Clinicogenomic characterization of inflammatory breast cancer.

Background: Inflammatory breast cancer (IBC) is a rare and poorly characterized type of breast cancer with an aggressive clinical presentation. The biological mechanisms driving the IBC phenotype are relatively undefined-partially due to a lack of comprehensive, large-scale genomic studies and limited clinical cohorts. Patients and Methods: A retrospective analysis of 2457 patients with metastatic breast cancer who underwent targeted tumor-only DNA-sequencing was performed at Dana-Farber Cancer Institute. Clinicopathologic, single nucleotide variant (SNV), copy number variant (CNV) and tumor mutational burden (TMB) comparisons were made between clinically confirmed IBC cases within a dedicated IBC center versus non-IBC cases. Results: Clinicopathologic differences between IBC and non-IBC cases were consistent with prior reports-including IBC being associated with younger age at diagnosis, higher grade, and enrichment with hormone receptor (HR)-negative and HER2-positive tumors. The most frequent somatic alterations in IBC involved TP53 (72%), ERBB2 (32%), PIK3CA (24%), CCND1 (12%), MYC (9%), FGFR1 (8%) and GATA3 (8%). A multivariate logistic regression analysis revealed a significant enrichment in TP53 SNVs in IBC; particularly in HER2-positive and HR-positive disease which was associated with worse outcomes. Tumor mutational burden (TMB) did not differ substantially between IBC and non-IBC cases and a pathway analysis revealed an enrichment in NOTCH pathway alterations in HER2-positive disease. Conclusion: Taken together, this study provides a comprehensive, clinically informed landscape of somatic alterations in a large cohort of patients with IBC. Our data support higher frequency of TP53 mutations and a potential enrichment in NOTCH pathway activation-but overall; a lack of major genomic differences. These results both reinforce the importance of TP53 alterations in IBC pathogenesis as well as their influence on clinical outcomes; but also suggest additional analyses beyond somatic DNA-level changes are warranted.

TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have overall poor clinical outcomes, with triple-negative IBC (TN-IBC) being associated with the worst survival, warranting the investigation of novel therapies. Preclinical studies implied that ruxolitinib (RUX), a JAK1/2 inhibitor, may be an effective therapy for TN-IBC. METHODS: We conducted a randomized phase II study with nested window-of-opportunity in TN-IBC. Treatment-naïve patients received a 7-day run-in of RUX alone or RUX plus paclitaxel (PAC). After the run-in, those who received RUX alone proceeded to neoadjuvant therapy with either RUX + PAC or PAC alone for 12 weeks; those who had received RUX + PAC continued treatment for 12 weeks. All patients subsequently received 4 cycles of doxorubicin plus cyclophosphamide prior to surgery. Research tumor biopsies were performed at baseline (pre-run-in) and after run-in therapy. Tumors were evaluated for phosphorylated STAT3 (pSTAT3) by immunostaining, and a subset was also analyzed by RNA-seq. The primary endpoint was the percent of pSTAT3-positive pre-run-in tumors that became pSTAT3-negative. Secondary endpoints included pathologic complete response (pCR). RESULTS: Overall, 23 patients were enrolled, of whom 21 completed preoperative therapy. Two patients achieved pCR (8.7%). pSTAT3 and IL-6/JAK/STAT3 signaling decreased in post-run-in biopsies of RUX-treated samples, while sustained treatment with RUX + PAC upregulated IL-6/JAK/STAT3 signaling compared to RUX alone. Both treatments decreased GZMB+ T cells implying immune suppression. RUX alone effectively inhibited JAK/STAT3 signaling but its combination with PAC led to incomplete inhibition. The immune suppressive effects of RUX alone and in combination may negate its growth inhibitory effects on cancer cells. CONCLUSION: In summary, the use of RUX in TN-IBC was associated with a decrease in pSTAT3 levels despite lack of clinical benefit. Cancer cell-specific-targeting of JAK2/STAT3 or combinations with immunotherapy may be required for further evaluation of JAK2/STAT3 signaling as a cancer therapeutic target. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , NCT02876302. Registered 23 August 2016.

Preoperative Risk Factors for Lymphedema in Inflammatory Breast Cancer.

