Contemporary Axillary Surgical Management in Patients with Pathologically Node Positive Disease After Neoadjuvant Chemotherapy: A Survey of Members of the American Society of Breast Surgeons.

BACKGROUND: Axillary lymph node dissection (ALND) is increasingly omitted for breast cancer patients with pathologic nodal disease after neoadjuvant chemotherapy (NAC). This study aimed to understand when and why surgeons consider omitting ALND after NAC. METHODS: The American Society of Breast Surgeons membership was surveyed, and responses were tabulated. To identify patterns, multiple correspondence analyses followed by cluster analysis on coordinates provided by the former were performed. Chi-squared analyses determined whether cluster characteristics were significantly (P < 0.05) associated with omission of ALND. RESULTS: Of members, 328/2172 (15.1%) completed the survey. Most (60.7%) always offer sentinel lymph node surgery to cN1 patients who respond to NAC, and many (43.9%) sometimes omit ALND in the setting of residual nodal disease. Respondents less often consider omitting ALND with increasing volume of pathologic nodal disease after NAC and are less likely to omit ALND among patients with cN1 disease at presentation than cN0 (P < 0.05 across all volumes). Respondents cited radiation administration (74.1%) and belief that ALND would not improve locoregional (48.2%), distant recurrence or survival (47.6%) outcomes when axillary radiation is administered as reasons to omit ALND. The respondent group comprising male private practice surgeons, practicing ≥ 21 years, consider omitting ALND significantly more frequently. CONCLUSIONS: Surgeons sometimes consider ALND omission for patients with pathologic nodal disease after NAC but are more likely to do so in cN0 patients and patients with smaller volumes of nodal disease. These decisions are largely based on perceived lack of oncologic benefit despite absence of prospective data supporting this deescalation.

Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial.

Importance: Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. Objective: To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. Design, Setting, and Participants: A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Interventions: Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs >30], stage II vs III, and time since diagnosis [<18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. Main Outcomes and Measures: The primary outcome was invasive disease-free survival. Overall survival was a key secondary outcome. Results: A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease-free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease-free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Conclusion and Relevance: Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02927249.

Systemic Therapy Advances for HER2-Positive and Triple Negative Breast Cancer: What the Surgeon Needs to Know.

Neoadjuvant systemic therapy (NST) was initially reserved for unresectable patients however it has been increasingly used to facilitate breast conservation, downstage the axilla, and inform adjuvant therapy decisions based on response. For patients with HER2+ and triple-negative breast cancer (TNBC), clinical trials have resulted in the ability to individualize treatment regimens. For HER2+ breast cancer, de-escalation of neoadjuvant regimens to minimize cytotoxic chemotherapy and de-escalation or escalation of adjuvant regimens based on response have been effective. For TNBC, the approval of the combination of chemotherapy plus immunotherapy in the neoadjuvant setting has resulted in a major practice shift and opened the door to many additional treatment questions including de-escalation of the chemotherapy backbone or the adjuvant regimen. For both HER2+ and TNBC, most patients are treated with NST except those with very small tumors. Efforts are also being made to optimally identify patients with T1c tumors who may benefit from more aggressive NST. For patients treated according to or enrolled in NST de-escalation trials, breast conservation (even those who become eligible based on response to NST) and sentinel lymph node biopsy when cN0 at the completion of NST are safe and feasible. Continued involvement of surgeons and multidisciplinary teams in the design and reporting of trials will streamline their adoption into clinical practice. Surgeons need to remain aware of ongoing systemic therapy trials to appropriately select patients for NST and plan for appropriate post-neoadjuvant surgical care.

Clinicopathological characteristics and eligibility for adjuvant olaparib of germline BRCA1/2 mutation carriers with HER2-negative early breast cancer.

Following the survival benefit demonstrated in the OlympiA trial, one year of adjuvant olaparib is now recommended for all patients with germline BRCA1/2 pathogenic/likely pathogenic variants (PV) and high-risk, HER2-negative early breast cancer after chemotherapy. However, optimal identification of high-risk patients who may derive benefit from this genomically-directed therapy is debated. In this study, we sought to characterize the real-world proportion of gBRCA1/2 PV carriers eligible for adjuvant olaparib according to the OlympiA criteria, and to compare clinicopathologic characteristics and outcomes between eligible and ineligible patients.

