Encapsulated papillary carcinoma with and without frank invasion: Comparison of clinicopathologic features and role of axillary staging.

To investigate clinical and pathologic features of encapsulated papillary carcinomas (EPCs) that may be associated with invasive disease and characterize the axillary staging practices for EPCs at our institution. A pathology database search for cases containing "papillary carcinoma" was performed. Slides were reviewed by two pathologists. Clinicopathological features and axillary staging practices of EPCs with and without invasion were compared. Twenty-five cases of EPCs were identified. Fifteen cases contained a frank invasive tumor (60%), which were all pT1 (0.7 ± 0.56 cm), and the majority were ER-positive, HER2-negative, low-grade IDC-NST. Seventeen patients underwent sentinel lymph node biopsies (SLNB). No nodal metastases were identified. Follow-up was available for 24 patients (mean = 39 ± 29 months); 23 had no NED. Patients that presented with a self-palpated mass (versus screening) were more likely to have an invasive component; however, no pathologic or radiologic features differentiated EPCs with and without frank invasion. Pathologic and radiologic characteristics did not differentiate EPCs with and without frank invasion. EPCs have an excellent prognosis supported by the notable disease-free survival and negative nodal status in our cohort, which supports the notion that patients with EPCs may forgo axillary staging.

Cosmetic Outcomes Following Breast-Conservation Surgery and Radiation for Multiple Ipsilateral Breast Cancer: Data from the Alliance Z11102 Study.

BACKGROUND: Diagnoses of multiple ipsilateral breast cancer (MIBC) are increasing. Historically, the primary treatment for MIBC has been mastectomy due to concerns about in-breast recurrence risk and poor cosmetic outcome. The Alliance Z11102 study prospectively assessed cosmetic outcomes in women with MIBC treated with breast-conserving therapy (BCT). PATIENTS AND METHODS: Z11102 was a multicenter trial enrolling women with two or three separate sites of biopsy-proven malignancy separated by ≥ 2 cm within the same breast. Cosmetic outcome was a planned secondary endpoint. Data were collected with a four-point cosmesis survey (1 = excellent, 4 = poor) and the BREAST-Q (scored 0-100). All patients undergoing successful breast-conserving therapy were treated with whole-breast radiation. Associations were assessed with Chi square or Fisher's exact tests as appropriate. RESULTS: Cosmetic outcome data for 216 eligible women who completed therapy are included in this analysis. Of the 136 patients who completed the survey 2 years postoperatively, 70.6% (N = 96) felt the result was good or excellent, while 3.7% (N = 5) felt the result was poor. We found no significant differences in patient-reported cosmetic outcomes when stratifying by patient age, number of lesions (two or three), number of incisions, number of lumpectomies, or size of largest area of disease. Mean satisfaction score on the BREAST-Q was 77.2 at 6 months following whole-breast radiation and 73.7 at 3 years following surgery. CONCLUSIONS: BCT performed for MIBC results in good or excellent cosmesis for the majority of women. From a cosmetic perspective, BCT is a valid surgical approach to women with MIBC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01556243.

Screening vs staging magnetic resonance imaging-guided core needle breast biopsies: Does MRI indication impact upgrade rate?

Adjunct magnetic resonance imaging (MRI) for both screening high-risk patients and staging for patients with newly diagnosed breast cancer leads to an increased number of biopsies and increased detection of atypical lesions. We assessed whether the malignancy upgrade frequency for high-risk atypia identified via MRI-guided biopsies varied based on indication: high-risk screening vs staging for malignancy. Among 399 MRI-guided biopsies, 46 (11.5%) high-risk lesions (ADH, ALH, and LCIS) were identified. Surgical excision was performed on 37% of 46%, and 24.3% were upgraded to invasive malignancy or DCIS. Of lesions identified by staging MRI, a slightly higher percentage, 28.5%, were upgraded (P = .36). Our data suggest that surgeons should carefully consider excisional biopsy for atypia identified on MRI regardless of indication.

Papillary and sclerosing lesions of the breast detected and biopsied by MRI: Clinical management, upgrade rate, and association with apocrine metaplasia.

