Are there patients with T1 to T2, lymph node-negative breast cancer who are "high-risk" for locoregional disease recurrence?

BACKGROUND: Indications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node-negative (N0) breast cancer with "high-risk" features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10-year disease-free survival with lymph node irradiation included patients with high-risk N0 disease, but, to the authors' knowledge, benefits in patients receiving modern systemic therapy are uncertain. METHODS: The authors retrospectively identified patients with T1 to T2N0 disease who were treated with mastectomy from January 2006 through December 2011. High-risk features included age <40 years, multifocality/multicentricity, lymphovascular invasion, medial/central tumor location, and high nuclear grade. RESULTS: Among 672 eligible patients, only 15 received PMRT and were excluded. Of the remaining 657 patients, 187 (28%) had 1 high-risk feature and 449 patients (68%) had ≥ 2 high-risk features. A total of 36 patients with unknown tumor grade were excluded from risk analysis. Approximately 98% of patients underwent sentinel lymph node biopsy alone and 86% received adjuvant systemic therapy. At a median of 5.6 years of follow-up, the locoregional disease recurrence (LRR) rate was 4.7% (31 patients). Increasing tumor size was found to be associated with LRR (hazard ratio, 1.70; P = .006), whereas other high-risk features were not (all P > .05). Receipt of systemic therapy decreased the LRR rate (hazard ratio, 0.40; P = .03). Although crude LRR rates increased from 3.8% to 9.4% with 1 versus ≥ 4 high-risk features, the number of risk factors was not found to be significantly associated with LRR (P = .54). CONCLUSIONS: In the current study, a low crude LRR rate (4.7%) was observed in a large unselected cohort of patients with T1 to T2N0 breast cancer with high-risk features who were treated with mastectomy and systemic therapy without PMRT. Although increasing tumor size and the omission of systemic therapy were found to be predictive, other features did not confer a higher LRR risk either independently or together, and do not by themselves mandate the use of PMRT in this patient population. Cancer 2017;123:2626-33. © 2017 American Cancer Society.

Do Calcifications Seen on Mammography After Neoadjuvant Chemotherapy for Breast Cancer Always Need to Be Excised?

BACKGROUND: This study aimed to determine the relationship between mammographic calcifications and magnetic resonance imaging (MRI) tumoral enhancement before and after neoadjuvant chemotherapy (NAC) and to assess the impact of these findings on surgical management. METHODS: This Institutional Review Board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study involved breast cancer patients who underwent NAC between 2009 and 2015. The study cohort comprised 90 patients with pre- and posttreatment MRI and mammograms demonstrating calcifications within the tumor bed either at presentation or after treatment. The data gathered included pre- and post-NAC imaging findings and post-NAC histopathology, particularly findings associated with calcifications. Comparisons were made using Fisher's exact test, with p values lower than 0.05 considered significant. RESULTS: Complete resolution of MRI enhancement occurred for 44% of the patients, and a pathologic complete response (pCR) was achieved for 32% of the patients. No statistically significant correlation between changes in mammographic calcifications and MRI enhancement was found (p = 0.12). Resolution of enhancement was strongly correlated with pCR (p < 0.0001). The majority of the patients with pCR demonstrated complete resolution of enhancement (79%, 23/29). No statistically significant relationship was found between changes in calcifications and rates of pCR (p = 0.06). A pCR was achieved most frequently for patients with resolution of enhancement and new, increasing, or unchanged calcifications (p < 0.0001). CONCLUSIONS: Although calcifications seen on post-NAC mammography may be associated with benign disease, loss of MRI enhancement does not predict the absence of residual tumor with sufficient accuracy to leave calcifications in place. Complete excision of tumor bed calcifications remains standard practice and a substantial limitation to NAC use for downstaging patients to be eligible for breast conservation treatment.

Estimating the OncotypeDX score: validation of an inexpensive estimation tool.

