Prediction of breast cancer-related lymphedema by dermal backflow detected with near-infrared fluorescence lymphatic imaging.

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4-8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. RESULTS: By 18 months after RT, 30 of 42 study subjects (71%) developed mild-moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by "dermal backflow" of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. CONCLUSION: BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.

Lymphedema in Inflammatory Breast Cancer Patients Following Trimodal Treatment.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating sequela of breast cancer treatment and is becoming a greater concern in light of improved long-term survival. Inflammatory breast cancer (IBC) is a rare and aggressive malignancy for which systemic therapy, surgery, and radiotherapy remain the standard of care, thereby making IBC patients highly susceptible to developing BCRL. This study evaluated BCRL in IBC following trimodal therapy. METHODS: IBC patients treated from 2016 to 2019 were identified from an institutional database. Patients were excluded if they presented with recurrent disease, underwent bilateral axillary surgery, did not complete trimodal therapy, or were lost to follow-up. Demographic, clinicopathologic factors, oncologic outcomes, and perometer measurements were recorded. BCRL was defined by clinician diagnosis and/or objective perometer measurements when available. Time to development of BCRL and treatment received were captured. RESULTS: Eighty-three patients were included. Median follow-up was 33 months. The incidence of BCRL was 50.6% (n = 42). Mean time to BCRL from surgery was 13 (range 2-24) months. Demographic and clinicopathologic features were similar between patients with and without BCRL with exception of higher proportion receiving delayed reconstruction in the BCRL group (38.1% vs. 14.6%, p = 0.03). Forty patients (95.2%) underwent BCRL treatment, which included physical therapy (n = 39), compression (n = 38), therapeutic lymphovenous bypass (n = 13), and/or vascularized lymph node transfer (n = 12). CONCLUSIONS: IBC patients are at high-risk for BCRL after treatment, impacting 51% of patients in this cohort. Strategies to reduce or prevent BCRL and improve real-time diagnosis should be implemented to better direct early management in this patient population.

Recent progress in the treatment and prevention of cancer-related lymphedema.

This article provides an overview of the recent developments in the diagnosis, treatment, and prevention of cancer-related lymphedema. Lymphedema incidence by tumor site is evaluated. Measurement techniques and trends in patient education and treatment are also summarized to include current trends in therapeutic and surgical treatment options as well as longer-term management. Finally, an overview of the policies related to insurance coverage and reimbursement will give the clinician an overview of important trends in the diagnosis, treatment, and management of cancer-related lymphedema.

Association of statin use with clinical outcomes in patients with triple-negative breast cancer.

BACKGROUND: Previous studies have examined the association of statin therapy and breast cancer outcomes with mixed results. The objective of this study was to investigate the clinical effects of incident statin use among individuals with triple-negative breast cancer (TNBC). METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare and Texas Cancer Registry-Medicare databases were used, and women aged ≥66 years who had stage I, II, and III breast cancer were identified. Multivariable Cox proportional hazards regression models were used to examine the association of new statin use in the 12 months after a breast cancer diagnosis with overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: When examining incident statin use, defined as the initiation of statin therapy in the 12 months after breast cancer diagnosis, a significant association was observed between statin use and improved BCSS (standardized hazard ratio, 0.42; 95% confidence interval [CI], 0.20-0.88; P = .022) and OS (hazard ratio, 0.70; 95% CI, 0.50-0.99; P = .046) among patients with TNBC (n = 1534). No association was observed with BCSS (standardized hazard ratio, 0.99; 95% CI, 0.71-1.39; P = .97) or OS (hazard ratio, 1.04; 95% CI, 0.92-1.17; P = .55) among those without TNBC (n = 15,979). The results were consistent when examining statin exposure as a time-varying variable. CONCLUSIONS: Among women with I, II, and III TNBC, initiation of statin therapy in the 12 months after breast cancer diagnosis was associated with an OS and BCSS benefit. Statins may have a role in select patients with breast cancer, and further investigation is warranted.

