Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Accelerated Partial Breast Irradiation for HER2-Positive Early-Stage Breast Cancer.

PURPOSE: HER2-positive (HER2+) breast cancer historically exhibited the most adverse local outcomes and, consequently, has had limited representation among trials of partial breast irradiation (PBI). We hypothesized that with contemporary HER2-targeted agents, patients may now exhibit excellent disease control outcomes after adjuvant PBI. METHODS AND MATERIALS: Using a prospectively maintained institutional database, we identified patients with HER2+ breast cancer treated with breast conserving surgery (BCS) and PBI from 2000 to 2022. Salient clinicopathologic and treatment parameters were collected. All patients received external beam PBI to 40 Gy in 10 daily fractions. Cumulative incidence functions were calculated to estimate the incidence of local recurrence (LR) with the competing risk of death. RESULTS: We identified 1248 patients who underwent PBI at our institution, of whom the study cohort comprised 52 (4%) with HER2+ breast cancer (median age, 64 years; range, 44-87). Nearly all had T1 tumors (98%; median size, 12 mm [range, 1-21 mm]). Most had estrogen receptor positive disease (88%), and all patients had negative surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. Forty-two (81%) received chemotherapy; 40 (77%), hormone therapy; and 42 (81%), HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range, 7-226 months for each patient), we observed 2 LR events at 14 and 26 months, respectively, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any breast-specific mortality events. Two deaths were observed, both without evidence of disease. CONCLUSIONS: Among a cohort of patients with HER2+ early-stage breast cancer managed with BCS and PBI, we observed a 2-year LR rate of 3.8%, with no regional or distant recurrences and excellent overall survival. These findings require confirmation with longer follow-up among larger cohorts but appear consistent with the excellent results of contemporary randomized trials of PBI unselected for HER2 status.

Impact of Imaging-Guided Localization on Performance of Tailored Axillary Surgery in Patients with Clinically Node-Positive Breast Cancer: Prospective Cohort Study Within TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

BACKGROUND: Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting. This study assessed whether/how imaging-guided localization (IGL) influenced TAS. PATIENTS AND METHODS: This was a prospective observational cohort study preplanned in the randomized phase-III OPBC-03/TAXIS trial. IGL was performed at the surgeon's discretion for targeted removal of LNs during TAS. Immediate back-up axillary lymph node dissection (ALND) followed TAS according to TAXIS randomization. RESULTS: Five-hundred patients were included from 44 breast centers in six countries, 151 (30.2%) of whom underwent NACT. IGL was performed in 84.4% of all patients, with significant variation by country (77.6-100%, p < 0.001). No difference in the median number of removed (5 vs. 4, p = 0.3) and positive (2 vs. 2, p = 0.6) LNs by use of IGL was noted. The number of LNs removed during TAS with IGL remained stable over time (p = 0.8), but decreased significantly without IGL, from six (IQR 4-6) in 2019 to four (IQR 3-4) in 2022 (p = 0.015). An ALND was performed in 249 patients, removing another 12 (IQR 9-17) LNs, in which a median number of 1 (IQR 0-4) was positive. There was no significant difference in residual nodal disease after TAS with or without IGL (68.0% vs. 57.6%, p = 0.2). CONCLUSIONS: IGL did not significantly change either the performance of TAS or the volume of residual nodal tumor burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513614.

Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?

BACKGROUND: Breast cancer subtypes, distinguished by hormone receptor (HR) and HER2 status, have different clinicopathologic features. With recognition of the clinical relevance of HER2-low, there is debate as to whether this is a distinct subtype. Our study aimed to determine whether HER2-low breast cancers have specific clinicopathologic features that differ from those of HER2-negative and HER2-positive cancers. PATIENTS AND METHODS: A total of 11,072 patients undergoing upfront surgery from 1998 to 2010 were identified from a single-institution prospectively maintained database. HER2 status was classified by immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) as HER2 negative (41.2%), HER2 low (45%; IHC 1+ or 2+ with negative FISH), and HER2 positive (13.7%), and stratified by HR status. Univariate (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. RESULTS: Compared with HER2-negative tumors, HER2 low was associated with lymphovascular invasion [odds ratio (OR) 1.2, 95% confidence interval (CI) 1.06-1.36; p = 0.003], multifocality (OR 1.26, 95% CI 1.12-1.42; p < 0.001), nodal micrometastasis (OR 1.15, 95% CI 1.02-1.31; p = 0.024), and lower rates of ≥ 3 positive nodes (OR 0.77, 95% CI 0.66-0.90, p = 0.001). When stratified by HR expression, in both HR-positive and HR-negative tumors, age and multifocality were associated with HER2 low on UVA. On MVA, no variables were independently associated with both HR-negative and HR-positive/HER2-low tumors compared with HER2-negative tumors. In contrast, HER2-positive tumors, regardless of HR status, were associated with multifocality and an extensive intraductal component. CONCLUSION: Clinicopathologic features of HER2-low tumors appear to be primarily related to HR status. Our findings do not support the characterization of HER2 low as a separate subtype.

Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer.

Background: Opioids are the primary analgesics for cancer pain. Recent clinical evidence suggests opioids may counteract the effect of immune checkpoint inhibition (ICI) immunotherapy, but the mechanism for this interaction is unknown. The following experiments study how opioids and immunotherapy modulate a common RNA expression pathway in triple negative breast cancer (TNBC), a cancer subtype in which immunotherapy is increasingly used. This study identifies a mechanism by which opioids may decrease ICI efficacy, and compares ketamine, a non-opioid analgesic with emerging use in cancer pain, for potential ICI interaction. Methods: Tumor RNA expression and clinicopathologic data from a large cohort with TNBC (N=286) was used to identify RNA expression signatures of disease. Various drug-induced RNA expression profiles were extracted from multimodal RNA expression datasets and analyzed to estimate the RNA expression effects of ICI, opioids, and ketamine on TNBC. Results: We identified a RNA expression network in CD8+ T-cells that was relevant to TNBC pathogenesis and prognosis. Both opioids and anti-PD-L1 ICI regulated RNA expression in this network, suggesting a nexus for opioid-ICI interaction. Morphine and anti-PD-L1 therapy regulated RNA expression in opposing directions. By contrast, there was little overlap between the effect of ketamine and anti-PD-L1 therapy on RNA expression. Conclusions: Opioids and ICI may target a common immune network in TNBC and regulate gene expression in opposing fashion. No available evidence supports a similar interaction between ketamine and ICI.

Managing the Morbidity: Individualizing Risk Assessment, Diagnosis, and Treatment Options for Upper Extremity Lymphedema.

In the setting where breast cancer-related lymphedema (BCRL) remains a feared and common complication of breast cancer, here we review important factors for the development, diagnosis, prevention, and treatment of BCRL. We find that race/ethnicity affect BCRL development risk, that future studies should focus on understanding the biological reasons behind the increased susceptibility of certain racial minorities to BCRL, that surveillance, early detection, exercise programs, and arm compression can reduce the risk of BCRL, and that surgical techniques to preserve and restore lymphatic drainage being evaluated in randomized trials may become transformative in reducing BCRL risk for high-risk patients.

The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

Conventional and assisted suicide in Switzerland: Insights into a divergent development based on cancer-associated self-initiated deaths.

BACKGROUND: We tested the hypothesis of supporters of assisted dying that assisted suicide (AS) might be able to prevent cases of conventional suicide (CS). METHODS: By using data from the Federal Statistical Office, we analyzed the long-term development of 30,756 self-initiated deaths in Switzerland over a 20-year period (1999-2018; CS: n = 22,018, AS: n = 8738), focusing on people suffering from cancer who died from AS or CS. RESULTS: While cancer was the most often listed principal disease for AS (n = 3580, 41.0% of AS cases), cancer was listed in only a small minority of CS cases (n = 832, 3.8% of CS cases). There was a significant increase in the absolute number of cancer-associated AS cases: comparing four 5-year periods, there was approximately a doubling of cases every 5 years (1999-2003: n = 228 vs.2004-2008: n = 474, +108% compared with the previous period; 2009-2013: n = 920, +94%; 2014-2018: n = 1958, +113%). The ratio of cancer-associated AS in relationship with all cancer-associated deaths increased over time to 2.3% in the last observation period (2014-2018). In parallel, the numbers of cancer-associated CS showed a downward trend only at the beginning of the observation period (1999-2003, n = 240 vs. 2004-2008, n = 199, -17%). Thereafter, the number of cases remained stable in the subsequent 5-year period (2009-2013, n = 187, -6%), and increased again toward the most recent period (2014-2018, n = 206, +10%). CONCLUSION: The assumption that, with the increasingly accessible option of AS for patients with cancer, CS suicide will become "superfluous" cannot be confirmed. There are strong reasons indicating that situations and circumstances of cancer-associated CS are different from those for cancer-associated AS.

Current practice in assessment and management of malnutrition in surgical oncology practice - An ESSO-EYSAC snapshot analysis.

INTRODUCTION: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments. MATERIAL AND METHODS: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team. RESULTS: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation. CONCLUSIONS: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

PURPOSE: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. METHODS: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively. RESULTS: A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022. CONCLUSION: Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer.

