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Background: The benefit of adding radiation therapy after excision of ductal carcinoma in situ (DCIS) is widely debated. Randomized clinical trials are underpowered to delineate long-term outcomes after radiation.Methods: The authors of this report constructed a Markov decision model to simulate the clinical course of DCIS in a woman aged 60 years who received treatment with either of 2 breast-conserving strategies: excision alone or excision plus radiation therapy. Sensitivity analyses were used to study the influence of risk of local recurrence, likelihood of invasive disease at recurrence, surgical choice at recurrence, and patient age at diagnosis on treatment outcomes.Results: The addition of radiation therapy was associated with slight improvements in invasive disease-free and overall survival. However, radiation therapy decreased the chance of having both breasts intact over a patient's lifetime. Radiation therapy improved survival by 2.1 months for women who were diagnosed with DCIS at age 60 years but decreased the chance of having both breasts by 8.6% relative to excision alone. The differences in outcomes between the treatment strategies became smaller with increasing age at diagnosis. Sensitivity analyses revealed a greater benefit for radiation with an increased likelihood of invasive recurrence. The decrement in breast preservation with radiation therapy was mitigated by an increased likelihood of mastectomy at the time of recurrence or new breast cancer diagnosis.Conclusions: The current analysis quantified the benefits of radiation after excision of DCIS but also revealed that radiation therapy may increase the likelihood of eventual mastectomy. Therefore, the authors concluded that patient age and preferences should be considered when making the decision to add or forgo radiation for DCIS. [ABSTRACT FROM AUTHOR]

Background: A study was undertaken to determine the survival benefit of postoperative chemoradiation therapy for elderly patients with resected gastric adenocarcinoma.Methods: The authors identified 1023 individuals aged 65 years and older (median = 76) who underwent gastrectomy for nonmetastatic stage IB-IV gastric adenocarcinoma diagnosed between 2000 and 2002 in the linked Surveillance, Epidemiology, and End Results-Medicare database. They examined factors associated with receiving postoperative chemoradiation and analyzed the survival benefit associated with receiving postoperative chemoradiation.Results: Thirty percent of patients received adjuvant chemoradiation. On multivariate analysis, younger age (P < .0001), lymph node involvement (P < .0001), and more recent diagnosis (P = .0284) were associated with receiving chemoradiation. There was a trend toward increased use among patients with less comorbidity (P = .0515). The median follow-up was 25.5 months, and 62% died. On multivariate survival analysis, older patients (P < .0001) and those with lymph node involvement (P < .0001), T3 or T4 disease (P = .0472), higher grade disease (P = .0355), and more comorbidity (P = .0411) were more likely to die. After adjustment for other factors, receipt of adjuvant chemoradiation therapy did not significantly increase survival (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12; P = .3453) and did not increase survival in a multivariate analysis that included propensity scores (P = .2090).Conclusions: The authors did not detect a survival benefit, suggesting that some elderly patients with resected gastric adenocarcinoma may not gain a survival benefit from the administration of adjuvant chemoradiation. The analysis had limitations, and the results are hypothesis generating. Future gastric cancer trials should enroll more elderly patients and stratify patients by age to better understand the impact of treatment regimens on older patients. [ABSTRACT FROM AUTHOR]

Purpose: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer.Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen.Results: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adjusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women.Conclusions: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local. [ABSTRACT FROM AUTHOR]

Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined., Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction., Design, Setting, and Participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023., Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event., Main Outcomes and Measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence., Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02)., Conclusions and Relevance: In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction., Trial Registration: ClinicalTrials.gov Identifier: NCT03422003.

Purpose: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries., Materials and Methods: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests., Results: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC., Conclusion: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. Patients with high-risk breast lesions (HRLs) or preinvasive breast cancers face an elevated risk of future breast cancer diagnoses. Endocrine therapy in this setting reduces the risk of a future diagnosis but does not confer improved survival, thus the side effects of primary/secondary prevention must be considered relative to the benefits. Here, we discuss the available chemoprevention regimens for patients with HRLs and considerations for selecting a regimen, as well as the decision making surrounding use of adjuvant endocrine therapy for patients with ductal carcinoma in situ (DCIS). For patients with HRLs, available chemoprevention regimens differ by menopausal status, including tamoxifen 20 mg once daily for 5 years and more recently tamoxifen 5 mg once daily for 3 years in both premenopausal and postmenopausal women as well as raloxifene or aromatase inhibitors for postmenopausal women. We recommend a shared decision-making approach with attention to patient preferences related to risk tolerance and side-effect profiles. Low-dose tamoxifen appears to be a particularly favorable choice that is well tolerated, without risk of serious adverse events and offers comparable risk reduction to other regimens. For DCIS, the benefit of endocrine therapy in addition to radiation is small, and appears to be driven mainly by a reduction in contralateral breast diagnoses or new breast cancers. A strategy that reduces the side-effect profile of chemoprevention such as low-dose tamoxifen may be especially appealing in the setting of secondary prevention.