BACKGROUND: Prophylactic lymphatic bypass or LYMPHA (LYmphatic Microsurgical Preventive Healing Approach) is increasingly offered to prevent lymphedema following breast cancer treatment, which develops in up to 47% of patients. Previous studies focused on intraoperative and postoperative lymphedema risk factors, which are often unknown preoperatively when the decision to perform LYMPHA is made. This study aims to identify preoperative lymphedema risk factors in the high-risk inflammatory breast cancer (IBC) population. METHODS: Retrospective review of our institution's IBC program database was conducted. The primary outcome was self-reported lymphedema development. Multivariable logistic regression analysis was performed to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during axillary lymph node dissection (ALND), number of positive lymph nodes, residual disease on pathology, and need for adjuvant chemotherapy. RESULTS: Of 356 patients with IBC, 134 (mean age: 51 years, range: 22-89 years) had complete data. All 134 patients underwent surgery and radiation. Forty-seven percent of all 356 patients (167/356) developed lymphedema. Obesity (body mass index > 30) (odds ratio [OR]: 2.7, confidence interval [CI]: 1.2-6.4, p = 0.02) and non-white race (OR: 4.5, CI: 1.2-23, p = 0.04) were preoperative lymphedema risk factors. CONCLUSION: Patients with IBC are high risk for developing lymphedema due to the need for ALND, radiation, and neoadjuvant chemotherapy. This study also identified non-white race and obesity as risk factors. Larger prospective studies should evaluate potential racial disparities in lymphedema development. Due to the high prevalence of lymphedema, LYMPHA should be considered for all patients with IBC.

Clinical outcomes after 1 versus 2-3 lines of neoadjuvant therapy in stage III inflammatory breast cancer.

PURPOSE: Many stage III inflammatory breast cancer (IBC) patients experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to allow surgery, while some require additional NAC. We evaluated the pathologic complete response (pCR), breast cancer-free survival (BCFS) and overall survival (OS) among patients requiring 1 vs. 2-3 lines (L) of NAC prior to surgery. METHODS: Stage III IBC patients from 2 institutions who received 1L or 2-3L of NAC prior to surgery were identified. Hormone receptor and HER2 status, grade, and pCR were evaluated. BCFS and OS were evaluated by the Kaplan-Meier method. Multivariable Cox models were utilized to estimate the hazard ratio (HR). RESULTS: 808 eligible patients (1997-2020) were identified (median age 51 years, median follow-up 69 months). 733 (91%) had 1L and 75 (9%) had 2-3L of NAC. Grade III, triple-negative and HER2-positive disease were more prevalent in 2-3L patients. 178 (24%) 1L and 14 (19%) 2-3L patients had pCR. 376 1L patients and 41 2-3L patients had recurrences. The 5-year BCFS was worse for the 2-3L group (33 vs. 46%, HR = 1.37; 95% CI 0.99-1.91). However, in 192 patients with a pCR, BCFS was similar (76 vs. 83% in 1L vs. 2-3L, respectively). There were 308 deaths (276 among 1L and 32 among 2-3L patients). The 5-year OS in 1L vs. 2-3L was 60 vs. 53% (HR = 1.32, 95% CI 0.91-1.93). CONCLUSIONS: Among stage III IBC patients, pCR rates were similar, irrespective of the NAC lines number, and BCFS and OS were comparable with pCR after 1L and 2-3L.

Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

BACKGROUND: Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients. METHODS: The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as 'not performed/not acted on' if ALND was either not performed or performed at a later date than SLNB, or 'performed/acted on' if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT. RESULTS: Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p < 0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70-10.5; p < 0.001). CONCLUSIONS: We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.

Clinical outcomes of de novo metastatic HER2-positive inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer that presents as de novo metastatic disease in 20-30% of cases, with one-third of cases demonstrating HER2-positivity. There has been limited investigation into locoregional therapy utilization following HER2-directed systemic therapy for these patients, and their locoregional progression or recurrence (LRPR) and survival outcomes. Patients with de novo HER2-positive metastatic IBC (mIBC) were identified from an IRB-approved IBC registry at Dana-Farber Cancer Institute. Clinical, pathology, and treatment data were abstracted. Rates of LRPR, progression-free survival (PFS), overall survival (OS), and pathologic complete response (pCR) were determined. Seventy-eight patients diagnosed between 1998 and 2019 were identified. First-line systemic therapy comprised chemotherapy for most patients (97.4%) and HER2-directed therapy for all patients (trastuzumab [47.4%]; trastuzumab+pertuzumab [51.3%]; or trastuzumab emtansine [1.3%]). At a median follow-up of 2.7 years, the median PFS was 1.0 year, and the median OS was 4.6 years. The 1- and 2-year cumulative incidence of LRPR was 20.7% and 29.0%, respectively. Mastectomy was performed after systemic therapy in 41/78 patients (52.6%); 10 had a pCR (24.4%) and all were alive at last follow-up (1.3-8.9 years after surgery). Among 56 patients who were alive and LRPR-free at one year, 10 developed LRPR (surgery group = 1; no-surgery group = 9). In conclusion, patients with de novo HER2-positive mIBC who undergo surgery have favorable outcomes. More than half of patients received systemic and local therapy with good locoregional control and prolonged survival, suggesting a potential role for local therapy.

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial.

BACKGROUND: The impact of abbreviated neoadjuvant regimens for HER2+ breast cancer on rates of breast conservation therapy (BCT) is unclear. We aimed to determine BCT rates in a single-arm prospective trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) in patients with stage II or III HER2+ breast cancer. STUDY DESIGN: BCT eligibility was prospectively recorded before and after THP. Pre- and posttreatment mammogram and breast ultrasound were required; breast MRI was encouraged. Patients with a large tumor to breast size ratio were eligible for downsizing. Multifocal/multicentric tumors, extensive calcifications, and contraindications to radiation were considered BCT contraindications. RESULTS: Overall, 92 patients who received neoadjuvant THP on trial were included. At presentation, 39 (42.4%) were considered eligible for BCT and 53 (57.6%) were not. BCT-eligible patients were older (median 54 vs 47 years, respectively; p = 0.006) and had smaller tumors by palpation (median 2.5 vs 3 cm, respectively; p = 0.004). Of 53 BCT-ineligible patients, 28 were candidates for tumor downsizing, whereas 25 had contraindications to BCT. Overall, 51 (55.4%) patients underwent BCT. Of the 28 patients who were candidates for downsizing, 22 (78.6%) became BCT-eligible after THP and 18 of 22 (81.8%) underwent BCT. In total, 44 of 92 (47.8%) patients experienced breast pathologic complete response (ypT0), including 11 of 25 (44.0%) patients with BCT contraindications at presentation. CONCLUSIONS: De-escalated neoadjuvant systemic therapy led to high BCT rates in this cohort. The impact of de-escalated systemic therapy on local therapy and outcomes in early stage HER2+ breast cancer warrants further investigation.

Copy Number Variation in Inflammatory Breast Cancer.

Identification of a unique genomic biomarker in de novo inflammatory breast cancer (IBC) may provide an insight into the biology of this aggressive disease. The goal of our study was to elucidate biomarkers associated with IBC. We examined breast biopsies collected from Dana-Farber Cancer Institute patients with IBC prior to initiating preoperative systemic treatment (30 samples were examined, of which 14 were eligible). Patients without available biopsies (n = 1), with insufficient tumor epithelial cells (n = 10), or insufficient DNA yield (n = 5) were excluded from the analysis. Molecular subtype and tumor grade were abstracted from a medical records' review. Ten IBC tumors were estrogen-receptor-positive (ER+) and human epidermal growth factor receptor 2 (HER2)-negative (n = 10 out of 14). Sufficient RNA and DNA were simultaneously extracted from 14 biopsy specimens using the Qiagen AllPrep Kit. RNA was amplified using the Sensation kit and profiled using the Affymetrix Human Transcriptome Array 2.0. DNA was profiled for genome-wide copy number variation (CNV) using the Affymetrix OncoScan Array and analyzed using the Nexus Chromosome Analysis Suite. Among the 14 eligible samples, we first confirmed biological concordance and quality control metrics using replicates and gene expression data. Second, we examined CNVs and gene expression change by IBC subtype. We identified significant CNVs in IBC patients after adjusting for multiple comparisons. Next, to assess whether the CNVs were unique to IBC, we compared the IBC CNV data to fresh-frozen non-IBC CNV data from The Cancer Genome Atlas (n = 388). On chromosome 7p11.2, we identified significant CN gain located at position 58,019,983-58,025,423 in 8 ER+ IBC samples compared to 338 non-IBC ER+ samples (region length: 5440 bp gain and 69,039 bp, False Discovery Rate (FDR) p-value = 3.12 × 10-10) and at position 57,950,944-58,025,423 in 3 TN-IBC samples compared to 50 non-IBC TN samples (74,479 base pair, gain, FDR p-value = 4.27 × 10-5; near the EGFR gene). We also observed significant CN loss on chromosome 21, located at position 9,648,315-9,764,385 (p-value = 4.27 × 10-5). Secondarily, differential gene expression in IBC patients with 7p11.2 CN gain compared to SUM149 were explored after FDR correction for multiple testing (p-value = 0.0016), but the results should be interpreted with caution due to the small sample size. Finally, the data presented are hypothesis-generating. Validation of CNVs that contribute to the unique presentation and biological features associated with IBC in larger datasets may lead to the optimization of treatment strategies.

