Miniplate Versus Reconstruction Bar Fixation for Oncologic Mandibular Reconstruction with Free Fibula Flaps.

BACKGROUND: Fibula free flaps (FFF) are the gold standard tissue for the reconstruction of segmental mandibular defects. A comparison of miniplate (MP) and reconstruction bar (RB)-based fixation of FFFs has been previously described in a systematic review; however, long-term, single-center studies comparing the two plating methods are lacking. The authors aim to examine the complication profile between MPs and RBs at a single tertiary cancer center. We hypothesized that increased components and a lack of rigid fixation inherent to MPs would lead to higher rates of hardware exposure/failure. METHODS: A retrospective review was performed from a prospectively maintained database at Memorial Sloan Kettering Cancer Center. All patients who underwent FFF-based reconstruction of mandibular defects between 2015 and 2021 were included. Data on patient demographics, medical risk factors, operative indications, and chemoradiation were collected. The primary outcomes of interest were perioperative flap-related complications, long-term union rates, osteoradionecrosis (ORN), return to the operating room (OR), and hardware exposure/failure. Recipient site complications were further stratified into two groups: early (<90 days) and late (>90 days). RESULTS: In total, 96 patients met the inclusion criteria (RB = 63, MP = 33). Patients in both groups were similar with respect to age, presence of comorbidities, smoking history, and operative characteristics. The mean follow-up period was 17.24 months. In total, 60.6 and 54.0% of patients in the MP and RB cohorts received adjuvant radiation, respectively. There were no differences in rates of hardware failure overall; however, in patients with an initial complication after 90 days, MPs had significantly higher rates of hardware exposure (3 vs. 0, p = 0.046). CONCLUSION: MPs were found to have a higher risk of exposed hardware in patients with a late initial recipient site complication. It is possible that improved fixation with highly adaptive RBs designed by computer-aided design/manufacturing technology explains these results. Future studies are needed to assess the effects of rigid mandibular fixation on patient-reported outcome measures in this unique population.

Association of High-Deductible Health Plans and Time to Surgery for Breast and Colon Cancer.

BACKGROUND: High-deductible health plans (HDHPs) have been shown to delay timing of breast and colon cancer screening, although the relationship to the timing of cancer surgery is unknown. The objective of this study was to characterize timing of surgery for breast and colon cancer patients undergoing cancer operations following routine screening. STUDY DESIGN: Data from the IBM MarketScan Commercial Claims Database from 2007 to 2016 were queried to identify patients who underwent screening mammogram and/or colonoscopy. The calendar quarters of screening and surgery were analyzed with ordinal logistic regression. The time from screening to surgery (time to surgery, TTS) was evaluated using a Cox proportional hazard function. RESULTS: Among 32,562,751 patients who had screening mammograms, 0.7% underwent breast cancer surgery within the following year. Among 9,325,238 patients who had screening colonoscopies, 0.9% were followed by colon cancer surgery within a year. The odds of screening (OR 1.146 for mammogram, 1.272 for colonoscopy; p < 0.001) and surgery (OR 1.120 for breast surgery, 1.219 for colon surgery; p < 0.001) increased each quarter for HDHPs compared to low-deductible health plans. Enrollment in an HDHP was not associated with a difference in TTS. Screening in Q3 or Q4 was associated with shorter TTS compared to screening in Q1 (hazard ratio 1.061 and 1.046, respectively; p < 0.001). CONCLUSIONS: HDHPs were associated with delays in screening and surgery. However, HDHPs were not associated with delays in TTS. Interventions to improve cancer care outcomes in the HDHP population should concentrate on reducing barriers to timely screening.

Missing Data in Patient-Reported Outcomes Research: Utilizing Multiple Imputation to Address an Unavoidable Problem.