Impact of adjuvant endocrine therapy in older patients with comorbidities and estrogen receptor-positive, node-negative breast cancer-A National Cancer Database analysis.

BACKGROUND: Data are lacking about the benefit of adjuvant endocrine therapy (ET) in older patients with multiple comorbidities. The authors sought to determine the effect of ET on the survival of older patients who had multiple comorbidities and estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, pathologic node-negative (pN0) breast cancer. METHODS: Women aged ≥70 years in the National Cancer Database (2010-2014) with Charlson/Deyo comorbidity scores of 2 or 3 who had pathologic tumor (pT1)-pT3/pN0, ER-positive/HER2-negative breast cancer were divided into 2 cohorts: adjuvant ET and no ET. Propensity scores were used to match patients based on age, comorbidity score, facility type, pT classification, chemotherapy, surgery, and radiation therapy. A Cox proportional hazards model was used to estimate the effect of ET on overall survival (OS). RESULTS: In the nonmatched cohort (n = 3716), 72.8% of patients received ET (n = 2705), and 27.2% did not (n = 1011). The patients who received ET were younger (mean age, 76 vs 79 years; P < .001) and had higher rates of breast conservation compared with those who did not receive ET (lumpectomy plus radiation: 43.4% vs 23.8%, respectively; P < .001). In the matched cohort (n = 1972), the median OS was higher in the ET group (79.2 vs 67.7 months; P < .0001). In the adjusted analysis, ET was associated with improved survival (hazard ratio, 0.70; 95% CI, 0.59-0.83). CONCLUSIONS: In older patients who have pN0, ER-positive/HER2-negative breast cancer with comorbidities, adjuvant ET was associated with improved OS, which may have been overestimated given the confounders inherent in observational studies. To optimize outcomes in these patients, current standard recommendations should be considered stage-for-stage based on life expectancy and the level of tolerance to treatment.

A Randomized Phase II Study of Sequential Eribulin Versus Paclitaxel Followed by FAC/FEC as Neoadjuvant Therapy in Patients with Operable HER2-Negative Breast Cancer.

LESSONS LEARNED: The combination of eribulin with 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) was not superior to the combination of paclitaxel with FAC/FEC and was associated with greater hematologic toxicity. Eribulin followed by an anthracycline-based regimen is not recommended as a standard neoadjuvant therapy in nonmetastatic operable breast cancer. BACKGROUND: Neoadjuvant systemic therapy is the standard of care for locally advanced operable breast cancer. We hypothesized eribulin may improve the pathological complete response (pCR) rate compared with paclitaxel. METHODS: We conducted a 1:1 randomized open-label phase II study comparing eribulin versus paclitaxel followed by 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) in patients with operable HER2-negative breast cancer. pCR and toxicity of paclitaxel 80 mg/m2 weekly for 12 doses or eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle for 4 cycles followed by FAC/FEC were compared. RESULTS: At the interim futility analysis, in March 2015, 51 patients (28 paclitaxel, 23 eribulin) had received at least one dose of the study drug and were thus evaluable for toxicity; of these, 47 (26 paclitaxel, 21 eribulin) had undergone surgery and were thus evaluable for efficacy. Seven of 26 (27%) in the paclitaxel group and 1 of 21 (5%) in the eribulin group achieved a pCR, and this result crossed a futility stopping boundary. In the paclitaxel group, the most common serious adverse events (SAEs) were neutropenic fever (grade 3, 3 patients, 11%). In the eribulin group, nine patients (39%) had neutropenia-related SAEs, and one died of neutropenic sepsis. The study was thus discontinued. For the paclitaxel and eribulin groups, the 5-year event-free survival (EFS) rates were 81.8% and 74.0% (hazard ratio [HR], 1.549; 95% confidence interval [CI], 0.817-2.938; p = .3767), and the 5-year overall survival (OS) rates were 100% and 84.4% (HR, 5.813; 95% CI, 0.647-52.208; p = .0752), respectively. CONCLUSION: We did not observe a higher proportion of patients undergoing breast conservation surgery in the eribulin group than in the paclitaxel group. The patients treated with eribulin were more likely to undergo mastectomy and less likely to undergo breast conservation surgery, but the difference was not statistically significant. As neoadjuvant therapy for operable HER2-negative breast cancer, eribulin followed by FAC/FEC is not superior to paclitaxel followed by FAC/FEC and is associated with a higher incidence of neutropenia-related serious adverse events.

