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Lisa V Doan,1 Anna Li,1 Lee Brake,1 Deborah Ok,1 Hyun Jung Jee,1 Hyung Park,2 Randy Cuevas,1 Steven Calvino,1 Amber Guth,3 Freya Schnabel,3 Karen Hiotis,3 Deborah Axelrod,3 Jing Wang1,4 1Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University Grossman School of Medicine, New York, NY, USA; 2Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA; 3Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA; 4Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, USACorrespondence: Lisa V Doan, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University Grossman School of Medicine, 240 E 38th St, 14th Floor, New York, NY, 10016, USA, Tel +1 212201-1004, Email Lisa.Doan@nyulangone.orgBackground and Objectives: Perioperative ketamine has been shown to reduce opioid consumption and pain after surgery. Ketamine is most often given as an infusion, but an alternative is single-dose ketamine. Single-dose ketamine at up to 1 mg/kg has been shown to reduce symptoms of depression, and a wide range of dosages has been used for pain in the emergency department. However, limited data exists on the tolerability and efficacy of a single-dose of ketamine at 0.6 mg/kg for pain when administered immediately after surgery. We conducted a pilot study of single-dose ketamine in patients undergoing mastectomy with reconstruction, hypothesizing that a single-dose of ketamine is well tolerated and can relieve postoperative pain and improve mood and recovery.Methods: This is a randomized, single-blind, placebo-controlled, two-arm parallel, single-center study. Thirty adult women undergoing mastectomy with reconstruction for oncologic indication received a single-dose of ketamine (0.6mg/kg) or placebo after surgery in the post-anesthesia care unit (PACU). Patients were followed through postoperative day (POD) 7. The primary outcome was postoperative pain measured by the Brief Pain Inventory (BPI) pain subscale on POD 1 and 2. Secondary outcomes include effects on opioid use, PROMIS fatigue and sleep, mood, Quality of Recovery-15, and the Breast Cancer Pain Questionnaire.Results: Side effects were minor and not significantly different in frequency between groups. The ketamine group reported lower scores on the BPI pain severity subscale, especially at POD 7; however, the difference was not statistically significant. There were no statistically significant differences between ketamine and placebo groups for the secondary outcomes.Conclusion: A single-dose of ketamine at 0.6mg/kg administered postoperatively in the PACU is well tolerated in women undergoing mastectomy and may confer better pain control up to one week after surgery. Future studies with larger sample sizes are necessary to adequately characterize the effect of postoperative single-dose ketamine on pain control in this population.Keywords: postoperative pain, non-opioid, analgesia

Background: Post-mastectomy pain syndrome (PMPS) affects up to 60% of women undergoing mastectomy. Standard perioperative multimodal analgesia remains only moderately effective in preventing PMPS, and many patients continue to rely on opioids for their chronic pain. In the context of the opioid overdose crisis, alternative interventions are urgently needed. Ketamine targets risks factors for PMPS including acute pain and negative mood, making it an ideal candidate for the prevention of PMPS. Trial Design: This is a multisite, three-arm, double-blind, RCT to test the effectiveness of ketamine in reducing PMPS in women undergoing mastectomy for oncologic indication. Arm 1 consists of continuous perioperative ketamine infusion that begins during surgery and continues for 2 hours in the post-anesthesia care unit (PACU). Arm 2 consists of a single-dose of ketamine in the PACU given over 50-60 minutes. Arm 3 consists of placebo. Standard surgical and postsurgical care remain unchanged across all arms. Eligibility Criteria: Inclusion criteria are: women ≥18 years of age undergoing total mastectomy for oncologic indication +/- lymph node dissection and +/- immediate or delayed reconstruction with no distant metastases. Exclusion criteria include: (1) history of cognitive impairment (2) past ketamine or phencyclidine misuse or abuse, (3) schizophrenia or history of psychosis, (4) history of post-traumatic stress disorder, (5) known sensitivity or allergy to ketamine, (6) liver or renal sufficiency, (7) uncontrolled hypertension, chest pain, cardiac arrhythmia, stroke, head trauma, intracranial mass or