Incidence, characteristics, and management of central nervous system metastases in patients with inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC. METHODS: The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS-free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS. RESULTS: A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1-, 2-, and 5-year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow-up: 5.6 years) and 17%, 30%, and 42% in stage IV patients (1.8 years). Multivariate analysis identified triple-negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple-negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS. CONCLUSIONS: Patients with IBC, particularly those with triple-negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted.

HER2-low inflammatory breast cancer: Clinicopathologic features and prognostic implications.

BACKGROUND: HER2)-low expression is a predictive biomarker for novel anti-HER2 antibody-drug conjugates. However, little is known about its clinical significance in inflammatory breast cancer (IBC). METHODS: Patients diagnosed with HER2-negative IBC between December 1999 and December 2020 were identified from the Dana-Farber Cancer Institute IBC registry. Patients were divided into HER2-low (IHC 1+ or 2+/ISH-) and HER2-zero (IHC 0), comparing clinicopathologic features and disease outcomes between the two subgroups. RESULTS: The study included 276 patients. Among patients with stage III (n = 209) and stage IV (n = 67) IBC, 54% and 39% had HER2-low tumours, respectively. Oestrogen receptor (ER)-expressing tumours were more common in patients with HER2-low versus HER2-zero stage III IBC (65% versus 38%, p < 0.01). Among stage III patients undergoing surgery (n = 182), pathologic complete response (pCR) rates were higher for HER2-zero versus HER2-low IBC (11% versus 6%, OR: 1.8, 95%CI:0.6-5.3), but minimal differences persisted when separately analysing pCR by ER status. Similar invasive disease-free survival (iDFS) outcomes were observed among ER-positive HER2-zero versus HER2-low IBC (48-month iDFS: 63% versus 63%, HR: 1.10, 95%CI:0.57-2.13) and ER-negative HER2-zero versus HER2-low IBC (48-month iDFS: 28% versus 25%, HR: 1.19, 95%CI:0.69-2.04). Differences in overall survival (OS) were small, both among ER-positive HER2-zero versus HER2-low IBC (48-month OS: 80% versus 81%, HR: 0.82, 95%CI:0.39-1.73) and ER-negative HER2-zero versus HER2-low IBC (48-month OS: 34% versus 47%, HR: 1.34, 95%CI: 0.74-2.41). CONCLUSIONS: Marginal differences in clinicopathologic features and outcomes were observed in HER2-low versus HER2-zero IBC when controlling for ER status, not supporting the definition of HER2-low as a distinct subtype of IBC.

Rates of pathologic nodal disease among cN0 and cN1 patients undergoing routine axillary ultrasound and neoadjuvant chemotherapy.

PURPOSE: Routine axillary ultrasound (AxUS) in patients receiving neoadjuvant chemotherapy (NAC) remains controversial. Here, we report rates of AxUS-detected nodal disease among patients with normal clinical exams, and rates of pathologic nodal disease after NAC based on method of nodal disease detection. METHODS: Clinicopathologic findings were prospectively collected for stage I-III breast cancer patients selected for NAC. All patients had pre-treatment AxUS, suspicious nodes were biopsied. The following four patient cohorts were examined: patients with suspicious exam or AxUS but negative biopsy (Suspicious cN0); those with normal exam and normal AxUS (Not Suspicious cN0); those with normal exam but suspicious AxUS and positive biopsy (AxUS-detected cN1); and those with abnormal exam and positive biopsy (exam-detected cN1). Sentinel (SLN) and non-sentinel lymph nodes (non-SLN) were evaluated by immunohistochemistry; nodal metastases of any size were considered positive. RESULTS: 500 patients were included. Of 310 patients with normal axillary exams, 160 had suspicious AxUS, 65 were biopsy-negative (Suspicious cN0) and 95/310 (30.6%) were biopsy-positive (AxUS-detected cN1). Of 190 with abnormal axillary exams, 166 were biopsy-proven node-positive (exam-detected cN1) and 24 were AxUS or biopsy-negative (Suspicious cN0). Rates of pathologic nodal disease were 20/150 (13.3%) among Not Suspicious cN0 patients, 12/89 (13.5%) among Suspicious cN0 (p = 0.97). Rates of residual nodal disease were 55/95 (57.9%) among AxUS-detected cN1 patients, 102/166 (61.4%) among exam-detected cN1 (p = 0.57). CONCLUSION: AxUS detected nodal disease in 30.6% of patients with normal clinical exams selected for NAC. Rates of pathologic nodal disease were similar among AxUS-detected and exam-detected cN1 patients.

