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Triple-negative breast cancer (TNBC) highly infiltrated with CD8+ tumor-infiltrating lymphocytes (TIL) has been associated with improved prognosis. This observation led us to hypothesize that CD8+ TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8+ TILs in solid cancers other than in melanoma. To overcome this obstacle, we used an agonistic antibody (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8+ T cells. This approach was first utilized in melanoma and, in this study, led to advantageous growth of TILs for the majority of TNBC tumors tested. The agonistic antibody was only added in the initial setting of the culture and yet favored the propagation of CD8+ TILs from TNBC tumors. These expanded CD8+ TILs were capable of cytotoxic functions and were successfully utilized to demonstrate the presence of immunogenic mutations in autologous TNBC tumor tissue without recognition of the wild-type counterpart. Our findings open the way for a successful adoptive immunotherapy for TNBC. Cancer Immunol Res; 5(6); 439–45. ©2017 AACR.

Background In 2017, the American Society of Breast Surgeons (ASBrS) published expert panel recommendations for patients at risk for breast cancer-related lymphedema (BCRL) and those affected by BCRL. This study sought to determine BCRL practice patterns. Methods A survey was sent to 2975 ASBrS members. Questions evaluated members' clinical practice type, practice duration, and familiarity with BCRL recommendations. Descriptive statistics, the chi-square test, and Fisher's exact test were used. Results Of the ASBrS members surveyed, 390 (13.1%) responded. Most of the breast surgeons (58.5%, 228/390) indicated unfamiliarity with recommendations. Nearly all respondents (98.7%, 385/390) educate at-risk patients. Most (60.2%, 234/389) instruct patients to avoid venipuncture, injection or blood pressure measurements in the at-risk arm, and 35.6% (138/388) recommend prophylactic compression sleeve use during air travel. Nearly all (97.7%, 380/389) encourage those at-risk to exercise, including resistance exercise (86.2%, 331/384). Most do not perform axillary reverse mapping (ARM) (67.9%, 264/389) or a lymphatic preventive healing approach (LYMPHA) (84.9%, 331/390). Most (76.1%, 296/389) screen at-risk patients for BCRL. The most frequently used screening tools include self-reported symptoms (81%, 255/315), circumferential tape measure (54%, 170/315) and bioimpedance spectroscopy (27.3%, 86/315). After a BCRL diagnosis, most (90%, 351/390) refer management to a lymphedema-certified physical therapist. For affected patients, nearly all encourage exercise (98.7%, 384/389). Many (49%, 191/390) refer affected patients for consideration of lymphovenous bypass or lymph node transfer. Conclusion Most respondents were unfamiliar with the ASBrS expert panel recommendations for patients at risk for BCRL and those affected by BCRL. Opportunities exist to increase awareness of best practices and to acquire ARM and LYMPHA technical expertise.

Background Inflammatory breast cancer (IBC) is a rare breast malignancy with poor outcomes compared with non-IBC. Age-related differences in tumor biology, treatment, and clinical outcomes have been described in non-IBC. This study evaluated age-related differences in IBC. Methods From an institutional prospective database, patients with an IBC diagnosed from 2010 to 2019 were identified. Age was categorized as 40 years or younger, 41 to 64 years, and 65 years or older. Demographics, clinicopathologic features, and treatment received were compared. Recurrence and survival outcomes were analyzed using the log-rank test and the Cox proportional hazards model. Results Of 523 IBC patients, 113 (21.6%) were age 40 years or younger, and 72 (13.8%) were age 65 years or older. The groups did not differ statistically by race/ethnicity, N stage, clinical stage, or tumor subtype. The younger patients included a higher proportion of Hispanic and Asian patients, triple-negative breast cancer (TNBC), and clinical N2/N3. Trimodality therapy was received by 92% of the stage 3 patients, with no difference in pathologic complete response (pCR) by age (23.3% vs 28.6%; p = 0.46). During a median follow-up period of 40 months, 17% of the patients experienced locoregional recurrence and 42.8% had distant metastasis. No difference in 3-year recurrence-free survival (57.9% vs 42.6% vs 54%; p = 0.42, log rank) or overall survival (OS) (75.6% vs 77.1% vs 64.4%; p = 0.31, log rank) by age was observed, and no difference in OS by age in de novo stage 4 disease was observed. In the multivariate analysis, worse OS was associated with TNBC (hazard ratio [HR], 1.99, 95% confidence interval [CI], 1.31-3.05) and no pCR (HR, 4.45; 95% CI, 2.16-9.18). Conclusion No significant differences were observed in demographics, treatment patterns, or clinical outcomes for IBC patients age 40 years or younger compared with those age 65 years or older treated by a specialized multidisciplinary team. These findings do not support age-related treatment de-escalation in IBC.