Implementation of a Trauma-Informed Challenging Interactions Reporting Tool to Improve our Clinical Learning Environment.

PROBLEM: Workplace mistreatment is a contributor to resident burnout; understanding and intervening against mistreatment is one key tool in mitigating burnout. While Accreditation Council for Graduate Medical Education (ACGME) survey data alerts programs to general mistreatment trends, those data are not detailed enough to inform local interventions. Our team designed and implemented a Challenging Interactions Reporting Tool (CIRT) to characterize the experiences of our trainees at a granular level and to inform targeted interventions for improvement. APPROACH: Our CIRT was offered to 158 residents in August 2020 via REDCap. Residents submit electronic reports that are reviewed weekly by program leaders who develop action plans for each report. Reporters can identify themselves or can choose to remain anonymous. When "hot spots" for mistreatment are identified in our hospital, we implement a targeted systems-level intervention. OUTCOMES: Residents filed 275 reports between August 2020 and December 2022. Reports represented all training environments and involved all interprofessional members of clinical teams. Residents reported awareness of, use of, and satisfaction with the tool. NEXT STEPS: Our program created the CIRT as a tool to inform local interventions for improving the safety of our clinical learning environment. We continue to disseminate our tool across our hospital's GME programs and are now measuring the impact of our interventions.

Updates in the Surgical Management of Benign and High-Risk Breast Lesions.

Benign breast disease (BBD) is a heterogenous group of lesions often classified as nonproliferative or proliferative, with the latter group further categorized based on the presence of atypia. Although nonproliferative lesions are more common, the risk of breast cancer is elevated in women with proliferative lesions. Historically, the majority of proliferative lesions were excised due to concern for future and/or concomitant breast cancer at the site of the index lesion. However, contemporary data suggest that the risk of cancer associated with various proliferative lesions may be lower than previously thought, and management of BBD has become more nuanced. In this review, we will focus on recent updates in the management of a select group of benign and high-risk lesions.

Recent Advances in the Upfront Surgical Management of the Axilla in Patients with Breast Cancer.

Nodal status is an important prognostic indicator. Upfront axillary surgery for patients with breast cancer has historically been both diagnostic and therapeutic-serving to determine nodal status and inform adjuvant therapies, and to remove clinically significant disease. However, trials of de-escalation or omission of axillary surgery altogether consistently demonstrate noninferior oncologic outcomes in a wide variety of patient subsets. These strategies also reduce the morbidity associated with either sentinel lymphadenectomy or axillary lymph node dissection. Here we will briefly review landmark trials that have shaped upfront axillary surgery as well as recent advances, and discuss areas of ongoing investigation and future needs.

Single versus Double Drainage for Immediate Two-Stage Implant-Based Breast Reconstruction: A Propensity Score-Matched Analysis.

BACKGROUND: Reports evaluating plastic surgeons' practices indicate there are conflicting trends regarding the use of one or two drains for implant-based breast reconstruction (IBBR). Our study aimed to perform a matched cohort analysis to examine the postoperative outcomes and complications of immediate IBBR with tissue expander (TE) using two drains versus a single drain. METHODS: A propensity score-matched analysis (nearest neighbor, 1:1 matching) of immediate reconstructions using two versus one drain was conducted. Female patients undergoing immediate two-stage IBBR with TEs between January 2011 and May 2021 were included. The covariables were as follows: BMI, mastectomy weight, lymph node surgery, TE surface, plane of reconstruction, use of acellular dermal matrix products, fluorescence imaging use, and intraoperative TE volume. RESULTS: After matching using propensity scores, 192 reconstructions were included in the final analysis: 96 in each group. The rate of 30-day complications and overall complications during the first phase of IBBR were comparable between groups. The time for drain removal, time to initiate and finalize expansions, and time for TE-to-implant exchange were comparable between groups. Diabetes (OR 3.74, p = 0.025) and an increased estimated blood loss (OR 1.004, p = 0.01) were the only independent predictors for seroma formation. CONCLUSION: In this matched cohort analysis evaluating the role of one versus two drains for two-stage IBBR, we found a comparable rate of complications and surgical outcomes between the two cohorts. Using two drains for immediate IBBR needs to be tailored depending on intraoperative findings. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

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.