Uncertainties and controversies in axillary management of patients with breast cancer.

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.

The effect of insurance status on treatment modality in advanced oral cavity cancer.

BACKGROUND: Insurance status has been shown to impact survival outcomes. We sought to determine whether insurance affects the choice of treatment modality among patients with advanced (T4) oral cavity squamous cell carcinoma. METHODS: This is a retrospective, population-based cohort study using the Survival, Epidemiology, and End Results Program database. The population included all adult (age ≥ 18) patients with advanced (T4a or T4b) oral cavity squamous cell carcinoma diagnosed from 2007 to 2016. The main outcome was the odds of receiving definitive treatment, defined as primary surgical resection. Insurance status was categorized into uninsured, any Medicaid, and insured groups. Univariable, multivariable, and subgroup analyses were performed. RESULTS: The study population consisted of 2628 patients, of whom 1915 (72.9%) were insured, 561 (21.3%) had Medicaid, and 152 (5.8%) were uninsured. The multivariable model showed that patients who were 80 years or older, unmarried, received treatment in the pre-Affordable Care Act (ACA) period, and who were on Medicaid or uninsured were significantly less likely to receive definitive treatment. Insured patients were significantly more likely to receive definitive treatment compared to those on Medicaid or uninsured (OR = 0.59, 95% CI 0.46-0.77, p < 0.0001 [Medicaid vs. Insured]; and OR = 0.48, 95% CI 0.31-0.73 p = 0.001 [Uninsured vs. Insured]), however these differences did not persist when considering only those patients treated following the 2014 expansion of the ACA. CONCLUSIONS: Insurance status is significantly associated with treatment modality among adults with advanced stage (T4a) oral cavity squamous cell carcinoma. These findings support the premise of expanding insurance coverage in the US.

Long-term development of assisted suicide in Switzerland: analysis of a 20-year experience (1999-2018).

AIMS OF THE STUDY: The legalisation of assisted suicide is one of the most debated topics in the field of medical ethics worldwide. In countries in which assisted suicide is not legal, public discussions about its approval also encompass considerations of the long-term consequences that such legalisation would bring, for example, how many people will use this option, from what conditions would they be suffering, would there be differences between male and female assisted suicide and which developments and trends could be expected if there were to be a marked increase of cases of assisted suicide over time? METHODS: In order to answer these questions, we present the development of assisted suicide in Switzerland over a 20-year period (1999-2018; 8738 cases) using data from the Swiss Federal Statistical Office. RESULTS: During the observation period, the number of assisted suicides rose significantly: when four 5-year periods (1999-2003, 2004-2008, 2009-2013, 2014-2018) were analysed, the number of assisted suicide cases doubled over each period compared with the preceding one (Χ = 206.7, 270.4 and 897.4; p <0.001). The percentage of assisted suicides among all deaths rose from 0.2% (1999-2003; n = 582) to 1.5% (2014-2018: n = 4820). The majority of people who chose assisted suicide were elderly, with increasing age over time (median age in 1999-2003: 74.5 years vs 2014-2018: 80 years), and with a predominance of women (57.2% vs 42.8%). The most common underlying condition for assisted suicide was cancer (n = 3580, 41.0% of all assisted suicides). Over time, assisted suicide increased similarly for all underlying conditions; however, the proportion in each disease group remained unchanged. CONCLUSIONS: It is a matter of one's viewpoint whether the rise of assisted suicide cases should be considered alarming or not. These figures reflect an interesting social development but still do not appear to represent a mass phenomenon.

Should Acellular Dermal Matrices Be Used for Implant-based Breast Reconstruction after Mastectomy? Clinical Recommendation Based on the GRADE Approach.

Acellular dermal matrices (ADMs) entered the market in the early 2000s and their use has increased thereafter. Several retrospective cohort studies and single surgeon series reported benefits with the use of ADMs. However, robust evidence supporting these advantages is lacking. There is the need to define the role for ADMs in implant-based breast reconstruction (IBBR) after mastectomy. Methods: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints, and establish recommendation for the use of ADMs for subpectoral one-/two-stage IBBR (compared with no ADM use) for adult women undergoing mastectomy for breast cancer treatment or risk reduction using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Based on the voting outcome, the following recommendation emerged as a consensus statement: the panel members suggest subpectoral one- or two-stage IBBR either with ADMs or without ADMs for adult women undergoing mastectomy for breast cancer treatment or risk reduction (with very low certainty of evidence). Conclusions: The systematic review has revealed a very low certainty of evidence for most of the important outcomes in ADM-assisted IBBR and the absence of standard tools for evaluating clinical outcomes. Forty-five percent of panel members expressed a conditional recommendation either in favor of or against the use of ADMs in subpectoral one- or two-stages IBBR for adult women undergoing mastectomy for breast cancer treatment or risk reduction. Future subgroup analyses could help identify relevant clinical and pathological factors to select patients for whom one technique could be preferable to another.