Nearly one-third of patients with inflammatory breast cancer (IBC) present with de novo stage IV disease. There are limited data on frequency and clinical outcomes of contralateral axillary metastasis (CAM) in IBC with no consensus diagnostic and treatment guidelines. Frequency of synchronous CAM was calculated in unilateral IBC patients at a single center (10/2004–6/2019). Clinicopathologic variables, diagnostic evaluation, treatment received, and overall survival (OS) were assessed and compared. Of 588 unilateral IBC patients, 49 (8.3%) had synchronous CAM. Of these, 32 (65.3%) also presented with metastatic disease at another distant site. CAM was not associated with age, tumor laterality, breast cancer subtype, grade, or cN stage (p > 0.05). The sensitivity/specificity to detect CAM was as follows: mammography (18.2%/99.2%), ultrasound (92.3%/95.5%), PET (90.1/99.1%), and MRI (76.0%/98.6%). Following systemic therapy, 22 patients had contralateral axillary surgery, and 18 received adjuvant contralateral nodal radiation. On multivariable analysis including tumor receptor subtypes, patients with stage IV-isolated CAM has statistically similar survival to stage III patients (HR 1.37, 95% CI 0.70–2.69, p = 0.36). Patients with Stage IV non-CAM (HR 2.18, 95% CI 1.66–2.85, p < 0.001) and stage IV-CAM plus other distant metastasis (HR 2.57, 95% CI 1.59–4.16, p < 0.001) had higher risk of death (reference: stage III disease). CAM in IBC was diagnosed in 8.3% of patients at presentation and was best identified by ultrasound and PET. We recommend routine contralateral axillary ultrasound as part of staging for all IBC patients. Diagnosis of CAM is a key first step toward much-needed prospective clinical trials evaluating management and outcomes of CAM in IBC.

Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response.This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1-2N0-1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579.Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2-75·4). At a median follow-up of 26·4 months (IQR 15·2-39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred.Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed.US National Cancer Institute (National Institutes of Health).