Purpose: We examined radiation therapy (RT) use among patients with early-stage breast cancer and analyzed the contribution of patient, cancer, and regional factors to the likelihood of RT receipt across Health Service Areas., Methods and Materials: We identified 13,176 patients aged 66 to 79 years in the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare database who were diagnosed with lymph node-negative breast cancer in 2007 to 2011 and were treated with breast-conserving surgery. Patients were stratified as being at high risk or low risk for recurrence based on National Comprehensive Cancer Network Guidelines. Receipt of RT was studied with 5 modeling approaches to determine whether RT use and regional variation in its use changed based on the risk level of the cohort. Multivariable mixed-effects logistic regression was performed for each outcome. Choropleth maps were used to describe patterns of RT use., Results: Among high-risk patients, 70.1% received RT, compared with 72.6% of low-risk patients ( P  = .002). Among patients receiving RT, 60.9% were classified as high-risk, compared with 63.0% of patients who did not receive RT ( P  = .002). In multivariable analyses, patients in all rural areas had lower odds of receiving RT compared with the entire cohort (odds ratio [OR], 0.73; P < .001) and had lower odds of being high-risk and receiving RT (OR, 0.69; P < .001). Black patients (OR, 0.73; P  = .001) and Asian patients (OR, 0.74; P  = .004) had decreased likelihood of receiving RT compared with the entire cohort. The regional interclass correlation coefficient (ICC) for the model predicting receipt of RT among all patients was 0.05 and among low-risk patients was 0.06. The regional ICC dropped to 0.02 for the model predicting being both high-risk and receiving RT among all patients., Conclusions: We observed regional and racial and ethnic disparities in RT receipt among our cohort. Reassuringly, less regional variability was observed for RT receipt among those at high risk for recurrence. Future work is needed to understand the causes of these regional disparities to better serve patients who may benefit from treatment., (© 2022 The Author(s).)

Even though Ductal Carcinoma in Situ (DCIS) can potentially be an invasive breast cancer (IBC) precursor, most DCIS lesions never will progress to IBC if left untreated. Because we cannot predict yet which DCIS lesions will and which will not progress, almost all women with DCIS are treated by breast-conserving surgery +/- radiotherapy, or even mastectomy. As a consequence, many women with non-progressive DCIS carry the burden of intensive treatment without any benefit. Multiple decision support tools have been developed to optimize DCIS management, aiming to find the balance between over- and undertreatment. In this systematic review, we evaluated the quality and added value of such tools. A systematic literature search was performed in Medline(ovid), Embase(ovid), Scopus and TRIP. Following the PRISMA guidelines, publications were selected. The CHARMS (prediction models) or IPDAS (decision aids) checklist were used to evaluate the tools' methodological quality. Thirty-three publications describing four decision aids and six prediction models were included. The decision aids met at least 50% of the IPDAS criteria. However, most lacked tools to facilitate discussion of the information with healthcare providers. Five prediction models quantify the risk of an ipsilateral breast event after a primary DCIS, one estimates the risk of contralateral breast cancer, and none included active surveillance. Good quality and external validations were lacking for all prediction models. There remains an unmet clinical need for well-validated, good-quality DCIS risk prediction models and decision aids in which active surveillance is included as a management option for low-risk DCIS.

Postmastectomy radiation therapy (PMRT) is a mainstay of local therapy for many breast cancer patients. Patients undergoing mastectomy typically are offered options for breast reconstruction. For patients who are candidates for PMRT, there are ongoing challenges with combining optimal radiation technique to prioritize oncologic outcomes, against the goals of minimizing toxicity and achieving the best reconstruction outcomes. The process by which these decisions are made continues to evolve as surgical and radiation techniques have improved and expanded, and as more patients with different risk profiles for local recurrence are receiving PMRT. We review the considerations regarding the different types of reconstruction and timing with radiation treatment. We also review the technical radiation consideration such as dose-fractionation, use of bolus and scar boost, exploring the controversies associated with the nuanced decisions regarding radiation and reconstructive surgery which are influenced by variables that are under continued investigation., (Published by Elsevier Inc.)

Purpose: We wanted to determine the prognosis and the phenotypic characteristics of hormone receptor-positive advanced breast cancer tumors harboring an ERBB2 mutation in the absence of a HER2 amplification., Experimental Design: We retrospectively collected information from the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange registry database from patients with hormone receptor-positive, HER2-negative, ERBB2-mutated advanced breast cancer. Phenotypic and co-mutational features, as well as response to treatment and outcome were compared with matched control cases ERBB2 wild type., Results: A total of 45 ERBB2-mutant cases were identified for 90 matched controls. The presence of an ERBB2 mutation was not associated with worse outcome determined by overall survival (OS) from first metastatic relapse. No significant differences were observed in phenotypic characteristics apart from higher lobular infiltrating subtype in the ERBB2-mutated group. ERBB2 mutation did not seem to have an impact in response to treatment or time-to-progression (TTP) to endocrine therapy compared with ERBB2 wild type. In the co-mutational analyses, CDH1 mutation was more frequent in the ERBB2-mutated group (FDR < 1). Although not significant, fewer co-occurring ESR1 mutations and more KRAS mutations were identified in the ERBB2-mutated group., Conclusions: ERBB2-activating mutation was not associated with a worse OS from time of first metastatic relapse, or differences in TTP on treatment as compared with a series of matched controls. Although not significant, differences in coexisting mutations (CDH1, ESR1, and KRAS) were noted between the ERBB2-mutated and the control group., (©2022 American Association for Cancer Research.)

Importance: Patient factors help explain disparities in breast cancer treatments and outcomes., Objective: To determine the extent to which geospatial variation in initial breast cancer care can be attributed to region vs patient factors with the aim of guiding quality improvement efforts., Design, Setting, and Participants: This was a retrospective population-based cohort study from January 1, 2007, through December 31, 2016, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database that included 31 571 patients diagnosed with stage I to III breast cancer from 2007 through 2013. Five metrics of care delivery were defined: stage I at diagnosis, chemotherapy receipt, radiation therapy receipt, endocrine therapy (ET) initiation (year 1), and ET continuation (years 3-5). Data analysis was performed from January to June 2021., Exposures: Stage I diagnosis and treatment with chemotherapy, radiation therapy, or ET., Main Outcomes and Measures: For each metric, total variance was attributed proportionally to 4 domains-random, patient factors (eg, age, race and ethnicity, socioeconomic status), region (health service area [HSA]), and unexplained-using hierarchical multivariable modeling., Results: Of 31 571 total patients (median [IQR] age, 71 [68-75] years), 19 391 (61.4%) had stage I disease at diagnosis. Among eligible patients, 17 297 of 21 190 (81.6%) received radiation therapy, 7204 of 9903 (72.8%) received chemotherapy, 13 115 of 26 855 (48.8%) initiated ET, and 13 944 of 26 855 (52.1%) continued ET. Geospatial density (ie, heat) maps highlight regional performance patterns. For all 5 metrics, region/HSA explained more observed variation (24%-48%) than patient factors (1%-4%); the largest share of variation was unexplained (35%-54%). The metrics with the largest proportion of total variance attributed to region/HSA were ET initiation and continuation (28% and 39%, respectively)., Conclusions and Relevance: In this cohort study, there was substantial unexplained geospatial variation in initial breast cancer care. The variance attributed to region/HSA was multifold larger than that explained by patient factors. The importance of patient factors such as race and ethnicity notwithstanding, future quality improvement efforts should focus on reducing unwarranted geospatial variation, especially including optimizing the delivery of ET in low-performing regions.

