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PDF file - 1392K, PTEN IHC changes from pre-trastuzumab to post-trastuzumab samples. Depicted are photomicrographs of PTEN change from reduced to loss of expression: a) PTEN expression by IHC in the primary breast invasive carcinoma with reduced nuclear and cytoplasmic staining as compared to the adjacent normal stroma (200X); b) HE staining of the primary lesion (200X); c) PTEN complete loss of expression in the secondary invasive carcinoma with absence of any staining in the lesion as compared to the adjacent normal stroma (200X); d) HE staining of the secondary lesion (200X)

PDF file - 109K, Supplementary Table 1. Changes in HER2 status Supplementary Table 2. Changes in PTEN status Supplementary Table 3. Changes in PIK3CA status Supplementary Table 4. PI3K mutation and PTEN loss are not mutually exclusive Supplementary Table 5. ER/PR status among PI3K activated tumors

Purpose: Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.Experimental Design: WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) of the breast. Two independent groups were examined in cross-sectional (cohort 1) and retrospective (cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90). Metabolic syndrome–associated circulating factors were compared by CLS-B status. The association between CLS of the breast and the metabolic syndrome was validated in cohort 2, which included 127 women who developed metastatic breast cancer. Distant recurrence-free survival (dRFS) was compared by CLS-B status.Results: In cohorts 1 and 2, breast WAT inflammation was detected in 52 of 100 (52%) and 52 of 127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and IL6 and lower high-density lipoprotein cholesterol and adiponectin (P < 0.05) in cohort 1. In cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P < 0.05). Compared with patients without breast WAT inflammation, the adjusted HR for dRFS was 1.83 (95% CI, 1.07–3.13) for patients with inflammation.Conclusions: WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis. Clin Cancer Res; 22(9); 2283–9. ©2015 AACR.

PDF file - 38K, Data flow diagram of the secondary/progressive lesions

Microcalcifications, primarily biogenic apatite, occur in cancerous and benign breast pathologies and are key mammographic indicators. Outside the clinic, numerous microcalcification compositional metrics (e.g., carbonate and metal content) are linked to malignancy, yet microcalcification formation is dependent on microenvironmental conditions, which are notoriously heterogeneous in breast cancer. We interrogate multiscale heterogeneity in 93 calcifications from 21 breast cancer patients using an omics-inspired approach: For each microcalcification, we define a “biomineralogical signature” combining metrics derived from Raman microscopy and energy-dispersive spectroscopy. We observe that (i) calcifications cluster into physiologically relevant groups reflecting tissue type and local malignancy; (ii) carbonate content exhibits substantial intratumor heterogeneity; (iii) trace metals including zinc, iron, and aluminum are enhanced in malignant-localized calcifications; and (iv) the lipid-to-protein ratio within calcifications is lower in patients with poor composite outcome, suggesting that there is potential clinical value in expanding research on calcification diagnostic metrics to include “mineral-entrapped” organic matrix.

Obesity, defined as a body mass index (BMI) ≥ 30, is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated BMI is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear because of inconsistent findings from epidemiological studies and a lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelia of women carrying a BRCA mutation is positively correlated with BMI and with biomarkers of metabolic dysfunction. In addition, RNA sequencing showed obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which affected neighboring breast epithelial cells. In breast tissue explants cultured from women carrying a BRCA mutation, we found that blockade of estrogen biosynthesis or estrogen receptor activity decreased DNA damage. Additional obesity-associated factors, including leptin and insulin, increased DNA damage in human BRCA heterozygous epithelial cells, and inhibiting the signaling of these factors with a leptin-neutralizing antibody or PI3K inhibitor, respectively, decreased DNA damage. Furthermore, we show that increased adiposity was associated with mammary gland DNA damage and increased penetrance of mammary tumors in Brca1 +/− mice. Overall, our results provide mechanistic evidence in support of a link between elevated BMI and breast cancer development in BRCA mutation carriers. This suggests that maintaining a lower body weight or pharmacologically targeting estrogen or metabolic dysfunction may reduce the risk of breast cancer in this population.

PURPOSE. Routine use of the Oncotype DX Recurrence Score (RS) in patients with early-stage, estrogen receptor-positive, HER2-negative (ER+/HER2−) breast cancer is limited internationally by cost and availability. We created a supervised machine learning model using clinicopathologic variables to predict RS risk category in patients aged over 50 years. METHODS. From January 2012–December 2018, we identified patients aged over 50 years with T1-2, ER+/HER2−, node-negative tumors. Clinicopathologic data and RS results were randomly split into training and validation cohorts. A random forest model with 500 trees was developed on the training cohort, using age, pathologic tumor size, histology, progesterone receptor (PR) expression, lymphovascular invasion (LVI), and grade as predictors. We predicted risk category (low: RS ≤25, high: RS >25) using the validation cohort. RESULTS. Of the 3880 tumors identified, 1293 tumors comprised the validation cohort in patients of median (IQR) age 62 years (56–68) with median (IQR) tumor size 1.2 cm (0.8–1.7). Most tumors were invasive ductal (80.3%) of low-intermediate grade (80.5%) without LVI (80.9%). PR expression was ≤20% in 27.3% of tumors. Specificity for identifying RS ≤25 was 96.3% (95% CI 95.0–97.4), and the negative predictive value was 92.9% (95% CI 91.2–94.4). Sensitivity and positive predictive value for predicting RS >25 was lower (48.3% and 65.1%, respectively). CONCLUSION. Our model was highly specific for identifying eligible patients aged over 50 years for whom chemotherapy can be omitted. Following external validation, it may be used to triage patients for RS testing, if predicted to be high risk, in resource-limited settings.