Benign papillary and sclerosing lesions of the breast (intraductal papillomas, complex sclerosing lesions, radial scars) are considered high-risk lesions due to the potential for upgrade to carcinoma on subsequent surgical excision. Optimal clinical management of such lesions remains unclear due to variable reported upgrade rates. Apocrine metaplasia is a common finding in breast tissue and its role in MRI enhancing lesions is increasingly being recognized. The purpose of this study was to investigate the MRI features of papillary and sclerosing lesions of the breast, evaluate the clinical management and upgrade rate of such lesions, and examine the contribution of apocrine metaplasia to the imaging findings. A 13-year retrospective review of MRI-guided biopsies identified 70 MRI-detected and -biopsied papillary and sclerosing lesions. Sixteen lesions without atypia underwent surgical excision; only one case (6%) was upgraded to pleomorphic lobular carcinoma in situ. The majority (64%) of biopsies contained apocrine metaplasia either within or adjacent to the targeted lesion. We found that half of MRI-detected lesions had T2 hyperintense foci (2-5 mm) or masses (>5 mm) adjacent to the lesion. Histologic correlation showed apocrine cysts were likely responsible for this imaging finding in 56% of these cases.

The Feasibility of Breast-Conserving Surgery for Multiple Ipsilateral Breast Cancer: An Initial Report from ACOSOG Z11102 (Alliance) Trial.

BACKGROUND: Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-conserving therapy (BCT). We report the feasibility of BCT in MIBC from the ACOSOG Z11102 trial [Alliance], a single arm noninferiority trial of BCT for women with two or three sites of malignancy in the ipsilateral breast. METHODS: Women who enrolled preoperatively in ACOSOG Z11102 were evaluated for conversion to mastectomy and need for reoperation to obtain negative margins. Characteristics of women who successfully underwent BCT and those who converted to mastectomy were compared. Factors were examined for association with the need for margin reexcision. RESULTS: Of 198 patients enrolled preoperatively, 190 (96%) had 2 foci of disease. Median size of the largest tumor focus was 1.5 (range 0.1-7.0) cm; 49 patients (24.8%) had positive nodes. There were 14 women who underwent mastectomy due to positive margins, resulting in a conversion to mastectomy rate of 7.1% (95% confidence interval [CI] 3.9-10.6%). Of 184 patients who successfully completed BCT, 134 completed this in a single operation. Multivariable logistic regression analysis did not identify any factors significantly associated with conversion to mastectomy or need for margin reexcision. CONCLUSIONS: Breast conservation is feasible in MIBC with 67.6% of patients achieving a margin-negative excision in a single operation and 7.1% of patients requiring conversion to mastectomy due to positive margins. No characteristic was identified that significantly altered the risk of conversion to mastectomy or need for reexcision. CLINICALTRIALS. GOV IDENTIFIER: NCT01556243.

Relationship of breast MRI to recurrence rates in patients undergoing breast-conservation treatment.

PURPOSE: The effect of pre-operative MRI on the in-breast tumor recurrence rate (IBTR) of patients undergoing breast-conservation treatment (BCT) remains uncertain. We began to routinely perform pre-operative MRI in 2006. Our goal was to determine the effect of pre-operative MRI on IBTR. METHODS: Retrospective review of a prospective database of all patients undergoing BCT (n = 1396) from 2000 to 2010. IBTR were calculated using Kaplan-Meier estimates. RESULTS: 664 (47.6%) patients underwent pre-operative MRI. The use of MRI increased from 13.9% in 2000-2005 to 80.7% in 2006-2010. Ten percent of patients who underwent MRI were found to have an additional ipsilateral cancer, with a mean diameter of 1.6 cm. The IBTR for patients with and without MRI were 4% vs. 8% at 8 years (p = 0.04). In multivariate analysis, radiation therapy and endocrine therapy were associated with decreased IBTR, but MRI was not (RR 0.77 (0.45-1.28)). For 1030 patients with invasive cancer, the IBTR at 8 years with and without MRI was 4.2% vs. 7.3% (p = 0.28). For 366 DCIS patients with and without MRI, the IBTR was 3.6% vs. 10.9% (p = 0.06). In the subgroup of DCIS patients who did not receive radiation, the IBTR with and without MRI was 0% vs. 18.2% (p = 0.08). Patients with an additional cancer found by MRI had a higher IBTR at 8 years (10.1% vs. 3.3%, p = 0.02). CONCLUSIONS: In a study analyzing BCT patients from one time period who rarely had a pre-operative MRI and a subsequent time period where most patients had MRI, the use of MRI was associated with a decrease in the IBTR on univariate, but not multivariate analysis. Patients who had additional cancers detected had a significantly higher IBTR.

Reviewing the Evidence to Guide Clinical Care: Proliferative Breast Lesions in Breast Reduction Specimens.

The number of reduction mammoplasties performed in the United States continues to increase annually. Given the high incidence of breast cancer in women, it is routine practice for breast tissue excised during routine breast reductions procedures to be sent for pathology review. During pathology assessment, occult malignancy and on-occasion proliferative breast lesions of unknown and/or variable malignancy may also be present. We provide a review of commonly diagnosed atypical proliferative breast lesions in breast reduction specimens and a guide to plastic surgeons for further management.

Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005­December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

The PI3K/mTOR dual inhibitor P7170 demonstrates potent activity against endocrine-sensitive and endocrine-resistant ER+ breast cancer.

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway has been implicated in anti-estrogen resistance in breast cancer. We tested the therapeutic potential of the novel PI3K/mTOR dual inhibitor P7170 in a panel of anti-estrogen-sensitive and anti-estrogen-resistant models of ER+ breast cancer. Estrogen receptor-positive (ER+) breast cancer cells were treated ±P7170. Fresh cores from primary ER+/HER2- tumors from two patients were treated ±P7170 ex vivo. Mice bearing breast cancer xenografts were randomized to treatment with vehicle, fulvestrant, P7170, or combinations, and tumor volumes were measured. Tissues and cells were analyzed for markers of pathway activity, cell viability, and apoptosis. In cell lines, P7170 exhibited IC50 values in the range of 0.9-7 nM and induced apoptosis. P7170 potently inhibited mTOR activity (≤ 25 nM) and inhibited PI3K at higher concentrations (≥ 200 nM). P7170 completely inhibited MCF-7 tumor growth, significantly inhibited growth of fulvestrant-resistant T47D tumors, and suppressed tumor cell proliferation but did not induce apoptosis. While P7170 inhibits PI3K and mTOR in ER+/HER2- human breast cancer cells and tumors ex vivo, in vivo data indicate that the primary mechanism of P7170 anti-tumor action is inhibition of mTOR and cell proliferation. P7170 is a novel agent worthy of further investigation for the treatment of ER+ breast cancer.

Locoregional Management of Multiple Ipsilateral Breast Cancers: A Review.

The incidence of preoperatively diagnosed multiple ipsilateral breast cancer (MIBC) is increasing due to improved sensitivity of screening and preoperative staging modalities including digital breast tomosynthesis (3D breast mammography) and magnetic resonance imaging (MRI). The surgical management of MIBC remains controversial. Many surgeons continue to recommend mastectomy due to high local recurrence rates in patients with MIBC undergoing breast conservation therapy reported in historic, retrospective studies. More recent retrospective studies report acceptable rates of local recurrence. Yet concerns persist due to a paucity of prospective data regarding recurrence as well as concerns for margin positivity, cosmetic outcomes and the feasibility of adequate and safe delivery of radiation following breast conserving surgery. Breast conservation has emerged as the preferred surgical strategy for eligible patients with unifocal disease. Benefits include improved quality of life, body image and sexual function and lower surgical complication rates. A recent prospective clinical trial has corroborated a large body of retrospective data confirming the safety of breast conserving therapy and adjuvant radiation in women with MIBC with good oncologic control, low rates of conversion to mastectomy and satisfactory patient-reported cosmetic outcomes. With the current rise in MIBC diagnoses, it is imperative that surgeons understand the existent evidence in order to guide shared decision-making conversations with patients diagnosed with MIBC. This comprehensive review synthesizes the best available data and offers current recommendations for management of both the primary sites of disease as well as management of the axilla in patients with MIBC.

Outcomes of the 2021-2022 APDS General Surgery Recruitment Process Recommendations.

BACKGROUND: In recent years, mounting challenges for applicants and programs in resident recruitment have catapulted this topic into a top priority in medical education. These challenges span all aspects of recruitment-from the time an applicant applies until the time of the Match-and have widespread implications on cost, applicant stress, compromise of value alignment, and holistic review, and equity. In 2021-2022, the Association of Program Directors in Surgery (APDS) set forth recommendations to guide processes for General Surgery residency recruitment. OBJECTIVES: This work summarizes the APDS 2021-2022 resident recruitment process recommendations, along with their justification and program end-of-cycle program feedback and compliance. This work also outlines the impact of these data on the subsequent 2022-2023 recommendations. METHODS: After a comprehensive review of the available literature and data about resident recruitment, the APDS Task Force proposed recommendations to guide 2021-2022 General Surgery resident recruitment. Following cycle completion, programs participating in the categorical General Surgery Match were surveyed for feedback and compliance. RESULTS: About 122 of the 342 programs (35.7%) participating in the 2022 categorical General Surgery Match responded. Based on available data in advance of the cycle, recommendations around firm application and interview numbers could not be made. About 62% of programs participated in the first round interview offer period with 86% of programs limiting offers to the number of slots available; 95% conducted virtual-only interviews. Programs responded they would consider or strongly consider the following components in future cycles: holistic review (90%), transparency around firm requirements (88%), de-emphasis of standardized test scores (54%), participation in the ERAS Supplemental application (58%), single first round interview release period (69%), interview offers limited to the number of available slots (93%), 48-hour minimum interview offer response time (98%), operationalization of applicant expectations (88%), and virtual interviews (80%). There was variability in terms of the feedback regarding the timing of the single first round offer period as well as support for a voluntary, live site visit for applicants following program rank list certification. CONCLUSIONS: The majority of programs would consider implementing similar recommendations in 2022-2023. The greatest variability around compliance revolved around single interview release and the format of interviews. Future innovation is contingent upon the ongoing collection of data as well as unification of data sources involved in the recruitment process.

How Did We Get Here and Where Are We Going? Career Trajectories of United States General Surgery Residency Program Directors.

OBJECTIVE: To develop the future of United States (US) surgical education leadership, surgical trainees and early career faculty who aspire to become program directors (PDs) must understand the potential career pathways and requisite skills and experience to become a general surgery residency PD. The objective of this study was to understand the demographics, career experiences, and professional satisfaction of US PDs in general surgery. DESIGN: An anonymous, cross-sectional survey utilizing a novel instrument. SETTING: An electronic survey distributed to US general surgery PDs between June and November 2022 PARTICIPANTS: PDs of US general surgery residency programs. A list of the Accrediting Council for Graduate Medical Education (ACGME)-accredited general surgery PDs was created from the ACGME list from the 2022 to 23 academic year. RESULTS: The survey achieved a response rate of 46.2% (159/344). Only 32.1% of PDs identified as female and 67.3% identified as male with 1 respondent preferring not to identify their gender. PDs were White or Caucasian (68.6%), Asian (13.8%), and Black (3.7%); 4.4% were Hispanic or Latino. Only 83.7% of PDs completed fellowship training. PDs have been in the role for an average of 5.5 ± 4.9 years. The PDs were compensated for an average of 54.7% (±14.9% SD, 0%-100% range) of their time towards clinical duties. They were compensated on average for 35.7% (±12.6%, 0%-100%) of effort for residency-related administrative duties. Only 5% of PDs had obtained or were enrolled in an education-related degree. Only 55.4% of PDs had received formal surgical education training in teaching and assessment. 54.1% of PDs were interested in obtaining a more senior leadership position in the future. Most PDs (38.4%) expect to serve as PD for 5 to 8 years in total. Overall, the majority of PDs were very satisfied (29.6%) or satisfied (51.6%) professionally; similarly 28.9% were very satisfied and 48.4% satisfied personally. CONCLUSIONS: This study represents the most up-to-date characterization of the personal, academic, and career-related features of current surgical residency PDs across the US. PDs enjoy a high degree of professional and personal satisfaction and most aspire to increasing leadership within their organizations. Compared to prior data, PDs have become more diverse in terms of both gender and race over time. Opportunities exist for increased mentorship of aspiring and current PDs as well as increased training in teaching and assessment.

Update on the Financial Well-Being of Surgical Residents in New England.

BACKGROUND: Poor personal financial health has been linked to key components of health including burnout, substance abuse, and worsening personal relationships. Understanding the state of resident financial health is key to improving their overall well-being. STUDY DESIGN: A secondary analysis of a survey of New England general surgery residents was performed to understand their financial well-being. Questions from the National Financial Capability Study were used to compare to an age-matched and regionally matched cohort. RESULTS: Overall, 44% (250 of 570) of surveyed residents responded. Residents more frequently reported spending less than their income each year compared to the control cohort (54% vs 34%, p < 0.01). However, 17% (39 of 234) of residents reported spending more than their income each year. A total of 65% of residents (152 of 234), found it "not at all difficult" to pay monthly bills vs 17% (76 of 445) of the control cohort (p < 0.01). However, 32% (75 of 234) of residents reported it was "somewhat" or "very" difficult to pay monthly bills. Residents more frequently reported they "certainly" or "probably" could "come up with" $2,000 in a month compared to the control cohort (85% vs 62% p < 0.01), but 16% (37 of 234) of residents reported they could not. In this survey, 21% (50 of 234) of residents reported having a personal life insurance policy, 25% (59 of 234) had disability insurance, 6% (15 of 234) had a will, and 27% (63 of 234) had >$300,000 worth of student loans. CONCLUSIONS: Surgical residents have better financial well-being than an age-matched and regionally matched cohort, but there is still a large proportion who suffer from financial difficulties.

Local Recurrence After Breast-Conserving Therapy in Patients With Multiple Ipsilateral Breast Cancer: Results From ACOSOG Z11102 (Alliance).

PURPOSE: Breast-conserving therapy (BCT) is the preferred treatment for unifocal breast cancer (BC). The oncologic safety of BCT for multiple ipsilateral breast cancer (MIBC) has not been demonstrated in a prospective study. ACOSOG Z11102 (Alliance) is a phase II, single-arm, prospective trial designed to evaluate oncologic outcomes in patients undergoing BCT for MIBC. PATIENTS AND METHODS: Women age 40 years and older with two to three foci of biopsy-proven cN0-1 BC were eligible. Patients underwent lumpectomies with negative margins followed by whole breast radiation with boost to all lumpectomy beds. The primary end point was cumulative incidence of local recurrence (LR) at 5 years with an a priori rate of clinical acceptability of <8%. RESULTS: Among 270 women enrolled between November 2012 and August 2016, there were 204 eligible patients who underwent protocol-directed BCT. The median age was 61 years (range, 40-87 years). At a median follow-up of 66.4 months (range, 1.3-90.6 months), six patients developed LR for an estimated 5-year cumulative incidence of LR of 3.1% (95% CI, 1.3 to 6.4). Patient age, number of sites of preoperative biopsy-proven BC, estrogen receptor status and human epidermal growth factor receptor 2 status, and pathologic T and N categories were not associated with LR risk. Exploratory analysis showed that the 5-year LR rate in patients without preoperative magnetic resonance imaging (MRI; n = 15) was 22.6% compared with 1.7% in patients with a preoperative MRI (n = 189; P = .002). CONCLUSION: The Z11102 clinical trial demonstrates that breast-conserving surgery with adjuvant radiation that includes lumpectomy site boosts yields an acceptably low 5-year LR rate for MIBC. This evidence supports BCT as a reasonable surgical option for women with two to three ipsilateral foci, particularly among patients with disease evaluated with preoperative breast MRI.