Outcomes with Partial Breast Irradiation vs. Whole Breast Irradiation: a Meta-Analysis.

BACKGROUND: Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques. METHODS: A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI. RESULTS: A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68-3.2%) and WBI (1.7%, 95% HPD 0.92-2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI. CONCLUSIONS: IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques.

Anatomy and physiology of the sentinel lymph nodes of the upper extremity: Implications for axillary reverse mapping in breast cancer.

BACKGROUND: This study characterizes the physiological drainage of the normal upper extremity using single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (ARM). METHODS: A consecutive series of patients assessed with SPECT/CT lymphoscintigraphy ARM of the upper extremity were included. Anatomical localization of the axillary sentinel lymph nodes (SLN) was completed in normal axillae in relation to consistent anatomic landmarks. Retrospective case note analysis was performed to collect patient demographic data. RESULTS: A total of 169 patients underwent SPECT/CT lymphoscintigraphy, and imaging of 182 normal axillae was obtained. All patients (100%) had an axillary SLN identified: 19% had a single contrast-enhanced SLN in the axilla and the remainder had multiple. The SLN(s) of the upper extremity was located in the upper outer quadrant (UOQ) of the axilla in 97% of cases (177 axillae). When the SLN(s) was found in the UOQ of the axilla, second-tier lymph nodes were found predominantly in the upper inner quadrant (50% of cases). CONCLUSIONS: The upper extremity SLN(s) is located in a constant region of the axilla. This study provides the most complete investigation to date and results can be directly applied clinically to ARM techniques and adjuvant radiation planning.

Exclusion of Men from Randomized Phase III Breast Cancer Clinical Trials.

Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using ClinicalTrials.gov, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p < .001). Twenty-seven trials included male patients (20.6%). Lower rates of male inclusion were seen in trials that randomized or mandated hormone therapy as part of the trial protocol compared with trials that did not randomize or mandate endocrine therapy (2.5% vs. 28.6% male inclusion; p < .001). It is imperative for breast cancer clinical trials to include men when allowable in order to improve generalizability and treatment decisions in male patients with breast cancer.

Effect of Surgeon Factors on Long-Term Patient-Reported Outcomes After Breast-Conserving Therapy in Older Breast Cancer Survivors.

BACKGROUND: The effect of surgeon factors on patient-reported quality-of-life outcomes after breast-conserving therapy (BCT) is unknown and may help patients make informed care decisions. METHODS: We performed a survey study of women aged ≥ 67 years with non-metastatic breast cancer diagnosed in 2009 and treated with guideline-concordant BCT, to determine the association of surgeon factors with patient-reported outcomes. The treating surgeon was identified using Medicare claims, and surgeon factors were identified via the American Medical Association Physician Masterfile. The primary outcome was patient-reported cosmetic satisfaction measured by the Cancer Surveillance and Outcomes Research Team (CanSORT) Satisfaction with Breast Cosmetic Outcome instrument, while secondary outcomes included BREAST-Q subdomains. All patient, treatment, and surgeon covariables were included in a saturated multivariable linear regression model with backward elimination applied until remaining variables were p < 0.1. RESULTS: Of 1650 women randomly selected to receive the questionnaire, 489 responded, of whom 289 underwent BCT. Median age at diagnosis was 72 years and the time from diagnosis to survey was 6 years. The mean adjusted CanSORT score was higher for patients treated by surgical oncologists than patients treated by non-surgical oncologists (4.01 [95% confidence interval [CI] 3.65-4.38] vs. 3.53 [95% CI 3.28-3.77], p = 0.006). Similarly, mean adjusted BREAST-Q Physical Well-Being (91.97 [95% CI 86.13-97.80] vs. 83.04 [95% CI 80.85-85.22], p = 0.006) and Adverse Radiation Effects (95.28 [95% CI 91.25-99.31] vs. 88.90 [95% CI 86.23-91.57], p = 0.004) scores were better among patients treated by surgical oncologists. CONCLUSIONS: Specialized surgical oncology training is associated with improved long-term patient-reported outcomes. These findings underscore the value of specialized training and may be useful to patients choosing their care team.

Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes.

PURPOSE: The optimal management of breast cancer patients with a positive sentinel lymph node (SLN) who undergo mastectomy remains controversial. This study aimed to describe treatment patterns of patients with positive SLNs who undergo mastectomy using a large population-based database. METHODS: The NCDB was queried for cT1-2N0 breast cancer patients treated with mastectomy between 2006 and 2014 who had 1-2 positive SLNs. Patients receiving neoadjuvant chemotherapy were excluded. Axillary management included SLN dissection (SLND) alone, axillary lymph node dissection (ALND), post-mastectomy radiation (PMRT) alone, and ALND + PMRT. Trends of axillary management and patient characteristics were examined. RESULTS: Among 12,190 patients who met study criteria, the use of ALND dropped with a corresponding increase in other approaches. In 2006, 34% of patients had SLND alone, 47% ALND, 8% PMRT and 11% ALND + PMRT. By 2014, 37% had SLND, 23% ALND, 27% PMRT and 13% ALND + PMRT. Patients who underwent SLND alone were older (mean 60.6 years) with more comorbidities (Charlson-Deyo score > 2), smaller primary tumors (mean 2.1 cm), well-differentiated histology, hormone receptor-positive, HER2-negative tumors, without lymphovascular invasion (all P values < 0.01). Treatment with SLND alone was more likely if patients had only one positive SLN (P < 0.001) or micrometastatic disease (P < 0.001), and were treated at community centers compared with academic centers (P < 0.001). CONCLUSIONS: The management of breast cancer patients undergoing mastectomy with positive SLNs has evolved over time with decreased use of ALND and increased use of radiation. Some patient subsets are underrepresented in recent clinical trials, and therefore, future trials should focus on these patients.

Trends in Regional Nodal Management of Breast Cancer Patients with Low Nodal Burden.

BACKGROUND: American College of Surgeons Oncology Group Z0011 confirms the safety of omitting axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) in breast cancer patients with one to two positive sentinel lymph nodes (SLNs), without compromising disease-free survival (DFS) and overall survival (OS). In contrast, the NCIC MA20 trial showed improved DFS in node-positive patients undergoing ALND and RNI. We sought to examine how these data have influenced the management of patients with limited nodal burden. METHODS: Using the National Cancer Database, patients diagnosed between 2010 and 2015 and who met the criteria for Z0011 were identified. Logistic regression was used to analyze factors associated with practice patterns. The Cox proportional hazards model was used to assess the association of ALND and RNI with OS. RESULTS: Omission of ALND in Z0011-eligible patients reached 89.2% in 2015. This Z0011-compliant group was more likely to undergo RNI compared with the non-compliant group (36.4% vs. 31.3%; p < 0.05), with RNI increasing to 43.8% by 2015. Factors associated with the use of RNI included later year of diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.6-2.1], hormone receptor-negative tumor (OR 1.2, 95% CI 1.1-1.4), grade 3 tumor (OR 1.2, 95% CI 1.1-1.3), treatment at a non-academic site (OR 1.2, 95% CI 1.1-1.3) and two versus one positive SLN (OR 2.0, 95% CI 1.8-2.2). With 43 months median follow-up, RNI was not associated with improved OS. CONCLUSION: Since the publication of Z0011, the omission of ALND has become widespread; however nearly half of these women now receive RNI. The optimal radiation therapy approach for this low nodal burden population warrants further study.