Purpose: Patients with triple-negative breast cancer (TNBC) experience higher local-regional recurrence rates than those with luminal or HER2-positive tumors. This prospective, phase 1B trial was designed to assess the safety and to establish the maximum tolerated dose (MTD) of cisplatin with radiation therapy for women with early-stage TNBC., Methods and Materials: Eligible patients had stage II or III TNBC. Cisplatin was initiated at 10 mg/m 2 intravenously once weekly during radiation and then escalated in a 3 + 3 design by 10 mg/m 2 at each dose level until 40 mg/m 2 , or the MTD, was reached. Patients undergoing breast-conserving therapy (BCT) or mastectomy were accrued in separate parallel cohorts during dose escalation, followed by a 10-patient expansion at the MTD., Results: During 2013 to 2018, 55 patients were accrued. Four patients developed dose-limiting toxicity. In the BCT cohort, 1 patient receiving 40 mg/m 2 developed tinnitus resulting in a cisplatin delay; therefore, this was the BCT cohort MTD. In the mastectomy cohort, 1 patient receiving 20 mg/m 2 developed a grade 3 urinary infection, and 2 additional patients had dose-limiting toxicities at 40 mg/m 2 (grade 3 neutropenia and grade 2 tinnitus), both resulting in cisplatin delay. Thus, 30 mg/m 2 was the mastectomy cohort MTD. Median follow-up was 48.5 months. Three-year disease-free survival was 74.7% for the BCT cohort and 64.4% for the mastectomy cohort., Conclusions: Adjuvant radiation therapy with concurrent cisplatin is feasible with a recommended phase 2 dose of 30 mg/m 2 and 40 mg/m 2 intravenously weekly in mastectomy and BCT cohorts, respectively., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although artificial intelligence algorithms are often developed and applied for narrow tasks, their implementation in other medical settings could help to improve patient care. Here we assess whether a deep-learning system for volumetric heart segmentation on computed tomography (CT) scans developed in cardiovascular radiology can optimize treatment planning in radiation oncology. The system was trained using multi-center data (n = 858) with manual heart segmentations provided by cardiovascular radiologists. Validation of the system was performed in an independent real-world dataset of 5677 breast cancer patients treated with radiation therapy at the Dana-Farber/Brigham and Women's Cancer Center between 2008-2018. In a subset of 20 patients, the performance of the system was compared to eight radiation oncology experts by assessing segmentation time, agreement between experts, and accuracy with and without deep-learning assistance. To compare the performance to segmentations used in the clinic, concordance and failures (defined as Dice < 0.85) of the system were evaluated in the entire dataset. The system was successfully applied without retraining. With deep-learning assistance, segmentation time significantly decreased (4.0 min [IQR 3.1-5.0] vs. 2.0 min [IQR 1.3-3.5]; p < 0.001), and agreement increased (Dice 0.95 [IQR = 0.02]; vs. 0.97 [IQR = 0.02], p < 0.001). Expert accuracy was similar with and without deep-learning assistance (Dice 0.92 [IQR = 0.02] vs. 0.92 [IQR = 0.02]; p = 0.48), and not significantly different from deep-learning-only segmentations (Dice 0.92 [IQR = 0.02]; p ≥ 0.1). In comparison to real-world data, the system showed high concordance (Dice 0.89 [IQR = 0.06]) across 5677 patients and a significantly lower failure rate (p < 0.001). These results suggest that deep-learning algorithms can successfully be applied across medical specialties and improve clinical care beyond the original field of interest.

Background: Although the 21-gene recurrence score (RS) assay is widely used to predict distant recurrence risk and benefit from adjuvant chemotherapy among women with hormone receptor-positive (HR+) breast cancer, the relationship between the RS and isolated locoregional recurrence (iLRR) remains poorly understood. Therefore, we examined the association between the RS and risk of iLRR for women with stage I-II, HR+ breast cancer., Methods: We identified 1758 women captured in the national prospective Breast Cancer-Collaborative Outcomes Research Database who were diagnosed with stage I-II, HR+ breast cancer from 2006 to 2012, treated with mastectomy or breast-conserving surgery, and received RS testing. Women who received neoadjuvant therapy were excluded. The association between the RS and risk of iLRR was examined using competing risks regression., Results: Overall, 19% of the cohort (n = 329) had a RS ≥25. At median follow-up of 29 months, only 22 iLRR events were observed. Having a RS ≥25 was not associated with a significantly higher risk of iLRR compared to a RS < 25 (hazard ratio 1.14, 95% confidence interval 0.39-3.36, P = 0.81). When limited to women who received adjuvant endocrine therapy without chemotherapy (n = 1199; 68% of the cohort), having a RS ≥25 (n = 74) was significantly associated with a higher risk of iLRR compared to a RS < 25 (hazard ratio 3.66, 95% confidence interval 1.07-12.5, P = 0.04). In this group, increasing RS was associated with greater risk of iLRR (compared to RS < 18, hazard ratio of 1.66, 3.59, and 7.06, respectively, for RS 18-24, 25-30, and ≥ 31; P trend  = 0.02)., Conclusions: The RS was significantly associated with risk of iLRR in patients who did not receive adjuvant chemotherapy. The utility of the RS in identifying patients who have a low risk of iLRR should be further studied.