BACKGROUND Multimodal analgesia (MMA) during breast surgery reduces postoperative pain and opioid requirements, but the relative contribution of local anesthetic dosing as a component of MMA is not well defined among patients undergoing lumpectomy and sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS We identified consecutive patients who underwent lumpectomy and SLNB with MMA from 1/2019 to 4/2020. Univariable and multivariable linear and logistic regression were used to examine associations between local anesthetics, opioid requirements in the post-anesthesia care unit (PACU), and pain scores in the PACU and on postoperative day (POD) 1. RESULTS In total, 1603 patients [median tumor size, 14 mm (interquartile range 8-20 mm)] were included. The median PACU opioid requirement was 0 morphine milligram equivalents (interquartile range 0-5). PACU maximum pain was none or mild in 58% of patients and moderate to severe in 42%; among 420 survey respondents, 56% reported no or mild pain and 44% reported moderate to severe pain on POD 1. On multivariable analysis that adjusted for routine components of MMA, increasing doses of 0.5% bupivacaine were associated with reduced PACU opioid requirements (β -0.04, 95% confidence interval -0.07 to -0.01, p = 0.011) and lower odds of moderate to severe pain (odds ratio 0.98, 95% confidence interval 0.97-0.99, p < 0.001). Local anesthetics were not associated with pain scores on POD 1. CONCLUSIONS Higher amounts of local anesthetics reduce acute postoperative pain and opioid requirement after lumpectomy and SLNB. Maximizing dosing within weight-based limits is a low-risk, cost-effective pain control strategy that can be used in diverse practice settings.

The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the farreaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.

Do patient-reported outcome measures differ among clinical T4 patients undergoing mastectomy with and without reconstruction?Neither reconstruction nor timing of reconstruction were associated with superior outcomes for breast satisfaction, physical well-being of the chest, or psychosocial well-being at any timepoint.

Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.

Despite advances in neoadjuvant systemic therapy (NST), some patients with aggressive T4 breast cancers do not respond. The efficacy of ‘heroic’ mastectomy in maintaining local control is unclear. In consecutive patients with primary or recurrent T4 cancers with < 50% shrinkage on NST who underwent mastectomy from 2007 to 2017, clinicopathologic characteristics and locoregional recurrence (LRR) were examined. Among 104 patients, 59 (57%) had primary T4M0, 12 (12%) had locally recurrent T4M0, and 33 (32%) had T4M1 disease. Median age was 58.5 years and the majority had high-grade (74%) ductal cancers (85%); 45 (44%) were estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−), 26 (25%) were HER2 positive (HER2+), and 31 (30%) were triple negative (TN). Postoperative complications developed in 41 (39%) patients. At a median follow-up of 37 months, 42 (40%) patients developed LRR. TN (hazard ratio [HR] 7.5) and HER2+ (HR 2.67) subtypes, lymphovascular invasion (LVI; HR 3.80), and positive margins (HR 4.09) were predictive of LRR. The 3-year LRR rate was highest and overall survival (OS) was lowest among patients with TN cancers, at 66% (95% confidence interval [CI] 48–83%) and 30% (95% CI 14–47%), respectively. After heroic mastectomy, postoperative complications were frequent and LRR occurred in 40% of patients despite a median OS of 3.8 years. Among TN patients, the 3-year LRR rate of 66% and 3-year OS of 30% suggest limited surgery benefit. Careful patient selection is prudent when considering heroic mastectomy.

Background Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting. Methods Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Women were included who had stages I-IV breast cancer or ovarian cancer diagnosed in 2013-2017, received chemotherapy, and were linked to genetic testing results. Multivariable Cox proportional hazard models were used to examine the association of genetic results with cancer-specific mortality. Results 22 495 breast cancer and 4320 ovarian cancer patients were analyzed, with a median follow-up of 41 months. PVs were present in 12.7% of breast cancer patients with estrogen and/or progesterone receptor-positive, HER2-negative cancer, 9.8% with HER2-positive cancer, 16.8% with triple-negative breast cancer, and 17.2% with ovarian cancer. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35 to 0.69) and BRCA2 PVs (HR = 0.60, 95% CI = 0.41 to 0.89), and equivalent with PVs in other genes (HR = 0.65, 95% CI = 0.37 to 1.13), vs noncarriers. Among ovarian cancer patients, cancer-specific mortality was lower with PVs in BRCA2 (HR = 0.35, 95% CI = 0.25 to 0.49) and genes other than BRCA1/2 (HR = 0.47, 95% CI = 0.32 to 0.69). No PV was associated with higher cancer-specific mortality. Conclusions Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than noncarriers. These results may reassure newly diagnosed patients, and longer follow-up is ongoing.

Obesity is a risk factor for the development of post-menopausal breast cancer. Breast white adipose tissue (WAT) inflammation, which is commonly found in women with excess body fat, is also associated with increased breast cancer risk. Both local and systemic effects are probably important for explaining the link between excess body fat, adipose inflammation and breast cancer. The first goal of this cross-sectional study of 196 women was to carry out transcriptome profiling to define the molecular changes that occur in the breast related to excess body fat and WAT inflammation. A second objective was to determine if commonly measured blood biomarkers of risk and prognosis reflect molecular changes in the breast. Breast WAT inflammation was assessed by immunohistochemistry. Bulk RNA-sequencing was carried out to assess gene expression in non-tumorous breast. Obesity and WAT inflammation were associated with a large number of differentially expressed genes and changes in multiple pathways linked to the development and progression of breast cancer. Altered pathways included inflammatory response, complement, KRAS signaling, tumor necrosis factor α signaling via NFkB, interleukin (IL)6-JAK-STAT3 signaling, epithelial mesenchymal transition, angiogenesis, interferon γ response and transforming growth factor (TGF)-β signaling. Increased expression of several drug targets such as aromatase, TGF-β1, IDO-1 and PD-1 were observed. Levels of various blood biomarkers including high sensitivity C-reactive protein, IL6, leptin, adiponectin, triglycerides, high-density lipoprotein cholesterol and insulin were altered and correlated with molecular changes in the breast. Collectively, this study helps to explain both the link between obesity and breast cancer and the utility of blood biomarkers for determining risk and prognosis.

