Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT).

The aim of this study was to report 3-year outcomes of toxicity, cosmesis, and local control using a once daily fractionation scheme (49.95 Gy in 3.33 Gy once daily fractions) for accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT). Between July 2008 and August 2010, women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study. Women were treated with APBI using 3-5 photon beams, delivering 49.95 Gy over 15 once daily fractions over 3 weeks. Patients were assessed for toxicities, cosmesis, and local control rates before APBI and at specified time points. Thirty-four patients (mean age 60 years) with Tis 0 (n = 9) and T1N0 (n = 25) breast cancer were treated and followed up for an average of 39 months. Only 3% (1/34) patients experienced a grade 3 subcutaneous fibrosis and breast edema and 97% of the patients had good/excellent cosmetic outcome at 3 years. The 3-year rate of ipsilateral breast tumor recurrence (IBTR) was 0% while the rate of contralateral breast events was 6%. The 3-year disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) was 94%, 100%, and 100%, respectively. Our novel accelerated partial breast fractionation scheme of 15 once daily fractions of 3.33 Gy (49.95 Gy total) is a remarkably well-tolerated regimen of 3D-CRT-based APBI. A larger cohort of patients is needed to further ascertain the toxicity of this accelerated partial breast regimen

Using Nodal Ratios to Predict Risk of Regional Recurrences in Patients Treated with Breast Conservation Therapy with 4 or More Positive Lymph Nodes

Purpose. The value of nodal ratios (NRs) as a prognostic variable in breast cancer is continually being demonstrated. The purpose of this study was to use NR in patients with ≥4+ nodes to assess a correlation of NR with regional (lymph node) recurrence. Methods. Inclusion criteria was ≥8 nodes dissected with ≥4+ nodes after breast conservation therapy. Of 1060 patients treated from 1975 to 2003 who had a minimum of 8 nodes dissected, 273 were node+; 56 patients had ≥4+ involved nodes and were the focus of this study. Nodal ratios were calculated for each patient and grouped into 3 categories: high (≥70%), intermediate (40%–69%) and low (<40%). Each nodal ratio was correlated with patterns of local, regional, and distant failures and OS. Results. Outcomes for the entire cohort were BRFS-83%, NRFS-93%, DMFS-61%, and OS 63% at 10 yrs. The OS, DMFS, and NRFS correlated with N2 (4–9 nodes+) versus N3 (≥10+) status but did not correlate with BRFS, as expected. When evaluating NR, 18 pts had high NR (>70%). Only 3 patients experienced nodal recurrences, all within previously radiated supraclavicular fields. All 3 in-field regional failures occurred in the N3 group of patients with NR >70%. All were treated with a single AP field prescribed to a dose of 46 Gy at a standard depth of 3 cm. Conclusions. In this group of N2/N3 patients treated with BCT, we were able to identify patients at high risk for regional failures as those with high NR of >70% and ≥10+ nodes. While these findings need to be reproduced in larger datasets, this group of patients with NR of >70% in 4 or more positive axillary lymph nodes may benefit from meticulous targeting of regional nodes, dose escalation, and/or more intensive systemic therapies

Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance)

AXXXXX ZXXXX was a prospective trial evaluating the false negative rate of sentinel node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC

NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring \u3e1 year after whole-breast irradiation, \u3c3 \u3ecm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 \u3e1 to ≤2 cm, and 1 \u3e2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 ( CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare

Clinical Study Evaluation of Diabetic Patients with Breast Cancer Treated with Metformin during Adjuvant Radiotherapy

. Purpose. The purpose of this study was to evaluate acute locoregional toxicity in patients with breast cancer receiving concurrent metformin plus radiation therapy. Methods and Materials. Diabetic breast cancer patients receiving concurrent metformin and radiation therapy were matched with nondiabetic patients and diabetic patients using an alternative diabetes medication. Primary endpoints included the presence of a treatment break and development of dry or moist desquamation. Results. There was a statistically significant increase in treatment breaks for diabetic patients receiving concurrent metformin when compared to the nondiabetic patients ( value = 0.02) and a trend toward significance when compared to diabetic patients receiving an alternate diabetes medication ( value = 0.08). Multiple logistic regression analysis demonstrated concurrent metformin use as being associated with a trend toward the predictive value of determining the incidence of developing desquamation in diabetic patients receiving radiation therapy compared to diabetic patients receiving an alternate diabetes medication ( value = 0.06). Conclusions. Diabetic patients treated with concurrent metformin and radiation therapy developed increased acute locoregional toxicity in comparison with diabetic patients receiving an alternate diabetes medication and nondiabetic patients. Further clinical investigation should be conducted to determine the therapeutic ratio of metformin in combination with radiation therapy