Background: Over the last decade, patients with early-stage breast cancer have been undergoing total mastectomy (TM) with increasing frequency. Our center reported that local recurrence rates with breast conserving therapy (BCT) declined throughout the 27-year period: from 7.1% for patients treated during 1970–1984 to 1.3% for patients treated during 1994–1996. More recently, several groups have published slightly improved survival rates in patients undergoing BCT compared with TM. The aim of this study was to evaluate trends in TM rates and compare overall survival (OS), distant metastasis-free survival (DMFS), local-regional recurrence (LRR) and disease-specific survival (DSS) between BCT and TM in patients with early-stage breast cancer undergoing upfront surgery. Methods: We identified women with clinical stage T1–2, N0–1, M0 breast cancer who underwent surgery as first treatment modality from 1/1/2000 to 12/31/2014 at our center. TM rates and survival outcomes were evaluated. Because the decision for surgery for those patients was not random, differences in patient, tumor and treatment characteristics with respect to surgery types were adjusted using inverse probability weighting (IPW) based on propensity scores. Variables in the model included age at diagnosis, clinical tumor T category, clinical nodal category, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) status and year of surgery, and a multinomial logit model was used for surgery treatment assignment and a Gamma model was used for the time to censor. IPW models were used to adjust for impact of surgery types on survival outcomes. Similar analysis was used in 6 subsets: Stage I & hormone receptor (HR)+/HER2-, Stage I & HER2+, Stage I &triple negative breast cancer (TNBC), Stage II & HR+/HER2-, Stage II & HER2+, Stage II & TNBC. Patients undergoing TM with RT were excluded from subset analysis due to small sample size. Results: A total of 8,256 patients were included, of them, 4701 (56.9%) underwent BCT, 2862 (34.7%) underwent TM without RT and 693 (8.4%) underwent TM+RT. Patients who underwent TM were younger and were more likely to have larger tumors, positive lymph nodes, higher grade, and HER2-positive tumors. TM rates increased in patients Table 1. Results from multivariable Cox models for factors associated with survival outcomes and IPW adjusted models for factors associated with survival outcomesCox ModelIPW adjusting modelsFactorsHRP95%CIRRP95% CIOSSurgery typeTM without RTBCT0.80.020.70.991.01.00.9-1.1TM with RT1.00.960.81.31.10.60.9-1.3DSSSurgery typeTM without RTRefBCT1.10.40.81.51.20.031.02-1.4TM with RT1.70.0051.22.61.30.021.04-1.6DMFSSurgery typeTM without RTRefBCT1.10.40.91.41.00.50.9-1.2TM with RT1.70.0021.22.40.90.70.7-1.2 LRRSurgery typeTM without RTRefBCT1.30.11.01.71.00.70.7-1.2TM with RT0.40.020.20.90.80.10.6-1.1Subsets IPW adjusted models for factors associated with LRRBCT vs. TM without RTStage I & HR+/HER2-No. of patientsTM without RT/BCTRRP95% CIStage I & HER2+1469/29451.00.90.8-1.3Stage I & TNBC199/2850.70.30.3-1.5Stage II & HR+/HER2-128/3170.4 Citation Format: Min Yi, Mariana Chavez Mac Gregor, Benjamin Smith, Abigail S Caudle, Sarah M DeSnyder, Henry M Kuerer, Kelly K Hunt. Comparing survival differences between breast-conserving therapy and mastectomy in patients with early-stage breast cancer undergoing upfront surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-17.

The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population. Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007–2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local–regional recurrence patterns were described and survival analyses were conducted. All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2−]: 31.1% vs. 44.2%; HR-negative [HR−]/HER2+: 24.4% vs. 15.4%; and HR−/HER2−: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p

IMPORTANCE: Treatment options for early breast cancer include breast-conserving surgery with radiation therapy (RT) or mastectomy and breast reconstruction without RT. Despite marked differences in these treatment strategies, little is known with regard to their association with long-term quality of life (QOL). OBJECTIVE: To evaluate the association of treatment with breast-conserving surgery with RT vs mastectomy and reconstruction without RT with long-term QOL. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness research study used data from the Texas Cancer Registry for women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008. The study sample was mailed a survey between March 2017 and April 2018. Data were analyzed from August 1, 2018 to October 15, 2021. EXPOSURES: Breast-conserving surgery with RT or mastectomy and reconstruction without RT. MAIN OUTCOMES AND MEASURES: The primary outcome was satisfaction with breasts, measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included BREAST-Q physical well-being, psychosocial well-being, and sexual well-being; health utility, measured using the EuroQol Health-Related Quality of Life 5-Dimension, 3-Level questionnaire; and local therapy decisional regret. Multivariable linear regression models with weights for treatment, age, and race and ethnicity tested associations of the exposure with outcomes. RESULTS: Of 647 patients who responded to the survey (40.0%; 356 had undergone breast-conserving surgery, and 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236). Among the 647 respondents, the median age was 53 years (range, 23-85 years) and the median time from diagnosis to survey was 10.3 years (range, 8.4-12.5 years). Multivariable analysis showed no significant difference between breast-conserving surgery with RT (referent) and mastectomy and reconstruction without RT in satisfaction with breasts (effect size, 2.71; 95% CI, –2.45 to 7.88; P = .30) or physical well-being (effect size, –1.80; 95% CI, –5.65 to 2.05; P = .36). In contrast, psychosocial well-being (effect size, –8.61; 95% CI, –13.26 to –3.95; P

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.