BACKGROUND: OncotypeDX, a multi-gene expression assay, has been incorporated into clinical practice as a prognostic and predictive tool. However, its use in resource-constrained international healthcare systems is limited. Here we develop and validate a simplified model using clinicopathologic criteria to predict OncotypeDX score. METHODS: Patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive and HER2-negative invasive ductal carcinoma for whom the OncotypeDX test was successfully performed between 09/2008 and 12/2011 were retrospectively identified. Tumor size, nuclear and histologic grade, lymphovascular invasion, and ER and PR status were extracted from pathology reports. Data were split into a training dataset comprising women tested 09/2008-04/2011, and a validation dataset comprising women tested 04/2011-12/2011. Using the training dataset, linear regression analysis was used to identify factors associated with OncotypeDX score, and to create a simplified risk score and identify risk cutoffs. RESULTS: Estrogen and progesterone receptors, tumor size, nuclear and histologic grades, and lymphovascular involvement were independently associated with OncotypeDX. The full model explained 39% of the variation in the test data, and the simplified risk score and cutoffs assigned 57% of patients in the test data to the correct risk category (OncotypeDX score <18, 18-30, >30). 41% of patients were predicted to have OncotypeDX score <18, of these 83, 16, and 2% had true scores of <18, 18-30, and >30, respectively. CONCLUSIONS: Awaiting an inexpensive test that is prognostic and predictive, our simplified tool allows clinicians to identify a fairly large group of patients (41%) with very low chance of having high-risk disease (2%).

A 10-year trend analysis of sentinel lymph node frozen section and completion axillary dissection for breast cancer: are these procedures becoming obsolete?

BACKGROUND: Recent results from the ACOSOG Z0011 trial question the use of intraoperative frozen section (FS) during sentinel lymph node (SLN) biopsy and the role of axillary dissection (ALND) for SLN-positive breast cancer patients. Here we present a 10-year trend analysis of SLN-FS and ALND in our practice. METHODS: We reviewed our prospective SLN database over 10 years (1997-2006, 7509 SLN procedures) for time trends and variation between surgeons in the use of SLN-FS and ALND in patients with cN0 invasive breast cancer. RESULTS: Use of SLN-FS decreased from 100% to 62% (P < 0.0001) and varied widely by surgeon (66% to 95%). There were no statistically significant trends in the performance of ALND for patients with SLN metastases detected by FS (n = 1370, 99-99%) or routine hematoxylin and eosin (H&E) (n = 333; 69-77%), but only for those detected by serial section H&E with or without immunohistochemistry (n = 438; 73-48%; P = 0.0054) or immunohistochemistry only (n = 294; 48-28%; P < 0.0001). These trends coincided with an increase in the proportion of completion versus immediate ALND (30-40%; P = 0.0710). CONCLUSIONS: Over 10 years, we have observed a diminishing rate of SLN-FS and, for patients with low-volume SLN metastases, fewer ALND, trends that suggest a more nuanced approach to axillary management. If the Z0011 selection criteria had been applied to our cohort, 66% of SLN-FS (4159 of 6327) and 48% of ALND (939 of 1953) would have been avoided, sparing 13% of all patients the morbidity of ALND.

Impact of breast density on the presenting features of malignancy.

PURPOSE: To determine the relationship between breast density, presenting features and molecular subtype of cancer, and surgical treatment received. METHODS: Retrospective review of a prospectively maintained database. Eligible patients had stage 1-3 cancer, were treated between 1/2005 and 6/2007, and had estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) measurements and films available for review. Density was classified at presentation as 1-4 using the Breast Imaging Reporting and Data System (BI-RADS) classification. RESULTS: 1,323 patients were included. Significant differences across the four density groups were present in age, race, multicentricity/focality, and presence of an extensive intraductal component (EIC). When density was combined into two groups, after adjustment for age, only an EIC and mammographically occult cancer were significantly more common in the dense groups. Extremely dense breasts (BI-RADS density 4) more commonly had luminal A tumors (p = 0.05), lobular cancers (p = 0.03), multicentricity (p = 0.02), and occult tumors (p < 0.0001). Greater density was associated with increased mastectomy use, with 61% of the extremely dense group having mastectomy versus 43% of those of lesser density (p = 0.01). CONCLUSIONS: Cancers in extremely dense breasts occur in younger women, are more often mammographically occult, and appear to be phenotypically different from those arising in other density groups. The more common use of mastectomy may be related to these features, although density itself is not a selection criterion for mastectomy.

Predictors of completion axillary lymph node dissection in patients with immunohistochemical metastases to the sentinel lymph node in breast cancer.