Reconstruction in the Metastatic Breast Cancer Patient: Results from the National Cancer Database.

PURPOSE: Modern treatments are prolonging life for metastatic breast cancer patients. Reconstruction in these patients is controversial. The purpose of this study was to characterize de novo metastatic breast cancer patients who undergo mastectomy and reconstruction and to report complication and survival rates. METHODS: We queried the National Cancer Database for de novo metastatic breast cancer patients, who underwent systemic therapy and mastectomy with reconstruction (R) or without reconstruction (NR) between 2004 and 2013. Patient-tumor characteristics, mortality, and readmissions were compared. Propensity score matched analysis was performed, and survival was calculated using the Kaplan-Meier method. RESULTS: A total of 8554 patients fulfilled study criteria (n = 980/11.5% R vs. n = 7574/88.5% NR). There was a significant increase in reconstruction rates by year: 5.2% in 2004, 14.3% in 2013 (p < 0.0001). Compared with the NR patients, R patients were younger (mean age 49 vs. 58 years, p < 0.0001), more hormone receptor-positive (76.1% vs. 70.5%, p = 0.0004), had lower grade disease (p = 0.0082), and fewer sites of metastases (85.7% had 1 metastasis; 14.3% had ≥ 2 R vs. 79% had 1; 21% had ≥ 2 NR, p = 0.0002). R patients received more hormonal and chemotherapy than NR but equally received radiation. Median overall survival of the total cohort was 45 months, and median overall survivals of R and NR groups by matched analysis were 56.7 and 55.3 months respectively (p = 0.86). Thirty-day mortality (0.2%-R, 0.3%-NR, p = 0.56) and readmissions (5.9%-R, 5.8%-NR, p = 0.81) were similar; 90-day mortality also was similar (1.1%-R vs. 1.6%-NR, p = 0.796). CONCLUSIONS: There is an increasing trend to reconstruct metastatic breast cancer patients with low complication rates, without survival compromise. Impact on quality of life warrants further assessment.

Using the National Cancer Data Base for quality evaluation to assess adherence to treatment guidelines for nonmetastatic inflammatory breast cancer.

BACKGROUND: Guidelines for the treatment of nonmetastatic inflammatory breast cancer (IBC) using trimodality therapy (TT) (chemotherapy, surgery, and radiotherapy) have remained largely unchanged since 2000. However, many patients with nonmetastatic IBC do not receive TT. It is unknown how patient-level (PL) and facility-level (FL) factors contribute to TT use. METHODS: Using the National Cancer Data Base, patients with nonmetastatic IBC who underwent locoregional treatment from 2003 through 2011 were identified. The authors correlated PL factors, including demographic and tumor characteristics, with TT use. An observed-to-expected ratio for the number of patients treated with TT was calculated for each hospital by adjusting for significant PL factors. Hierarchical mixed effects models were used to assess the percentage of variation in TT use attributable to PL and FL factors, respectively. RESULTS: Of the 542 hospitals examined, 55 (10.1%) and 24 (4.4%), respectively, were identified as significantly low and high outliers for TT use (P<.05). The percentage of the total variance in the use of TT attributable to the facility (11%) was nearly triple the variance attributable to the measured PL factors (3.4%). The nomogram generated from multivariate logistic regression of PL factors only allows a facility to assess TT use given their PL data. CONCLUSIONS: FL factors rather than PL factors appear to contribute disproportionately to the underuse of TT in patients with nonmetastatic IBC. To improve treatment guideline adherence for patients with nonmetastatic IBC, it is critical to identify the specific FL factors associated with TT underuse. More organized FL intervention is required to train physicians and to build multidisciplinary teams. Cancer 2017;123:2618-25. © 2017 American Cancer Society.