HER2 +- amplified breast cancer patients derive benefit from treatment with anti-HER2-targeted therapy. Though adjuvant treatment is based on final pathology, decisions regarding neoadjuvant chemotherapy are made in the preoperative setting with imaging playing a key role in staging. We examined the accuracy of pre-operative imaging in determining pathological tumor size (pT) in patients undergoing upfront surgery. Early (cT1–T2N0) HER2 + breast cancer patients who underwent upfront surgery between 2015 and 2016 were identified from a prospective institutional database. We compared data for both clinical and final pathologic stage. Only those who underwent magnetic resonance imaging (MRI), mammography, and ultrasound in the preoperative setting were included in the analysis. Adjuvant treatment regimens were reviewed. We identified 87 cT1–2N0 patients with invasive HER2 + breast cancer who underwent upfront surgery. Median age was 52 years (IQR 43, 58) and median tumor size was 1.1 cm (IQR 0.5, 1.6). Fifteen patients (17%) were upstaged to stage II/III based on final pathology. Thirty-seven patients were T1cN0 on final pathology; 8 were cT1a–bN0 preop and 12 had pT overestimated by MRI by an average of 1.5 cm (> 0.5–1.5 cm). Compared to both mammography and MRI, the imaging modality most predictive of pT was ultrasound (p = 0.000072 ultrasound vs mammography and 0.000042 ultrasound vs MRI). For small HER2 + cN0 tumors undergoing upfront surgery, ultrasound was the imaging modality most predictive of pT. MRI overestimated tumor size in approximately 40% of patients. MRI may not accurately discriminate low-volume tumor burden in the breast and carries the potential of overtreatment in the upfront setting.

Obesity is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated bodyweight is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear due to inconsistent findings from epidemiological studies and lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelium of BRCA mutation carriers is positively correlated with body mass index and with biomarkers of metabolic dysfunction. Additionally, RNA-sequencing reveals significant obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which impacts neighboring breast epithelial cells. We found that blockade of estrogen biosynthesis or estrogen receptor activity decreases DNA damage, whereas treatment with leptin or insulin increases DNA damage in BRCA heterozygous epithelial cells. Furthermore, we show that increased adiposity is associated with mammary gland DNA damage and increased penetrance of mammary tumors in Brca1+/- mice. Overall, our results provide mechanistic evidence in support of a link between bodyweight and breast cancer development in BRCA mutation carriers and suggests that maintaining a healthy bodyweight or pharmacologically targeting estrogen or metabolic dysfunction may reduce the risk of breast cancer in this population.One Sentence SummaryElevated bodyweight is positively associated with DNA damage in breast epithelium of BRCA mutation carriers

Breast cancer has significant biologic heterogeneity, which influences treatment decisions. We hypothesized that in postmenopausal women (≥ 50 years) with clinical T1-2, N0, hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer of special histology (mucinous, tubular, cribriform, papillary), information from sentinel lymph node biopsy (SLNB) may not change adjuvant therapy recommendations.We constructed a cohort from the National Cancer Database of women aged ≥ 18 years with cT1-2 N0 HR+ HER2- invasive breast cancer. We calculated the frequency of nodal positivity by histology. We measured the frequency of N2/N3 disease, the distribution of Oncotype DX 21-gene assay recurrence score (ODX RS) across special histology by nodal status, and frequency of chemotherapy use by ODX RS and pathologic N stage.In women with cN0 HR+/HER2- special histologic subtype breast cancer, the likelihood of pathologic nodal positivity is less than 5%, and 99.7% of patients had N0 or N1 disease. Among women aged ≥ 50 years with HR+/HER2- special histologic subtype breast cancer, there was low prevalence of high ODX RS25 in both N0 and N1 patients (7% overall). Receipt of chemotherapy correlated with Oncotype DX scores as anticipated, with the lowest use in women with a low/intermediate RS (from 2 to 6% for N0 and 6-24% for N1) and the highest use in women with high risk Oncotype scores (from 74 to 92%).Our study suggests that SLNB could potentially be omitted in select postmenopausal women with cT1-2 N0 HR+/HER2- special histologic subtype breast cancer when ODX RS is available.

Historically, axillary lymph node dissection was considered necessary for regional control of breast cancer. Moreover, nodal status was the major determinant of the need for chemotherapy. The increased use of systemic therapy coupled with expanding indications for nodal irradiation has led to interest in optimizing patient outcomes by leveraging the local control benefits of radiotherapy and systemic therapy to decrease the extent of surgery. A series of landmark surgical and radiotherapeutic trials has demonstrated low rates of disease recurrence with concomitant improvements in treatment-associated lymphedema and quality of life with the use of sentinel node biopsy and nodal irradiation as opposed to complete axillary dissection in the management of node positive breast cancer. This chapter will explore the evolution of regional nodal management, culminating in current approaches to tailored patient selection for axillary lymph node dissection, sentinel lymph node biopsy, and adjuvant regional nodal irradiation.