Purpose: Radiation therapy interruption (RTI) worsens cancer outcomes. Our purpose was to benchmark and map RTI across a region in the United States with known cancer outcome disparities., Methods and Materials: All radiation therapy (RT) treatments at our academic center were cataloged. Major RTI was defined as ≥5 unplanned RT appointment cancellations. Univariate and multivariable logistic and linear regression analyses identified associated factors. Major RTI was mapped by patient residence. A 2-sided P value <.0001 was considered statistically significant., Results: Between 2015 and 2017, a total of 3754 patients received RT, of whom 3744 were eligible for analysis: 962 patients (25.8%) had ≥2 RT interruptions and 337 patients (9%) had major RTI. Disparities in major RTI were seen across Medicaid versus commercial/Medicare insurance (22.5% vs 7.2%; P < .0001), low versus high predicted income (13.0% vs 5.9%; P < .0001), Black versus White race (12.0% vs 6.6%; P < .0001), and urban versus suburban treatment location (12.0% vs 6.3%; P < .0001). On multivariable analysis, increased odds of major RTI were seen for Medicaid patients (odds ratio [OR], 3.35; 95% confidence interval [CI], 2.25-5.00; P < .0001) versus those with commercial/Medicare insurance and for head and neck (OR, 3.74; 95% CI, 2.56-5.46; P < .0001), gynecologic (OR, 3.28; 95% CI, 2.09-5.15; P < .0001), and lung cancers (OR, 3.12; 95% CI, 1.96-4.97; P < .0001) compared with breast cancer. Major RTI was mapped to urban, majority Black, low-income neighborhoods and to rural, majority White, low-income regions., Conclusions: Radiation treatment interruption disproportionately affects financially and socially vulnerable patient populations and maps to high-poverty neighborhoods. Geospatial mapping affords an opportunity to correlate RT access on a neighborhood level to inform potential intervention strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Achieving a pathologic complete response (pCR) with neoadjuvant therapy for HER2-positive breast cancer is associated with less recurrence and improved clinical outcomes compared to having residual cancer at surgery. However, recent data have demonstrated favorable outcomes for patients with residual HER2-positive cancer who received adjuvant trastuzumab emtansine (TDM-1). Therefore, we sought to determine the optimal chemotherapy/anti-HER2 treatment strategy., Methods: We created a decision-analytic model for patients with stage II-III HER2-positive cancer that incorporated utilities based on toxicity and recurrence. We separately modeled hormone receptor-negative (HR-) and positive (HR+) disease and calculated quality-adjusted life years (QALYs) and costs through 5 years. Simulated patients received one of the following neoadjuvant treatments: three 'intensive' regimens (TCHP: docetaxel, carboplatin, trastuzumab, pertuzumab; THP + AC: taxol, trastuzumab, pertuzumab then doxorubicin and cyclophosphamide; THP: taxol, trastuzumab, pertuzumab) and two 'de-escalated' regimens (TH: taxol, trastuzumab; TDM-1) followed by adjuvant treatment based on pathologic response., Results: Among 'intensive' neoadjuvant strategies, treatment with THP was more effective and less costly than TCHP or THP + AC. When 'de-escalated' strategies were included, TH became the most cost-effective. For HR-negative cancer, TH had 0.003 fewer quality-adjusted life years (QALYs) than THP but was less costly by $55,831, resulting in an incremental cost-effectiveness ratio of over $18M/QALY for THP, well above any threshold. For HR-positive cancer, neoadjuvant TH dominated the THP strategy., Conclusion: An adaptive-treatment strategy beginning with neoadjuvant THP or TH followed by tailoring post-operative therapy reduces treatment costs, and spares toxicity compared to more intensive chemotherapy regimens for women with HER2-positive breast cancer.

The DCISionRT test estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) as well as the benefit of adjuvant radiation therapy (RT). We determined the cost-effectiveness of DCISionRT using a Markov model simulating 10-year outcomes for 60-year-old women with DCIS based on nonrandomized data. Three strategies were compared: no testing, no RT (strategy 1); test all, RT for elevated risk only (strategy 2); and no testing, RT for all (strategy 3). We used utilities and costs from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women irradiated per IBE prevented. In the base-case scenario, strategy 1 was the cost-effective strategy. Strategy 2 was cost-effective compared with strategy 3 when the cost of DCISionRT was less than $4588. The number irradiated per IBE prevented were 8.37 and 15.46 for strategies 2 and 3, respectively, relative to strategy 1., (© The Author(s) 2020. Published by Oxford University Press.)

Purpose: Improved imaging, surgical techniques, and pathologic evaluation likely have decreased local recurrence rates for patients with ductal carcinoma in situ (DCIS). We present long-term outcomes of a large single-institution series after breast-conserving surgery (BCS) and adjuvant radiation therapy (RT)., Methods: We retrospectively reviewed the records of 245 women treated for DCIS with BCS and RT between 2001 and 2007. Competing risk analysis was used to calculate local recurrence (LR) as a first event with the development of a second non-breast malignancy, contralateral breast cancer, and death as competing first events., Results: At a median follow-up of 10.6 years, 4 patients had a LR (2 DCIS, 2 invasive) as a first event with a cumulative LR incidence of 0.0% and 1.5% at 5 and 10 years, respectively. Most patients had > 2 mm margins (90%), specimen radiographs (93%), and received a tumor bed boost (99%). The majority (60%) of patients with hormone receptor-positive disease received adjuvant endocrine therapy. Ten-year cumulative incidence of contralateral breast cancer (CBC) was 7.9%, second non-breast malignancy was 4.5%, and death unrelated to breast cancer was 3.5%. Family history, age at diagnosis, and receipt of endocrine therapy were not significantly associated with the development of CBC (all P > 0.05)., Conclusions: With mature follow-up, our rates of local recurrence following breast-conserving therapy for DCIS remain very low (1.5% at 10 years). The incidence of CBC was higher than the LR incidence. Predisposing factors for the development of CBC are worthy of investigation.

Background: Women with a history of ductal carcinoma in situ (DCIS) are at increased risk for developing a second breast cancer (SBC). A prior meta-analysis of randomized studies of radiotherapy (RT) for DCIS has shown a trend toward increased breast cancer-specific mortality after SBC, but it did not have the power needed to detect a significant difference, due to a limited number of recurrences. This study sought to evaluate the impact of RT for DCIS on mortality after SBC in a larger cohort., Patients and Methods: Using the SEER database, 3,407 patients were identified who received breast-conserving therapy with or without RT for primary DCIS in 2000 through 2013 and subsequently developed a stage I-III invasive SBC within the same time period. Fine-Gray competing risk models were used to study the association between receipt of RT and mortality after SBC., Results: Prior RT was found to be associated with higher rates of breast cancer-specific mortality (hazard ratio [HR], 1.70; 95% CI, 1.18-2.45; P=.005), even after controlling for cancer stage. Interaction analysis suggested that this risk trended higher in patients with ipsilateral versus contralateral SBC (HR, 2.07 vs 1.26; P=.16). Furthermore, compared with patients who developed contralateral SBC, those with ipsilateral SBC were younger (P<.001) and more often lacked estrogen receptor expression (P<.001)., Conclusions: Patients who previously received RT for DCIS had higher mortality after developing an invasive SBC than those who did not receive RT. This finding may have implications for initial treatment decisions in the management of DCIS.

Purpose: Postmastectomy radiation therapy (PMRT) delivered to an immediate reconstruction increases the risk of surgical complications. Although acellular dermal matrix (ADM) has been used with immediate tissue expander (TE) reconstruction to improve cosmetic outcomes and minimize capsular contracture, there is a paucity of data on this approach in the setting of PMRT., Methods and Materials: Thirty-two patients with stage I to III breast cancer were treated with mastectomy, immediate TE-ADM reconstruction, and PMRT between 2009 and 2012 in a prospective single-arm study. The primary objective was the "success" rate, determined by the number of patients at 2 years after PMRT having an intact final reconstruction, no major complications, and a cosmetic outcome rated by a physician as excellent or good., Results: The median follow-up was 24 months. Final reconstruction status was known in 31 of 32 patients (96.9%; 1 patient left the country) and completed in 29 of 31 patients (93.5%; implant, n = 26; flap, n = 1; both, n = 2; none, n = 2). At 2 years, 6 patients were unevaluable (metastatic disease, n = 3; withdrawn consent, n = 1; left the country, n = 2). Of 26 evaluable patients, the success rate was 65.4% (17 of 26). Lack of success was the result of "fair" cosmesis (n = 2), infection (n = 2), severe capsular contracture (n = 1), major revision (n = 2), and no final reconstruction (n = 2). Most patients had good-to-excellent 2-year overall cosmesis based on patient perception (15; 62.5%) and physician evaluation (19; 79.2%)., Conclusions: To the best of our knowledge, this is the first dedicated prospective trial evaluating long-term cosmetic and complication outcomes in patients treated with immediate TE-ADM reconstruction followed by PMRT. Most patients (65.4%) met the success criteria in this prospective single-arm series. The great majority (93.5%) achieved final reconstruction; most had good-to-excellent overall cosmetic outcomes (79.2%). The results with longer follow-up will be of interest, and further investigation of strategies to optimize reconstruction with PMRT are warranted., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the cost-effectiveness of using the Oncotype DX Genomic Prostate Score (GPS), a 17-gene expression assay that can be used to inform decisions regarding active surveillance (AS) vs immediate treatment., Methods: We developed a Markov model simulating 20-year outcomes for 65-year-old men with very low-, low-, or favorable intermediate-risk prostate cancer undergoing AS vs immediate treatment using GPS vs no testing. Utilities, costs, and probabilities were extracted from the literature and National Medicare Fee Schedules to determine incremental cost-effectiveness ratios (ICER) from a payer perspective., Results: In the overall cohort, the ICER of GPS-guided therapy was $31,394 per quality-adjusted life-year (QALY). When stratified by risk group, the ICER was $25,343 per QALY in very low-risk, $28,911 per QALY in low-risk, and $39,695 per QALY in favorable intermediate-risk patients. On sensitivity analysis, findings were robust against a willingness-to-pay of $100,000 per QALY to variations in key model parameters, including the cost of annual management of AS, probability of exiting AS to treatment, cost of treatment, and probability of biochemical failure post-treatment. However, the cost-effectiveness was sensitive to small differences in the utility of AS and the utility of no evidence of disease post-treatment states., Conclusion: The use of the GPS was cost-effective in guiding treatment decisions regarding AS vs immediate treatment. The cost-effectiveness was sensitive to small differences in the utilities of the AS and no evidence of disease post-treatment states, highlighting the importance of assessing patient preferences., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To examine whether pre-diagnosis patient-reported health-related quality of life (HRQOL) and depressive symptoms are associated with local treatment for older women with ductal carcinoma in situ (DCIS) and stage I breast cancer (BC)., Methods: Using the SEER-MHOS dataset, we identified women ≥ 65 years old with DCIS or stage I BC diagnosed 1998-2011 who completed surveys ≤ 24 months before diagnosis. Depressive symptoms were measured by major depressive disorder (MDD) risk and HRQOL was measured by Physical and Mental Component Summary scores (PCS and MCS, respectively) of the SF-36/VR-12. Associations with treatment choice (breast-conserving surgery [BCS] and radiation therapy [RT], BCS alone, mastectomy) were assessed with multivariable multinomial logistic regression, controlling for patient characteristics., Results: We identified 425 women with DCIS and 982 with stage I BC. Overall, 20.4% endorsed depressive symptoms placing them at risk for MDD pre-diagnosis; mean MCS and PCS scores were 52.3 (SD = 10.1) and 40.5 (SD = 11.5), respectively. Among women with DCIS, those at risk for MDD were more likely to receive BCS (adjusted odds ratio [AOR] 2.04, 95% CI 1.04-4.00, p = 0.04) or mastectomy (AOR 1.88, 95% CI 0.91-3.86, p = 0.09) compared to BCS + RT. For DCIS, MCS score was not associated with treatment; higher PCS score was associated with decreased likelihood of receiving mastectomy versus BCS + RT (AOR 0.71 per 10-point increase, 95% CI 0.54-0.95, p = 0.02). For BC, none of the measures were significantly associated with treatment., Conclusion: Older women at risk for MDD before DCIS diagnosis were less likely to receive RT after BCS, compared to BCS alone or mastectomy.