BACKGROUND: Patient-reported outcomes (PROs) have become a focus in postoperative surgical care. Unfortunately, studies using PROs can be subject to missing data, which may lead to biases or inaccurate conclusions. Multiple imputation (MI) is a statistical method for addressing missing data in clinical research. The aim of this study was to explore MI as a way to address missing data in PRO research. METHODS: A working example of MI using real-world data was performed using the BREAST-Q PRO measure in postmastectomy reconstruction. A retrospective review of immediate tissue expander breast reconstruction patients in 2019 was conducted to compare BREAST-Q physical well-being of the chest scores between prepectoral and subpectoral cohorts at 2 weeks postoperatively. The observed dataset and three hypothetical missingness situations were created to assess how increasing missingness affects MI results. RESULTS: Overall, 916 patients were included in the analysis. When excluding patients with missing information and solely performing analysis on the completed cases, prepectoral patients had significantly higher physical well-being of the chest scores at 2 weeks postoperatively; however, this trend was reversed with increasing missingness scenarios, where subpectoral patients had higher scores. In comparison, all MI results showed that prepectoral patients had higher scores on average compared with subpectoral patients regardless of missingness scenario. CONCLUSIONS: MI demonstrated consistent results with increasing missingness scenarios, whereas performing analysis in higher missingness scenarios without MI led to varying results. This working example emphasizes the need for missing data methodology to be considered in PRO research.

Plastic surgery market share of breast reconstructive procedures: An analysis of two nationwide databases.

BACKGROUND AND OBJECTIVES: Given advances that streamline breast reconstruction (e.g., prepectoral placement, acellular dermal matrix [ADM], oncoplastic surgery), there is concern that nonplastic surgeons are performing a growing proportion of breast reconstructive procedures. The purpose of this study was to evaluate US trends in the market share of breast reconstruction performed by plastic compared to general surgeons. METHODS: IBM® MarketScan® Commercial Claims 2006-2017 and NSQIP 2005-2020 were queried to identify women who underwent mastectomy with alloplastic (tissue expander or implant-based) or free flap reconstruction, or lumpectomy with oncoplastic reconstruction (breast reduction, mastopexy, or local/regional flap). MarketScan included immediate and delayed reconstructions, while all NSQIP reconstructions were immediate. Poisson regression with incident rate ratios (IRRs) modeled trends in surgeon type over time. RESULTS: The cohort included 65 168 encounters from MarketScan and 73 351 from NSQIP. Plastic surgeons performed 95.8% of free flap, 93.8% of alloplastic, and 64.9% of oncoplastic reconstructions. Plastic surgeons performed an increasing proportion of immediate oncoplastic reduction and mastopexy (MarketScan IRR: 1.077, 95% confidence interval [CI]: 1.060-1.094, p < 0.001; NSQIP IRR: 1.041, 95% CI: 1.030-1.052, p < 0.001). There were no clinically significant trends for delayed oncoplastic, alloplastic, or free flap reconstructions. Plastic surgeons were more likely to use ADM compared to general surgeons in NSQIP (p < 0.001). CONCLUSIONS: Plastic surgeons gained market share in immediate oncoplastic breast reduction and mastopexy over the past two decades without any loss in alloplastic or free flap breast reconstruction. Plastic surgeons should continue collaboration with breast surgical oncologists to reinforce the shared surgeon model for management of breast cancer.

Paravertebral Blocks in Tissue Expander Breast Reconstruction: Propensity-Matched Analysis of Opioid Consumption and Patient Outcomes.

BACKGROUND: The paravertebral block (PVB) is an adjunctive perioperative pain control method for patients undergoing breast reconstruction that may improve perioperative pain control and reduce narcotic use. This study determined the efficacy of preoperative PVBs for perioperative pain management in patients undergoing tissue expander breast reconstruction. METHODS: A retrospective review was performed of patients who underwent tissue expander breast reconstruction from December of 2017 to September of 2019. Two patients with PVBs were matched using propensity scoring to one no-block patient. Perioperative analgesic use, pain severity scores on days 2 to 10 after discharge, and BREAST-Q Physical Well-Being scores before surgery and at 2 weeks, 6 weeks, and 3 months after surgery were compared between the two groups. RESULTS: The propensity-matched cohort consisted of 471 patients (314 PVB and 157 no block). The PVB group used significantly fewer morphine milligram equivalents than the no-block group (53.7 versus 69.8; P < 0.001). Average daily postoperative pain severity scores were comparable, with a maximum difference of 0.3 points on a 0-point to 4-point scale. BREAST-Q Physical Well-Being scores were significantly higher for the PVB group than the no-block group at 6 weeks after surgery (60.6 versus 51.0; P = 0.015) but did not differ significantly at 2 weeks or 3 months after surgery. CONCLUSIONS: PVBs may help reduce perioperative opioid requirements but did not reduce pain scores after discharge when used as part of an expander-based reconstruction perioperative pain management protocol. Continued research should examine additional or alternative regional block procedures as well as financial cost and potential long-term impact of PVBs. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Risk of Breast Implant-Associated Anaplastic Large Cell Lymphoma in Patients with Textured Tissue Expanders.