Latissimus dorsi flap with immediate fat transfer (LIFT) for autologous breast reconstruction: Single institution experience.

BACKGROUND: Few studies have reported the outcomes of LDF and immediate fat transfer (LIFT) during breast reconstruction. The aim of this study was to compare the perioperative outcomes and complications of LIFT and standard LDF (without immediate fat transfer) for breast reconstruction. METHODS: We retrospectively reviewed charts from patients undergoing autologous breast reconstruction after total mastectomy between 2011 and 2021. We compared intraoperative and postoperative outcomes between groups. RESULTS: One hundred nineteen reconstructions (61.02%) were performed with LIFT, while seventy-six (38.98%) were performed with standard LDF. The median volume of total fat transferred during LIFT was 125-cc [110-170 â€‹cc]. The rates of donor site wound disruption (23.7% versus 12.6%, p â€‹= â€‹0.044) were higher using the standard LDF compared to LIFT. Reconstructions performed with LIFT (HR 4.01, p â€‹< â€‹0.001) were found to be associated with secondary fat grafting procedures. CONCLUSION: LIFT is a safe procedure to enhance the volume of LDF in patients desiring autologous reconstruction without increasing recipient-site morbidity. On a time-to-event analysis, LIFT was associated with the requirement of further revision procedures using secondary fat grafting.

Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial.

BACKGROUND: Patients with ERBB2 (HER2)-positive breast cancer experience high pathologic complete response (pCR) rates after standard neoadjuvant anti-HER2 systemic therapy. We examined axillary pathologic nodal response to neoadjuvant dual HER2-targeted therapy alone, based on breast pathologic response, in a multi-institution clinical trial. STUDY DESIGN: Patients with HER2-positive breast cancer were enrolled to a phase II single-arm trial, which administered 6 cycles of neoadjuvant trastuzumab emtansine (T-DM1) plus pertuzumab. Rates of pathologic nodal disease (ypN) in patients who were clinically node-negative (cN0) and node-positive (cN1) were analyzed, by residual breast disease (pCR and residual cancer burden [RCB] I to III). RESULTS: One hundred fifty-eight patients completed preoperative treatment and proceeded to surgery. Of 92 patients who were cN0, 48 (52.2%) and 10 (10.9%) experienced breast pCR and RCB I, respectively. Of these, 100% were ypN0. Of 34 with RCB II to III, 26 (76.5%) were ypN0. Of 30 patients who were cN1 with breast pCR, 100% were ypN0; of the 12 patients who were cN1 with RCB I, 66.7% were ypN0; and of the 24 patients who were cN1 with RCB II to III, 25% were ypN0. ypN0 rates were significantly different between patients who did and did not experience a pCR, in both cN0 (p = 0.002) and cN1 (p < 0.001) subgroups. CONCLUSIONS: Patients with HER2-positive breast cancer treated with dual HER2-targeted therapy who experienced a breast pCR or RCB I response were frequently ypN0. These findings support future trials considering omission of axillary surgical staging for patients with HER2-positive breast cancer in neoadjuvant trials of active HER2-targeted regimens, particularly if they experience breast pCR or RCB I.

Positive predictive value of axillary lymph node cortical thickness and nodal, clinical, and tumor characteristics in newly diagnosed breast cancer patients.