hemorrhage, glaucoma, porphyria, uncontrolled thyroid disease, or other contraindication to ketamine, (8) lamotrigine alfentanil, physostigmine, or 4-aminopyridine use, (9) currently pregnant, (10) body mass index greater than 35, (11) non-English or non-Spanish speaker, (12) currently participating in another pain interventional trial, (13) patient has started or undergone hormone therapy for gender transition into male, or (14) patient is scheduled for bilateral (or greater) flap reconstruction. Specific Aims: The primary outcome is pain intensity on the Brief Pain Inventory short form scale at the surgical site three months after mastectomy. Secondary outcomes include pain severity and interference at the surgical site, incidence of PMPS, anxiety, and depression over 12 months after surgery. Tertiary outcomes include neuropathic symptoms, fatigue, sleep, physical function, and opioid use. Statistical Methods: We will test the differences in the primary outcome between 1) the continuous ketamine infusion and the control; and 2) the single-dose ketamine and the control, each at 0.025 significance level (adjusted for multiple comparisons using the Bonferroni correction), based on the two-sample t-tests (allowing unequal variances) if outcome variables are approximately normal, or Wilcoxon’s rank-sum tests otherwise. Accrual: The target accrual for this study is ~750. Recruitment began January 2022. Recruitment is expected to be complete by October 2025. As of July 14, 2022, 43 participants have been enrolled across all sites. If interested in the KALPAS Study, please contact kalpas@nyulangone.org, jing.wang@nyulangone.org, or lisa.doan@nyulangone.org This research is supported by the National Institutes of Health through the NIH HEAL Initiative under UH3CA261067. It is also supported by the NCATS Trial Innovation Network under award numbers U24TR001608 (CCC), U24TR001597 (DCC), U24TR001609 (SSC), U24TR001579 (RIC) Citation Format: Lisa Doan, Raven Perez, Jeana Chun, Randy Cuevas, Pabel Miah, Amber Guth, Karen Hiotis, Freya Schnabel, Michele Curatolo, Robert Edwards, Hyung Park, John Rotrosen, Deborah Axelrod, Jing Wang. Ketamine Analgesia for Long Lasting Pain Relief after Surgery (KALPAS) 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 OT3-20-01.

Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT.Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS).Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%.In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Introduction: Positive lumpectomy margins are associated with an increased risk for ipsilateral tumor recurrence, and necessitate additional procedures to achieve acceptable margins. Re-excision rates are higher in patients with ductal carcinoma in situ (DCIS) versus those with invasive carcinoma. The purpose of this study was to investigate the clinicopathologic characteristics, surgical techniques, and other outcomes associated with re-excision over time following primary breast conserving surgery for DCIS. Methods: Our institutional Breast Cancer Database was queried for patients treated with lumpectomy as the primary procedure for pure DCIS from 2010-2021. Cases of microinvasive disease were excluded. The primary endpoint was the rate of re-excision following lumpectomy. Variables of interest included patient demographics and clinicopathologic characteristics. As a secondary analysis, adjusted odds ratios for the association of MarginProbe® with re-excisions were calculated using a multivariable logistic regression model controlling for age, tumor size, breast density and DCIS subtype. Individual comparisons of continuous variables were based on t-tests, group proportions compared with one-way ANOVA, and categorical variables compared using Chi Square tests. Results: Out of a total of 695 patients in our cohort, 221 (32%) had re-excisions. There was a statistically significant 2% decline per year in the number of re-excisions (p=0.005). Patients who underwent re-excision had larger size of DCIS (2.37 cm vs 1.37 cm, p Table 1.Clinicopathologic CharacteristicsVariableNo Re-excision (n=313)Re-Excision (n=100)P-ValueAge; mean (SD)61.48 (12.01)58.04 (13.39)0.016Age of Menopause; mean (SD)50.22 (5.18)48.13 (5.45)0.004Size of DCIS; mean (SD)1.37 (1.25)2.37 (2.00)0 and Citation Format: Joshua A Feinberg, Charles DiMaggio, Nakisa Pourkey, Jennifer Chun Kim, Jenny Goodgal, Amber Guth, Deborah Axelrod, Freya Schnabel. Meeting the challenge of successful one-stage lumpectomy for DCIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-11.

Background: Neoadjuvant endocrine therapy (NET) has long been limited to patients who were deemed medically unfit for immediate surgery or on clinical trials. Coronavirus disease 2019 (COVID-19) resulted in a global pandemic, which led to deferral of elective surgeries including breast surgeries for early stage breast cancer patients during March - June 2020. Institutional guidelines were developed based on societal recommendations, including NCCN, to use NET as a bridge to surgery. Objective: Primary objective was to establish a database of early stage HR+ Her2/neu- breast cancer patients diagnosed during COVID-19 who were treated with NET as a bridge to surgery. Secondary endpoints include correlation between duration of NET and changes in pathological variables. Method: This was a single institution, retrospective observational study from Perlmutter Cancer Center at NYU Langone Hospital and NYU Langone Hospital - Long Island of DCIS and early stage breast cancer patients diagnosed from March 15, 2020 - June 1, 2020 during COVID-19 pandemic. Inclusion criteria were males and females older than 18 years of age and initial diagnosis of DCIS or early stage HR+ Her2/neu- breast cancer who did not require neoadjuvant chemotherapy by established guidelines. Descriptive statistics were calculated separately by DCIS and invasive breast cancer using SAS version 9.4. Results: From March 15 - June 1, 2020, 13 patients who were diagnosed with DCIS and 41 patients with early stage HR+ Her2/neu- invasive breast cancer received NET (Table 1). Of the 41 patients with invasive breast cancer, 19 (46%) had Oncotype DX assay on biopsy specimens; 12/19 (63%) had scores 10-14 and 7/19 (37%) had scores 15-25. 38/41 (92.7%) had post-surgery Ki-67% and 16/38 (42.1%) demonstrated maturation arrest (Ki-67 4 weeks (Table 2). Median duration of NET in invasive breast cancer was 6.85 weeks. 1 patient had a complete pathological response after NET and 2 patients were upstaged from DCIS to invasive carcinoma at the time of surgery. Conclusion: While the sample sizes are small, this is a unique cohort of early stage surgically resectable breast cancer patients who were treated with NET during the COVID-19 pandemic. This real-world data confirms pathological changes, especially decrease in Ki-67% even with short duration use of NET that has been reported in trials of neoadjuvant AI. Long term follow-up for survival outcome is planned. Table 1.Demographics of early stage breast cancer patients diagnosed during COVID-19.DCIS (n=13)Invasive Breast Cancer (n=41)Total (n=54)Menopause status (n, %)Pre-menopause7 (53.8)6 (14.6)13 (24.1)Post-menopause6 (46.2)35 (85.4)41 (75.9)Diagnosis (n, %)Self-Palpated08 (19.5)8 (14.8)Screening13 (100)33 (80.5)46 (85.2)Age (n, %)≤503 (23.1)5 (12.2)8 (14.8)50+10 (76.9)36 (87.8)46 (85.2)Clinical Stage (n, %)Tis13 (100)013 (24.1)I037 (90.2)37 (68.5)II04 (9.8)4 (7.4)NET in weeks (n, %)≤43 (23.1)11 (26.8)14 (25.9)4+10 (76.9)30 (73.2)40 (74.1)Genomic Testing (n, %)Oncotype DX019 (86.4)19 (86.4)ProSigna03 (13.6)3 (13.6)Mammaprint000 Table 2.No significant associations with changes in pre to post in T stage, ER%, PR% or Ki-67% in patients treated with NET for ≤4 weeks and >4 weeks.≤4 weeks>4 weeksp-valueChange in T stage0.5810Decrease2 (27.27%)8 (26.67%)No change7 (63.64%)15 (50%)Increase1 (9.09%)7 (23.33%)Change in ER%0.2444Decrease4 (36.36%)9 (30%)No change4 (36.36%)5 (16.67%)Increase3 (27.27%)16 (53.33%)Change in PR%1.0000Decrease7 (70%)21 (70%)No change2 (20%)5 (16.67%)Increase1 (10%)4 (13.33%)Change in Ki-67%0.3224Decrease4 (66.67%)17 (85%)No Change1 (16.67%)1 (5%)Increase1 (16.67%)2 (10%) Citation Format: Julie Huang, Joshua Feinberg, Bahram Dabiri, Jordan Baum, Meredith Akerman, Anthony Pasquarella, Abhinav Rohatgi, Shubhada Dhage, Amber Guth, Nina D'Abreo. Neoadjuvant endocrine therapy (NET) as bridge therapy for early stage breast cancer during COVID-19: A single institution experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-15-03.

Background: Coronavirus disease 2019 (COVID-19) resulted in a global pandemic, which led to deferral of surgeries for early stage breast cancer during March - June 2020. Institutional guidelines were developed to use neoadjuvant endocrine therapy (NET) as a bridge to surgery. As a follow up to initial data presented at SABCS 2020 demonstrating patient acceptance of NET, the present study provides results from a survey which explored psychosocial factors associated with medication compliance. Objective: Primary objective was to identify any barriers to compliance with NET. Method: This was a single institution, prospective study that surveyed patients diagnosed with DCIS and early stage breast cancer at Perlmutter Cancer Center at NYU Langone Hospital and NYU Langone Hospital - Long Island from March 15, 2020 - June 1, 2020. Questions were based on the Beliefs about Medicines Questionnaire specific for endocrine therapy (BMQ-AET) and the Medication Adherence Report Scale. Responses were recorded on a Likert scale and included 7 questions regarding perceptions about breast cancer treatment, 10 questions addressing experience with NET, and 5 questions gauging at adherence to NET. Inclusion criteria were males and females older than 18 years old, with an initial diagnosis of DCIS or early stage HR+ Her2/neu- breast cancer, who were prescribed NET. Descriptive statistics were calculated and subgroups were compared using Fisher’s exact tests. Analyses were performed using SAS version 9.4. Results: From March 15 - June 1, 2020, 13 patients were diagnosed with DCIS and 29 patients with HR+ Her2/neu- breast cancer for whom NET was recommended. Demographics are shown in Table 1. All 42 patients were female with an average age of 60.9 years. Majority of patients were post-menopause (74%) and predominantly white (64%), with an income of less than $60,000 (52.4%). Average NET duration was 6.7 weeks. Survey responses displayed in Table 2 indicate statistically significant p values in bold. Patients >50 years old, post-menopause and invasive breast cancer had a stronger belief that NET would be helpful, resulting in greater perception to breast cancer treatment and higher adherence to NET. Patients treated with NET for greater than 4 weeks also felt that NET would make them feel well compared to ≤4 weeks. Interestingly, no significant differences in responses based on education or income level were observed. Conclusion: COVID-19 pandemic presented a unique opportunity to use NET, which is often underutilized outside of clinical trials. In this single institution prospective study, we found that post-menopause patients greater than 50 years old with invasive breast cancer perceived hormonal therapy as beneficial to their health, resulting in increased medication compliance. These findings can be used when counseling patients currently treated with NET as well as those patients may be appropriate for NET in the post-COVID era. Table 1.Demographics of early stage breast cancer patients diagnosed during COVID-19.DCIS (n=13)Invasive Breast Cancer (n=29)Total (n=42)Menopause Status (n, %)Pre-menopause7 (53.8)4 (13.8)11 (26.2)Post-menopause6 (46.2)25 (86.2)31 (73.8)Diagnosis (n, %)Self-Palpated06 (20.7)6 (14.3)Screening13 (100)23 (79.3)36 (85.7)Age (n, %)≤504 (30.8)4 (13.8)8 (19)50+9 (69.2)25 (86.2)34 (80.9)Average Age (range)54.9 (40 – 72)63.6 (32 – 85)60.9 (32 – 85)Race (n, %)White7 (53.8)20 (69%)27 (64.3)Non-White6 (46.2)9 (31%)15 (35.7)Education (n, %)K-121 (7.7)6 (20.7)7 (16.7)College and Graduate12 (92.3)23 (79.3)35 (83.3)Income (n, %)$0 – $60,0005 (38.5)17 (58.6)22 (52.4)$>60,0017 (53.8)12 (41.3)19 (45.2)No response1 (7.7)01 (2.4)NET in Weeks (n, %)≤45 (38.5)7 (24.1)12 (28.6)4+8 (61.5)22 (75.9)30 (71.4) Table 2.Perceptions of breast cancer and hormonal therapy.Perceptions About Hormonal TherapyPerceptions About Breast Cancer TreatmentAdherence To Hormonal TherapyMy health at present depends on me taking hormone treatment (p-value)Hormone treatment is a mystery to me (p-value)My health in the future will depend on me taking hormone treatment (p-value)Taking hormone treatment makes me feel I am taking positive steps to remain well (p-value)How much do you feel that your current hormone therapy can help? (p-value)How much do you feel that you need your current hormone therapy? (p-value)I miss out on a dose (p-value)I stop taking medication for a while (p-value)Age >50 vs. ≤500.04020.56510.00580.08330.04770.87370.04831.0000Post-Menopause vs. Pre-Menopause0.00330.02720.00530.13380.00060.24520.01661.0000Invasive vs. DCIS0.00381.00000.00450.16480.01810.00011.00000.0133Non-White vs. White0.47420.04340.76400.05220.91430.77730.61280.1369Duration of NET: ≤4 vs. >4 weeks0.43190.49971.00000.02840.11390.75430.05220.8833Screening vs. Self-Palpated0.51100.02560.62571.00000.44230.05930.47760.6353K-12 vs. College/Graduate0.43660.65400.16151.00000.41450.67531.00000.8321Income: ≤$60,000 vs. >$60,0000.54590.27860.59900.85690.09530.07000.78980.0581 Citation Format: Julie Huang, Joshua Feinberg, Meredith Akerman, Anthony Pasquarella, Abhinav Rohatgi, Bahram Dabiri, Jordan Baum, Shubhada Dhage, Amber Guth, Nina D'Abreo. Neoadjuvant endocrine therapy (NET) during COVID-19: Single institution survey of patients’ perspectives [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-14-20.

In patients with non-palpable breast cancer, the availability of wireless localization techniques facilitates removal of the target lesion. One such technique uses a radar reflector for localization (RRL). This study evaluates the feasibility and effectiveness of RRL to guide excision of axillary lymph nodes in patients with node-positive breast cancer.Our Breast Cancer Database was queried for patients diagnosed with breast cancer, between 5/2017 and 10/2021, who underwent preoperative placement of a radar reflector into a biopsy proven axillary lymph node. Clinicopathologic data were reported using descriptive statistics.Twenty patients underwent preoperative placement of a radar reflector into the axilla. Intraoperatively, the clip and radar reflector were successfully removed in all patients. Among the 10 patients treated with NAC, 5 patients achieved an axillary pathologic complete response (pCR) and were spared a complete axillary lymph node dissection (cALND). Among the entire cohort, RRL resulted in a 53% reduction in the number of lymph nodes removed.Wireless localization of axillary lymph nodes is safe and feasible. The technique ensures excision of biopsy proven positive axillary lymph nodes and enables a targeted approach to assessing the axilla, both in the setting of NAC and upfront surgery.

Purpose: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This multi-institutional study reports safety and efficacy among women treated with repeat BCS and reRT. Methods and Materials: Patients who underwent repeat BCS followed by RT from 2015–2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan Meier estimates were used to evaluate overall survival (OS), distant metastasis free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). Results: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3–60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5Gy BID; 27% with 1.8Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. Conclusion: In this multi-institutional series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens.

Background: Fatigue and lymphatic pain are the most common and debilitating long-term adverse effects of breast cancer treatment. Fatigue and pain independently have negative effects on quality of life, physical functions, and cancer recurrence-free survival. The interactions between fatigue and pain may aggravate their negative effects. Objectives: Examine the effects of co-occurring fatigue and lymphatic pain on activities of daily living (ADLs), emotional distress, and overall health of breast cancer patients. Methods: A cross-sectional and observational design was used to enroll 354 breast cancer patients. Valid and reliable instruments were used to assess fatigue, lymphatic pain, ADLs, emotional distress, and overall health. Descriptive statistics and multivariable regression models were used for data analysis. Results: After controlling for demographic and clinical factors, patients with co-occurring fatigue and lymphatic pain had higher odds of having impaired ADLs (OR = 24.43, CI = [5.44-109.67], P Conclusions: Fatigue and lymphatic pain affected 66.4% of breast cancer patients. Findings from this study suggest that co-occurring fatigue and lymphatic pain have negative effects on breast cancer patients’ ADLs, emotional distress, and overall health. The synergistic interactions between fatigue and lymphatic pain incrementally aggravated their negative effects on ADLs and emotional distress. Findings of the study highlight the need to evaluate the underlying mechanisms for co-occurring fatigue and lymphatic pain and develop interventions that target both fatigue and lymphatic pain to improve breast cancer patients’ the quality of life.

There is evidence that supports the association of dense tumor infiltrating lymphocyte (TILs) with an increased risk of ipsilateral recurrence in ductal carcinoma in situ (DCIS). However, the association of cellular composition of DCIS immune microenvironment with the histopathologic parameters and outcome is not well understood.We queried our institutional database for patients with pure DCIS diagnosed between 2010 and 2019. Immunohistochemical studies for CD8, CD4, CD68, CD163, and FOXP3 were performed and evaluated in the DCIS microenvironment using tissue microarrays. Statistical methods included Fisher's exact test for categorical variables and the two-sample t-test or the Wilcoxon Rank-Sum test for continuous variables.The analytic sample included 67 patients. Median age was 62 years (range = 53 to 66) and median follow up was 6.7 years (range = 5.3 to 7.8). Thirteen patients had ipsilateral recurrence. Of all the clinicopathologic variables, only the DCIS size and TIL density were significantly associated with recurrence (p = 0.023 and 0.006, respectively). After adjusting for age and TIL density, only high CD68 (50) and high CD68/CD163 ratio (0.46) correlated with ipsilateral recurrence (p = 0.026 and 0.013, respectively) and shorter time to recurrence [hazard ratio 4.87 (95% CI: 1.24-19, p = 0.023) and 10.32 (95% CI: 1.34-80, p = 0.025), respectively].In addition to DCIS size and TIL density, high CD68

Context.—Both atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) have traditionally been considered to be risk factors for the development of invasive carcinoma and are followed by close observation. Recent studies have suggested that these lesions may represent true precursors with progression to invasive carcinoma. Due to the debate over the significance of these lesions and the small number of cases reported in the literature, the treatment for lobular neoplasia diagnosed by percutaneous core biopsy (PCB) remains controversial. Objective.—To review our experience with pure LCIS or ALH diagnosed by PCB and correlate the radiologic findings and surgical excision diagnoses to develop management guidelines for lobular neoplasia diagnosed by PCB. Design.—We searched the pathology database for patients who underwent PCB with a diagnosis of either pure LCIS or ALH and had subsequent surgical excision. We compared the core diagnoses with the surgical excision diagnoses and the radiologic findings. Results.—Thirty-eight PCBs with a diagnosis of ALH (18 cases) or LCIS (20 cases) were identified. Carcinoma was present at excision in 1 (6%) of the ALH cases and in 2 (10%) of the LCIS cases. In summary, 8% (3/38) of PCBs diagnosed as lobular neoplasia (ALH or LCIS) were upgraded to carcinoma (invasive carcinoma or ductal carcinoma in situ) at excision. Conclusions.—Surgical excision is indicated for all PCBs diagnosed as ALH or LCIS, as a significant percentage will show carcinoma at excision.

Nonoperative management is presently considered the treatment modality of choice in over 50% of adult patients sustaining blunt hepatic trauma who meet inclusion criteria. A multicenter study was retrospectively undertaken to assess whether the combined experiences at level I trauma centers could validate the currently reported high success rate, low morbidity, and virtually nonexistent mortality associated with this approach. Thirteen level I trauma centers accrued 404 adult patients sustaining blunt hepatic injuries managed nonoperatively over the last 5 years. Seventy-two percent of the injuries resulted from motor vehicle crashes. The mean injury severity score for the entire group was 20.2 (range, 4-75), and the American Association for the Surgery of Trauma-computerized axial tomography scan grading was as follows: grade I, 19% (n = 76); grade II, 31% (n = 124); grade III, 36% (n = 146); grade IV, 10% (n = 42); and grade V, 4% (n = 16). There were 27 deaths (7%) in the series, with 59% directly related to head trauma. Only two deaths (0.4%) could be attributed to hepatic injury. Twenty-one (5%) complications were documented, with the most common being hemorrhage, occurring in 14 (3.5%). Only 3 (0.7%) of these 14 patients required surgical intervention, 6 were treated by transfusions alone (0.5 to 5 U), 4 underwent angio-embolization, and 1 was further observed. Other complications included 2 bilomas and 3 perihepatic abscesses (all drained percutaneously). Two small bowel injuries were initially missed (0.5%), and diagnosed 2 and 3 days after admission. Overall, 6 patients required operative intervention: 3 for hemorrhage, 2 for missed enteric injuries, and 1 for persistent sepsis after unsuccessful percutaneous drainage. Average length of stay was 13 days. Nonoperative management of blunt hepatic injuries is clearly the treatment modality of choice in hemodynamically stable patients, irrespective of grade of injury or degree of hemoperitoneum. Current data would suggest that 50 to 80% (47% in this series) of all adult patients with blunt hepatic injuries are candidates for this form of therapy. Exactly 98.5% of patients analyzed in this study successfully avoided operative intervention. Bleeding complications are infrequently encountered (3.5%) and can often be managed nonoperatively. Although grades IV and V injuries composed 14% of the series, they represented 66.6% of the patients requiring operative intervention and thus merit constant re-evaluation and close observation in critical care units. The optimal time for follow-up computerized axial tomography scanning seems to be within 7 to 10 days after injury.

Tamoxifen or raloxifen for 5 years reduces the risk of developing invasive breast cancer by 40%. To address safety concerns and seek enhanced efficacy, studies of new chemopreventive agents using mammographic density as a surrogate end point are attractive.Postmenopausal women with risk factors for developing breast cancer were given letrozole 2.5 mg daily for one year, and mammographic density was the biomarker of breast cancer risk modification. It was assessed (blinded to the reader) at baseline, 6, and 12 months in 16 evaluable women among 20 enrolled.Eight patients exhibited decreased mammographic density at six months, and eleven at 12 months. Toxicities included joint aches not precluding continued treatment.This pilot study supports the use of letrozole for reducing breast cancer risk. In addition, it encourages prospective studies of serial changes in mammographic density as a biomarker of risk modification within a selected high-risk population.