As neoadjuvant chemotherapy (NAC) for breast cancer has become more widely used, so has nipple-sparing mastectomy. A common criterion for eligibility is a 1 cm tumor-to-nipple distance (TND), but its suitability after NAC is unclear. In this study, we examined factors predictive of negative nipple pathologic status (NS−) in women undergoing total mastectomy after NAC. Women with invasive breast cancer treated with NAC and total mastectomy from August 2014 to April 2018 at our institution were retrospectively identified. Following review of pre- and post-NAC magnetic resonance imaging (MRI) and mammograms, the association of clinicopathologic and imaging variables with NS− was examined and the accuracy of 1 cm TND on imaging for predicting NS− was determined. Among 175 women undergoing 179 mastectomies, 74% of tumors were cT1-T2 and 67% were cN+ on pre-NAC staging; 10% (18/179) had invasive or in situ carcinoma in the nipple on final pathology. On multivariable analysis, after adjusting for age, grade, and tumor stage, three factors, namely number of positive nodes, pre-NAC nipple-areolar complex retraction, and decreasing TND, were significant predictors of nipple involvement (p

Radiotherapy (RT) after breast-conserving surgery (BCS) halves the risk of local recurrence, and it is considered the standard of care for the vast majority of patients with early invasive breast cancer. However, the majority of patients treated with BCS will not recur locally, even in the absence of RT. Over the past several decades, the improved and widespread use of systemic therapy has significantly decreased the rate of local recurrence. This has stimulated interest in identifying favorable patient subsets not requiring RT. Randomized controlled trials have shown in women aged ≥ 70 years with stage I estrogen receptor-positive (ER+) tumors, RT can be safely omitted. To better identify patients with favorable prognosis, ongoing trials have incorporated biological markers and genomic assays. Despite great research efforts to de-escalate locoregional treatment, real-world data indicate that omission of RT in low-risk patients is inconsistent. Better decision-making is warranted to reduce overtreatment and financial toxicity.

Obesity is associated with an increased risk of breast cancer in post-menopausal women and decreased risk in pre-menopausal women. Conversely, in BRCA1/2 mutation carriers, pre-menopausal obesity is associated with early-onset breast cancer. Here we show that obese, pre-menopausal BRCA1/2 mutation carriers have increased levels of aromatase and inflammation in the breast, as occurs in post-menopausal women. In a prospective cohort study of 141 women with germline BRCA1 (n = 74) or BRCA2 (n = 67) mutations, leptin, and aromatase expression were higher in the breast tissue of obese versus lean individuals (P P P BRCA1/2 mutation carriers.

Although ketorolac is an effective adjunct for managing pain in the perioperative period, it is associated with a risk of postoperative bleeding. This study retrospectively investigated the association between ketorolac use and both reoperation and postoperative opioid use among mastectomy patients. The study identified all women undergoing mastectomy (unilaterally or bilaterally) at our ambulatory surgery cancer center from January 2016 to June 2019. The primary outcome was reoperation for bleeding on postoperative day 0 or 1, and the secondary outcome was postoperative opioid use. The association between ketorolac and outcomes was assessed using multivariable regression models. The covariates were age, body mass index, breast reconstruction, bilateral surgery, peripheral nerve block, and preoperative antiplatelet and/or anticoagulation medication. A cohort of 3469 women were identified. Ketorolac was given to 1549 (45%) of the women, with 922 women (60%) receiving 30 mg and 627 women (40%) receiving 15 mg. The overall reoperation rate for bleeding was 3.1% (1.8% without ketorolac vs 4.8% with ketorolac). In the multivariable analysis, ketorolac was associated with a higher risk of reoperation [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.60–3.70; P < 0.0001]. Ketorolac also was associated with a lower proportion of patients receiving any postoperative narcotic within 24 h (15 mg: OR 0.73; 95% CI 0.57–0.94; P = 0.014 vs 30 mg: OR 0.52; 95% CI 0.42–0.66; P < 0.0001). Ketorolac use decreased postoperative opioid use, but this benefit was outweighed by the increased risk of bleeding requiring reoperation. This finding led to a change in practice at the authors’ center, with ketorolac no longer administered in the perioperative care of the mastectomy patient.

BACKGROUND For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both. METHODS This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis. RESULTS There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups. CONCLUSIONS LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.

Breast conservation therapy (BCT) is well established for the management of primary operable breast cancer, with oncologic outcomes comparable to those of mastectomy. It remains unclear whether re-conservation therapy (RCT) is suitable for those patients who develop ipsilateral breast tumor recurrence (IBTR), for whom mastectomy is generally recommended. We identified women who underwent BCT for invasive or ductal carcinoma in situ and developed IBTR as a first event, comparing the pattern of subsequent events and survival for those treated by RCT versus mastectomy. Of 16,968 patents who had BCT, 322 (1.9%) developed an isolated IBTR as a first event between 1999 and 2019. 130 (40%) had RCT and 192 (60%) mastectomy. Compared to mastectomy, the RCT patients were older (66 vs 53

BACKGROUND. Among patients with multifocal or multicentric (MF/MC) breast cancer (BC) of similar morphology, concordance in Oncotype DX recurrence scores (RS) between tumors has been reported to be 87%. The effect of age and variation in histologic subtypes on RS concordance according to TAILORx criteria is unknown. METHODS. We identified patients with MF/MC, estrogen receptor–positive, HER2-negative, node-negative BC with ≥2 RS results treated at our institution from 2009 to 2018. Patients were analyzed by age group (≤50 and >50). Low- and high-risk cutoffs were RS ≤25 and >25 for >50 years and RS ≤20 and >20 for ≤50 years. RS concordance was defined as no change in management based on RS variation between lesions. RESULTS. One hundred twenty patients with MF/MC BC were identified: 82 (68.3%) aged >50 years and 38 (31.7%) aged ≤50 years. Patients aged ≤50 years had higher mean RS for both multifocal (20 vs. 14; p=0.006) and multicentric (17 vs. 13; p=0.003) tumors and more frequently had high-risk tumors (p50 years, 95.1% had RS concordance between tumors (same subtype, 98.2%; variable subtype, 88.9%; p=0.1). Among patients aged ≤50, RS concordance was 81.6%. CONCLUSIONS. Among patients with MF/MC BC, RS concordance was high, particularly in those aged >50 with tumors of the same histologic subtype. RS testing of one focus may be sufficiently prognostic and predictive in patients aged >50, regardless of subtype concordance. Testing of individual foci should be considered in patients aged ≤50 due to higher likelihood of RS discordance.

Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer. Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method. Of 132 MBC patients, those with heterologous mesenchymal MBC (n = 45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78–0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32–0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6–3.3; p

Patient-reported outcome measures (PROM) are used to assess value-based care. Little is known as to whether PROM response in breast cancer reflects the diverse patient population. The BREAST-Q, a validated measure of satisfaction and quality of life, and Recovery Tracker, a postoperative assessment tool, are PROM routinely delivered to all patients undergoing breast surgery at our institution. Here we determine whether response to PROM differs by age, race, language, or disease stage.All patients who had a breast operation between January 2020 and July 2021 were requested to complete the BREAST-Q and Recovery Tracker. Non-responders did not complete the PROM at any timepoint; responders completed 1 or more. Primary outcomes included rates of non-response versus response overall.Of 6374 patients identified, 5653 (88.7%) responded to either PROM [4366/4751 (91.9%) BREAST-Q; 2746/3384 (81.1%) Recovery Tracker]. On univariate analysis, non-responders were older (60 years versus 55 years, p0.001) and more often non-English speaking (p0.001), Hispanic ethnicity (p = 0.031), and Black race (p0.001), versus responders. On multivariate analysis, non-responders were significantly more often Black race and non-English speaking (p0.001). Non-English speakers were significantly less responsive among all ethnicities and races except Black race. Although breast cancer stage did not reach significance for response, patients with malignant disease and those receiving neoadjuvant chemotherapy responded more often.Our findings demonstrate high patient engagement using 2 different PROM following breast surgery, but suggest that PROM results may not reflect the experience of the entire breast cancer population. Care process changes based solely on PROM should consider these findings to ensure that the views of the entire spectrum of patients with breast cancer are represented.

In cN1 patients rendered cN0 with neoadjuvant chemotherapy, the false-negative rate of sentinel lymph node biopsy (SLNB) is 10% when ≥ 3 sentinel lymph nodes (SLNs) are removed. The added value of nodal clipping in this scenario is unknown. Here we determine how often the clipped node is a sentinel node when ≥ 3 SLNs are retrieved.We identified cT1-3N1 patients treated between 02/2018 and 10/2021 with a clipped lymph node at presentation. SLNB was performed with a standardized approach of dual-tracer mapping and retrieval of ≥ 3 SLNs. Clipped nodes were not localized; SLNs were X-rayed intraoperatively to determine clip location. Axillary lymph node dissection (ALND) was performed for any residual disease or retrieval of 3 SLNs.Of 269 patients, 251 (93%) had ≥ 3 SLNs. Median age was 51 years; the majority (92%) had ductal histology; 46% were HR+/HER2-. The median number of SLNs removed was 4 (IQR 3,5). The clipped node was an SLN in 88% (220/251) of cases. Of the 31 where the clipped node was not, 13 had a positive SLN mandating ALND, and the clip was identified in the ALND specimen. In the remaining 18, where ≥ 3 negative SLNs were retrieved and an ALND was not performed, the clip was not retrieved, with no axillary failures in this group (median follow-up: 55 months).When the SLNB procedure is optimized with dual tracer and retrieval of ≥ 3 SLNs, the clipped node is an SLN in the majority of cases, suggesting that failure to retrieve the clipped node should not be an indication for ALND.

PURPOSE: Upgrade rates of conventional ADH are reported at 10–30%; however, rates for ADH bordering on DCIS (ADH-BD) are largely unknown. We examined the upgrade rate of ADH-BD and core needle biopsy (CNB) features associated with upgrade. Surgical management in patients with concurrent ipsilateral breast cancer (BC) was also examined. METHODS: From 2000–2018, women with CNB diagnosis of ADH-BD were prospectively identified. Women with pure ADH-BD and concurrent ipsilateral ADH-BD/BC were analyzed separately, and upgrade rates were calculated. CNB features associated with upgrade and type of surgery were examined in women with pure ADH-BD; CNB features and concurrent pathology associated with upgrade were examined in women with ipsilateral BC. RESULTS: 108/236 (46%) patients with pure ADH-BD on CNB had DCIS (40%) or invasive carcinoma (6%) on surgical excision. DCIS or invasive carcinoma was more frequently found on excision of a mass that yielded ADH-BD on biopsy than excision of calcifications (65% vs. 38%; p

BACKGROUND: Whether routinely prescribed opioids are necessary for pain control after discharge among lumpectomy/sentinel node biopsy (Lump/SLNB) patients is unclear. We hypothesized that Lump/SLNB patients could be discharged without opioids with a failure rate of

