Tina J. Hieken

Impact of analysis of frozen-section margin on reoperation rates in women undergoing lumpectomy for breast cancer: Evaluation of the National Surgical Quality Improvement Program data

BACKGROUND Reoperation for positive margins after lumpectomy for breast cancer is common. Intraoperative analysis of frozen-section (FS) margins permits immediate re-excision, avoiding reoperation. The aim of this study was to compare reoperation rates between an institution using routine FS analysis of all margins and the National Surgical Quality Improvement Program (NSQIP) data. METHODS We designed a retrospective cohort analysis comparing the NSQIP data from a FS single institution with the national NSQIP data from 2006 to 2010. Women undergoing lumpectomy for cancer were identified (N = 24,217), and reoperation rates were compared by the use of χ(2) analyses and multivariable logistic regression. During this time period, NSQIP did not differentiate between reoperations for complications or oncologic reasons. Reoperation rates for mastectomy patients (N = 21,734) and lumpectomy patients without cancer (N = 2,777) over the same time period were analyzed as controls, because reoperations after these procedures likely would be for reasons other than positive margins. RESULTS The 30-day reoperation rate after lumpectomy for cancer was greater nationally than at the FS institution (13.2% vs 3.6%, P < .001). Multivariable analysis showed that patients in the national NSQIP data set were over four times as likely to undergo reoperation as those at the FS institutions (odds ratio 4.19). The reoperation rates were similar between the two, both for patients undergoing mastectomy (4.7% vs 4.5%, P = .84) and those undergoing lumpectomy for benign diagnosis (2.9% vs 5.9%, P = .39). CONCLUSION Intraoperative FS margin analysis decreases the number of reoperations for patients undergoing breast conservation for breast cancer. This technique has important implications for patient satisfaction and cost of care.

Preoperative axillary imaging with percutaneous lymph node biopsy is valuable in the contemporary management of patients with breast cancer

BACKGROUND ACOSOG Z11 and other studies showing little benefit to axillary dissection (ALND) for early-stage breast cancers with limited nodal disease have led to questioning the value of preoperative axillary imaging ± ultrasound-guided needle biopsy (USNB). Data are lacking on the value of this approach in identifying cases that fall outside Z11 guidelines. METHODS We studied 988 consecutive patients with invasive breast cancers who underwent operation including axillary surgery in 2010-2011. RESULTS Preoperative axillary ultrasonography (AUS) was performed in 92% and breast/axillary magnetic resonance imaging (MRI) in 51%; 82 (33.5%) of 245 patients with suspicious lymph nodes (LN) were USNB-positive. Regarding nodal status, AUS, MRI, and USNB had negative and positive predictive values of 78%, 76%, 70% and 54%, 58%, 100%, respectively. AUS/MRI visualization of one versus multiple abnormal LNs visualized predicted >2LN+ on final pathology (13.5%/15.1% % vs 30.8%/32.6%, P < .009). Among USNB-LN+ T1/T2 patients, 51.6% had 1-2 LN+ while 60% with multiple and 31% with one AUS-abnormal LN(s) had > 2LN+, P = .001. CONCLUSION In our contemporary series, preoperative AUS±USNB streamlined surgical care for 29% of node-positive patients. Two-thirds of T1/T2 USNB-LN+ patients with multiple AUS-suspicious LNs had >2LN+, suggesting they should undergo ALND without SLNB. AUS±USNB helps identify node-positive breast cancer patients who fall outside Z11 guidelines.

NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor–Positive Breast Cancer

Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor–positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design: Eligible patients with clinical stage II/III ER+/HER2− breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1–21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%). Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P < 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression. Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055–65. ©2017 AACR.

Model for Individualized Prediction of Breast Cancer Risk After a Benign Breast Biopsy

PURPOSE Optimal early detection and prevention for breast cancer depend on accurate identification of women at increased risk. We present a risk prediction model that incorporates histologic features of biopsy tissues from women with benign breast disease (BBD) and compare its performance to the Breast Cancer Risk Assessment Tool (BCRAT). METHODS We estimated the age-specific incidence of breast cancer and death from the Mayo BBD cohort and then combined these estimates with a relative risk model derived from 377 patient cases with breast cancer and 734 matched controls sampled from the Mayo BBD cohort to develop the BBD-to-breast cancer (BBD-BC) risk assessment tool. We validated the model using an independent set of 378 patient cases with breast cancer and 728 matched controls from the Mayo BBD cohort and compared the risk predictions from our model with those from the BCRAT. RESULTS The BBD-BC model predicts the probability of breast cancer in women with BBD using tissue-based and other risk factors. The concordance statistic from the BBD-BC model was 0.665 in the model development series and 0.629 in the validation series; these values were higher than those from the BCRAT (0.567 and 0.472, respectively). The BCRAT significantly underpredicted breast cancer risk after benign biopsy (P = .004), whereas the BBD-BC predictions were appropriately calibrated to observed cancers (P = .247). CONCLUSION We developed a model using both demographic and histologic features to predict breast cancer risk in women with BBD. Our model more accurately classifies a womans breast cancer risk after a benign biopsy than the BCRAT.

The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease

Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs, and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention.