Inflammatory Breast Cancer: Is There a Role for Deescalation of Surgery?

Inflammatory breast cancer (IBC) is a rare and aggressive presentation of breast cancer, characterized by higher propensity for locoregional recurrence and distant metastasis compared with non-IBC. Because of extensive parenchymal and overlying dermal lymphatic involvement by carcinoma, IBC is unresectable at diagnosis. Trimodality therapy (neoadjuvant chemotherapy followed by modified radical mastectomy and adjuvant comprehensive chest wall and regional nodal radiotherapy) has been a well-accepted treatment algorithm for IBC. Over the last few decades, several innovations in systemic therapy have resulted in rising rates of pathologic complete response (pCR) in both the affected breast and the axilla. The latter may present an opportunity for deescalation of lymph node surgery in patients with IBC, as those with an axillary pCR may be able to avoid an axillary dissection. To this end, feasibility data are necessary to address this question. There are very limited data on the safety of breast conservation of IBC; therefore, mastectomy remains the standard of care for this disease. There are also no data addressing the safety of immediate reconstruction in patients with IBC. Considering that some degree of deliberate skin-sparing to facilitate immediate breast reconstruction would be expected, given the extensive skin involvement by disease at diagnosis, the safest oncologic strategy to breast reconstruction in IBC would be the delayed approach.

Presence of Non-classic LCIS Is Not a Contraindication to Breast Conservation in Patients with Concomitant Invasive Breast Cancer or DCIS.

BACKGROUND: Non-classic lobular carcinoma in situ (NC-LCIS) represents a spectrum of lesions, histologically distinct from classic LCIS (C-LCIS) and ductal carcinoma in situ (DCIS). Several studies have reported on the safety of breast conservation (BCS) in patients with DCIS or invasive breast cancer and concomitant C-LCIS, yet there are no data addressing this question for patients with concomitant NC-LCIS. We evaluated local recurrence (LR) after BCS in patients with DCIS or invasive cancer and concomitant NC-LCIS. PATIENTS AND METHODS: We searched institutional databases using natural language processing to identify patients with DCIS or invasive breast cancer and concomitant NC-LCIS treated with BCS between 2000 and 2015. Charts were reviewed to collect demographics, disease and treatment details, and recurrence events. All results represent descriptive analyses. RESULTS: We identified 71 patients with DCIS (n = 13) or invasive cancer (n = 58) and concomitant NC-LCIS treated with BCS. Median patient age was 59 years (33-77 years), and median invasive tumor size was 1.2 cm (0.1-6.9 cm); 62% of DCIS and 79% of invasive cancer patients had hormone receptor (HR)-positive disease. Among DCIS patients, seven (54%) received radiation and none hormonal therapy. Among those with invasive cancer, 52 (90%) received radiation, 17 (29%) received chemotherapy and 44 of 55 with HR-positive disease (78%) received hormonal therapy. At median follow-up of 79 months (1-265 months), the LR rate was 8% and 2% among patients with DCIS and invasive cancer, respectively. CONCLUSION: NC-LCIS is rarely present in association with DCIS or invasive cancer, and it does not appear to impact LR outcomes following BCS.

How Often Does Retrieval of a Clipped Lymph Node Change Adjuvant Therapy Recommendations? A Prospective, Consecutive, Patient Cohort Study.

BACKGROUND: Prior studies examining sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for cN1 patients have demonstrated that 20% of biopsied, clipped lymph nodes (cLNs) are nonsentinel lymph nodes (non-SLNs). Our goal was to determine how often the cLN was a non-SLN among both cN0 and cN1 patients and how often cLN pathology impacted management. METHODS: Overall, 238 patients treated with NAC and surgery January 2019 to June 2020 were prospectively examined. Patients underwent routine axillary ultrasound, biopsy of suspicious nodes, and clip placement. Radioactive iodine-125 seed localization of the cLN was performed in cN1 patients only. Isolated tumor cells (ITCs) were considered node positive (ypN+) for both cN0 and cN1 cohorts. Chart review was performed to determine if cLNs were non-SLN and their ypN status. RESULTS: Of 118 cN0 patients, 115 of 118 (97%) underwent successful SLNB, 33 of whom had a cLN present; 21 of 33 (64%) cLNs were non-SLNs. Overall, 9 of 118 (8%) were ypN+; no cLN was ypN+ without additional +SLNs. Of 120 cN1 patients, 104 of 120 (87%) converted to cN0, 98 of 104 (94%) of which had attempted SLNB, and 95 of 98 (97%) successfully mapped. The cLN was a non-SLN in 18 of 95 (19%). Overall, 58 of 104 (56%) cN1 patients were ypN+. One patient had a positive cLN in the absence of +SLNs. This patient underwent axillary lymph node dissection (ALND); adjuvant treatment recommendations were unchanged. CONCLUSIONS: The cLN was a non-SLN in 19% of cN1 patients. cLN pathology did not impact adjuvant therapy recommendations, calling into question the utility of routinely clipping biopsied lymph nodes.

Atypical Lobular Hyperplasia and Classic Lobular Carcinoma In Situ Can Be Safely Managed Without Surgical Excision.

BACKGROUND: Based on modern series demonstrating low upgrade rates for pure lobular neoplasia (LN) diagnosed on core needle biopsy (CNB), our institution no longer recommends routine excision, provided imaging is concordant. This study describes outcomes in patients managed without surgical excision. METHODS: From an institutional database, we identified all patients with a diagnosis of pure atypical lobular hyperplasia and/or classic lobular carcinoma in situ on CNB managed without surgical excision (i.e., conservative management) from 2015 to 2019. The primary outcome of interest was failure of conservative management, defined as development of ipsilateral same-quadrant ductal carcinoma in situ or invasive breast cancer within 2 years of CNB, or need for ipsilateral same-quadrant excisional biopsy. We also evaluated rates of ipsilateral same-quadrant CNB during follow-up. RESULTS: Among 96 pure LN lesions on CNB since 2015, 80 (83%) were managed without surgical excision. Median follow-up was 27 months (IQR: 16-28), with only 2 (2%) patients lost to follow-up. No patients developed an ipsilateral, same-quadrant breast cancer. The 3-year risk of conservative management failure was 6.2% (95% CI 2.3-15.7%). All failures were a result of need for excisional biopsy due to progressive imaging abnormalities at the initial CNB site, with benign final pathology. The 3-year risk of ipsilateral same-quadrant CNB was 9.2% (95% CI 3.8-21.5%). CONCLUSION: Non-surgical management of pure LN is safe, and the likelihood of requiring subsequent surgical excision or repeat CNB during follow-up is low. These data provide reassurance that routine excision of pure LN in the setting of radiologic-pathologic concordance is not required.

MRI Changes in Breast Skin Following Preoperative Therapy for Patients with Inflammatory Breast Cancer.

RATIONALE AND OBJECTIVES: Preoperative systemic therapy (PST) followed by mastectomy and radiation improves survival for patients with inflammatory breast cancer (IBC). Residual disease within the skin post-PST adversely impacts surgical outcome and risk of local-regional recurrence (LRR). We aimed to assess magnetic resonance imaging (MRI) breast skin changes post-PST with pathologic response and its impact on surgical resectability. MATERIALS AND METHODS: We retrospectively reviewed 152 baseline and post-PST breast MRIs of 76 patients with IBC. Using the ACR-BIRADS MRI lexicon, we correlated skin thickness, qualitative enhancement, and kinetic analysis with pathologic response in the skin at mastectomy. RESULTS: Baseline MRI showed skin thickening in all 76 patients, 75/76 (99%) showed skin enhancement, 54/75 (72%) had medium/fast initial kinetics, usually with persistent delayed kinetics in 49/54 (91%). Following PST, 66/76 (87%) had residual skin thickening with 64/76 (84%) showing a decrease; 33/76 (43%) had persistent enhancement. The median thickness post-PST was 4.7 mm with residual tumor in the skin, and 3.0 mm without residual tumor (p = 0.008). Regardless of pathologic response, the majority of patients had persistent skin thickening on MRI following PST (100% [14/14] with residual tumor and 84% [52/62] without residual tumor). There was no association between post-PST skin thickness on breast MRI and rate of LRR. CONCLUSION: Patients with IBC have skin thickening and enhancement on baseline breast MRI, with a statistically significant reduction in skin thickness following successful PST. Despite persistent skin changes on MRI, patients achieving a partial or complete parenchymal response to PST may proceed to mastectomy with low LRR rates.