Radiation therapy targets and the risk of breast cancer-related lymphedema: a systematic review and network meta-analysis.

PURPOSE: New indications have been found for regional nodal irradiation (RNI) in breast cancer treatment, yet the relationship of RNI and lymphedema risk is uncertain. We sought to determine the association of RNI and lymphedema. METHODS: We searched MEDLINE, EMBASE, and Scopus for articles in English on humans published from 1995 to 2015, using search terms breast neoplasm, treatment, and morbidity. Two investigators independently selected articles and extracted information, including manuscripts reporting incidence of lymphedema by radiation targets. Meta-analyses, review papers, case-control studies, matched-pair studies, repetitive datasets, and retrospective studies were excluded. A total of 2399 abstracts were identified and 323 corresponding articles reviewed. Twenty-one studies met inclusion criteria. Data were pooled using a random effects mixed model. Network meta-analyses were performed to determine the association of radiation targets alone and radiation targets plus extent of axillary surgery on incidence of lymphedema. RESULTS: The addition of RNI to breast/CW irradiation was associated with an increased incidence of lymphedema (OR 2.85; 95% CI 1.24-6.55). In patients treated with sentinel lymph node biopsy or axillary sampling, there was no association of lymphedema with the addition of RNI to breast/CW irradiation (OR 1.58; 95% CI 0.54-4.66; pooled incidence 5.7 and 4.1%, respectively). Among patients treated with axillary lymph node dissection (ALND), treatment with RNI in addition to breast/CW radiation was associated with a significantly higher risk of lymphedema (OR 2.74; 95% CI 1.38-5.44; pooled incidence 18.2 and 9.4%, respectively). CONCLUSIONS: RNI is associated with a significantly higher risk of lymphedema than irradiation of the breast/CW, particularly after ALND.

A 10-Year Experience with Mastectomy and Tissue Expander Placement to Facilitate Subsequent Radiation and Reconstruction.

BACKGROUND: An integrated approach to skin sparing mastectomy with tissue expander placement followed by radiotherapy and delayed reconstruction was initiated in our institution in 2002. The purpose of this study was to assess the surgical outcomes of this strategy. METHODS: Between September 2002 and August 2013, a total of 384 reconstructions had a tissue expander placed at the time of mastectomy and subsequently underwent radiotherapy. Rates and causes of tissue expander explantation before, during, and after radiotherapy, as well as tumor specific outcomes and reconstruction approaches, were collected. RESULTS: Median follow-up after diagnosis was 5.6 (range 1.3-13.4) years. In the study cohort, 364 patients (94.8%) had stage II-III breast cancer, and 7 patients (1.8%) had locally recurrent disease. The 5-year rates of actuarial locoregional control, disease-free survival, and overall survival were 99.2, 86.1, and 92.4%, respectively. The intended delayed-immediate reconstruction was subsequently completed in 325 of 384 mastectomies (84.6% of the study cohort). Of the remaining 59 tissue expanders, 1 was explanted before radiotherapy, 1 during radiotherapy, and 7 patients (1.8%) were lost to follow-up. Fifty patients (13.0%) required tissue expander explantation after radiation and before their planned final reconstruction, primarily due to cellulitis. Nonetheless, the cumulative rate of completed reconstructions was 89.6%. The median time from placement of the tissue expander until reconstruction was 12 (interquartile range 9-15) months. CONCLUSIONS: Tissue expander placement at skin-sparing mastectomy in patients who require radiotherapy appears to be a viable strategy for combining reconstruction and radiotherapy.