Background: In pancreatic adenocarcinoma (PDAC), increasing tumor size usually correlates with a worse prognosis. However, patients with a very small primary tumor who experience lymph node involvement may have a different disease biology. This study sought to determine the interaction between tumor size and lymph node involvement in terms of overall survival (OS)., Methods: The study identified 17,073 patients with a diagnosis of M0 resected PDAC between 1983 and 2013 using the Surveillance, Epidemiology, and End Results database. The patients were stratified by lymph node involvement (N0 vs N+) and T stage (T1a-T1b vs T1c vs T2 vs T3 vs T4). The Kaplan-Meier method was used to estimate OS, and Cox regression analysis was used to compare survival between subgroups after adjustment for patient-specific factors., Results: Lymph node involvement and T stage significantly interacted (p < 0.001). Among the patients with node-negative disease, 5-year OS decreased monotonically with increasing T stage (59.1%, 30.6%, 22.9%, 16.6%, and 8.0%, respectively; p < 0.001). In contrast, among the patients with node-positive disease, those with T1a-T1b tumors (< 10 mm) had worse 5-year OS than those with T1c tumors (7.4% vs 17.6%; adjusted hazard ratio, 0.70; 95% confidence interval, 0.50-0.97; p = 0.034) and similar survival compared with those who had T2, T3, or T4 tumors (9.7%, 8.2%, and 4.8%, respectively; p > 0.2 in all cases)., Conclusions: Among patients with lymph node-positive PDAC, very small primary tumors are associated with decreased OS. This finding raises the possibility that small tumors capable of lymph node metastasis might represent more biologically aggressive cancers.

Ductal carcinoma in situ (DCIS) is a highly heterogeneous disease. It presents in a variety of ways and may or may not progress to invasive cancer, which poses challenges for both diagnosis and treatment. On May 15, 2017, the Dana-Farber/Harvard Cancer Center hosted a retreat for over 80 breast specialists including medical oncologists, surgical oncologists, radiation oncologists, radiologists, pathologists, physician assistants, nurses, nurse practitioners, researchers, and patient advocates to discuss the state of the science, treatment challenges, and key questions relating to DCIS. Speakers and attendees were encouraged to explore opportunities for future collaboration and research to improve our understanding and clinical management of this disease. Participants were from Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Duke University Medical Center, and MD Anderson Cancer Center. The discussion focused on three main themes: epidemiology, detection, and pathology; state of the science including the biology of DCIS and potential novel treatment approaches; and risk perceptions, communication, and decision-making. Here we summarize the proceedings from this event.

Purpose: As local therapies improve, contralateral breast cancer (CBC) risk for women with ductal carcinoma in situ (DCIS) may exceed the risk of a second ipsilateral breast cancer. We sought to determine whether estrogen-receptor (ER) status influenced CBC risk., Methods: We identified women aged 40-79 with DCIS diagnosed between 1990 and 2002 using the Surveillance, Epidemiology, and End Results database. We used multivariable competing risk regression to examine predictors of time from index DCIS to CBC (invasive or in situ)., Results: Multivariable competing risk regression found ER status to be a highly significant predictor of CBC. The 10-year cumulative incidence was estimated to be 5.3% (95% CI 4.8-5.8%) among ER positive (ER+) cases and 3.3% (95% CI 2.6-4.0%) among ER negative (ER-)., Conclusions: This finding suggests that ER+ DCIS may represent a field effect that confers increased propensity for developing cancer across breast tissue, regardless of laterality. In contrast, ER- DCIS may represent an isolated local event. Given that the majority of DCIS is ER+, and only a minority of DCIS patients receive hormonal therapy, consideration of ER status may influence treatment and surveillance approaches.