Conservative management of Paget disease of the breast with radiotherapy

BACKGROUND At 5-year follow-up, patients with Paget disease of the breast who were treated with breast-conserving surgery (BCS) and radiotherapy (RT) had excellent results. The current report provides 10- and 15-year rates of tumor control in the breast, as well as disease-free and overall survival rates following BCS and RT in a cohort of patients with Paget disease presenting without a palpable mass or mammographic density. METHODS Through a collaborative review of patients treated with BCS and RT from seven institutions, 38 cases of Paget disease of the breast presenting without a palpable mass or mammographic density were identified. All patients had pathologic confirmation of typical Paget cells at time of diagnosis. Thirty-six of 38 patients had a minimum follow-up greater than 12 months and constitute the study cohort. Ninety-four percent of patients underwent complete or partial excision of the nipple-areola complex and all patients received a median external beam irradiation dose of 50 Gy (range, 45–54 Gy) to the whole breast. Ninety-seven percent of patients also received a boost to the remaining nipple or tumor bed, a median total dose of 61.5 Gy (range, 50.4–70 Gy). RESULTS With median follow-up of 113 months (range, 18–257 months), 4 of 36 patients (11%) developed a first recurrence of disease in the treated breast only. Two of the four recurrences in the breast were ductal carcinoma in situ (DCIS) only and two were invasive with DCIS. Two additional patients had a recurrence in the breast as a component of first failure. Actuarial local control rates for the breast as the only site of first recurrence were 91% at 5 years (95% confidence interval [CI], 80–100%) and 87% (95% CI, 75–99%) at both 10 and 15 years. Actuarial local control rates for breast recurrence, as a component of first failure, were 91% (95% CI, 80–100%), 83% (95% CI, 69–97%), and 76% (95% CI, 58–94%) at 5, 10, and 15 years, respectively. No clinical factors were identified as significant predictors for breast recurrence. Five-, 10- and 15-year actuarial rates for survival without disease of 97% (95% CI, 90–100%) and 5-, 10-, and 15-year actuarial rates of overall survival of 93% (95% CI, 84–100%) at 5 years and 90% (95% CI, 78–100%) at 10 and 15 years were reported. CONCLUSIONS These data confirm excellent rates of local control, disease-free survial, and overall survival at 10 and 15 years following BCS and RT for Paget disease of the breast. This study continues to support the recommendation of local excision and definitive breast irradiation as an alternative to mastectomy in the treatment of patients with Paget disease presenting without a palpable mass or mammographic density. Cancer 2003;97:2142–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11337Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34369/1/11337_ftp.pd

Identification of Novel Variants of Metadherin in Breast Cancer

Metadherin (MTDH, also known as AEG-1, and Lyric) has been demonstrated to play a potential role in several significant aspects of tumor progression. It has been reported that overexpression of MTDH is associated with progression of disease and poorer prognosis in breast cancer. However, there are no studies to date assessing variants of the MTDH gene and their potential relationship with breast cancer susceptibility. Thus, we investigated all variants of the MTDH gene and explored the association of the variants with breast cancer development. Our cohort consisted of full-length gene sequencing of 108 breast cancer cases and 100 healthy controls; variants were detected in 11 breast cancer cases and 13 controls. Among the variants detected, 9 novel variants were discovered and 2 were found to be associated with the susceptibility of breast cancer. However, additional studies need to be conducted in larger sample sizes to validate these findings and to further investigate whether these variants are prognostic in breast cancer patients

Reconstructive complications and early toxicity in breast cancer patients treated with proton-based postmastectomy radiation therapy

BackgroundPostmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT.MethodsA retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician.ResultsA total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946).ConclusionsAcute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities