Comparison of Clinical Breast Exam to Breast MRI Surveillance in Patients Following Nipple-Sparing Mastectomy.

BACKGROUND: Nipple sparing mastectomy (NSM) is increasingly being performed for patients with breast cancer. However, optimal postoperative surveillance has not been defined. METHODS: A prospectively maintained database identified patients with in-situ and invasive cancer who underwent NSM between 2007-2021. Clinical data on postoperative breast surveillance and interventions were collected. Patients who had MRI surveillance versus clinical breast exam (CBE) alone were compared with respect to tumor characteristics, recurrence, and survival. RESULTS: A total of 483 NSMs were performed on 399 patients. 255 (63.9%) patients had invasive ductal carcinoma, 31 (7.8%) invasive lobular carcinoma, 92 (23.1%) DCIS, 6 (1.5%) mixed ductal and lobular carcinoma, 9 (2.3%) others, and 6 (1.5%) unknown. Postoperatively, 265 (66.4%) patients were followed with CBE alone and 134 (33.6%) had surveillance MRIs. At a median follow-up of 33 months, 20 patients (5.0%) developed in-breast recurrence, 6 patients had (1.5%) an axillary recurrence, and 28 with (7.0%) distant recurrence. 14 (53.8%) LRR were detected in the CBE group and 12 (46.2%) were detected in the MRI group (P = .16). Overall survival (OS) was 99%, with no difference in OS between patients who had CBE alone versus MRI (P = .46). MRI was associated with higher biopsy rates compared to CBE alone (15.8% vs. 7.8%, P = .01). CONCLUSIONS: Compared to CBE alone, the use of screening MRI following NSM results in higher rate of biopsy and no difference in overall survival.

A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer.

Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer.

De-Implementation of Low-Value Care for Women 70 Years of Age or Older with Low-Risk Breast Cancer During the COVID-19 Pandemic.

BACKGROUND: Older women with early-stage estrogen receptor-positive (ER+) invasive breast cancer (IBC) are at risk for overtreatment. Guidelines allow for sentinel lymph node biopsy (SLNB) and radiotherapy omission after breast-conserving surgery (BCS) for women 70 years of age or older with T1, clinical node negativity (cN0), and ER+ IBC. The study objective was to evaluate radiotherapy and SLNB de-implementation in older women with low-risk IBC after the resource limitations of the COVID-19 pandemic. METHODS: An institutional database was analyzed to identify women 70 years of age or older who received BCS for IBC from 2012 to 2022. The patients were divided into two cohorts: (1) patients with low-risk IBC (pT1, cN0, and ER+/HER2-) who were eligible for radiotherapy and SLNB omission and (2) patients with high-risk IBC (pT2-T4, cN+, ER-, or HER2+) who were ineligible for therapy omission. Clinicopathologic variables in both cohorts were analyzed. RESULTS: The study enrolled 881 patients. For the patients with low-risk IBC, the annual rates of radiotherapy were stable from 2012 to 2019. However, radiotherapy utilization decreased significantly from 2020 to 2022 (58% in 2012 vs 36% in 2022; p = 0.04). In contrast, radiotherapy usage among the patients with high-risk IBC was stable from 2012 to 2022 (79% in 2012 vs 79% in 2022; p = 0.95). Among the patients with low-risk IBC, SLNB rates decreased from 86% in 2012 to 56% in 2022, but this trend predated those in 2020. The factors significantly associated with SLNB and receipt of radiotherapy among the patients with low-risk IBC were younger age, larger tumors, grade 3 disease, and involved nodal status (p < 0.01). CONCLUSION: This study demonstrated appropriate and sustained de-escalation of radiotherapy in older women with low-risk IBC after the COVID-19 pandemic.

Incidence of Cancer and Role of Sentinel Lymph Node Biopsy in BRCA Mutation Carriers Undergoing Prophylactic Mastectomies.

INTRODUCTION: Breast surveillance in patients with BRCA mutations include mammography (MMG) and MRI. Patients may elect to undergo risk-reducing bilateral prophylactic mastectomies (BPM). Sentinel lymph node biopsies (SLNB) are frequently performed and associated with increased morbidity. This study sought to determine the correlation between preoperative imaging and the final pathology and evaluate the role of SLNB in these high-risk patients. METHODS: A prospective database identified BRCA patients who underwent BPM between 2006 and 2022. Imaging, pathology, and operative reports were reviewed. RESULTS: 170 patients with BRCA 1/2 mutations were identified. 162 (95.3%) had imaging within one year of BPM. Of these, 28 (17.3%) patients had a MMG/ultrasound, 53 (32.7%) had an MRI, and 81 (50%) had both; 21/162 (13.0%) patients had abnormal imaging. Bilateral SLNB were performed in 31 (18.2%) patients, of which 7 had abnormal imaging; unilateral SLNB were performed in 4 (2.4%) patients, of which 3 had abnormal imaging. 11/170 (6.4%) patients had a malignancy and only one (9%) of these patients had imaging abnormalities. 1/170 (0.6%) patient had an invasive carcinoma requiring an axillary lymph node dissection (ALND), and 10/170 (5.9%) patients had ductal carcinoma in situ (DCIS). 25/170 (14.7%) had ADH/ALH. Only 7/170 (4.1%) patients had imaging abnormalities and abnormal pathology. All SLNB and ALND performed demonstrated no metastatic disease. DISCUSSION: There is a high rate of discordance between preoperative imaging prior to surgery in BRCA patients undergoing prophylactic mastectomies and final pathology. This study does not support routine SLNB at the time of BPM.

Invasive Lobular Carcinoma-Correlation Between Imaging and Final Pathology: Is MRI Better?

BACKGROUND: Invasive lobular carcinoma (ILC) is associated with high re-excision rates following breast-conserving surgery (BCS). The correlation between lesion size on different imaging modalities and final tumor size has not been well characterized. METHODS: A prospective database of patients with stage I-III breast cancer undergoing BCS between 2006 and 2016 was reviewed. Pearson correlation analysis was used to correlate tumor size on breast imaging to final pathology. RESULTS: Of these, 111 patients with ILC were identified. Mean lesion size was 1.93 cm for MMG, 1.61 cm for US, and 2.51 cm for MRI. Mean tumor size on surgical excision was 2.64 cm. The correlation coefficient between pathology and the different imaging modalities were as follows: MMG .17, US 0.37, and MRI .58. Actual tumor size was underestimated by 1 cm in 27.1% of MMGs, 50% of USs, and in 13.3% of MRIs. 38 patients (34.2%) underwent re-excision. No differences in re-excision rates were noted in patients with and without MRI, 30.3% vs 40.0%, respectively (P = .31). CONCLUSION: While MRI provides a better estimate of tumor size than MMG and US, the size of the tumor on imaging only weakly correlated with pathology. The use of MRI does not decrease re-excision rates.

The impact of pre-transplant weight loss on survival following cardiac transplantation.

BACKGROUND: Significant weight loss due to cardiac cachexia is an independent predictor of mortality in many heart failure (HF) clinical trials. The impact of significant weight loss while on the waitlist for heart transplant (HT) has yet to be studied with respect to post-transplant survival. METHODS: Adult HT recipients from 2010 to 2021 were identified in the UNOS registry. Patients who experienced an absolute weight change from the time of listing to transplant were included and classified into two groups by percent weight loss from time of listing to time of transplant using a cut-off of 10%. The primary endpoint was 1-year survival following HT. RESULTS: 5951 patients were included in the analysis, of whom 763 (13%) experienced ≥10% weight loss from the time of listing to transplant. Weight loss ≥ 10% was associated with reduced 1-year post-transplant survival (86.9% vs. 91.0%, long-rank p = .0003). Additionally, weight loss ≥ 10% was an independent predictor of 1-year mortality in a multivariable model adjusting for significant risk factors (adjusted HR 1.23, 95% CI 1.04-1.46). In secondary analyses, weight loss ≥ 10% was associated with reduced 1-year survival independent of hospitalized status at time of transplant as well as obesity status at listing (i.e., body mass index [BMI] < 30 kg/m2 and BMI ≥ 30 kg/m2 ). CONCLUSIONS: Preoperative weight loss ≥ 10% is associated with reduced survival in patients listed for HT. Nutrition interventions prior to transplant may prove beneficial in this population.

Effects of paravertebral blocks versus liposomal bupivacaine on hospital utilization after mastectomy with reconstruction.

INTRODUCTION: Inadequate pain control frequently extends length of stay (LOS) and costs for patients undergoing mastectomy with implant-based reconstruction (IBR). We sought to examine the effects of Paravertebral blocks (PVB) and liposomal bupivacaine (LB) and compare LOS, pain scores and costs of hospitalization. METHODS: Prospective database review of patients undergoing mastectomy with IBR was performed. RESULTS: 541 patients were identified. 51/491 (9.4%) received PVB and 50 (9.2%) received LB. LOS in the PVB group was significantly less than that of the no block (NB) group (1 [1-2] days PVB vs 3 [2-4] days NB (p < 0.0001), but was not different from the LB group (1 [1-2] days LB, p = 0.23). PVB patients had lower PACU pain scores compared to NB patients (3.2 ± 2.9 PVB vs 5.7 ± 2.6 NB, p < 0.0001), but similar PACU pain scores to LB patients (4.1 ± 2.3). Patients who received PVB had higher total costs compared to NB patients ($27148±$7053 PVB vs $23113 ± 6860 NB, p = 0.003) but similar to LB patients ($26183 ± $3761). CONCLUSION: PVB and LB are associated with shorter LOS and lower pain scores compared to NB.

Upstaging of Fibroepithelial Lesions: A Single-Institution Experience.

INTRODUCTION: Fibroepithelial lesions of the breast (FEL) are heterogeneous lesions ranging from fibroadenomas (FA) to phyllodes tumors (PT). FEL with cellular stroma are diagnostic challenges on core needle biopsy (CNB) as it is difficult to distinguish cellular FA from PT. The purpose of this study was to determine the features of FEL on CNB that may be predictive of PT, the upstage rate to PT after excision, and the outcomes of those who did not undergo excision. METHODS: Overall, 305 patients with FEL on CNB between 2009 and 2019 were identified from a prospectively maintained institutional database. Presentation, imaging, and pathology were evaluated. RESULTS: Mean age at diagnosis was 43.8 years. Pathology on CNB included 97 cases of FEL favoring FA, 19 cases of FEL favoring PT, 3 cases of FEL versus pseudoangiomatous stromal hyperplasia, and 186 cases of FEL not otherwise specified. Following CNB, 96 (31.5%) patients were observed, 158 (51.8%) patients had an excisional biopsy, 48 (15.7%) patients underwent segmental mastectomy, and 3 (1.0%) patients underwent a mastectomy. The upgrade rate from FEL on CNB to PT upon excision was 25.8%. PT on final pathology was more commonly seen when the CNB identified stromal overgrowth, necrosis, and diagnosis of FEL favoring PT. On multivariable analysis, a final diagnosis of PT was associated with age >50 years, larger tumor size >2 cm, stromal overgrowth, and ≥1 mitoses/10 high power fields (HPF) on CNB. Patients who were observed had smaller tumors compared with those who underwent excision. CONCLUSION: In this 10-year single-institution experience of FEL, the upstage rate to PT was 25.8%. Excision of FEL is recommended. Furthermore, the observation of lesions appeared to be safe in select cases, specifically in patients with smaller tumor size.

Clinicopathologic Characteristics and Patient Outcomes of Phyllodes Tumors: A Single Institution Experience.

Phyllodes tumors (PT) are rare fibroepithelial neoplasms that are classified as benign, borderline, or malignant. Patients with PT diagnosed between 2009 and 2019 were identified from a prospectively maintained single institutional database. 76 patients with PT were included; 47 (61.8%) were benign, 9 (11.8%) were borderline, and 20 (26.3%) were malignant. The mean age at diagnosis was 52. Surgical treatment of benign PT included excisional biopsy in 31 (66.0%) patients, segmental mastectomy in 15 (31.9%), and mastectomy in 1 (2.1%). Among patients with borderline PT, operative management was excisional biopsy in 4 (44.4%) and segmental mastectomy in 5 (55.6%). Of those with malignant PT, 7 (35.0%) were treated with excisional biopsy alone, 9 (45.0%) had lumpectomy (segmental mastectomy), and 4 (20.0%) underwent mastectomy. Malignant PT had a higher rate of necrosis compared to borderline or benign PT (25.0% vs 0% vs 4.3%, P = .016). Four patients had recurrent PT. Final positive margins were associated with recurrence (P = .044). The median overall follow-up time was 86.3 months (range 1.5-1414.1 months), and no deaths occurred among patients with malignant PT. Overall, recurrence rates of PT are low but may be increased by presence of positive margins.

Commission on Cancer CP3R Compliance Rates for Treatment of Patients With Triple Negative and HER2+ Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: Cancer Program Practice Profile Reports (CP3R) metrics were released by the Commission on Cancer to provide standards for high-quality care. One metric is the recommendation of combination chemotherapy or chemo-immunotherapy (CIT) within 120 days of diagnosis for women under 70 with AJCC T1cN0M0 or Stage IB-III HER2+ or hormone receptor negative breast cancer ([Multi-agent chemotherapy] MAC). Our study assesses national concordance rates for MAC and CIT. METHODS: The National Cancer Database was queried from 2004-2014. RESULTS: 122,045 patients met criteria, of whom treatment for 101,800 (83.4%) patients was concordant with MAC and CIT. Treatment concordance increased from 75.7% in 2004 to 89.5% in 2014. For HER2+ patients, use of CIT treatment downtrended with progression of pathological stage, from 70.1% (stage I) to 58.1% (stage III). Mean overall survival of patients whose treatment was concordant with MAC and CIT was longer than that of patients who were non-concordant (146.6 vs 143.8 months, P <.01). On Cox regression, there was a survival benefit for concordant patients who were treated at academic hospitals (HR .89, 95% CI 0.802-.976) and had private insurance (HR .76, 95% CI 0.65-.89). CONCLUSION: Compliance with MAC and CIT has improved over the past decade and is associated with a significant improvement in overall survival.

Non-healing Wound After Mastopexy: Cautionary Case Report for a Unique Source of a Marjolin's Ulcer of the Breast.

Marjolin's ulcers (MUs) represent a unique degenerative process that results in malignancy. Classically, sites of previous burns are associated with MU but, in fact, any non-healing wound has been found to be a potential source of degeneration. Malignancies that arise include typically cutaneous squamous cell carcinoma (SCC), but SCC at the site of a previous wound is a more aggressive, lethal variant. This report represents a cautionary case of the management of an open wound and highlights a previously undescribed etiology of an MU in the breast.

Contemporary Cancer Program Practice Profile Report (CP3R) Compliance Rates for Breast Cancer: A National Cancer Database Analysis.

INTRODUCTION: The Commission on Cancer (CoC) issues Cancer Program Practice Profile Reports (CP3R) that set standards for high-quality care. Three metrics for breast cancer include radiation within 1 year for women < 70 years of age receiving breast-conserving surgery, radiation within 1 year after mastectomy for women with four or more positive lymph nodes (MASTRT), and hormonal therapy within 1 year of a stage IB-III hormone receptor-positive breast cancer (HT). Our study evaluates national trends in quality metric compliance. METHODS: The National Cancer Database was queried from 2004 to 2014 to identify patients who met the criteria for the three quality metrics. National trends in compliance were compared. RESULTS: Overall, 1,094,264 patients qualified for BCSRT (n = 534,147), MASTRT (n = 66,291), or HT (n = 493,826). In 2014, 91.1% of patients met BCSRT, 88.4% met MASTRT, and 90.7% met HT. BCSRT, MASTRT, and HT compliance rates were lower in community hospitals compared with Integrated Network Cancer Programs (INCP) (BCSRT: 89.0% vs. 92.8%, p < 0.01; MASTRT: 85.5% vs. 90.6%, p < 0.01; HT: 87.3% vs. 93.7%, p < 0.01). On multivariate analysis, patients receiving care at an INCP facility [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.37-1.58] and insured patients (OR 1.70, 95% CI 1.54-1.87) had higher odds of BCSRT compliance, and minorities (OR 0.76, 95% CI 0.73-0.80) had lower odds. Similar results were seen for MASTRT and HT. CONCLUSION: In more recent years, overall compliance rates for breast cancer quality metrics of BCSRT and HT by Comprehensive Community Cancer Programs, Academic/Research Programs, and INCPs have increased to meet the 90% CoC standards, while MASTRT has regressed. Community programs were least compliant with meeting the CoC standards.

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy.

INTRODUCTION: Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2- no change, triple negative (TN) no change, HR+HER2- to TN, TN to HR+HER2]. RESULTS: Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2- to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2- no change. CONCLUSIONS: Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

Changes in utilization of axillary dissection in women with invasive breast cancer and sentinel node metastasis after the ACOSOG Z0011 trial.

The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial demonstrated no survival advantage for women with clinical T1-T2 invasive breast cancer with 1-2 positive sentinel lymph nodes (SLN) who received whole-breast radiation, and no further axillary surgery when compared to women who did undergo axillary lymph node dissection (ALND). We used the National Cancer Database (NCDB) to study changes in utilization of ALND after the publication of this trial. NCDB was queried for female patients from 2012 to 2015 who met Z0011 criteria. Patients were divided into four groups based on Commission on Cancer facility accreditation. Outcome measures include the rate of ALND (nonadherence to Z0011) and the average number of nodes retrieved with ALND. 27,635 patients were identified, with no significant differences in T stage and receptor profiles between groups. Overall rate of ALND decreased from 34.0% in 2012 to 22.7% in 2015. Nonadherence was lowest in Academic Programs (decreasing from 30.1% in 2012 to 20.5% in 2015) and was highest in Community Cancer Programs (41.2% in 2012 to 29.1% in 2015). Median number of positive SLN did not differ between groups (p = .563). Median number of nodes retrieved on ALND decreased from 9 (IQR 5-14) in 2012 to 7 (IQR 4-12) in 2015 (p < .001). In patients who met the ACOSOG Z11 trial guidelines, rates of ALND have decreased over time. However, rates of nonadherence to Z0011 are significantly higher in Community Cancer Programs compared to Academic Programs.

Incidental radiologic findings in breast cancer patients who undergo staging prior to neo-adjuvant chemotherapy.

NCCN guidelines discourage the use of staging imaging for newly diagnosed patients with early breast cancer (BC). When performed, incidental radiologic findings of uncertain significance are often encountered. The purpose of this study was to compare incidental findings seen on staging imaging with distant recurrence in patients undergoing neo-adjuvant chemotherapy (NAC). 396 patients with BC who had NAC from 2008 to 2016 were identified from a prospectively maintained data base. Staging imaging was reviewed. Of 396 patients with BC treated with NAC, patients with a positive PET/CT for metastatic disease (n = 36, 9.1%), those that did not undergo staging imaging (n = 49, 12.4%), or those that did not have a reported incidental finding (n = 49, 12.4%) were excluded from analysis. Of the 262 patients who met criteria, mean age was 50 years (range: 26-88). 201 (76.7%) patients had stage I-II cancer, and 61 (23.3%) patients had stage III cancer. Overall, 146 (55.7%) patients had an incidental finding on imaging. 90 (34.4%) patients had one finding, 42 (16.0%) patients had two, and 14 (5.3%) patients had three or more findings. The majority of incidental findings were seen in the ovary/uterus (29.7%), followed by lung (18.4%), liver (10.3%), and bone (9.0%). 5 (3.4%) patients had additional imaging performed. At mean follow-up of 3.7 years (range: 0.7-10.8), 43 (15.6%) patients had a distant recurrence. Of these patients, only 5 (1.9%) patients had distant metastasis in the same organ that was initially thought to be an incidental finding. Our results suggest that breast cancer patients with incidental findings on preoperative staging imaging are unlikely to be indicative of sites for future metastasis.