Historically, more than one-third of patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) underwent additional surgery. The SSO-ASTRO guidelines advise 2 mm margins for patients with DCIS having BCS and whole-breast radiation (WBRT). Here we examine guideline impact on additional surgery and factors associated with re-excision. Patients treated with BCS for pure DCIS from August 2015 to January 2018 were identified. Guidelines were adopted on September 1, 2016, and all patients had separately submitted cavity-shave margins. Clinicopathologic characteristics, margin status, and rates of additional surgery were examined. Among 650 patients with DCIS who attempted BCS, 50 (8%) converted to mastectomy. Of 600 who had BCS as final surgery, 336 (56%) received WBRT and comprised our study group. One hundred twenty-eight (38%) were treated pre-guideline and 208 (62%) were treated post-guideline. Characteristics and margin status were similar between groups. The re-excision rate was 38% pre-guideline adoption and 29% post-guideline adoption (p = 0.09), with 91% having only one re-excision. Re-excision for ≥ 2 mm margins was uncommon (6% pre-guideline vs. 5% post-guideline). On multivariate analysis, younger age (OR 0.97, 95% CI 0.94–0.99, p = 0.02) and larger DCIS size (OR 1.43, 95% CI 1.2–1.8, p

Axillary lymph node dissection (ALND) can be avoided in node-positive patients who receive neoadjuvant chemotherapy (NAC) if three or more negative sentinel lymph nodes (SLNs) are retrieved. We evaluate how often node-positive patients avoid ALND with NAC, and identify predictors of identification of three or more SLNs and of nodal pathological complete response (pCR). From November 2013 to July 2019, all patients with cT1-3, biopsy-proven N1 tumors who converted to cN0 after NAC received SLN biopsy (SLNB) with dual mapping and were identified from a prospectively maintained database. 630 consecutive N1 patients were eligible for axillary downstaging with NAC; 573 (91%) converted to cN0 and had SLNB, and 531 patients (93%) had three or more SLNs identified. Lymphovascular invasion (LVI; odds ratio [OR] 0.46, 95% confidence interval [CI] 0.24–0.87; p = 0.02) and increasing body mass index (BMI; OR 0.77, 95% CI 0.62–0.96 per 5-unit increase; p = 0.02) were significantly associated with failure to identify three or more SLNs. 255/573 (46%) patients achieved nodal pCR; 237 (41%) had adequate mapping. Factors associated with ALND avoidance included high grade (OR 2.51, 95% CI 1.6–3.94, p = 0.001) and receptor status (HR+/HER2− [referent]: OR 1.99, 95% CI 1.15–3.46 [p = 0.01] for HR−/HER2−, OR 3.93, 95% CI 2.40–6.44 [p

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated the safety of omitting axillary lymph node dissection (ALND) in T1–T2cN0 patients with fewer than three positive sentinel nodes (SLNs) undergoing breast-conservation therapy. While microscopic extracapsular extension (mECE) > 2 mm is associated with increased nodal burden, the significance of extranodal tumor deposits (ETDs) in the axillary fat is uncertain. Consecutive patients with T1–T2cN0 breast cancer undergoing sentinel node biopsy and ALND for SLN metastases from January 2010 to December 2018 were identified. ETDs were defined as intravascular tumor emboli or metastatic deposits in the axillary fat. Clinicopathologic characteristics and nodal burden were compared by ETD status. Among 1114 patients, 113 (10%) had ETDs: 81 (72%) were intravascular tumor emboli and 32 (28%) were soft tissue deposits. Patients with ETDs had larger tumors (median 2.2 vs. 2.1 cm; p = 0.033) and more often had mECE (83% vs. 44%; p

Nipple-sparing mastectomy (NSM) is being performed increasingly for risk reduction in high-risk groups. There are limited data regarding complications and oncological outcomes in women undergoing bilateral prophylactic NSM. This study reviewed institutional experience with prophylactic NSM, and examined the indications, rates of postoperative complications, incidence of occult malignant disease and subsequent breast cancer diagnosis.Women who had bilateral prophylactic NSM between 2000 and 2016 were identified from a prospectively maintained database. Rates of postoperative complications, incidental breast cancer, recurrence and overall survival were evaluated.A total of 192 women underwent 384 prophylactic NSMs. Indications included BRCA1 or BRCA2 mutations in 117 patients (60·9 per cent), family history of breast cancer in 35 (18·2 per cent), lobular carcinoma in situ in 29 (15·1 per cent) and other reasons in 11 (5·7 per cent). Immediate breast reconstruction was performed in 191 patients. Of 384 NSMs, 116 breasts (30·2 per cent) had some evidence of skin necrosis at follow-up, which resolved spontaneously in most; only 24 breasts (6·3 per cent) required debridement. Overall, there was at least one complication in 129 breasts (33·6 per cent); 3·6 and 1·6 per cent had incidental findings of ductal carcinoma in situ and invasive breast cancer respectively. The nipple-areola complex was preserved entirely in 378 mastectomies. After a median follow-up of 36·8 months, there had been no deaths and no new breast cancer diagnoses.These findings support the use of prophylactic NSM in high-risk patients. The nipples could be preserved in the majority of patients, postoperative complication rates were low, and, with limited follow-up, there were no new breast cancers.La mastectomía con preservación del pezón (nipple-sparing mastectomy, NSM) se realiza cada vez más para reducir riesgos en los grupos de pacientes de alto riesgo. Se dispone de pocos datos sobre complicaciones y resultados oncológicos en mujeres sometidas a NSM bilateral profiláctica. Este estudio revisó la experiencia institucional de la NSM profiláctica, y analizó las indicaciones, tasas de complicaciones postoperatorias, incidencia de enfermedad maligna oculta y diagnóstico de subsiguiente cáncer de mama. MÉTODOS: Se identificaron mujeres sometidas a NSM bilateral profiláctica durante el periodo 2000-2016 a partir de una base de datos prospectiva. Se evaluaron tasas de complicaciones postoperatorias, cáncer de mama incidental, recidiva y supervivencia global.Un total de 192 mujeres fueron sometidas a 384 NSMs profilácticas. Las indicaciones incluyeron mutaciones BRCA1 o BRCA2 en 117 (61%) pacientes, historia familiar de cáncer de mama en 35 (18%), carcinoma lobulillar in situ en 29 (15%) y otros motivos en 11 (5,7%). La reconstrucción mamaria inmediata se realizó en 191 pacientes. De las 384 NSMs, 116 (30%) presentaron alguna evidencia de necrosis de la piel durante el seguimiento y la mayoría se resolvieron de forma espontánea, con solo 24 (6,2%) mamas que requirieron desbridamiento. Globalmente hubo al menos una complicación en 129 (34%) mamas; 3,6% y 1,6% tuvieron hallazgos incidentales de carcinoma ductal in situ o cáncer de mama invasivo, respectivamente. El complejo areola-pezón se preservó completamente en 378 mastectomías. Tras una mediana de seguimiento de 36,8 meses, no hubo fallecimientos ni ningún diagnóstico nuevo de cáncer de mama. CONCLUSIÓN: Estos hallazgos apoyan la utilización de la NSM profiláctica en pacientes de alto riesgo. En la mayoría pacientes fue posible la preservación del pezón, las tasas de complicaciones postoperatorias fueron bajas y, con un seguimiento limitado, no hubo nuevos casos de cáncer de mama.