Purpose: To compared the cost-effectiveness of intensity modulated proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) in the management of stage III-IVB oropharynx cancer (OPC)., Methods and Materials: A Markov model was constructed to compare IMRT with PBT for a 65-year-old patient with stage IVA OPSCC. We assumed PBT led to a 25% reduction in long-term xerostomia, short-term dysgeusia, and the need for gastrostomy tube. Fewer dental complications were also expected with PBT. Incremental cost-effectiveness ratios (ICERs) were calculated, and value of information analyses were performed. The societal willingness-to-pay was defined as $100K per quality-adjusted life year (QALY)., Results: The ICERs for PBT for favorable human papillomavirus (HPV)-positive OPC were $288,000/QALY and $390,000/QALY in the payer perspective (PP) and societal perspective, respectively. Under nearly every scenario, PBT was not cost-effective, with ICERs above $150,000/QALY in the PP. The ICERs for HPV-negative OPC were typically greater than $250K/QALY in both perspectives. For HPV-positive patients, the ICER was less than $100,000/QALY in the PP only in younger patients who experienced a 50% reduction in both xerostomia and gastrostomy use. On probabilistic sensitivity analyses, there were 0% and 0.4% probabilities that PBT was cost-effective for 65- and 55-year old patients, respectively. The value of information was zero or negligible for all ages and perspectives at willingness-to-pay of $100,000/QALY and only meaningful in the PP for younger patients at a willingness-to-pay of $150,000/QALY., Conclusions: Intensity modulated proton beam therapy was only cost-effective in the PP if assumed to achieve profound reductions in long-term morbidity for younger patients; it was never cost-effective in the societal perspective. Prospective data are needed (and may be valuable) to better characterize the comparative toxicities of these treatments but are unlikely to change this calculation, except potentially in the most favorable cohort of patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Ductal carcinoma in situ (DCIS) can be a precursor to invasive breast cancer. Since the advent of screening mammography in the 1980's, the incidence of DCIS has increased dramatically. The value of screen detection and treatment of DCIS, however, is a matter of controversy, as it is unclear the extent to which detection and treatment of DCIS prevents invasive disease and reduces breast cancer mortality. The aim of this paper is to provide an overview of existing Cancer Intervention and Surveillance Modelling Network (CISNET) modeling approaches for the natural history of DCIS, and to compare these to other modeling approaches reported in the literature., Design: Five of the 6 CISNET models currently include DCIS. Most models assume that some, but not all, lesions progress to invasive cancer. The natural history of DCIS cannot be directly observed and the CISNET models differ in their assumptions and in the data sources used to estimate the DCIS model parameters., Results: These model differences translate into variation in outcomes, such as the amount of overdiagnosis of DCIS, with estimates ranging from 34% to 72% for biennial screening from ages 50 to 74 y. The other models described in the literature also report a large range in outcomes, with progression rates varying from 20% to 91%., Limitations: DCIS grade was not yet included in the CISNET models., Conclusion: In the future, DCIS data by grade from active surveillance trials, the development of predictive markers of progression probability, and evidence from other screening modalities, such as tomosynthesis, may be used to inform and improve the models' representation of DCIS, and might lead to convergence of the model estimates. Until then, the CISNET model results consistently show a considerable amount of overdiagnosis of DCIS, supporting the safety and value of observational trials for low-risk DCIS.

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor-positive SBE contingent on AET use for the initial DCIS diagnosis., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Purpose: A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions., Methods: Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC)., Results: Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well., Conclusions: This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

Background: Optimal distant recurrence (DR) surveillance strategies for extremity soft tissue sarcoma (STS) are unknown. We performed a cost-effectiveness analysis of different imaging modalities performed at guideline-specified intervals., Methods: We developed a Markov model simulating lifetime outcomes for 54-year-old patients after definitive treatment for American Joint Committee on Cancer stage II-III extremity STS using four surveillance strategies: watchful waiting (WW), chest X-ray (CXR), chest computed tomography (CCT), and positron emission tomography-computed tomography (PET/CT). Probabilities, utilities, and costs were extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios (ICER)., Results: CCT was the most effective and most costly strategy with CXR the most cost-effective strategy at a societal willing-to-pay (WTP) of $100,000/quality-adjusted life year (QALY). The ICER was $12,113/QALY for CXR versus $104,366/QALY for CCT while PET/CT was never cost-effective. Sensitivity analyses demonstrated CCT becomes the preferred imaging modality as the lifetime risk of DR increases beyond 33% or as the WTP increases beyond $120,000/QALY., Conclusions: Optimal DR surveillance imaging for stage II-III extremity STS should be individualized based on patients' risks for DR. These results suggest CXR, or CCT performed at more protracted intervals, may be preferred for lower-risk patients (i.e., DR risk <33%), whereas CCT may be preferred for higher-risk patients (i.e., DR risk >33%). Further study of optimal strategies is needed. In the interim, these findings may help to refine guidelines to reduce resource overutilization during routine surveillance of lower-risk sarcoma patients.

Importance: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking., Objective: To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis., Design, Setting, and Participants: Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort., Main Outcomes and Measures: Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer., Results: We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR-positive HER2-positive subtype displayed the longest median survival (21.0 months); patients with triple-negative subtype had the shortest median survival (6.0 months)., Conclusions and Relevance: The findings of this study provides population-based estimates of the incidence and prognosis for patients with brain metastases at time of diagnosis of breast cancer. The findings lend support to consideration of screening imaging of the brain for patients with HER2-positive or triple-negative subtypes and extracranial metastases.

Background: Women diagnosed with lobular carcinoma in situ (LCIS) have a 3-fold to 10-fold increased risk of developing invasive breast cancer. The objective of this study was to evaluate the life expectancy (LE) and differences in survival offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy among women with LCIS., Methods: A Markov simulation model was constructed to determine average LE and quality-adjusted LE (QALE) gains for hypothetical cohorts of women diagnosed with LCIS at various ages under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, other-cause mortality and the effectiveness of preventive strategies were derived from published studies and from the National Cancer Institute's Surveillance, Epidemiology, and End Results database., Results: Assuming a breast cancer incidence from 1.02% to 1.37% per year under active surveillance, a woman aged 50 years diagnosed with LCIS would have a total LE of 32.78 years and would gain 0.13 years (1.6 months) in LE by adding chemoprevention and 0.25 years (3.0 months) in LE by adding bilateral prophylactic mastectomy. After quality adjustment, chemoprevention resulted in the greatest QALE for women ages 40 to 60 years at LCIS diagnosis, whereas surveillance remained the preferred strategy for optimizing QALE among women diagnosed at age 65 years and older., Conclusions: In this model, among women with a diagnosis of LCIS, breast cancer prevention strategies only modestly affected overall survival, whereas chemoprevention was modeled as the preferred management strategy for optimizing invasive disease-free survival while prolonging QALE form women younger than 65 years. Cancer 2017;123:2609-17. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose: Risk factors for local recurrence (LR) following breast-conserving therapy (BCT) inform the need for local therapy. A Danish population-based cohort study identified residual disease on reexcision as an independent risk factor for LR but was limited by incomplete data on biologic subtype (Bodilsen et al. 2015 in Ann Surg Oncol 22: S476-S485). We sought to elaborate this risk in an independent cohort with clearly defined biologic subtypes., Methods: The study population included patients with localized invasive breast cancer with complete biologic subtype data treated with BCT with one or zero reexcisions at one institution from 1998 to 2008. Cumulative incidence of LR was calculated using competing risk analysis, and associated risk factors were evaluated using Cox proportional hazards regression., Results: A total 1073 consecutive patients were included with a median follow-up of 10 years. The 10-year LR rates were 2.4% [95% confidence interval (CI) 1.4-3.9%] without reexcision, 6.0% (95% CI 3.8-8.9%) with reexcision, and 8.2% (95% CI 4.1-14.0%) with any reexcised residual disease. On univariate regression, residual disease [hazard ratio (HR) = 1.50, p = 0.31] was not significantly associated with LR. Subtype other than luminal A/luminal-HER2 (luminal B HR = 2.29, p = 0.033; HER2/triple-negative HR = 2.85, p = 0.004), age (HR = 0.95 per year, p < 0.001), and nodal involvement (HR = 1.12 per involved node, p = 0.001) remained significant on multivariate regression. The impact of residual disease was confounded by its association (p < 0.001) with nodal involvement., Conclusions: Our findings suggest that LR is associated with younger age, nodal involvement, and biologic subtype but not with residual disease at reexcision. The study's power is limited by the low incidence of LR despite detailed clinical data and long-term follow-up. Further study is required.

