Racial Disparities in Time to Treatment Persist in the Setting of a Comprehensive Breast Center.

BACKGROUND: Racial disparities in breast cancer care have been linked to treatment delays. We explored whether receiving care at a comprehensive breast center could mitigate disparities in time to treatment. METHODS: Retrospective chart review identified breast cancer patients who underwent surgery from 2012 to 2018 at a comprehensive breast center. Time-to-treatment intervals were compared among self-identified racial and ethnic groups by negative binomial regression models. RESULTS: Overall, 2094 women met the inclusion criteria: 1242 (59%) White, 262 (13%) Black, 302 (14%) Hispanic, 105 (5%) Asian, and 183 (9%) other race or ethnicity. Black and Hispanic patients more often had Medicaid insurance, higher American Society of Anesthesiologists (ASA) scores, advanced-stage breast cancer, mastectomy, and additional imaging after breast center presentation (p < 0.05). After controlling for other variables, racial or ethnic minority groups had consistently longer intervals to treatment, with Black women experiencing the greatest disparity (incidence rate ratio 1.42). Time from initial comprehensive breast center visit to treatment was also significantly shorter in White patients versus non-White patients (p < 0.0001). Black race, Medicaid insurance/being uninsured, older age, earlier stage, higher ASA score, undergoing mastectomy, having reconstruction, and requiring additional pretreatment work-up were associated with a longer time from initial visit at the comprehensive breast center to treatment on multivariable analysis (p < 0.05). CONCLUSION: Racial or ethnic minority groups have significant delays in treatment even when receiving care at a comprehensive breast center. Influential factors include insurance delays and necessity of additional pretreatment work-up. Specific policies are needed to address system barriers in treatment access.

Impact of Screening Mammography on Treatment in Young Women Diagnosed with Breast Cancer.

BACKGROUND: There is little data exploring the impact of screening mammography on subsequent treatment in the 40-49-year age group with breast cancer. We sought to assess the association between frequency of mammography in young women and extent of surgery and chemotherapy required. METHODS: An IRB-approved retrospective review was performed of patients diagnosed with breast cancer between ages 40 and 49 years from 1 January 2010 to 19 November 2018 within a single health system. Patients were grouped based on last screening 1-24 months prior to diagnosis (1-24 group), > 25 months prior to diagnosis (> 25 group), never screened, and > 25+ never screened (combination group). Multivariate logistic regression models were used to assess for associations between screening intervals and tumor and nodal stage, chemotherapy use, and extent of surgery. RESULTS: Of 869 patients included for analysis, 20% were never screened, 60% screened 1-24 months, and 19% screened > 25 months prior to diagnosis. Compared with the 1-24 months group, the never-screened group, > 25 months group, and combined group were more likely to receive chemotherapy. The never-screened and combined groups were more likely to undergo mastectomy and/or axillary lymph node dissection. Of patients undergoing upfront surgery, the > 25 months and combined groups were more likely to receive adjuvant chemotherapy, while the never-screened and combined groups were more likely to have nodal disease. CONCLUSION: Our findings support the initiation of screening mammography at age 40 years to reduce the risk of aggressive treatments for newly diagnosed breast cancers in this group.

Choice of Mastectomy May Increase the Extent of Axillary Surgery in Women with Breast Cancer.

INTRODUCTION: Based on the ACOSOG Z0011 trial, women who undergo breast conservation therapy (BCT) and have limited disease in the axilla on sentinel lymph node (SLN) biopsy do not require axillary lymph node dissection (ALND). In this study we investigate the incidence of ALND in patients undergoing elective mastectomy with limited disease in the axilla to identify how many women may have been spared additional axillary surgery if they chose BCT. METHODS: All women with invasive breast cancer treated at a single tertiary care breast center from 2010-2018 who were candidates for BCT but elected mastectomy and underwent SLN biopsy were identified through retrospective review of a prospectively maintained database. The primary outcome of interest was the incidence of ALND in women found to have a limited burden of disease in the axilla (1-2 positive SLNs). RESULTS: The study population comprised 151 patients with invasive breast cancer eligible for BCT who chose mastectomy. On final pathology, 34 patients had 1-2 positive SLNs, and 16 of these patients underwent completion ALND. These 16 patients out of 151 overall lumpectomy candidates electing mastectomy (10.6%) could have been spared ALND if they did not elect mastectomy. DISCUSSION: BCT candidates electing mastectomy have a 10.6% chance of undergoing more extensive axillary surgery than would have been recommended with BCT alone. The increased risk of undergoing additional axillary surgery should be incorporated into the preoperative discussion for patients choosing between BCT and mastectomy.

Does previous history of cancer or atypia predict histologic upgrade for pure intraductal papillomas diagnosed via core biopsy? A study of 490 cases at a single institution.

BACKGROUND: Management of pure intraductal papillomas (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial given highly variable rates of upgrade in the literature. AIM: We sought to identify clinical and histologic factors that predict upgrade to atypia or malignancy in a large population. METHODS AND RESULTS: A retrospective review was performed of all cases of pure IDP diagnosed on CNB and then surgically excised at a single institution from 2008 to 2018. Clinical, radiologic, and pathologic factors were compared in the no upgrade, upgrade to atypia, or upgrade to cancer groups. Univariate analysis was performed comparing no upgrade and upgrade to cancer or atypia. Four hundred and thirty nine patients were identified with a total of 490 IDP and a median age of 50 years (range 16-85). Of these patients, 54 (12.3%) were upgraded to atypia after surgical excision and five (1.1%) were upgraded to cancer. The presence of multiple papillomas in a single patient was a significant predictor of upgrade to cancer or atypia (p < .01), as well as age over ≥55 years (p < .01) and a prior history of cancer (p < .01). No other clinical, radiologic and histologic factors were found to be significant predictors of upgrade. 40/439 (9.1%) patients in the total cohort had prior history of cancer, and of these, 2/40 (5%) were found to have a new cancer after excision. CONCLUSIONS: In patients with pure IDP on CNB, the upgrade rate to malignancy was 1.1%, while 12.3% were upgraded to atypia. The clinical significance of identifying atypia in a papilloma is unknown, especially in a patient with a prior history of atypia or cancer. However, the majority of patients who were upgraded to either atypia or cancer had no prior history of high-risk or malignant breast disease and are therefore considered true clinical upgrades. As such excision for IDP should be considered.

Natural language inference for curation of structured clinical registries from unstructured text.

OBJECTIVE: Clinical registries-structured databases of demographic, diagnosis, and treatment information-play vital roles in retrospective studies, operational planning, and assessment of patient eligibility for research, including clinical trials. Registry curation, a manual and time-intensive process, is always costly and often impossible for rare or underfunded diseases. Our goal was to evaluate the feasibility of natural language inference (NLI) as a scalable solution for registry curation. MATERIALS AND METHODS: We applied five state-of-the-art, pretrained, deep learning-based NLI models to clinical, laboratory, and pathology notes to infer information about 43 different breast oncology registry fields. Model inferences were evaluated against a manually curated, 7439 patient breast oncology research database. RESULTS: NLI models showed considerable variation in performance, both within and across fields. One model, ALBERT, outperformed the others (BART, RoBERTa, XLNet, and ELECTRA) on 22 out of 43 fields. A detailed error analysis revealed that incorrect inferences primarily arose through models' tendency to misinterpret historical findings, as well as confusion based on abbreviations and subtle term variants common in clinical text. DISCUSSION AND CONCLUSION: Traditional natural language processing methods require specially annotated training sets or the construction of a separate model for each registry field. In contrast, a single pretrained NLI model can curate dozens of different fields simultaneously. Surprisingly, NLI methods remain unexplored in the clinical domain outside the realm of shared tasks and benchmarks. Modern NLI models could increase the efficiency of registry curation, even when applied "out of the box" with no additional training.

Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer DataBase (NCDB).

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced HER2 + breast cancer (BC). Optimal sequencing of treatment (NAC vs. surgery first) is less clear cut in stage I (T1N0) HER2 + BC, where information from surgical pathology could impact adjuvant treatment decisions. Utilizing the NCDB, we evaluated the trend of NAC use compared to upfront surgery in patients with small HER2 + BC. METHODS: We identified NCDB female patients diagnosed with T1 N0 HER2 + BC from 2010 through 2015. Prevalence ratios (PR) using multivariable robust Poisson regression models were calculated to measure the association between baseline characteristics and the receipt of NAC. Analysis of trends over time was denoted by annual percent change (APC) of NAC versus surgery upfront. RESULTS: Of the 14,949 that received chemotherapy and anti-HER2 therapy during the study period, overall 1281 (8.6%) received NAC and 13,668 (91.4%) received adjuvant treatment. Patients receiving NAC increased annually from 4.2% in 2010 to 17.3% in 2015, with the most rapid increase occurring between years 2013 (8.5%) and 2014 (14.2%). The greatest increase was seen in patients with cT1c tumors with an APC of 37.8% over the study period (95% CI 29.0, 47.3%, p < 0.01), although a significant trend was likewise seen in patients with cT1a (APC = 26.1%,95% CI 1.59, 56.6%), and cT1b (APC = 27.4%, 95% CI 18.0, 37.7%) tumors. Predictors of neoadjuvant therapy receipt were age younger than 50 (PR = 1.69, 95% CI 1.52, 1.89), Mountain/Pacific area (PR = 1.24, 95% CI 1.05, 1.46), and estrogen receptor negativity (ER- PR + : PR = 2.01, 95% CI 1.51, 2.68; ER- PR- : PR = 1.49, 95% CI 1.32, 1.69). CONCLUSIONS: Neoadjuvant therapy for T1 N0 HER2 + BC increased over the study period and was mostly due increased use in clinical T1c tumors. This may be consistent with secular change in Pertuzumab treatment following FDA approval in 2013.

Response in breast vs axilla after neoadjuvant treatment and implications for nonoperative management of invasive breast cancer.

Improved imaging and neoadjuvant chemotherapy (NAT) have led to higher pathologic complete response rates (pCR) in patients with invasive breast cancer. This has questioned the necessity of surgery and axillary lymph node (ALN) dissection in these patients. Prospective clinical trials are implementing extensive core biopsies of the tumor bed of patients with clinical complete response as a means to identify and spare them breast surgery. In addition, it is anticipated that patients with pCR are most likely going to have no or minimal disease in ALN as well. To verify the feasibility of these trials, we performed a pathologic analysis of all our patients who have undergone NAT from 2009 to present. Using pathology data base, we identified 362 patients treated with neoadjuvant chemotherapy followed by surgery. Clinical and pathologic information including gross and microscopic descriptions as well as biomarker status was collected. pCR was 50% for patients with negative ALN pretreatment but only 28% for patients with positive ALN at diagnosis. Despite achieving pCR in the breast, up to 10% of patients with positive ALN and 1% with negative ALN had persistent disease. Eight percent of patients that were presumed to have no ALN disease either clinically and or by imaging were found to have metastatic carcinoma in ALN. The metastases were predominantly (80%) <5 mm, and not palpable on physical examination and or due to biopsy sampling error. pCR in breast and ALN directly correlated with tumor size, ALN disease, and Her2 positive and triple negative receptor phenotype. In breast cancer patients who are node positive at time of diagnosis with pCR in the breast after neoadjuvant chemotherapy, residual lymph node disease was very uncommon. Further study is warranted to select patients who may avoid breast and axillary surgery post neoadjuvant chemotherapy.

Adherence to NCCN Guidelines for Genetic Testing in Breast Cancer Patients: Who Are We Missing?

BACKGROUND: Genetic predisposition accounts for 5-10% of all breast cancers (BC) diagnosed. NCCN guidelines help providers identify appropriate candidates for counseling and testing. Concerns about underutilization of genetic testing have spurred interest in broader peri-diagnostic testing. We evaluated surgeon adherence to NCCN guidelines and studied patterns of testing in newly diagnosed BC patients. METHODS: A total of 397 patients were identified with newly diagnosed BC treated at our institution between 2016 and 2017 with no prior genetic testing. Eligibility for genetic testing based on NCCN criteria, referral, and patient compliance were recorded. RESULTS: In total, 212 of 397 (53%) met NCCN testing criteria. Fifty-nine of 212 (28%) patients went untested despite meeting one or more criteria. Fourteen of 59 (24%) of these were referred but did not comply. Most common criteria for meeting eligibility for testing both in the overall cohort and among missed patients were family history-based. Age > 45 years old and non-Ashkenazi Jewish descent were predictive of missed referral (p < 0.01). We identified pathogenic mutations in 16 of 153 (10%) patients who did undergo testing (11 (7%) BRCA1 or 2 and 5 (3%) with other predisposition gene mutations) or 16 of 397 (4%) among the overall group. CONCLUSIONS: Our data highlight the underutilization of genetic testing. Even in the setting of a full-service breast center with readily available genetic counseling, there is a substantial miss rate for identifying eligible patients, related to assessment of family history, patient age, and ethnicity, as well as patient compliance. Broader peri-diagnostic testing should be considered, and higher compliance rates with patients referred should be sought.

Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a National Cancer Database (NCDB) study.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is a well-established therapeutic option for patients with locally advanced disease often allowing downstaging and facilitation of breast conserving therapy. With evolution of better targeted treatment regimens and awareness of improved outcomes for significant responders, use of NAC has expanded particularly for triple negative and HER2-positive (HER2+) breast cancer. In this study, we explore utility of neoadjuvant chemotherapy for hormone receptor-positive HER2-negative (HR+ HER2-) patients. METHODS: Patients with HR+ HER2- breast cancer treated with chemotherapy before or after surgery were identified from 2010 to 2015 in the NCDB. Multivariable regression models adjusted for covariates were used to determine associations within these groups. RESULTS: Among 134,574 patients (clinical stage 2A, 64%; 2B, 21%; 3, 15%), 105,324 (78%) had adjuvant chemotherapy (AC) and 29,250 (22%) received NAC. Use of NAC increased over time (2010-2015; 13.2-19.4% and PR = 1.34 for 2015; p < 0.0001). Patients were more likely to receive NAC with cT3, cT4, and cN+ disease. Patients less likely to receive NAC were age ≥ 50, lobular carcinoma, increased Charlson-Deyo score, and government insurance. Complete response (pCR) was noted in 8.3% of NAC patients. Axillary downstaging occurred in 21% of patients, and predictors included age < 50 years, black race, poorly differentiated grade, invasive ductal histology, and either ER or PR negativity. CONCLUSIONS: NAC use among HR+ HER2- breast cancer patients has expanded over time and offers downstaging of disease for some patients, with pCR seen in only a small subset, but downstaging of the axilla in 21%. Further analysis is warranted to determine the subgroup of patients with HR+ HER2- disease who benefit from this approach.

Practice Changing Potential of TAILORx: A Retrospective Review of the National Cancer Data Base from 2010 to 2015.

BACKGROUND: Uncertainty regarding chemotherapy benefit among breast cancer patients with intermediate Oncotype Dx® recurrence scores (RS; 11-25) led to the TAILORx study. We evaluated chemotherapy use in patients with intermediate RS to determine practice change potential based on the TAILORx results. METHODS: National Cancer Data Base patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative, N0 breast cancer were identified and were divided into three groups: Group A, ≤ 50 years of age (RS 11-15); Group B, ≤ 50 years of age (RS 16-25); and Group C, > 50 years of age (RS 11-25). Demographic and clinical factors were compared using Chi square tests and Poisson regression models to determine predictors of chemotherapy receipt. RESULTS: Overall, 37,087 patients met the inclusion criteria, with 6.3% in Group A and 11.7% in Group C having received chemotherapy that may have been avoided based on TAILORx. The majority of Group B (64.7%) did not receive chemotherapy, whereas TAILORx showed potential benefit from treatment. Chemotherapy use decreased over time for all intermediate RS patients. T2 tumors, high grade, and treatment before 2012 increased the likelihood of chemotherapy receipt among both groups. Younger patients with the lower intermediate RS (Group A) were more likely to receive chemotherapy if they had treatment at community or comprehensive centers, whereas moderate grade was also a significant factor to receive chemotherapy in Group B. Significant factors in older patients (Group C) were Black race, estrogen receptor-positive/progesterone receptor-negative, and moderate/high grade. CONCLUSIONS: The most potential impact of TAILORx findings on practice change is for patients ≤ 50 years of age with RS of 16-25 who did not receive chemotherapy but may benefit. These findings may serve as a baseline for future analysis of practice patterns related to TAILORx.

Defining the Need for Imaging and Biopsy After Mastectomy.

BACKGROUND: The proportion of patients eligible for breast-conservation therapy (BCT) yet opting for mastectomy is increasing. This decision is often driven by the desire to eliminate future screening and/or biopsy of the remaining breast or breasts. This study investigated the incidence of post-mastectomy imaging and biopsy. METHODS: A retrospective review of all unilateral mastectomy (UM) and bilateral mastectomy (BM) cases managed at a single institution was undertaken. Post-mastectomy imaging and biopsy rates were determined. RESULTS: Between 2009 and 2015, 185 UM and 200 BM cases managed for breast cancer were identified. The mean follow-up period was 30 months (range 3-75 months). For the patients with UM, imaging studies and biopsies done on the contralateral side were excluded given the standard of care for continued surveillance of the contralateral breast. Of the 185 UM patients, 19 (10%) underwent ipsilateral imaging (all ultrasounds) for physical examination findings, 11 (6%) underwent biopsy, and 2 (1%) had malignant findings. Of the 200 BM patients, 31 (15.5%) required imaging (29 ultrasounds and 2 MRIs), with 76% of the ultrasounds performed on the side with previous cancer. Subsequently, 16 (8%) of the BM patients had biopsy, with 11 (69%) of the 16 biopsies performed on the ipsilateral side. Three (1.5%) of the biopsies done on ipsilateral side demonstrated malignancy, whereas all the contralateral biopsies were benign. CONCLUSIONS: For 10-15.5% of patients who undergo mastectomy, either UM or BM, subsequent imaging is required, whereas 6-8% undergo biopsy. The yield of malignancy is low, approximately 1%. Thus, after mastectomy, the need for imaging and biopsy is not eliminated. This information is critical for patient understanding and expectation related to surgical decision making.

Impact of Screening Mammography on Treatment in Women Diagnosed with Breast Cancer.

BACKGROUND: Screening mammography reduces breast cancer mortality; however, screening recommendations, ordering, and compliance remain suboptimal and controversies regarding the value of screening persist. We evaluated the influence of screening mammography on the extent of breast cancer treatment. METHODS: Patients ≥ 40 years of age diagnosed with breast cancer from September 2008 to May 2016 at a single institution were divided into two groups: those with screening 1-24 months prior to diagnosis, and those with screening at 25+ months, including patients with no prior mammography. The association between the two groups and various clinical factors were assessed using logistic regression models. Subgroup analysis was performed based on age groups. RESULTS: Analysis included 1125 patients, 819 (73%) with screening at 1-24 months, and 306 (27%) with screening at 25+ months, including 65 (6%) who never had mammography. Overall, patients in the 25+ months group were more likely to receive chemotherapy [odds ratio (OR) 1.51, p = 0.0040], undergo mastectomy (OR 1.32, p = 0.0465), and require axillary dissection (AD; OR 1.66, p = 0.0045) than those in 1-24 months group. On subgroup analysis, patients aged 40-49 years with no prior mammography were more likely to have larger tumors (p = 0.0323) and positive nodes (OR 4.52, p = 0.0058), undergo mastectomy (OR 3.44, p = 0.0068), undergo AD (OR 4.64, p = 0.0002), and require chemotherapy (OR 2.52, p = 0.0287) than the 1-24 months group. CONCLUSIONS: Screening mammography is associated with decreased stage at diagnosis and receipt of less-extensive treatment. This was evident in all groups, including the 40-49 years age group, where controversy exists on whether screening is even necessary.

Noncompaction cardiomyopathy in children with congenital heart disease: evaluation using cardiovascular magnetic resonance imaging.

Noncompaction of the left ventricle, a genetic cardiomyopathy with a reported incidence of 0.05% to 0.24%, can lead to sudden cardiac death, particularly among children, if left undetected. Because the diagnosis of isolated noncompaction cardiomyopathy (NCM) can be overlooked, its association with other congenital heart diseases (CHDs) makes the diagnosis of NCM even more difficult. This study aimed to assess the impact of NCM on the cardiovascular physiology of children with coexisting CHDs evaluated by cardiovascular magnetic resonance imaging. A case-control study was performed with 12 children (6 patients with combined NCM and CHD and 6 control subjects with isolated CHD). The mean left ventricular end-diastolic and end-systolic volume indices were significantly higher in the CHD patients presenting with NCM than in the CHD patients with no NCM (P = 0.028). However, no differences were observed for right ventricular end-diastolic and end-systolic volume indices, biventricular ejection fractions, stroke volumes and indices, left ventricular wall thickness, left ventricular fractional shortening, cardiac output, or cardiac index. This study suggests that NCM in children with CHDs increases left ventricular volumes, and larger studies are required to demonstrate other changes (e.g., ejection fraction, stroke volume) that were close to being significant.