INTRODUCTION: The contralateral prophylactic mastectomy (CPM) rate in the U.S. has been steadily increasing. This is of particular concern because many women who undergo this procedure are candidates for breast-conserving surgery. AREAS COVERED: CPM’s medical benefit is related to the risk of contralateral cancer development and whether CPM provides a survival benefit. Contralateral cancer rates have decreased, and CPM does not provide a survival benefit. Other potential benefits of the procedure may be improved quality of life; these data are reviewed. Research efforts have been undertaken to better understand the decision-making process of patients who consider, and ultimately undergo, this procedure. EXPERT OPINION: Decisional traits, personal values, the desire for peace of mind, and the desire to obtain breast symmetry are important factors that drive a woman’s decision to undergo CPM. Additionally, many patients lack knowledge on how different types of breast surgery impact outcomes. To improve the shared decision-making process, a stepwise approach to address possible misconceptions, and clarify the real risks/benefits of this procedure should be utilized. A clear recommendation (for/against) should be made for every patient with newly diagnosed breast cancer who considers CPM. Communication tools to assist patients and surgeons in this process are sorely needed.

Background: With advances in neoadjuvant chemotherapy (NAC), an increasing number of breast cancer patients achieve a pathologic complete response (pCR). Efforts are underway to non-invasively identify pCR in the breast, such that characterization of the concomitant nodal response will be invaluable for locoregional treatment planning. Here, we sought to evaluate the correlation between in-breast response and residual nodal disease among early stage breast cancer patients. Materials/Methods: We identified 728 patients who received NAC at our institution from 2006 to 2016. Breast and nodal response rates were evaluated and further stratified by clinicopathologic features, and biologic subtype approximation (hormone receptor positive [HR+], HER2 negative [HER2-] and low or intermediate grade = luminal A; HR+/HER2- and high grade = luminal B; HER2/neu-amplified = HER2+; ER-/HER2- = triple negative). Descriptive statistics and univariate analyses were employed to evaluate the correlation between breast and nodal response. Results: Of 728 patients, 269 (37%) were clinically node negative (cN0) and 459 (63%) were clinically node positive (cN+). Median age was 51 and median tumor size was 4.0cm (IQR 2.7 - 5.5cm). The cohort comprised 13% luminal A patients, 20% luminal B, 38% HER2, and 29% triple negative. Following NAC, the overall pCR rate (breast and nodes) was 29.8%. Among all cN0 patients who had a breast pCR (ypT0; n = 96), none exhibited residual nodal disease (100% ypN0). Among cN+ patients who had a breast pCR (n = 128), only 5.4% (n = 7) had residual nodal disease (ypN+). Rates of residual nodal disease among cN+ patients who achieved breast pCR varied by biologic subtype: luminal A patients with pCR in the breast had a 50.0% probability of residual nodal disease (n = 1/2 were ypT0N+), luminal B 6.7% (1/15), HER2+ 2.5% (2/80) and triple-negative 9.6% (3/31) (p=0.03). Conversely, among cN+ patients who exhibited nodal pCR following NAC, the rate of residual in-breast disease varied by receptor subtype: 80.0% of clinically node-positive luminal A patients who became ypN0 had residual in-breast disease (ypT+N0; n = 4/5), 60.0% of luminal B (21/35), 38.1% HER2+ (48/126), and 50.9% triple negative (29/57) (p=0.03). Conclusions: Among early stage breast cancer patients receiving NAC, in-breast pCR is predictive of nodal pCR. Among 96 cN0 patients who had in-breast pCR, we found none with residual nodal disease, representing a population that may be suitable for further limiting nodal therapy. The ability to pre-operatively identify in-breast pCR in this population would be particularly valuable if nodal pCR can consequently be inferred, potentially paving the way for studies of therapeutic de-escalation. Citation Format: Achraf Shamseddine, Jessica Flynn, Zhigang Zhang, Monica Morrow, Boris Mueller, Erin Gillespie, Atif Khan, Beryl McCormick, Oren Cahlon, Simon Powell, Andrea Barrio, Lior Z Braunstein. In-breast pathologic complete response (pCR) following neoadjuvant chemotherapy predicts nodal pCR in early stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-06.

