are described. The addition of RT in the post-lumpectomy setting was associated with higher OS, in addition to pT3-4/N+ in the post-mastectomy setting. Although not implying causation, further work is required to corroborate the conclusions herein.

Use of simultaneous radiation boost achieves high control rates in patients with non-small-cell lung cancer who are not candidates for surgery or conventional chemoradiation.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) has improved the local disease control at a variety of anatomic sites. However, little is known about its use in lung cancer, especially in the context of shorter treatment schedules (hypofractionation). We analyzed the feasibility, toxicity, and patterns of failure of this approach for patients with non-small-cell lung cancer (NSCLC) who were not candidates for surgery or standard concurrent chemoradiation therapy. PATIENTS AND METHODS: We retrospectively identified 71 patients with NSCLC who received IMRT+SIB in 15 fractions to ≥ 52.5 Gy from January 2007 to February 2013. Toxicity and local control were evaluated for all patients. RESULTS: Of the 71 patients, 11 (16%) had stage I to II NSCLC, 15 (21%) stage III, and 45 (63%) stage IV. The esophagitis rate was grade 0 to 1 in 55%, grade 2 in 39%, and grade ≥ 3 in 6%. One patient developed a bronchoesophageal fistula 6 months after radiation. The pneumonitis rate was grade 0 to 1 in 93%, grade 2 in 6%, and grade 3 in 1%. At the time of analysis, 17 (24%) patients had local failure at a median of 5.2 months (range, < 1-16.1) after treatment. All but 1 failure occurred within the higher dose region. CONCLUSION: Hypofractionated IMRT+SIB is a viable option for some patients with NSCLC, with little high-grade toxicity overall. Nearly all local failures occurred within the higher dose region, implying strong radioresistance or some other mechanism for recurrence in a subgroup of patients.

Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiae.

Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs), such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA). Among the factors important for translocation formation by SSA is the central mismatch repair (MMR) and homologous recombination (HR) factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage.