Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

BACKGROUND: Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). METHODS: Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. RESULTS: Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p = 0.04), more than three suspicious nodes on initial US (30% vs 13%; p ≤ 0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p = 0.0004), and more positive TAD nodes (median, 2 vs 1; p ≤ 0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p ≤ 0.0001), more positive TAD nodes (OR, 1.1; p ≤ 0.0001), larger clipped node metastasis (OR, 1.1; p ≤ 0.0001), and larger residual tumor on pathology (OR, 1.1; p = 0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. CONCLUSION: Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Evaluation of traditional targeted axillary dissection eligibility criteria for node-positive breast cancer after neoadjuvant chemotherapy in a prospective multicenter registry.

INTRODUCTION: Targeted axillary dissection (TAD) is performed after neoadjuvant systemic therapy (NST) to decrease the rate of non-therapeutic axillary dissection (ALND) for patients with node-positive breast cancer. In order to ensure the oncologic safety of TAD, eligibility criteria resulting in a low false negative rate (FNR) have been proposed. The purpose of this study was to evaluate the utility of the traditional criteria. METHODS: Data was collected from a prospective multicenter registry. In order to ascertain FNRs, pathologic findings in the sentinel lymph nodes (LN)s, malignant clipped LN, and axillary contents were determined. The FNRs within TAD eligibility criterion groups were compared. RESULTS: A total of 110 patients underwent TAD and ALND, and were therefore eligible for analysis. TAD retained a low FNR in advanced clinical T-N stage compared with earlier disease (T stage: 95% CI 0.00-11.93, p = 0.42; N stage: 95% CI 0.00-8.76, p = 0.31). Presentation with ≥4 abnormal LNs on axillary ultrasound did not predict a high TAD FNR (95% CI 0.00-5.37, p = 0.16). No significant differences were noted in TAD FNR when single was compared with dual tracer (blue dye vs dual tracer 95% CI 0.72-52.49, p = 0.13; radiotracer vs dual tracer 0.04-20.11, p = 0.51). Excision of the clipped LN and only one SLN was as accurate as excision of the clipped LN and ≥2 SLNs (95% CI 0.00-10.61, p = 0.38). CONCLUSIONS: TAD retained a low FNR among patients traditionally considered ineligible for this technique. However, excision of the clipped LN and at least one SLN remained essential to a low FNR.

Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor-Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination: A Phase 3 Randomized Clinical Trial.

Importance: Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested in early-stage disease. Objective: To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone. Design, Setting, and Participants: A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or >66%)/ERBB2-negative breast cancer were included. All analyses were based on data frozen on March 2, 2023. Interventions: Patients received anastrozole, fulvestrant, or a combination for 6 months preoperatively. Tumor Ki67 was assessed at week 4 and optionally at week 12, and if greater than 10% at either time point, the patient switched to neoadjuvant chemotherapy or immediate surgery. Main Outcomes and Measures: The primary outcome was the endocrine-sensitive disease rate (ESDR). A secondary outcome was the percentage change in Ki67 after 4 weeks of neoadjuvant endocrine therapy (NET) (week 4 Ki67 suppression). Results: Between February 2014 and November 2018, 1362 female patients (mean [SD] age, 65.0 [8.2] years) were enrolled. Among the 1298 evaluable patients, ESDRs were 18.7% (95% CI, 15.1%-22.7%), 22.8% (95% CI, 18.9%-27.1%), and 20.5% (95% CI, 16.8%-24.6%) with anastrozole, fulvestrant, and A+F, respectively. Compared to anastrozole, neither fulvestrant-containing regimen significantly improved ESDR or week 4 Ki67 suppression. The rate of week 4 or week 12 Ki67 greater than 10% was 25.1%, 24.2%, and 15.7% with anastrozole, fulvestrant, and A+F, respectively. Pathologic complete response/residual cancer burden class I occurred in 8 of 167 patients and 17 of 167 patients, respectively (15.0%; 95% CI, 9.9%-21.3%), after switching to neoadjuvant chemotherapy due to week 4 or week 12 Ki67 greater than 10%. PAM50 subtyping derived from RNA sequencing of baseline biopsies available for 753 patients (58%) identified 394 luminal A, 304 luminal B, and 55 nonluminal tumors. A+F led to a greater week 4 Ki67 suppression than anastrozole alone in luminal B tumors (median [IQR], -90.4% [-95.2 to -81.9%] vs -76.7% [-89.0 to -55.6%]; P < .001), but not luminal A tumors. Thirty-six nonluminal tumors (65.5%) had a week 4 or week 12 Ki67 greater than 10%. Conclusions and Relevance: In this randomized clinical trial, neither fulvestrant nor A+F significantly improved the 6-month ESDR over anastrozole in ER-rich/ERBB2-negative breast cancer. Aromatase inhibition remains the standard-of-care NET. Differential NET response by PAM50 subtype in exploratory analyses warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT01953588.

Racial and Ethnic Differences in Long-Term Adverse Radiation Therapy Effects Among Breast Cancer Survivors.

PURPOSE: Breast and skin changes are underrecognized side effects of radiation therapy for breast cancer, which may have long-term implications for quality of life (QOL). Racial and ethnic disparities in breast cancer outcomes, including long-term QOL differences after breast radiation therapy, are poorly understood. METHODS AND MATERIALS: We conducted a cross-sectional survey study of patients from the Texas Cancer Registry who received diagnoses of stage 0-II breast cancer from 2009 to 2014 and treated with lumpectomy and radiation therapy; 2770 patients were sampled and 631 responded (23%). The BREAST-Q Adverse Effects of Radiation overall score and subindices measured the effect of radiation therapy on breast tissue. Multivariable logistic regression evaluated associations of demographic and treatment characteristics with outcomes. RESULTS: The median age was 57 years (IQR, 48-65), median time from diagnosis to survey response 9 years (IQR, 7-10), and the cohort included 62 Asian American or Pacific Islander (9.8%), 11 American Indian or Alaskan Native (AIAN) (1.7%), 161 Black (25.5%), 144 Hispanic (22.8%), and 253 White (40.1%) patients. Mean BREAST-Q Adverse Effects of Radiation score was worse for AIAN patients (-22.2; 95% CI, -39.9 to -4.6; P = .01), Black patients (-10.8; 95% CI, -16.1 to -5.5; P < .001), and Hispanic patients (-7.8; 95% CI, -13.0 to -2.5; P = .004) compared with White patients, age <50 compared with ≥65 (effect size -8.6; 95% CI, -14.0 to -3.2; P = .002), less than a college education (-5.8; 95% CI, -10.0 to -1.6; P = .01), bra cup size of D/E versus A/B (-5.3; 95% CI, -9.9 to -0.65; P = .03), and current smokers (-11.3; 95% CI, -18.3 to -4.2; P = .002). AIAN, Black, and Hispanic patients reported worse changes in skin pigmentation, telangiectasias, dryness, soreness, and/or irritation compared with White patients. CONCLUSIONS: AIAN, Black, and Hispanic patients reported substantially worse long-term breast and skin QOL outcomes after radiation therapy. Additional work is needed to understand these differences and how to alleviate them.

To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer?

BACKGROUND: Axillary lymph node (ALN) involvement is important for prognosis and guidance of multidisciplinary treatment of breast cancer patients. This study sought to identify preoperative clinicopathologic factors predictive of four or more pathologically positive ALNs in patients with cN0 disease and to develop a predictive nomogram to inform therapy recommendations. METHODS: Using an institutional prospective database, the study identified postmenopausal women with cN0 invasive breast cancer undergoing upfront sentinel lymph node biopsy (SLNB) with or without completion ALND (cALND) between 1993 and 2007. Logistic regression analyses identified factors predictive of four or more positive nodes in the cN0 population and patients with one, two, or more SLNs. RESULTS: The study identified 2532 postmenopausal women, 615 (24.3%) of whom underwent cALND. In the univariate analysis, tumor size, lymphovascular (LVI), histology, estrogen receptor (ER)-positive status, and multifocality/multicentricity were predictive of four or more positive nodes (n = 63; p < 0.05), and all except ER status were significant in the multivariate analysis. Of the 2532 patients, 1263 (49.2%) had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, and 30 (2.4%) were found to have four or more positive nodes. Of the 130 patients with exactly one positive SLN who underwent cALND (n = 130, 5.4%), 7 had four or more positive nodes, with grade as the only predictive factor (p = 0.01). Of the 33 patients with two or more positive SLNs who underwent cALND, 9 (27.3%) had four or more positive nodes after cALND, but no factors were predictive in this subset. CONCLUSION: Postmenopausal women with early-stage cN0 HR-positive, HER2-negative breast cancer with a single positive SLN had a very low risk (5%) of having four or more positive nodes on final pathology. With such a low risk of N2 disease, limited staging with SLNB may be sufficient to guide therapy decisions for this subset of patients.

Evidence-Based Strategies to Minimize the Likelihood of Axillary Lymph Node Dissection in Clinically Node-Positive Patients Following Neoadjuvant Chemotherapy.

De-escalation of axillary management after neoadjuvant chemotherapy in clinically node-positive patients is feasible. The current literature shows this may be accomplished by sentinel lymph node biopsy (SLNB) with the use of dual tracer and removal of at least 2 sentinel lymph nodes, or by targeted axillary dissection (TAD). The accuracy of TAD has been consistently shown as better than that of SLNB. However, these techniques should only be offered to select patients without extensive axillary disease, understanding that long-term outcomes of minimal axillary surgery in this population are limited at this time.

Molecular mechanisms of snoRNA-IL-15 crosstalk in adipocyte lipolysis and NK cell rejuvenation.

Obesity, in which the functional importance of small nucleolar RNAs (snoRNAs) remains elusive, correlates with risk for many cancer types. Here, we identify that the serum copies of adipocyte-expressed SNORD46 correlate with body mass index (BMI), and serum SNORD46 antagonizes interleukin-15 (IL-15) signaling. Mechanically, SNORD46 binds IL-15 via G11, and G11A (a mutation that significantly enhances binding affinity) knockin drives obesity in mice. Functionally, SNORD46 blocks IL-15-induced, FER kinase-dependent phosphorylation of platelet glycoprotein 4 (CD36) and monoglyceride lipase (MGLL) in adipocytes, leading to inhibited lipolysis and browning. In natural killer (NK) cells, SNORD46 suppresses the IL-15-dependent autophagy, leading to reduced viability of obese NK. SNORD46 power inhibitors exhibit anti-obesity effects, concurring with improved viability of obese NK and anti-tumor immunity of CAR-NK cell therapy. Hence, our findings demonstrate the functional importance of snoRNAs in obesity and the utility of snoRNA power inhibitors for antagonizing obesity-associated immune resistance.

Patient-reported Quality of Life After Breast-conserving Surgery With Radiotherapy Versus Mastectomy and Reconstruction.

OBJECTIVE: To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors. BACKGROUND: The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood. METHODS: We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. Multivariable linear regression models were implemented for each outcome. Minimal clinically important difference for BREAST-Q and PROMIS modules, respectively, was 4 points and 2 points. RESULTS: Of 1215 respondents (25.3% response rate), 631 received BCS+RT and 584 received Mast+Recon. The median interval from diagnosis to survey completion was 9 years. In adjusted analysis, Mast+Recon was associated with worse BREAST-Q psychosocial well-being (effect size: -3.80, P =0.04) and sexual well-being (effect size: -5.41, P =0.02), but better PROMIS physical function (effect size: 0.54, P =0.03) and similar BREAST-Q satisfaction with breasts, physical well-being, and PROMIS upper extremity function ( P >0.05) compared with BCS+RT. Only the difference in sexual well-being reached clinical significance. Older (≥65) patients receiving BCS+RT and younger (<50) patients receiving autologous Mast+Recon typically reported higher QOL scores. Receipt of chemotherapy was associated with detriments to multiple QOL domains. CONCLUSIONS: Patients who underwent Mast+Recon reported worse long-term sexual well-being compared with BCS+RT. Older patients derived a greater benefit from BCS+RT, while younger patients derived a greater benefit from Mast+Recon. These data inform preference-sensitive decision-making for women with early-stage breast cancer.

Invited Commentary: De-escalation of axillary surgery in node-positive breast cancer patients after neoadjuvant therapy.

The surgical management of patients presenting with node-positive breast cancer who receive neoadjuvant chemotherapy has been an area of focus and debate as neoadjuvant chemotherapy regimens increasingly eradicate the nodal disease. Axillary lymph node dissection has been the standard surgical approach, which carries morbidity risks of lymphedema, pain, and limited range of motion. Although there has been interest in de-escalating axillary surgery, hurdles must be addressed. The first is finding an accurate way to assess nodal response. Many trials have looked at this using the false negative rate as the defining endpoint, all finding that surgical techniques such as using a dual tracer technique, adding immunohistochemistry, and ensuring removal of the node that had biopsy-confirmed disease at diagnosis can impact the accuracy of minimally invasive approaches to evaluate the axilla. However, the second hurdle of defining the impact of minimizing axillary surgery on locoregional and overall outcomes has yet to be answered. Ongoing trials may give us insights over the next few years.

Tumor-associated nonmyelinating Schwann cell-expressed PVT1 promotes pancreatic cancer kynurenine pathway and tumor immune exclusion.

One of the major obstacles to treating pancreatic ductal adenocarcinoma (PDAC) is its immunoresistant microenvironment. The functional importance and molecular mechanisms of Schwann cells in PDAC remains largely elusive. We characterized the gene signature of tumor-associated nonmyelinating Schwann cells (TASc) in PDAC and indicated that the abundance of TASc was correlated with immune suppressive tumor microenvironment and the unfavorable outcome of patients with PDAC. Depletion of pancreatic-specific TASc promoted the tumorigenesis of PDAC tumors. TASc-expressed long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was triggered by the tumor cell-produced interleukin-6. Mechanistically, PVT1 modulated RAF proto-oncogene serine/threonine protein kinase-mediated phosphorylation of tryptophan 2,3-dioxygenase in TASc, facilitating its enzymatic activities in catalysis of tryptophan to kynurenine. Depletion of TASc-expressed PVT1 suppressed PDAC tumor growth. Furthermore, depletion of TASc using a small-molecule inhibitor effectively sensitized PDAC to immunotherapy, signifying the important roles of TASc in PDAC immune resistance.

Leveraging the Multidisciplinary Tumor Board for Dissemination of Evidence-Based Recommendations on the Staging and Treatment of Gastric Cancer: A Pilot Study.

BACKGROUND: Compliance with evidence-based treatment guidelines for gastric cancer across the United States is poor. This pilot study aimed to create and evaluate a change package for disseminating information on the staging and treatment of gastric cancer during multidisciplinary tumor boards and for identifying barriers to implementation. METHODS: The change package included a 10-min video, a brief knowledge assessment, and a discussion guide. Commission on Cancer-accredited sites that perform gastrectomy were invited to participate. Participants completed the Organizational Readiness for Implementing Change (ORIC) scale (range, 12-60) and scales to measure the feasibility, acceptability, and appropriateness (score range, 4-20). Semi-structured interviews were conducted to further define inner and outer setting barriers. RESULTS: Seven centers participated in the study. A total of 74 participants completed the pre-video knowledge assessment, and 55 participants completed the post-video assessment. The recommendations found to be most controversial were separate staging laparoscopy and modified D2 lymphadenectomy. Sum scores were calculated for acceptability (mean, 17.43 ± 2.51) appropriateness (mean, 16.86 ± 3.24), and feasibility (mean, 16.14 ± 3.07) of the change package. The ORIC scores (mean, 46.57 ± 8.22) correlated with responses to the open-ended questions. The key barriers identified were patient volume, skills in the procedures, and attitudes and beliefs. CONCLUSIONS: The change package was moderately to highly feasible, appropriate, and acceptable. The activity identified specific recommendations for gastric cancer care that are considered controversial and local barriers to implementation. Future efforts could focus on building skills and knowledge as well as the more difficult issue of attitudes and beliefs.

Long-term Quality of Life in Patients With Breast Cancer After Breast Conservation vs Mastectomy and Reconstruction.

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 < .001) and sexual well-being (effect size, -10.68; 95% CI, -16.60 to -4.76; P < .001) were significantly worse with mastectomy and reconstruction without RT. Health utility (effect size, -0.003; 95% CI, -0.03 to 0.03; P = .83) and decisional regret (effect size, 1.32; 95% CI, -3.77 to 6.40; P = .61) did not differ by treatment group. Conclusions and Relevance: The findings support equivalence of breast-conserving surgery with RT and mastectomy and reconstruction without RT with regard to breast satisfaction and physical well-being. However, breast-conserving surgery with RT was associated with clinically meaningful improvements in psychosocial and sexual well-being. These findings may help inform preference-sensitive decision-making for women with early-stage breast cancer.

Differences in Time Burden across Local Therapy Strategies for Early-stage Breast Cancer.