DCIS and axillary nodal evaluation: compliance with national guidelines.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) provide guidelines regarding axillary nodal evaluation in ductal carcinoma in situ (DCIS), but data regarding national compliance with these guidelines remains incomplete. METHODS: We conducted a retrospective review of the National Cancer Data Base (NCDB) analyzing all surgical approaches to axillary evaluation in patients with DCIS. Logistic regression analysis was used to assess the multivariate relationship between patient demographics, clinical characteristics, and probability of axillary evaluation. RESULTS: We identified 88,083 patients diagnosed with DCIS between 1998 and 2011; 31,912 (37%) underwent total mastectomy (TM) and 55,349 (63%) had breast conserving therapy (BCT). Axillary evaluation increased from 44.4% in 1998 to 63.3% in 2011. In TM patients, axillary evaluation increased from 74.3% in 1998 to 93.4% in 2011. This correlated with an increase in sentinel lymph node biopsy (SLNB) from 24.3 to 77.1%, while ALND decreased from 50.0 to 16.3% (p <0.01). In BCT patients, evaluation increased from 20.1 to 43.9%; SLNB increased from 7.2 to 39.4% and ALND decreased from 12.9 to 4.5%. Factors associated with axillary nodal evaluation in BCT patients included practice type and facility location. Among TM patients, use of axillary lymph node dissection (ALND) for axillary staging was associated with earlier year of diagnosis, black race, and older age, as well as community practice setting and practice location in the Southern US. CONCLUSIONS: Compliance with national guidelines regarding axillary evaluation in DCIS remains varied. Practice type and location-based differences suggest opportunities for education regarding the appropriate use of axillary nodal evaluation in patients with DCIS.

Longitudinal analysis of patient-reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole-breast irradiation.

BACKGROUND: The authors compared longitudinal patient-reported outcomes and physician-rated cosmesis with conventionally fractionated whole-breast irradiation (CF-WBI) versus hypofractionated whole-breast irradiation (HF-WBI) within the context of a randomized trial. METHODS: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes. RESULTS: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time). CONCLUSIONS: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society.

Locoregional Control According to Breast Cancer Subtype and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Undergoing Breast-conserving Therapy.

BACKGROUND: Our group previously published data showing that patients could be stratified by constructed molecular subtype with respect to locoregional recurrence (LRR)-free survival after neoadjuvant chemotherapy and breast-conserving therapy (BCT). That study predated use of trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive patients. The current study was undertaken to determine the impact of subtype and response to therapy in a contemporary cohort. METHODS: Clinicopathologic data from 751 breast cancer patients who received neoadjuvant chemotherapy (with trastuzumab if HER2(+)) and BCT from 2005 to 2012 were identified. Hormone receptor (HR) and HER2 status were used to construct molecular subtypes: HR(+)/HER2(-) (n = 369), HR(+)/HER2(+) (n = 105), HR(-)/HER2(+) (n = 58), and HR(-)/HER2(-) (n = 219). Actuarial rates of LRR were determined by the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed to determine factors associated with LRR. RESULTS: The pathologic complete response (pCR) rates by subtype were as follows: 16.5% (HR(+)/HER2(-)), 45.7% (HR(+)/HER2(+)), 72.4% (HR(-)/HER2(+)), and 42.0% (HR(-)/HER2(-)) (P < 0.001). Median follow-up was 4.6 years. The 5-year LRR-free survival rate for all patients was 95.4%. Five-year LRR-free survival rates by subtype were 97.2 % (HR(+)/HER2(-)), 96.1% (HR(+)/HER2(+)), 94.4% (HR(-)/HER2(+)), and 93.4% (HR(-)/HER2(-)) (P = 0.44). For patients with HR(-)/HER2(+) disease, the LRR-free survival rates were 97.4 and 86.7% for those who did and those who did not experience pCR, respectively. For patients with HR(-)/HER2(-) disease, the LRR-free survival rates were 98.6% (pCR) versus 89.9% (no pCR). On multivariate analysis, the HR(-)/HER2(-) subtype, clinical stage III disease, and failure to experience a pCR were associated with LRR. CONCLUSIONS: Patients undergoing BCT after neoadjuvant chemotherapy have excellent rates of 5-year LRR-free survival that are affected by molecular subtype and by response to neoadjuvant chemotherapy.