Modified radical mastectomy (MRM), which includes axillary dissection, is the standard of care for inflammatory breast cancer (IBC). While more limited axillary staging after neoadjuvant chemotherapy (NAC) in clinically node-positive non-IBC has been increasingly adopted, the impact of these techniques in IBC is not clear. To inform patient selection for further study of limited axillary surgery, we aimed to describe the frequency and factors associated with pathological node-negativity (ypN0) in IBC. Patients with IBC who received NAC and MRM were identified from a prospective institutional database (2004–2019). Binary logistic regression analyses were conducted to identify factors associated with ypN0. Of 453 patients, 189 (41.7%) had a post-NAC clinical nodal stage (ycN stage) of N0 (ycN1: 150, 33.1%; ycN2: 4, 0.9%; ycN3: 47, 10.4%; unknown: 63, 13.9%); 156 (34%) were ypN0. On multivariable analysis, higher tumor grade was not associated with ypN0 (odds ratio [OR] 1.59, 95% confidence interval [CI] 0.90–2.81, p =0.11). Compared with hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-negative tumors (n =113, 24.9%), HR-positive/HER2-negative tumors (n =169, 37.3%) had a trend toward less ypN0 (OR 0.55, 95% CI 0.29–1.02, p =0.06); HR-positive/HER2-positive tumors (n =79, 17.4%) were similar to HR-negative/HER2-negative tumors (OR 0.72, 95% CI 0.35–1.48, p =0.37); and HR-negative/HER2-positive tumors (n =92, 20.3%) were associated with increased ypN0 (OR 4.82, 95% CI 2.41–9.63, p

Purpose Study objectives were to examine: (a) biomarker trajectories (change from presurgical baseline values of Lymphedema index (L‐Dex) units and arm volume difference) and symptom cluster scores 24 months after breast cancer surgery and (b) associations of these objective biomarkers and symptom cluster scores. Patient/treatment characteristics influencing trajectories were also evaluated. Methods A secondary analysis of data from the published interim analysis of a randomized parent study was undertaken using trajectory analysis. Five hundred and eight participants included in the prior analysis with 24 months of postsurgical follow‐up were initially measured with bioelectric impedance spectroscopy (BIS) and tape measure (TM) and completed self‐report measures. Patients were reassessed postsurgery for continuing eligibility and then randomized to either BIS or TM groups and measured along with self‐report data at regular and optional* visits 3, 6,12,15*,18, 21*, and 24‐months. Results Three subclinical trajectories were identified for each biomarker (decreasing, stable, increasing) and symptom cluster scores (stable, slight increase/decrease, increasing). Subclinical lymphedema was identified throughout the 24‐month period by each biomarker. An L‐Dex increase at 15 months in the BIS group was noted. The self‐report sets demonstrated contingency coefficients of 0.20 (LSIDS‐A soft tissue, P = .031) and 0.19 (FACTB+4, P = .044) with the L‐Dex unit change trajectories. Conclusions These data support the need for long‐term (24 months) prospective surveillance with frequent assessments (every 3 months) at least 15 months after surgery. Statistically significant convergence of symptom cluster scores with L‐Dex unit change supports BIS as beneficial in the early identification of subclinical lymphedema., Long‐term (24 months) lymphedema prospective surveillance with frequent assessments (every 3 months) at least through 15‐months post‐surgery is indicated. Convergence of symptom cluster scores with L‐Dex unit change supports Bioelectric Impedance Spectroscopy as beneficial in the early identification of sub‐clinical lymphedema.

Objective To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave. Summary of background data The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years. Methods The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients. Results We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. Conclusions Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

