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.

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.

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.

Breast Imaging During Pregnancy and Lactation.

Breast imaging during pregnancy and lactation is important in order to avoid delays in the diagnosis and treatment of pregnancy-associated breast cancers. Radiologists have an opportunity to improve breast cancer detection by becoming familiar with appropriate breast imaging and providing recommendations to women and their referring physicians. Importantly, during pregnancy and lactation, both screening and diagnostic breast imaging can be safely performed. Here we describe when and how to screen, how to work up palpable masses, and evaluate bloody nipple discharge. The imaging features of common findings in the breasts of pregnant and lactating women are also reviewed. Finally, we address breast cancer staging and provide a brief primer on treatment options for pregnancy-associated breast cancers.