BACKGROUND: The association between textured implants and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is well established, but the risk of BIA-ALCL in patients with transient exposure to a textured tissue expander (TE) is not as well documented. The aim of this study was to assess the incidence and risk of BIA-ALCL in patients with temporary exposure to a textured TE with subsequent smooth implant placement. METHODS: This single-institution retrospective cohort study included all female patients who underwent two-stage breast reconstruction with placement of a textured TE from 1995 to 2016 with subsequent exchange to a smooth permanent implant. Primary outcome of interest was development of BIA-ALCL. Patients with exposure to textured implants were excluded. Follow-up was determined by last documented visit. The authors calculated summary statistics for exposure time and follow-up intervals. RESULTS: Overall, 3310 patients had temporary exposure to a textured TE with exchange to a smooth implant, totaling 5201 textured TEs. Average textured TE exposure time was 6.7 months (median, 5.8 months). Average follow-up was 6.8 years (median, 6.3 years), ranging from 3.7 months to 18 years. No cases of BIA-ALCL were identified. CONCLUSIONS: As no cases of BIA-ALCL were identified, the risk of BIA-ALCL with short exposure to textured TEs is likely lower than the risk from exposure to permanent textured implants. Although longer follow-up is needed, these results can help counsel patients with previous exposure to textured TEs who are concerned about their risk of BIA-ALCL and can contribute to discussions on potential continued utility of textured TEs. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Quality of Life in Breast Reconstruction Patients after Irradiation to Tissue Expander: A Propensity-Matched Preliminary Analysis.

BACKGROUND: Tissue expanders (TEs) are routinely placed as a first step in breast reconstruction for women who require postmastectomy radiation therapy (PMRT). The final reconstruction can then be performed with implants or conversion to autologous tissues. The purpose of this study was to compare patient-reported outcomes and surgical complications in autologous (ABR) versus implant-based breast reconstruction (IBR) patients following TE-PMRT. METHODS: The authors performed a propensity score preliminary analysis (1:1 matching, no replacement) in patients undergoing ABR or IBR following TE-PMRT. Matched covariates included age, race/ethnicity, smoking status, body mass index, history of psychiatric diagnosis, and laterality of reconstruction. Outcomes of interest included complications and BREAST-Q scores for Satisfaction with Breasts, Physical Well-Being of the Chest, Sexual Well-Being, and Psychosocial Well-Being domains. RESULTS: Of 341 patients with TE-PMRT, a total of 106 patients were included in the matched analysis: 53 ABR patients and 53 IBR patients. ABR and IBR did not differ significantly in matched baseline, cancer, and surgical characteristics. ABR patients had higher scores for Satisfaction with Breasts (greater than the four-point minimal clinically important difference) at all postreconstruction time points compared with IBR patients ( P < 0.05). There were no significant postoperative differences in other BREAST-Q domains. The incidence of complications after definitive reconstruction did not differ significantly among cohorts. CONCLUSIONS: In this matched preliminary analysis, patients who underwent ABR following irradiation to a TE demonstrated superior satisfaction with breast scores compared with IBR patients. Higher powered matched studies are needed to improve shared decision-making for patients who require mastectomy and PMRT as part of their treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Breast Surgical Oncology Epidemiologic Research: A Guide and Comparison of Four National Databases.

BACKGROUND: National databases are a rich source of epidemiologic data for breast surgical oncology research. However, these databases differ in the demographic, surgical, and oncologic variables provided. This study aimed to compare the strengths and limitations of four national databases in the context of breast surgical oncology research. METHODS: The study comprised a descriptive analysis of four national databases (the National Surgical Quality Improvement Program [NSQIP], the Nationwide Inpatient Sample [NIS], the Surveillance, Epidemiology and End Results [SEER] program, and the National Cancer Database [NCDB]) to assess their strengths and limitations in the context of breast surgical oncology. The study assessed the data available in each database for female patients with a breast cancer diagnosis between 2007 and 2017, and compared patient age, ethnicity, and race distributions. RESULTS: Data from 3.9 million female patients were examined, with most patients being between 60 and 69 years of age, non-Hispanic, and white. Age, ethnicity, and race distributions were similar in the databases. The NSQIP includes data on operative details, comorbidities, and postoperative outcomes. The NIS provides health services and inpatient utilization information, but does not evaluate outpatient procedures. The SEER program provides population-based oncologic detail including stage, histology, and neoadjuvant/adjuvant treatment. The NCDB offers hospital-based oncologic information and the largest population in the study period, with approximately 2.5 million breast cancer patients. CONCLUSION: Epidemiologic datasets offer tremendous potential for the examination of oncologic breast surgery, with each database providing unique data useful for addressing different epidemiologic questions. Understanding the strengths and limitations of each database creates a more efficient and productive research environment.

The Impact of Lymphedema on Patient-Reported Outcomes After Breast Reconstruction: A Preliminary Propensity Score-Matched Analysis.

BACKGROUND: Studies on the impact of secondary lymphedema on patient-reported satisfaction and quality of life following postmastectomy breast reconstruction are limited by their heterogeneity. We aimed to reduce heterogeneity in study sample populations and compare BREAST-Q Reconstruction Module scores of patients with lymphedema matched to patients without lymphedema. METHODS: We identified patients who underwent postmastectomy breast reconstruction from 2009 to 2017 and performed a propensity score-matched analysis to compare patient-reported outcomes of patients who developed lymphedema with those who did not. Matched covariates included age, body mass index, race/ethnicity, smoking history, radiation or chemotherapy exposure, postoperative infection, and reconstruction modality and laterality. Outcomes of interest were pre- and postoperative BREAST-Q scores for Satisfaction with Breasts, Physical Well-being of the Chest, Sexual Well-Being, and Psychosocial Well-Being; the minimal clinically important difference (MCID) was four points. RESULTS: Matched cohorts included 322 patients per group. Preoperative BREAST-Q scores did not differ between lymphedema and non-lymphedema matched cohorts. Postoperative BREAST-Q scores were significantly lower in lymphedema patients: Physical Well-Being of the Chest (all time points), Satisfaction with Breast (at 1 and 2 years), Sexual Well-Being (at 2 years), and Psychosocial Well-Being (at 2 and 3 years). All significant differences in average scores were greater than the MCID. CONCLUSIONS: Patients with breast cancer-related lymphedema reported significantly lower Physical Well-Being of the Chest, Satisfaction with Breasts, Sexual Well-Being, and Psychosocial Well-Being at various time points. Our findings may prove useful for patient counseling and justify the need for further research on the prevention and treatment of this devastating disease.

Impact of High-Deductible Health Plans on Breast Reconstruction: Considerations for Financial Toxicity.

BACKGROUND: High-deductible health plans (HDHPs) are used within the United States to curb unnecessary health care spending; however, the resulting increased out-of-pocket (OOP) costs may be associated with financial toxicity. The aim was to assess the impact of HDHPs on use and seasonality of mastectomy and breast reconstruction procedures. The hypothesis is that the high OOP costs of HDHPs will lead to decreased overall service use and greater fourth-quarter use after the deductible has been met. METHODS: MarketScan was queried from 2014 to 2017 for episodes of mastectomy, breast reconstruction (immediate and delayed), breast revision, and reduction. Only patients continuously enrolled for the full calendar year after the index operation were included. HDHPs and low-deductible health plans (LDHPs) were compared based on OOP cost sharing. Outcomes included surgery use rates, seasonality of operations, and median/mean OOP costs. RESULTS: Annual mastectomy and breast reconstruction use rates varied little between LDHPs and HDHPs. Mastectomies, delayed breast reconstruction, and elective breast procedures (P < 0.001) all showed significant increases in fourth-quarter use, whereas immediate breast reconstruction did not. Regardless of timing and reconstruction method, HDHPs had significantly greater median OOP costs compared to LDHPs (all P < 0.001). CONCLUSIONS: Mastectomy and breast reconstruction rates did not differ between LDHPs and HDHPs, but seasonality for all breast procedures was measured with the exception of immediate breast reconstruction, suggesting that women are rational economic actors. Regardless of service timing and reconstruction modality, HDHP patients had greater OOP costs compared to LDHP patients, which serves as a good starting point for provider engagement in financial toxicity.

The Impact of Psychiatric Diagnoses on Patient-reported Satisfaction and Quality of Life in Postmastectomy Breast Reconstruction.

OBJECTIVE: The purpose of this study was to determine the prevalence of psychiatric diagnoses among a sample of breast reconstruction patients and measure the association between these diagnoses and reconstruction-related, patient-reported outcomes. BACKGROUND: The impact of psychiatric disorders in conjunction with breast cancer diagnosis, treatment, and reconstruction have the potential to cause significant patient distress but remains not well understood. METHODS: A retrospective review of postmastectomy breast reconstruction patients from 2007 to 2018 at Memorial Sloan Kettering Cancer Center was conducted. Patient demographics, comorbidities, cancer characteristics, psychiatric diagnoses, and BREAST-Q Reconstruction Module scores (measuring satisfaction with breast, well-being of the chest, psychosocial, and sexual well-being) at postoperative years 1 to 3 were examined. Mixed-effects models and cross-sectional linear regressions were conducted to measure the effect of psychiatric diagnostic class type and number on scores. RESULTS: Of 7414 total patients, 50.1% had at least 1 psychiatric diagnosis. Patients with any psychiatric diagnoses before reconstruction had significantly lower BREAST-Q scores for all domains at all time points. Anxiety (50%) and depression (27.6%) disorders were the most prevalent and had the greatest impact on BREAST-Q scores. Patients with a greater number of psychiatric diagnostic classes had significantly worse patient-reported outcomes compared with patients with no psychiatric diagnosis. Psychosocial (ß: -7.29; 95% confidence interval: -8.67, -5.91), and sexual well-being (ß: -7.99; 95% confidence interval: -9.57, -6.40) were most sensitive to the impact of psychiatric diagnoses. CONCLUSIONS: Mental health status is associated with psychosocial and sexual well-being after breast reconstruction surgery as measured with the BREAST-Q. Future research will need to determine what interventions (eg, screening, early referral) can help improve outcomes for breast cancer patients with psychiatric disorders undergoing breast reconstruction.

Outcomes and Perioperative Risk Factors after Oncologic Free-Flap Scalp Reconstruction.

BACKGROUND: Little is known about the risk factors associated with complications after free flap scalp reconstruction. The purpose of this study was to identify patient, scalp defect, and flap characteristics associated with increased risk of surgical complications. METHODS: A retrospective study was performed of free-flap scalp reconstruction in oncologic patients at Memorial Sloan Kettering Cancer Center from 2002 to 2017. Data collection included patient, defect, flap, and complication characteristics. Complications were classified into major, defined as complications requiring surgical intervention, and minor, defined as complications requiring conservative treatment. Risk factors and outcome variables were compared using chi-square with Fisher's exact test. RESULTS: A total of 63 free flaps to the scalp in 58 patients were performed; average follow-up was 3.5 years. Most flaps were muscle-only or musculocutaneous. One-third of patients with free flaps experienced complications (n = 21, 15 major and 6 minor). Examining risk factors for complications, patients with cardiovascular disease were nearly three times more likely to have suffered a major complication than patients without cardiovascular disease (36.7 vs. 12.1%, p = 0.04). This was the only significant risk factor noted. Perioperative radiotherapy, prior scalp surgery, flap type, and recipient vessel selection were found to be nonsignificant risk factors. CONCLUSION: Cardiovascular disease may be a significant marker of risk for major complications in patients undergoing free-flap reconstruction of the scalp. This information should be used to help guide perioperative counseling and decision making in this challenging patient population.

Moving towards patient-reported outcomes in routine clinical practice: implementation lessons from the BREAST-Q.

PURPOSE: Longitudinal, routine utilization of patient-reported outcome measures (PROMs) in clinical care has been challenging. The purpose of this study is to describe a quality improvement initiative to improve patient engagement with the BREAST-Q, a gold-standard PROM for breast reconstruction. METHODS: In 2011, we implemented the BREAST-Q as part of routine care. In 2018, we began a quality improvement initiative to increase BREAST-Q patient participation. The BREAST-Q was administered at every clinic visit via an institutional patient portal or an in-clinic tablet; digital dashboard technologies were used to improve workflow integration, real-time accountability, and immediate data availability at clinic visits. High clinical staff engagement was encouraged by assigning "BREAST-Q Champions." BREAST-Q completion data and patient characteristics were examined to understand non-response to the assessment. RESULTS: Following quality improvement, the average annual BREAST-Q completion rate increased from 42.8% in 2011-2017 to 87.6% in 2019, the last full year of our study period. High completion rates were maintained January-July 2020; however, a significantly larger proportion of BREAST-Qs were completed at home in 2020 versus the same period in 2019 (49.7 vs. 38.8%, p < 0.001), potentially due to the COVID-19 pandemic. Compared with non-responders, responders were younger (49.7 vs. 52.2 years, p < 0.001), more likely to be white (76.9 vs. 73.6%, p < 0.001), and had private insurance (79.4 vs. 69.8%, p < 0.001). CONCLUSION: Our quality improvement initiative successfully increased routine completion of the BREAST-Q. Similar implementation techniques may prove beneficial at other institutions interested in incorporating PROMs into routine care.

Racial/Ethnic Disparities in Exposure, Disease Susceptibility, and Clinical Outcomes during COVID-19 Pandemic in National Cohort of Adults, United States.

We examined racial/ethnic disparities for COVID-19 seroconversion and hospitalization within a prospective cohort (n = 6,740) in the United States enrolled in March 2020 and followed-up through October 2021. Potential SARS-CoV-2 exposure, susceptibility to COVID-19 complications, and access to healthcare varied by race/ethnicity. Hispanic and Black non-Hispanic participants had more exposure risk and difficulty with healthcare access than white participants. Participants with more exposure had greater odds of seroconversion. Participants with more susceptibility and more barriers to healthcare had greater odds of hospitalization. Race/ethnicity positively modified the association between susceptibility and hospitalization. Findings might help to explain the disproportionate burden of SARS-CoV-2 infections and complications among Hispanic/Latino/a and Black non-Hispanic persons. Primary and secondary prevention efforts should address disparities in exposure, vaccination, and treatment for COVID-19.

Nipple-Sparing Mastectomy and Immediate Reconstruction: A Propensity Score-Matched Analysis of Satisfaction and Quality of Life.

BACKGROUND: Although it is intuitive that nipple-sparing mastectomy in selected patients would result in excellent cosmetic outcomes and high patient satisfaction, studies of clinical outcomes and health-related quality of life are limited and show mixed results. This study aimed to use a propensity score-matching analysis to compare satisfaction and health-related quality-of-life outcomes in patients who underwent implant-based reconstruction following bilateral nipple-sparing mastectomy or skin-sparing mastectomy. METHODS: A propensity score-matching analysis (1:1 matching, no replacement) was performed comparing patients undergoing nipple-sparing or skin-sparing mastectomy with immediate bilateral implant-based breast reconstruction. Patients with a history of any radiation therapy were excluded. Matched covariates included age, body mass index, race, smoking history, neoadjuvant chemotherapy, bra size, and history of psychiatric diagnosis. Outcomes of interest included BREAST-Q scores and complications. RESULTS: The authors examined 1371 patients for matching and included 460 patients (nipple-sparing mastectomy, n = 230; skin-sparing mastectomy, n = 230) in the final analyses. The authors found no significant differences in baseline, cancer, and surgical characteristics between matched nipple-sparing and skin-sparing mastectomy patients, who also had similar profiles for surgical complications. Interestingly, the authors found that postoperative Satisfaction with Breasts scores and all other health-related quality-of-life domains were stable over a 3-year period and did not differ significantly between the two groups. CONCLUSIONS: Compared with skin-sparing mastectomy, bilateral nipple-sparing mastectomy did not improve patient-reported or clinical outcomes when combined with immediate implant-based reconstruction. The impact that nipple-sparing mastectomy may have on breast aesthetics and the ability of the BREAST-Q to gauge an aesthetic result following nipple-sparing mastectomy warrant further investigation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Reversing the Genomic, Epigenetic, and Triple-Negative Breast Cancer-Enhancing Effects of Obesity.

The reversibility of the procancer effects of obesity was interrogated in formerly obese C57BL/6 mice that lost weight via a nonrestricted low-fat diet (LFD) or 3 distinct calorie-restricted (CR) regimens (low-fat CR, Mediterranean-style CR, or intermittent CR). These mice, along with continuously obese mice and lean control mice, were orthotopically injected with E0771 cells, a mouse model of triple-negative breast cancer. Tumor weight, systemic cytokines, and incidence of lung metastases were elevated in the continuously obese and nonrestricted LFD mice relative to the 3 CR groups. Gene expression differed between the obese and all CR groups, but not the nonrestricted LFD group, for numerous tumoral genes associated with epithelial-to-mesenchymal transition as well as several genes in the normal mammary tissue associated with hypoxia, reactive oxygen species production, and p53 signaling. A high degree of concordance existed between differentially expressed mammary tissue genes from obese versus all CR mice and a microarray dataset from overweight/obese women randomized to either no intervention or a CR diet. Assessment of differentially methylated regions in mouse mammary tissues revealed that obesity, relative to the 4 weight loss groups, was associated with significant DNA hypermethylation. However, the anticancer effects of the CR interventions were independent of their ability to reverse obesity-associated mammary epigenetic reprogramming. Taken together, these preclinical data showing that the procancer effects of obesity are reversible by various forms of CR diets strongly support translational exploration of restricted dietary patterns for reducing the burden of obesity-associated cancers. PREVENTION RELEVANCE: Obesity is an established risk and progression factor for triple-negative breast cancer (TNBC). Given rising global rates of obesity and TNBC, strategies to reduce the burden of obesity-driven TNBC are urgently needed. We report the genomic, epigenetic, and procancer effects of obesity are reversible by various calorie restriction regimens.