Diagnosis and Management of Benign, Atypical, and Indeterminate Breast Lesions Detected on Core Needle Biopsy

Imaging abnormalities detected by mammographic screening often lead to diagnostic evaluations, with suspicious abnormalities subjected to image-guided core needle biopsy (CNB) to exclude malignancy. Most CNBs reveal benign pathological alterations, termed benign breast disease (BBD). Adoption of CNB presents challenges with pathologic classification of breast abnormalities and management of patients with benign or atypical histological findings. Patient management and counseling after CNB diagnosis of BBD depends on postbiopsy determination of radiologic-pathologic concordancy. Communication between radiologists and pathologists is crucial in patient management. Management is dependent on the histological type of BBD. Patients with concordant pathologic imaging results can be reassured of benign biopsy findings and advised about the future risk of developing breast cancer. Surgical consultation is advised for patients with discordant findings, symptomatic patients, and high-risk lesions. This review highlights benign breast lesions that are encountered on CNB and summarizes management strategies. For this review, we conducted a search of PubMed, with no date limitations, and used the following search terms (or a combination of terms): atypical ductal hyperplasia, atypical hyperplasia, atypical lobular hyperplasia, benign breast disease, cellular fibroepithelial lesions, columnar cell lesions, complex sclerosing lesion, core needle biopsy, fibroadenomas, flat epithelial atypia, lobular carcinoma in situ, lobular neoplasia, mucocele-like lesions, phyllodes tumor, pseudoangiomatous stromal hyperplasia, radial scar, and vascular lesions. The selection of references included in this review was based on study relevance and quality. We used additional articles culled from the bibliographies of retrieved articles to examine the published evidence for risk factors of BBD.

Factors Associated with Surgical Decision Making in Women with Early-Stage Breast Cancer: A Literature Review

BACKGROUND Current recommendations for surgical management of early-stage breast cancer include breast-conserving surgery with postoperative irradiation. However, studies show that mastectomy is still being used by women with early-stage breast cancer. METHODS Review of the medical literature published between 2000 and 2010 to determine the factors associated with the decision of patients for surgical treatment in early-stage breast cancer. RESULTS The following patient characteristics affect the surgical decision-making process in early-stage breast cancer: age, socioeconomic factors, geographic area in which the patient lives, proximity to a radiation therapy center, testing for BRCA gene, breast imaging, and decision aids. CONCLUSIONS Of increasing importance in the decision making about treatment of women with early-stage breast cancer are the womans perception of having a surgical choice and the influence of that choice on postoperative quality of life.

Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women

Women with atypical hyperplasia (AH) on breast biopsy have a substantially increased risk of breast cancer (BC). Here the BC risk for the extent and subtype of AH is reported for 2 separate cohorts.

Postoperative T-tube tract choledochoscopy☆

One hundred twenty-six patients underwent postoperative fiberoptic T-tube tract choledochoscopy for the management of retained biliary calculi as demonstrated by T-tube cholangiography. Extraction was successful in 94% of patients with retained stones. Thirty-nine patients had more than 1 stone, 20 patients had heptic duct stones, and 14 patients had large stones requiring electrohydraulic lithotripsy or laser fragmentation. Stone removal was not possible in six patients, secondary to either slippage of the T-tube with obliteration of the tract, inability to remove the stones with available instruments, a tortuous tract, or choledochoscope malfunction. Minor complications, most commonly transient fever, occurred in 12 patients. No serious complications or deaths occurred. The advantages of T-tube tract choledochoscopy include direct visualization of the biliary tree, avoidance of radiation exposure, and easy access to hepatic duct stones. This is the preferred method for treating retained biliary calculi in patients with a T-tube in situ.

Radial scar/complex sclerosing lesions: a clinicopathologic correlation study from a single institution ☆ ☆☆

Radial scars (RSs) or complex sclerosing lesions (CSLs) of the breast are benign radiologic and histologic entities. With the introduction of population-based screening programs, their incidence has increased to 0.03% to 0.09% of all core needle biopsies (CNBs). They can pose diagnostic difficulty because their radiologic and histologic appearances mimic carcinoma. We retrospectively searched for and reviewed all cases of RS/CSL diagnosed on image-guided CNB from January 1, 1994, to August 31, 2013, at a single institution. We also assessed the pathologic reports from excisional biopsies to identify cases upstaged to atypia or neoplasm. After exclusions, 100 CNBs were identified from 97 women, which showed RS/CSL without concomitant atypia. Mean age of the women was 52.9 years. Thirty-five women (38/100 CNBs, 38%) had follow-up excision. The median size of the excised RS/CSLs was 1.2 cm; 69% were larger than 1.0 cm. Almost all excised cases (92%) showed radiologic and pathologic concordance, and 79% were designated as suspicious for malignancy (Breast Imaging Reporting and Data System level 4). The most common findings of 38 follow-up excisional biopsies were residual RS (22 [58%]), atypical lobular hyperplasia (5 [13%]), and no residual lesion (5 [13%]). Eleven excisional biopsies (29%) were upstaged to invasive or in situ carcinoma or to atypical hyperplasia. Follow-up excisional biopsy is warranted for RS/CSLs, specifically those larger than 1.0 cm with worrisome radiographic findings or with radiologic and pathologic discordance. Approximately 29% of cases were upstaged to in situ or invasive carcinomas or other high-risk lesions in our study.