Axillary Staging Is Not Justified in Postmenopausal Clinically Node-Negative Women Based on Nodal Disease Burden.

BACKGROUND: RxPONDER showed no benefit of adjuvant chemotherapy in postmenopausal women with estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer and limited nodal burden (pN1) with a recurrence score ≤ 25, suggesting that axillary staging could be omitted in cN0 patients if significant numbers of such women do not have pN2-3 disease. Here we evaluate the pN2-3 disease rate in a large cohort of postmenopausal women presenting with cN0 breast cancer. PATIENTS AND METHODS: Consecutive postmenopausal patients presenting with T1-2N0 breast cancer who underwent axillary surgery from February 2006 to December 2011 were identified. Clinicopathologic characteristics associated with pN2-3 disease were examined using chi-square or Fisher's exact tests. RESULTS: Of 3363 postmenopausal women with cT1-2N0 breast cancer (median age 58 years, IQR 48-67 years), median tumor size was 1.3 cm (IQR 0.90-1.90cm). Post-axillary staging, 2600 (77.3%) were pN0, 643 (19.1%) were pN1, and 120 (3.6%) were pN2-3. The pN2-3 disease rate did not differ across subtypes (4.4% HER2+, 3.5% HR-/HER2-, 3.5% HR+/HER2-, p = 0.70). In the subset with HR+/HER2- tumors, on multivariable analysis, age < 65 years (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.32-4.49), lymphovascular invasion (OR 5.29, 95% CI 2.72-11.2), multifocal/centric tumors (OR 3.08, 95% CI 1.79-5.32), and tumor size > 2 cm (OR 5.51, 95% CI 3.05-10.4) were significantly associated with pN2-3 nodal burden. Of 506 patients with tumors > 2 cm, 49 (9.7%) had pN2-3 disease; in the subset of 90 patients age < 65 years who had multifocal/centric tumors > 2 cm, 23 (25.6%) had pN2-3 disease. CONCLUSIONS: In postmenopausal women with cN0 disease, pN2-3 nodal burden is uncommon; omitting axillary staging would not miss a significant number of patients who might benefit from adjuvant chemotherapy. Information available preoperatively indicating a higher risk of nodal disease such as younger age and large, multifocal tumors should be considered in the multidisciplinary management of the axilla.

Outcomes of Breast Cancer Patients with High Volume of Residual Disease Following Neoadjuvant Chemotherapy.

PURPOSE: The use of neoadjuvant chemotherapy (NAC) in patients with operable breast cancer allows for assessment of treatment response and subsequent tailoring of adjuvant therapy. Data are limited with respect to outcomes among patients with a heavy residual tumor burden after NAC. We report outcomes in patients who had exceptionally poor responses to NAC: those with >9 involved nodes after NAC or with 5 cm or more of residual disease in the breast. METHODS AND MATERIALS: Between June 2014 and April 2020, 1511 patients with breast cancer received NAC followed by surgery at our institution. Poor responders, defined as those with positive nodes or residual tumor in the breast, were identified for analysis. Patients were further classified into 3 groups for comparison purposes: (1) 1 to 3 positive nodes; (2) 4 to 9 positive nodes; or (3) >9 positive nodes and/or >5 cm of residual tumor, which was defined as high-volume residual (HVR). Recurrence and survival outcomes were compared based on residual disease burden after NAC. RESULTS: Among 934 poor responders, 539 patients had 1 to 3 positive nodes (ypN1), 215 had 4 to 9 positive nodes (ypN2), and 180 had HVR disease. Specifically, 118 had >9 positive nodes (HVR), and 62 patients had >5 cm of residual tumor in the breast. With a median follow-up of 31 months (interquartile range, 18-46), the 5-year overall survival rate was 88% among ypN1, 76% among ypN2, and 72% among patients with HVR disease (P < .001). The 5-year distant recurrence-free survival and locoregional recurrence incidences were 82% and 7.6% among ypN1 versus 67% and 8.4% among ypN2 versus 53% and 12% among HVR, respectively. CONCLUSIONS: Our work suggests that patients with HVR disease are at high risk for locoregional and distant recurrence as well as death, despite best available standard-of-care treatment. Intensification of locoregional therapies and/or alternative adjuvant systemic treatment may improve outcomes in these poor responders.