PURPOSE Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (g BRCA-positive) and operable breast cancer. METHODS Eligibility included 1 cm or larger invasive tumor and g BRCA-positive disease. Human epidermal growth factor receptor 2–positive tumors were excluded. Twenty patients underwent a pretreatment biopsy, 6 months of once per day oral talazoparib (1 mg), followed by definitive surgery. Patients received adjuvant therapy at physician’s discretion. The primary end point was residual cancer burden (RCB). With 20 patients, the RCB-0 plus RCB-I response rate can be estimated with a 95% CI with half width less than 20%. RESULTS Twenty patients were enrolled from August 2016 to September 2017. Median age was 38 years (range, 23 to 58 years); 16 patients were g BRCA1 positive and 4 patients were g BRCA2 positive. Fifteen patients had triple-negative breast cancer (estrogen receptor/progesterone receptor < 10%), and five had hormone receptor-positive disease. Five patients had clinical stage I disease, 12 had stage II, and three had stage III, including one patient with inflammatory breast carcinoma and one with metaplastic chondrosarcomatous carcinoma. One patient chose to receive chemotherapy before surgery and was not included in RCB analyses. RCB-0 (pathologic complete response) rate was 53% and RCB-0/I was 63%. Eight patients (40%) had grade 3 anemia and required a transfusion, three patients had grade 3 neutropenia, and 1 patient had grade 4 thrombocytopenia. Common grade 1 or 2 toxicities were nausea, fatigue, neutropenia, alopecia, dizziness, and dyspnea. Toxicities were managed by dose reduction and transfusions. Nine patients required dose reduction. CONCLUSION Neoadjuvant single-agent oral talazoparib once per day for 6 months without chemotherapy produced substantial RCB-0 rate with manageable toxicity. The substantive pathologic response to single-agent talazoparib supports the larger, ongoing neoadjuvant trial (ClinicalTrials.gov identifier: NCT03499353 ).

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. 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

Background: Prospective lymphedema screening is recommended for breast cancer patients. We observed interoperator variation in perometer-acquired arm volume measurements (P-AVMs) due to pa...

Background: Bioimpedance spectroscopy (BIS) is an established tool for the measurement of extracellular fluid in lymphedema. This study assesses the validity of BIS measurements using the ...

Background Breast cancer-related lymphedema (BCRL) represents a major source of morbidity among breast cancer survivors. Increasing data support early detection of subclinical BCRL followed by early intervention. A randomized controlled trial is being conducted comparing lymphedema progression rates using volume measurements calculated from the circumference using a tape measure (TM) or bioimpedance spectroscopy (BIS). Methods Patients were enrolled and randomized to either TM or BIS surveillance. Patients requiring early intervention were prescribed a compression sleeve and gauntlet for 4 weeks and then re-evaluated. The primary endpoint of the trial was the rate of progression to clinical lymphedema requiring complex decongestive physiotherapy (CDP), with progression defined as a TM volume change in the at-risk arm ≥ 10% above the presurgical baseline. This prespecified interim analysis was performed when at least 500 trial participants had ≥ 12 months of follow-up. Results A total of 508 patients were included in this analysis, with 109 (21.9%) patients triggering prethreshold interventions. Compared with TM, BIS had a lower rate of trigger (15.8% vs. 28.5%, p

BACKGROUND Few guidelines exist for an opioid prescription after breast surgical oncology (BSO) procedures. We sought to characterize opioid prescribing and use patterns by surgery type. METHODS Patients (n = 332) undergoing BSO procedure were surveyed one week postoperatively for opioid use. The surgeons were surveyed about pain management preferences surgery type. CPT codes were collected for 2017 to calculate the amount of opioids used by surgery type relative to surgeon preference. RESULTS Mean oral morphine equivalent (OME) preferred prescription for surgeons who did not tailor prescriptions by surgery type (n = 7, group A) was 177, whereas for those who did tailor (n = 10, group B) varied from 137 to 257 OME. There was a significant difference in opioid use by surgery type: 32 OME for segmental mastectomy (SM) ± sentinel lymph node dissection (SLND), 63 for SM + axillary lymph node dissection (ALND), 76 for total mastectomy (TM) ± SLND, 115 for TM + ALND (P

OBJECTIVE: To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients. BACKGROUND: Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins < 2 mm. METHODS: One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT). RESULTS: A univariate analysis revealed that age