PURPOSE: Axillary lymph nodes (LNs) with cortical thickness > 3 mm have a higher likelihood of malignancy. To examine the positive predictive value (PPV) of axillary LN cortical thickness in newly diagnosed breast cancer patients, and nodal, clinical, and tumor characteristics associated with axillary LN metastasis. METHODS: Retrospective review of axillary LN fine needle aspirations (FNAs) performed 1/1/2018-12/31/2019 included 135 axillary FNAs in 134 patients who underwent axillary surgery. Patient demographics, clinical characteristics, histopathology, and imaging features were obtained from medical records. Hypothesis testing was performed to identify predictors of axillary LN metastasis. RESULTS: Cytology was positive in 72/135 (53.3%), negative in 61/135 (45.2%), and non-diagnostic in 2/135 (1.5%). At surgery, histopathology was positive in 84 (62.2%) and negative in 51 (37.8%). LN cortices were thicker in metastatic compared to negative nodes (p < 0.0001). PPV of axillary LNs with cortical thickness ≥ 3 mm, ≥ 3.5 mm, ≥ 4 mm and, ≥ 4.25 mm was 0.62 [95% CI 0.53, 0.70], 0.63 [0.54, 0.72], 0.67 [0.57, 0.76] , and 0.74 [0.64, 0.83], respectively. At multivariable analysis, abnormal hilum (OR = 3.44, p = 0.016) and diffuse cortical thickening (OR = 2.86, p = 0.038) were associated with nodal metastasis. CONCLUSION: In newly diagnosed breast cancer patients, increasing axillary LN cortical thickness, abnormal fatty hilum, and diffuse cortical thickening are associated with nodal metastasis. PPV of axillary LN cortical thickness ≥ 3 mm and ≥ 3.5 mm is similar but increases for cortical thickness ≥ 4 mm. FNA of axillary LNs with cortex < 4 mm may be unnecessary for some patients undergoing sentinel LN biopsy.

HER2 categorical changes after neoadjuvant chemotherapy: A study of 192 matched breast cancers with the inclusion of HER2-Low category.

Understanding the changes of HER2 expression after neoadjuvant chemotherapy (NAC) in breast cancer (BC) is more important than ever, since it may allow more patients to access the effective therapeutic drugs targeting HER2-low BC. 192 matched pre- and post-NAC BCs were analyzed. HER2 immunohistochemistry (IHC) was re-evaluated with consensus according to the current ASCO/CAP guidelines. Tumors were categorized into HER2-0 (IHC0+), HER2-low (IHC1+ or IHC2+/ISH-) and HER2-positive (IHC3+ or IHC2+/ISH+) subgroups. 55 (28.6 %) patients achieved pathologic complete response (pCR). HER2-low BC accounted for 75/192 (39.1 %) baseline tumors, and 48/133 (36.1 %) residual tumors. In the non-pCR cohort, 53 (39.9 %) patients had HER2 categorical change after NAC, most commonly converting from HER2-low to HER2-0 (20.3 %, n = 27). Among patients with residual tumor, 25.6 % (11/43) of patients with baseline HER2-0 expression experienced a categorical change to HER2-low after NAC, significantly higher (p < 0.05) in the hormone receptor (HR) positive (9/23, 39.1 %) compared to the HR negative tumors (10 %, 2/20). Exploratory analysis failed to reveal a statistically significant difference in disease free survival and overall survival in non-pCR patients with or without HER2 change. Our results suggest that a substantial number of patients may experience HER2 categorical change after NAC, supporting re-testing of HER2 status in post-NAC residual tumors. Retesting HER2 status may be particularly important for evaluating post-NAC HER2-low status, in order to better assess which patients will more likely benefit from therapeutic drugs targeting HER2-low BC.

A Systematic Review of Breast Implant-Associated Squamous Cell Carcinoma.

Breast augmentation is considered safe, but rare cases of breast implant-associated squamous cell carcinoma (BIA-SCC) have been reported. This study aimed to systematically review published cases of BIA-SCC, providing valuable clinical data. The review included 14 articles and 18 cases of BIA-SCC. An increasing trend in reported BIA-SCC cases was observed, with four cases in the 1990s and 14 cases since 2010. The mean age of affected patients was 56 years, and symptoms typically appeared around 21 years after breast augmentation. Silicone implants used in cosmetic procedures were most commonly associated with BIA-SCC. Implant removal was necessary in all cases, and some patients required a mastectomy. Treatment approaches varied, with the selective use of chemotherapy and/or radiotherapy. The estimated 6-month mortality rate was 11.1%, while the 12-month mortality rate was 23.8%. The estimated 6-month mortality rate should be cautiously interpreted due to the limited sample size. It appears lower than the rate reported by the American Society of Plastic Surgeons, without clear reasons for this discrepancy. This study highlights the importance of enhanced monitoring and information sharing to improve detection and management of BIA-SCC. Healthcare providers should maintain vigilance during the long-term follow-up of breast augmentation patients.