Best Practices for BREAST-Q Research: A Systematic Review of Study Methodology.

BACKGROUND: Data heterogeneity and methodologic errors hinder the ability to draw clinically meaningful conclusions from studies using the BREAST-Q Reconstruction Module patient-reported outcome measure. In this systematic review, the authors evaluate the quality of BREAST-Q Reconstruction Module administration in relation to the BREAST-Q version 2.0 user's guide and the reporting of key methodology characteristics. The authors also describe a framework for improving the quality of BREAST-Q data analysis and reporting. METHODS: The authors conducted a systematic search of PubMed, Embase, Cochrane CENTRAL, and Ovid HAPI databases to identify articles on the BREAST-Q Reconstruction Module to assess postmastectomy breast reconstruction outcomes. The authors registered the protocol before study implementation on Open Science Framework ( https://osf.io/c5236 ) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on mode of BREAST-Q administration, time horizon justification, and sample size calculation were collected. RESULTS: The authors included 185 studies in the analysis. Errors in BREAST-Q administration were identified in 36 studies (19.5 percent). Appropriate administration of the BREAST-Q could not be determined in 63 studies (34.1 percent) because of insufficient reporting. Time horizon for the primary outcome was reported in 71 studies (38.4 percent), with only 17 (9.2 percent) reporting a sample size calculation. CONCLUSIONS: The authors identified important yet actionable shortcomings in the BREAST-Q literature. Researchers are encouraged to review the BREAST-Q user's guide in the study design phase to mitigate errors in patient-reported outcome measure administration and reporting for future trials using the BREAST-Q Reconstruction Module. Adhering to these guidelines will allow for greater clinical utility and generalizability of BREAST-Q research.

Association of Radiation Timing with Long-Term Satisfaction and Health-Related Quality of Life in Prosthetic Breast Reconstruction.

BACKGROUND: Radiation therapy is increasingly used after breast cancer surgery, which may impact patients' postoperative quality of life. This study assessed differences in long-term patient satisfaction and health-related quality of life after radiation therapy administered at different stages of implant-based breast reconstruction or with no radiation after surgery. METHODS: In this observational study, long-term outcomes were evaluated for four cohorts of women who completed breast reconstruction and received (1) no radiation, (2) radiation before tissue expander placement, (3) radiation after tissue expander placement, or (4) radiation after permanent implant between 2010 and 2017 at Memorial Sloan Kettering. Satisfaction and health-related quality of life were assessed using the prospectively collected Satisfaction with Breasts and Physical Well-Being of Chest BREAST-Q subscales. Score distributions were examined by radiation exposure status for 3 years after surgery using nonparametric analyses and regression models. RESULTS: Of 2932 patients who met the inclusion criteria, 25.8 percent received radiation during breast cancer treatment, including before tissue expander placement ( n = 239; 8.2 percent), after tissue expander placement ( n = 290; 9.9 percent), and after implant placement ( n = 228; 7.8 percent). Radiotherapy patients had average scores 7 to 9 points lower at all postoperative time points for Satisfaction with Breasts and Physical Well-Being of Chest subscales ( p < 0.001). Although patient-reported outcomes did not differ by radiation timing, there were higher rates of severe capsular contracture with postimplant radiotherapy ( p < 0.001). CONCLUSIONS: Radiation therapy significantly affected patient satisfaction and health-related quality of life following implant breast reconstruction through 3 years postoperatively. Patient perception of outcome was unaffected by radiotherapy timing; however, capsular contracture was higher after postimplant radiotherapy, suggesting there may be an advantage to performing radiotherapy before placement of the final reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.