In 2017, the American Society of Breast Surgeons (ASBrS) published expert panel recommendations for patients at risk for breast cancer-related lymphedema (BCRL) and those affected by BCRL. This study sought to determine BCRL practice patterns.A survey was sent to 2975 ASBrS members. Questions evaluated members' clinical practice type, practice duration, and familiarity with BCRL recommendations. Descriptive statistics, the chi-square test, and Fisher's exact test were used.Of the ASBrS members surveyed, 390 (13.1%) responded. Most of the breast surgeons (58.5%, 228/390) indicated unfamiliarity with recommendations. Nearly all respondents (98.7%, 385/390) educate at-risk patients. Most (60.2%, 234/389) instruct patients to avoid venipuncture, injection or blood pressure measurements in the at-risk arm, and 35.6% (138/388) recommend prophylactic compression sleeve use during air travel. Nearly all (97.7%, 380/389) encourage those at-risk to exercise, including resistance exercise (86.2%, 331/384). Most do not perform axillary reverse mapping (ARM) (67.9%, 264/389) or a lymphatic preventive healing approach (LYMPHA) (84.9%, 331/390). Most (76.1%, 296/389) screen at-risk patients for BCRL. The most frequently used screening tools include self-reported symptoms (81%, 255/315), circumferential tape measure (54%, 170/315) and bioimpedance spectroscopy (27.3%, 86/315). After a BCRL diagnosis, most (90%, 351/390) refer management to a lymphedema-certified physical therapist. For affected patients, nearly all encourage exercise (98.7%, 384/389). Many (49%, 191/390) refer affected patients for consideration of lymphovenous bypass or lymph node transfer.Most respondents were unfamiliar with the ASBrS expert panel recommendations for patients at risk for BCRL and those affected by BCRL. Opportunities exist to increase awareness of best practices and to acquire ARM and LYMPHA technical expertise.

The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population.Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007-2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local-regional recurrence patterns were described and survival analyses were conducted.All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2-]: 31.1% vs. 44.2%; HR-negative [HR-]/HER2+: 24.4% vs. 15.4%; and HR-/HER2-: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p 0.001). Of the 47 patients who completed trimodality therapy, 6 (12.8%) had a local-regional recurrence. Median overall survival (OS) was 19 months in the non-MRM group and 58 months in the MRM group (p 0.001). On multivariable analysis, clinical N3 disease (hazard ratio 2.16, 95% confidence interval [CI] 1.07-4.37; p = 0.03) as well as tumor subtypes HR+/HER2- (hazard ratio 4.98, 95% CI 1.15-21.47; p = 0.03) and HR-/HER2- (hazard ratio 7.18, 95% CI 1.66-31.07; p = 0.008) were associated with decreased OS. Partial/complete response of distant disease to chemotherapy (hazard ratio 0.43, 95% CI 0.24-0.77; p = 0.005) and receipt of MRM (hazard ratio 0.52, 95% CI 0.29-0.93; p = 0.03) were independently associated with improved OS.In our retrospective study, MRM in de novo stage IV IBC patients is an independent factor associated with improved OS. Our findings strongly support the need for prospective randomized trials evaluating possible survival benefits of MRM in de novo stage IV IBC patients.

Nearly one-third of patients with inflammatory breast cancer (IBC) present with de novo stage IV disease. There are limited data on frequency and clinical outcomes of contralateral axillary metastasis (CAM) in IBC with no consensus diagnostic and treatment guidelines.Frequency of synchronous CAM was calculated in unilateral IBC patients at a single center (10/2004-6/2019). Clinicopathologic variables, diagnostic evaluation, treatment received, and overall survival (OS) were assessed and compared.Of 588 unilateral IBC patients, 49 (8.3%) had synchronous CAM. Of these, 32 (65.3%) also presented with metastatic disease at another distant site. CAM was not associated with age, tumor laterality, breast cancer subtype, grade, or cN stage (p0.05). The sensitivity/specificity to detect CAM was as follows: mammography (18.2%/99.2%), ultrasound (92.3%/95.5%), PET (90.1/99.1%), and MRI (76.0%/98.6%). Following systemic therapy, 22 patients had contralateral axillary surgery, and 18 received adjuvant contralateral nodal radiation. On multivariable analysis including tumor receptor subtypes, patients with stage IV-isolated CAM has statistically similar survival to stage III patients (HR 1.37, 95% CI 0.70-2.69, p = 0.36). Patients with Stage IV non-CAM (HR 2.18, 95% CI 1.66-2.85, p0.001) and stage IV-CAM plus other distant metastasis (HR 2.57, 95% CI 1.59-4.16, p0.001) had higher risk of death (reference: stage III disease).CAM in IBC was diagnosed in 8.3% of patients at presentation and was best identified by ultrasound and PET. We recommend routine contralateral axillary ultrasound as part of staging for all IBC patients. Diagnosis of CAM is a key first step toward much-needed prospective clinical trials evaluating management and outcomes of CAM in IBC.