Importance: Large regional variation exists in the use of radiotherapy after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Although patients who do not receive initial radiotherapy for DCIS are candidates for subsequent BCS if they experience a second breast event, many undergo mastectomy instead., Objective: To examine whether regional practice patterns of radiotherapy for DCIS affect the use of mastectomy in these patients., Design, Setting, and Participants: A retrospective analysis of population-based databases (Surveillance, Epidemiology, and End Results [SEER] and SEER-Medicare). Data were obtained for 2679 women in SEER with a diagnosis of DCIS between 1990 and 2011 and for 757 women in SEER-Medicare with a DCIS diagnosis between 1991 and 2009 who had not undergone radiotherapy for DCIS and experienced a subsequent breast cancer or DCIS diagnosis., Exposures: Treatment intensity for primary DCIS (high, medium, low), as defined by separating health service areas (HSAs) into 3 clusters based on radiotherapy use., Main Outcomes and Measures: Mastectomy vs BCS at a second breast event defined as DCIS recurrence or new invasive cancer., Results: The median (SD) ages of the participants was 64 (13) years for the 2679 SEER population and 79 (6) years for the SEER-Medicare cohort. Residence in an HSA characterized by greater radiotherapy use for DCIS increased the likelihood of receiving mastectomy vs BCS at a subsequent breast event, even among women who had not previously received radiotherapy for DCIS. Adjusted odds ratios for receiving mastectomy were 1.43 (95% CI, 1.10-1.85) and 1.90 (95% CI, 1.27-2.84) in SEER and SEER-Medicare databases, respectively, among women residing in an HSA with the greatest radiotherapy use vs the least, corresponding to an adjusted increase from 40.8% to 49.6%, and from 38.6% to 54.5%., Conclusions and Relevance: Areas with more radiotherapy use for DCIS had increased use of mastectomy at the time of a second breast event even among patients eligible for breast conservation. This association suggests that physician-related factors are affecting the likelihood of breast preservation.

Purpose/objectives: Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT., Methods: We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models., Results: With a median follow-up of 106 months, 69 LRs (3 %) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B = 3.01, HER2 = 6.29, triple-negative [TNBC] = 4.72; p < 0.001 each), younger age (HR of oldest vs. youngest quartile = 0.43; p = 0.005), regional nodal involvement (HR for 4-9 involved nodes = 3.04; >9 nodes = 5.82; p < 0.01 for each), positive margins (HR 2.43; p = 0.005), and high grade (HR 5.37; p < 0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B = 2.64, HER2 = 5.42, TNBC = 4.32; p < 0.001 for each), younger age (HR for age >50 = 0.56; p = 0.01), and nodal disease (HR 1.06 per involved node; p < 0.004) were associated with LR. The 8-year risk of LR was 2.8 % for node-negative patients and 5.2 % for node-positive patients., Conclusion: BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era.

Purpose The Oncotype DX DCIS Score short form (DCIS Score) estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery without adjuvant radiation therapy (RT). We determined the cost effectiveness of strategies using this test. Materials and Methods We developed a Markov model simulating 10-year outcomes for 60-year-old women eligible for the Eastern Cooperative Oncology Group E5194 study (cohort 1: low/intermediate-grade DCIS, ≤ 2.5 cm; cohort 2: high-grade DCIS, ≤ 1 cm) with each of five strategies: (1) no testing, no RT; (2) no testing, RT only for cohort 2; (3) no RT for low-grade DCIS, test for intermediate- and high-grade DCIS, RT for intermediate- or high-risk scores; (4) test all, RT for intermediate- or high-risk scores; and (5) no testing, RT for all. We used utilities and costs extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women needed to irradiate per IBE prevented. Results No strategy using the DCIS Score was cost effective. The most cost-effective strategy (RT for none or RT for all) was sensitive to small differences between the utilities of receiving or not receiving RT and remaining without recurrence. The numbers needed to irradiate per IBE prevented were 10.5, 9.1, 7.5, and 13.1 for strategies 2 to 5, respectively, relative to strategy 1. Conclusion Strategies using the DCIS Score lowered the proportion of women undergoing RT per IBE prevented. However, no strategy incorporating the DCIS Score was cost effective. The cost effectiveness of RT was exquisitely utility sensitive, highlighting the importance of engaging patient preferences in this decision. Physicians should discuss trade-offs associated with omitting or adding adjuvant RT with each patient to maximize quality-of-life outcomes.