Background Young age at breast cancer diagnosis is associated with negative prognostic outcomes, and breast cancer in black women often manifests at a young age. This study evaluated the effect of age on breast cancer management and outcomes in black women. Methods This was a retrospective cohort study of all black women treated for invasive breast cancer between 2005 and 2010 at a specialized tertiary-care cancer centre. Clinical and treatment characteristics were compared by age. Kaplan–Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS). Results A total of 666 black women were identified. Median BMI was 30 (range 17–56) kg/m2 and median tumour size was 16 (1–155) mm. Most tumours were oestrogen receptor-positive (66·4 per cent). Women were stratified by age: less than 40 years (74, 11·1 per cent) versus 40 years or more (592, 88·9 per cent). Younger women were significantly more likely to have a mastectomy, axillary lymph node dissection and to receive chemotherapy, and were more likely to have lymphovascular invasion and positive lymph nodes, than older women. The 5-year OS rate was 88·0 (95 per cent c.i. 86·0 to 91·0) per cent and the 5-year DFS rate was 82·0 (79·0 to 85·0) per cent. There was no statistically significant difference in OS by age (P = 0·236). Although DFS was inferior in younger women on univariable analysis (71 versus 88 per cent; P < 0·001), no association was found with age on multivariable analysis. Conclusion Young black women with breast cancer had more adverse pathological factors, received more aggressive treatment, and had worse DFS on univariable analysis. Young age at diagnosis was, however, not an independent predictor of outcome.

National Comprehensive Center Network guidelines recommend radiotherapy (RT) omission in women age ≥ 70 years with estrogen receptor-positive (ER+), cN0, T1 tumors post-lumpectomy if they receive endocrine therapy (ET). However, little is known about the impact of poor adherence on locoregional recurrence (LRR) in elderly women forgoing RT.Women age ≥ 70 years with pT1-2 ER+ breast cancer undergoing lumpectomy without RT from 2004 to 2019 were identified from a prospectively maintained database. ET adherence, calculated as treatment duration over follow-up time up to 5 years, was determined by chart review. We compared clinicopathologic characteristics and rates of LRR between women with high adherence (≥ 80%), low adherence (80%), and no ET.Of 968 women (27 bilateral cancers), adherence was high in 676 (70%) and low in 162 (17%); 130 (13%) took no ET. Younger age and use of aromatase inhibitor were associated with high adherence. On multivariable analysis, tumor size (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03-2.68, p = 0.04) and high adherence (HR 0.13, 95% CI 0.07-0.26, p0.001) were significantly associated with LRR. At 53 months median follow-up, the 5-year rate of LRR was 3.1% (95% CI 2.4-3.9%) with high adherence, 14.7% (95% CI 11.7-17.7%) with low adherence, and 17.9% (95% CI 13.9-21.8%) with no ET (p0.01).Although adherence to ET was high overall, in the 30% of women with low adherence or no ET, LRR rates were significantly increased. Counseling regarding the distinct toxicities of ET and RT can help patients choose the therapy to which they will likely adhere to.

Background: Data on the oncologic safety of omission of axillary lymph node dissection (ALND) in node positive (N+) patients who downstage to ypN0 with neoadjuvant chemotherapy (NAC) is sparse. Additionally, there is no consensus on which axillary staging procedure should be used in this setting, sentinel lymph node biopsy (SLNB) alone or in combination with localization and retrieval of the clipped positive node, also known as targeted axillary dissection (TAD). Whether the reduction in the false negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. We sought to evaluate oncologic outcomes after omission of ALND in a large, real-world cohort of breast cancer (BC) patients and to compare rates of axillary recurrence after SLNB with dual tracer mapping vs. TAD. Methods: Data were collected from 19 centers in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 BC who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumor or isolated tumor cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 785 patients (565 treated with SLNB and 220 with TAD) treated with NAC followed by surgery from 01/2014-12/2020. Median patient age was 50 years. The majority (57%) of patients had clinical T2 tumors, and 95% had N1 disease. Most (55%) were HER2+, and 21% were triple negative. Most patients (81%) received anthracycline and taxane-based chemotherapy regimens, but NAC regimens differed between patients treated with TAD and those treated with SLNB (Table 1). All patients with HER2+ tumors received anti HER2 therapy. Nodal radiotherapy was administered to 76% of patients, and was more common in patients who underwent TAD (82% TAD vs 74% SLNB, p=0.017). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (80% TAD vs. 66% SLNB, p< 0.001). TAD localization was with wire in 46%, radioactive seed in 40%, ultrasound in 5%, tattoo in 2%, and with a combination of these techniques in 7%. The clipped node was successfully retrieved in 94% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group [3 (IQR 3-5) vs 4 IQR 3-5), p< 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p< 0.001] (Table 1). The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.1% (95%CI 0.39-2.4%), 3.1% (95%CI 1.6-5.3%) and 10% (95%CI 7.6-13%), respectively. The two-year cumulative incidence of axillary recurrence did not differ between patients treated with TAD compared to SLNB (0% vs 0.9%, p=0.19). Conclusion: Early axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly lower in TAD than SLNB. Although longer follow-up is needed to confirm these findings, the main advantage of TAD seems to be a reduction in the number of lymph nodes removed. Overall, these results support omission of ALND in patients who successfully downstage to node negative disease after NAC. Table 1: Clinicopathological Features of the Study Cohort, Stratified by Axillary Staging Technique Citation Format: Giacomo Montagna, Mary Mrdutt, Astrid Botty, Andrea V. Barrio, Varadan Sevilimedu, Judy C. Boughey, Tanya L. Hoskin, Laura H. Rosenberger, E Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Diaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Maria Del Rosario Cueva Perez, Marcelo Chavez Diaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis Resende Paulinelli, Sebastian Sole Zarhi, Sherko Küemmel, Simona Bruzas, Simona Di Lascio, Tamara Parissenti, Uwe Güth, Valentina Ovalle, Christoph Tausch, Monica Morrow, Thorsten Kühn, Walter P. Weber. Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-02.