BACKGROUND: Axillary lymph node dissection (ALND) in patients with immunohistochemistry (IHC)-determined metastases to the sentinel lymph node (SLN) is controversial. The goal of this study was to examine factors associated with ALND in IHC-only patients. METHODS: Retrospective review of an institutional SLN database from July 1997 to July 2003 was performed. We compared sociodemographic, pathologic, and therapeutic variables between IHC-only patients who had SLN biopsy alone and those that had ALND. RESULTS: Our study group consisted of 171 patients with IHC-only metastases to the SLN. Young age, estrogen receptor negative status, high Memorial Sloan-Kettering Cancer Center nomogram score, and chemotherapy were associated with ALND. Among patients who had ALND (n = 95), 18% had a positive non-SLN. Rates of systemic therapy were similar between those with and without positive non-SLNs at ALND. No axillary recurrences were observed in this series with a median follow-up of 6.4 years. The percentage of patients who were recurrence-free after 5 years was 97% (95% confidence interval, 92.1-98.6). CONCLUSIONS: On the basis of our findings and the lack of prospective randomized data, the practice of selectively limiting ALND to IHC-only patients thought to be at high risk and to patients for whom the identification of additional positive nodes may change systemic therapy recommendations seems to be a safe and reasonable approach.

Surgical management of the axilla: do intramammary nodes matter?

BACKGROUND: The therapeutic significance of intramammary lymph nodes is uncertain. The purpose of this study was to identify the appropriate surgical management of the axilla in intramammary node-positive patients undergoing sentinel lymph node (SLN) biopsy. METHODS: A retrospective review of consecutive patients staged between September 1996 and December 2004 was performed. Intramammary node identification and pathologic findings were compared with the status of axilla. RESULTS: Among 7,140 patients, intramammary nodes were identified in 151 (2%). Positive intramammary nodes were identified in 36 patients (24%). Axillary disease was identified in 61% of intramammary node-positive patients. No additional axillary disease was identified when axillary lymph node dissection was performed in intramammary node-positive patients with negative axillary SLN biopsy results. CONCLUSIONS: The results suggest that completion axillary lymph node dissection may be based on the status of axillary SLN biopsies in clinically node negative patients when intramammary lymph node metastases are identified in the breast specimens.

Eighteen sensations after breast cancer surgery: a 5-year comparison of sentinel lymph node biopsy and axillary lymph node dissection.

BACKGROUND: The aim of this study is to evaluate prevalence, severity, and level of distress of 18 sensations at baseline (3-15 days) and 5 years after breast cancer surgery, and compare sensations after sentinel lymph node biopsy (SLNB) with those after SLNB plus immediate or delayed axillary lymph node dissection (ALND). METHODS: A total of 187 patients with breast cancer completed the Breast Sensation Assessment Scale at baseline and at 3, 6, 12, 24, and 60 months after surgery to assess prevalence, severity, and level of distress of sensations. Of these, 133 had SLNB, and 54 had SLNB and ALND. Additionally, of the 187 patients, 141 had breast-conservation therapy and 46 had total mastectomy. RESULTS: Sensations were less prevalent, severe, and distressing after SLNB compared with ALND at baseline and at 5 years. This difference was most evident in those who had breast-conservation therapy. Most sensations after SLNB and ALND, even if prevalent, were not severe or distressing. Some sensations remained notably prevalent at 5 years, including tenderness and twinges after SLNB, and tightness and numbness after ALND. Phantom sensations were frequently reported by mastectomy patients. CONCLUSIONS: Prevalence, severity, and level of distress of sensations were lower after SLNB compared with ALND, but some morbidity existed after SLNB. Certain sensations remained highly prevalent in both groups for up to 5 years.

Educational posters to reduce antibiotic use.

INTRODUCTION: Antibiotic overuse promotes resistant strains of bacteria and puts patients at risk for adverse reactions. Given the use of educational posters in government-sponsored public health campaigns, this study examined the effectiveness of a waiting room poster in reducing excessive antibiotic use in clinical practice. METHODS: Investigators conducted a 1-month trial of an educational poster with historical controls using three private pediatric group practices in Westchester County, New York. Children between the ages of 6 months and 10 years at the time of a visit to diagnose and treat symptoms of respiratory illness were enrolled as subjects. Antibiotic prescriptions for children with respiratory illnesses seen during the poster month were compared with prescriptions written during three 1-month historical control periods. The proportion of visits that resulted in a prescription for an antibiotic served as the outcome measure. RESULTS: Overall, 326 of the 720 patients (45.2%) enrolled in the study were treated with an antibiotic. Multiple logistic regression analysis revealed no statistically significant difference in the proportion of visits resulting in an antibiotic prescription among the 4 study months (P = .79), indicating that the educational poster had no effect on antibiotic use. DISCUSSION: Public education in the form of a waiting room poster was not sufficient to decrease antibiotic prescriptions. This finding has implications for current large-scale programs and for health care providers as they continue to attempt to educate patients on the appropriate use of antibiotics.