Background Enhanced recovery after surgery (ERAS) programs are being used increasingly in microvascular breast reconstruction. However, it is unclear as to what extent the benefits outweigh the costs. We hypothesized that an ERAS pathway for microvascular breast reconstruction would be cost-effective relative to the standard of care. Study Design A decision-analytic model was made incorporating clinically relevant health states after microvascular breast reconstruction with ERAS vs standard of care. Probabilities and utility scores were abstracted from published sources, and a third-party payer perspective was adopted. Time-driven activity-based costing was used to map and estimate costs attributed to ERAS. Sensitivity analyses were performed to examine the robustness of the results. Results The results of 5 studies, totaling 986 patients, were pooled to generate health state probabilities. ERAS was found to be dominant, being both less expensive and more effective than standard of care. On sensitivity analysis, ERAS becomes cost-ineffective (incremental cost-utility ratio > $50,000/quality-adjusted life year) at an amount > $19,336.75. Length of stay would have to be reduced from 5.96 days to 3.36 days for standard of care to become cost-effective. Monte-Carlo analysis demonstrated ERAS to be the more cost-effective option across a range of willingness-to-pay values. Conclusions Despite the increased medication and personnel costs attributed to ERAS, it is less costly overall and associated with superior outcomes compared with standard of care. These findings lend additional support to the value of ERAS implementation in microvascular breast reconstruction. Time-driven activity-based costing provides granular estimates and are useful in quality-improvement initiatives.

Background After publication of American College of Surgeons Oncology Group (ACOSOG) Z0011, surgeons at our institution limited axillary surgery to sentinel lymph node dissection (SLND) in 76% of patients meeting trial eligibility criteria. Our study objective was to assess incorporation of the trial data into practice 5 years later. Patients and Methods Patients with clinical T1-2, N0 invasive breast cancer undergoing breast conserving surgery were included. Comparisons were made between patients who underwent axillary lymph node dissection (ALND) and those that had no further surgery. Results A total of 396 patients were included. Twelve percent (48/396) had positive SLNs; ALND was performed in 8% (4/48). Patients who underwent ALND were more likely to have 2 positive SLNs (50%, 2/4 vs. 2%, 1/44; P = .02) and microscopic extranodal extension (75%, 3/4 vs. 18%, 8/44; P = .03) than those that did not undergo ALND. Patients who underwent ALND also had a higher nomogram-predicted probability of having additional positive non-SLNs (53%) than those who had SLND alone (22%) ( P = .0002). No patients had intraoperative assessment of SLNs performed. Conclusions The practice of omitting ALND in ACOSOG Z0011-eligible patients has expanded over 5 years. Clinicopathologic features continue to impact this decision. Intraoperative SLN assessment is no longer performed.

The SSO-ASTRO-ASCO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in ductal carcinoma in situ (DCIS) recommended a 2-mm margin. We sought to determine the impact of guideline publication on clinician practice. A total of 3081 members of the American Society of Breast Surgeons (ASBrS) received a survey. Respondents’ clinical practice type and duration, guideline familiarity, and margin width preferences before and after publication were assessed. Clinical practice pattern differences before and after publication were investigated using McNemar’s test. A total of 767 (24.9%) of those surveyed responded. Most (92.4%) indicated guideline familiarity. Of those familiar, re-excision preference for DCIS and a positive margin remained the same before (94.4%) and after (94.3%) publication (McNemar’s test p = 1.0). Following publication, surgeons were more likely to avoid re-excision to achieve margins wider than 2-mm (82.3% pre versus 87.5% post, p = 0.002). More surgeons performed re-excision for a close margin with pure DCIS (25.9% pre versus 36.5% post, p