"Time burden" (time required during treatment) is relevant when choosing a local therapy option for early-stage breast cancer but has not been rigorously studied. We compared the time burden for three common local therapies for breast cancer: (1) lumpectomy plus whole-breast irradiation (Lump+WBI), (2) mastectomy without radiation or reconstruction (Mast alone), and (3) mastectomy without radiation but with reconstruction (Mast+Recon). METHODS: Using the MarketScan database, we identified 35,406 breast cancer patients treated from 2000 to 2011 with these local therapies. We quantified the total time burden as the sum of inpatient days (inpatient-days), outpatient days excluding radiation fractions (outpatient-days), and radiation fractions (radiation-days) in the first two years postdiagnosis. Multivariable regression evaluated the effect of local therapy on inpatient-days and outpatient-days adjusted for patient and treatment covariates. RESULTS: Adjusted mean number of inpatient-days was 1.0 for Lump+WBI, 2.0 for Mast alone, and 3.1 for Mast+Recon (P < 0.001). Adjusted mean number of outpatient-days was 42.9 for Lump+WBI, 42.2 for Mast alone, and 45.8 for Mast+Recon (P < 0.001). The mean number of radiation-days for Lump+WBI was 32.4. Compared with Mast+Recon (48.9 days), total adjusted time burden was 4.7 days shorter for Mast alone (44.2 days) and 27.4 days longer for Lump+WBI (76.3 days). However, use of a 15 fraction WBI regimen would reduce the time burden differential between Lump+WBI and Mast+Recon to just 10.0 days. CONCLUSIONS: Although Mast+Recon confers the highest inpatient and outpatient time burden, Lump+WBI carries the highest total time burden. Increased use of hypofractionation will reduce the total time burden for Lump+WBI.

Clinical Course of Breast Cancer Patients with Local-Regional Progression During Neoadjuvant Systemic Therapy.

BACKGROUND: Neoadjuvant systemic therapy (NST) is standard for locally advanced breast cancer and is now frequently considered for those with early-stage and node-positive disease. We aimed to evaluate the treatment course and outcomes in patients with disease progression during NST. METHODS: Patients diagnosed with unilateral stage I-III breast cancer between 2005 and 2015 with documented local-regional progression while receiving NST, by clinical examination and/or imaging after two or more cycles of chemotherapy, were identified from a prospective database, stratified by receipt of surgery and outcomes analyzed. RESULTS: Of 6362 patients treated with NST during the study period, 124 (1.9%) developed disease progression. At a median live follow-up of 71 months, 23.4% were alive without disease and 70.2% had died from breast cancer. Median overall survival (OS) time for patients with progression was 26 months and median distant disease-free survival (DFS) was 14 months. Triple-negative breast cancer was associated with a higher likelihood of death (p < 0.001) and development of distant metastasis (p = 0.002). Among patients who had surgery (104, 89.3%), 40 (38.5%) developed local-regional recurrence, 67 (64.4%) developed distant metastasis, and 69 (66.3%) died from breast cancer. Median OS and median distant DFS in this subgroup was 31 and 16 months, respectively. CONCLUSIONS: High rates of local-regional and distant failure were seen following disease progression while receiving NST. This suggests aggressive tumor biology and the need to study novel systemic therapies. Poor survival outcomes despite surgical management highlight the importance of careful patient selection when considering operative intervention after progression while receiving NST.

Surgical Outcomes in Cancer Patients Undergoing Elective Surgery After Recovering from Mild-to-Moderate SARS-CoV-2 Infection.

BACKGROUND: An increasing number of patients with cancer diagnoses and prior SARS-CoV-2 infection will require surgical treatment. The objective of this study was to determine whether a history of SARS-CoV-2 infection increases the risk of adverse postoperative events following surgery in patients with cancer. METHODS: This was a propensity-matched cohort study from April 6, 2020 to October 31, 2020 at the UT MD Anderson Cancer Center. Cancer patients were identified who underwent elective surgery after recovering from SARS-CoV-2 infection and matched to controls based on patient, disease, and surgical factors. Primary study outcome was a composite of the following adverse postoperative events that occurred within 30 days of surgery: death, unplanned readmission, pneumonia, cardiac injury, or thromboembolic event. RESULTS: A total of 5682 patients were included for study, and 114 (2.0%) had a prior SARS-CoV-2 infection. The average time from infection to surgery was 52 (range 20-202) days. Compared with matched controls, there was no difference in the rate of adverse postoperative outcome (14.3% vs. 13.4%, p = 1.0). Patients with a SARS-CoV-2-related inpatient admission before surgery had increased odds of postoperative complication (adjusted odds ratio [aOR] 7.4 [1.6-34.3], p = 0.01). CONCLUSIONS: A minimal wait time of 20 days after recovering from minimally symptomatic SARS-CoV-2 infection appears to be safe for cancer patients undergoing low-risk elective surgery. Patients with SARS-CoV-2 infections requiring inpatient treatment were at increased risk for adverse events after surgery. Additional wait time may be required in those with more severe infections.

Influencers of the Decision to Undergo Contralateral Prophylactic Mastectomy among Women with Unilateral Breast Cancer.

(1) Background: The relatively high rate of contralateral prophylactic mastectomy (CPM) among women with early stage unilateral breast cancer (BC) has raised concerns. We sought to assess the influence of partners, physicians, and the media on the decision of women with unilateral BC to undergo CPM and identify clinicopathological variables associated with the decision to undergo CPM. (2) Patients and Methods: Women with stage 0 to III unilateral BC who underwent CPM between January 2010 and December 2017. Patients were surveyed regarding factors influencing their self-determined decision to undergo CPM. Partner, physician, and media influence factors were modeled by logistic regressions with adjustments for a family history of breast cancer and pathological stage. (3) Results: 397 (29.6%) patients completed the survey and were included in the study. Partners, physicians, and the media significantly influenced patients' decision to undergo CPM. The logistic regression models showed that, compared to self-determination alone, overall influence on the CPM decision was significantly higher for physicians (p = 0.0006) and significantly lower for partners and the media (p < 0.0001 for both). Fifty-nine percent of patients' decisions were influenced by physicians, 28% were influenced by partners, and only 17% were influenced by the media. The model also showed that patients with a family history of BC had significantly higher odds of being influenced by a partner than did those without a family history of BC (p = 0.015). (4) Conclusions: Compared to self-determination, physicians had a greater influence and partners and the media had a lower influence on the decision of women with unilateral BC to undergo CPM. Strong family history was significantly associated with a patient's decision to undergo CPM.

Acceptability of 3D-printed breast models and their impact on the decisional conflict of breast cancer patients: A feasibility study.

PURPOSE: To evaluate the acceptability and impact of 3D-printed breast models (3D-BMs) on treatment-related decisional conflict (DC) of breast cancer patients. METHODS: Patients with breast cancer were accrued in a prospective institutional review board-approved trial. All patients underwent contrast-enhanced breast magnetic resonance imaging (MRI). A personalized 3D-BM was derived from MRI. DC was evaluated pre- and post-3D-BM review. 3D-BM acceptability was assessed post-3D-BM review. RESULTS: DC surveys before and after 3D-BM review and 3D-BM acceptability surveys were completed by 25 patients. 3D-BM were generated in two patients with bilateral breast cancer. The mean patient age was 48.8 years (28-72). The tumor stage was Tis (7), 1 (8), 2 (8), and 3 (4). The nodal staging was 0 (19), 1 (7), and 3 (1). Tumors were unifocal (15), multifocal (8), or multicentric (4). Patients underwent mastectomy (13) and segmental mastectomy (14) with (20) or without (7) oncoplastic intervention. Neoadjuvant therapy was given to seven patients. Patients rated the acceptability of the 3D-BM as good/excellent in understanding their condition (24/24), understanding disease size (25/25), 3D-BM detail (22/25), understanding their surgical options (24/25), encouraging to ask questions (23/25), 3D-BM size (24/25), and impartial to surgical options (17/24). There was a significant reduction in the overall DC post-3D-BM review, indicating patients became more assured of their treatment choice (p = 0.002). Reduction post-3D-BM review was also observed in the uncertainty (p = 0.012), feeling informed about options (p = 0.005), clarity about values (p = 0.032), and effective (p = 0.002) Decisional Conflict Scale subscales. CONCLUSIONS: 3D-BMs are an acceptable tool to decrease DC in breast cancer patients.

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients.

BACKGROUND: Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. METHODS: This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. RESULTS: Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. CONCLUSIONS: Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds.

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.