National and international experts in inflammatory breast cancer (IBC) from high-volume centers treating IBC recently convened at the 10th Anniversary Conference of the Morgan Welch Inflammatory Breast Cancer Research Program at The University of Texas MD Anderson Cancer Center in Houston Texas. A consensus on the clinical management of patients with IBC was discussed, summarized, and subsequently reviewed. All participants at the conference (patients, advocates, researchers, trainees, and clinicians) were queried using the MDRing electronic survey on key management issues. A summary of the expert consensus and participant voting is presented. Bilateral breast and nodal evaluation, breast magnetic resonance imaging, positron emission tomography/computed tomography, and medical photographs were endorsed as optimal. Neoadjuvant systemic therapy, modified radical mastectomy and level I and II ipsilateral axillary node dissection, post-mastectomy radiotherapy, adjuvant targeted therapy and hormonal therapy as indicated, and delayed reconstruction were agreed-upon fundamental premises of standard non-protocol-based treatment for IBC. Consideration for local-regional therapy in de novo stage IV IBC was endorsed to provide local control whenever feasible. Variation across centers and special circumstances were discussed.

Background Most inflammatory breast cancer (IBC) patients have axillary disease at presentation. Current standard is axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic complete response (pCR) rates increasing interest in performing sentinel lymph node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not assess nodal response with imaging or use dual tracer mapping. We sought to prospectively determine false negative rates of SLNB in IBC patients using dual tracer mapping, and to correlate pathology with preoperative axillary imaging. Patients and Methods Patients with IBC were prospectively enrolled. Patients underwent axillary staging with physical examination and axillary ultrasound before and after NACT. All patients underwent SLNB using blue dye and radioisotope, followed by ALND. Results Sixteen patients were prospectively enrolled. Clinical N stage was N0 in 1 patient, N1 in 8, and N3 in 7. SLN mapping was successful in only 4 patients (25%) with 12 (75%) not draining either tracer to a SLN. Three of the 4 (75%) who mapped had an axillary pCR. The patient who mapped but did not have an axillary pCR had a positive SLNB with additional axillary nodal disease identified on ALND. All patients who successfully mapped had presumed residual nodal disease on preoperative axillary ultrasound. Conclusion SLNB was unsuccessful in most IBC patients. A small subset who have pCR might undergo successful SLNB, but preoperative axillary imaging failed to identify these patients. ALND should remain standard practice for IBC patients.

The goal of breast-conserving surgery is to excise the tumor with negative margins while achieving a successful cosmetic result. Although it is not feasible to have re-excision rates of zero, several techniques have been described to reduce the need for a return to the operating room. When rates of re-excision are high, consideration should be given to using 1 or more of these techniques. It is critical that re-excision rates are tracked when new techniques are implemented to ensure progress. In addition, attention must be paid to ensuring that cosmetic outcomes remain optimal.

Summary In the absence of histological criteria that distinguish between inflammatory and non-inflammatory breast cancer, diagnosis of inflammatory breast cancer relies entirely on the existence of clinical criteria as outlined by the TNM classification. This classification restricts patients presenting with clinical criteria characteristic of inflammatory breast cancer to subcategory T4d, which immediately relegates all patients with non-metastatic inflammatory breast cancer to stage 3, regardless of tumour size or nodal spread. Patients who present with metastatic disease are consigned to stage 4, and the TNM classification does not distinguish patients on the basis of the presence of inflammatory criteria. Evidence by our group and others suggests that patients with inflammatory breast cancer have significantly reduced overall survival among those who present with distant metastasis at diagnosis (stage 4). In light of these results, this Personal View addresses whether the current TNM staging classification accurately represents a distinction between patients with inflammatory and those with non-inflammatory breast cancer.

Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery.Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery. Citation Format: Kuerer HM, Rauch GM, Krishnamurthy S, Adrada BE, Caudle AS, DeSnyder SM, Santiago L, Lucci A, Hobbs BP, Gilcrease M, Hwang R, Candelaria RP, Chavez Mac-Gregor M, Arribas E, Moseley T, Teshome M, Miggins MV, Smith BD, Valero V, Hunt KK, Yang WT. Feasibility trial for identification of patients for eliminating breast cancer surgery following neoadjuvant systemic therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-30.

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. 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. 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). RNI is associated with a significantly higher risk of lymphedema than irradiation of the breast/CW, particularly after ALND.