Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

BACKGROUND: Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients. METHODS: The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as 'not performed/not acted on' if ALND was either not performed or performed at a later date than SLNB, or 'performed/acted on' if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT. RESULTS: Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p < 0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70-10.5; p < 0.001). CONCLUSIONS: We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.

Prognostic and Biologic Significance of ERBB2-Low Expression in Early-Stage Breast Cancer.

Importance: It is unclear whether ERBB2-low breast cancer should be considered an individual biologic subtype distinct from ERBB2-0 breast cancer. Objective: To investigate whether low ERBB2 expression is associated with distinct clinicopathologic characteristics and prognosis among patients with hormone receptor (HR)-positive and triple-negative breast cancer (TNBC). Design, Setting, and Participants: This cohort study was conducted using data from a prospectively maintained institutional database on all consecutive patients with breast cancer undergoing surgery between January 2016 and March 2021 at Dana-Farber Brigham Cancer Center. The study included 5235 patients with stage I through III, ERBB2-negative invasive breast cancer. Tumors were classified as ERBB2-low if they had an ERBB2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and ERBB2-0 if they had an ERBB2 IHC score of 0. Data were analyzed from September 2021 through January 2022. Exposures: Standard treatment according to institutional guidelines. Main Outcomes and Measures: Comparison of clinicopathologic characteristics and disease outcomes (pathologic complete response rate [pCR], disease-free survival, distant disease-free survival, and overall survival) between patients with ERBB2-low and ERBB2-0 breast cancer. Results: Among 5235 patients with ERBB2-negative invasive breast cancer (5191 [99.2%] women; median [range] age at primary surgery, 59.0 [21.0-95.0] years), 2917 patients (55.7%) and 2318 patients (44.3%) had ERBB2-low and ERBB2-0 tumors, respectively. Expression of HR was significantly more common among ERBB2-low compared with ERBB2-0 tumors (2643 patients [90.6%] vs 1895 patients [81.8%]; P < .001). The rate of ERBB2-low tumors increased progressively, from 296 of 739 estrogen receptor (ER)-negative tumors (40.1%) to 31 of 67 ER-low (ie, ER 1%-9%) tumors (46.3%), 37 of 67 ER-moderate (ie, ER, 10%-49%) tumors (55.2%), 2047 of 3542 ER-high (ie, ER, 50%-95%) tumors (57.8%), and 499 of 803 ER-very high (ie, ER > 95%) tumors (62.1%) (P < .001). Among 675 patients receiving neoadjuvant chemotherapy, those with ERBB2-0 tumors experienced higher pCR rates (95 patients [26.8%] vs 53 patients [16.6%]; P = .002). However, there were no statistically significant differences in pCR rate between ERBB2-low and ERBB2-0 tumors when separately analyzing HR-positive, ER-low, HR-positive without ER-low, or TNBC tumors. In exploratory survival analysis, no differences by ERBB2-low expression in disease-free survival, distant disease-free survival, or overall survival were observed among patients with HR-positive tumors or TNBC. Conclusions and Relevance: The results of this cohort study did not support the interpretation of ERBB2-low breast cancer as a distinct biologic subtype. ERBB2-low expression was positively associated with level of ER expression, and ER-low tumors were enriched among ERBB2-0 tumors, suggesting that, given the worse prognosis of ER-low tumors, they may be associated with confounding of prognostic analyses of ERBB2-low expression.

Clinicopathologic features of breast cancers diagnosed in women treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.

BACKGROUND: Childhood and young adult survivors of Hodgkin lymphoma (HL) are at elevated risk of developing breast cancer, yet little data exist on the tumor characteristics that develop in this high-risk patient population. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify breast cancers diagnosed between 1990 and 2016 in women who had received prior radiation therapy for HL at age 30 years or younger. Clinicopathologic features of subsequent breast cancers (breast cancer after radiation therapy for HL [BC-HL]) were examined and compared with breast cancers diagnosed in women who had no prior malignancy (breast cancer with no prior malignancy [BC-NPM]). RESULTS: In total, 321 breast cancers were identified in 257 women who had a history of radiation therapy for HL. The median age at HL diagnosis was 22 years (interquartile range, 18-26 years), and nearly all patients in the BC-HL group (97.9%) were diagnosed ≥8 years after radiation therapy. Overall, 56 patients in the BC-HL group (21.8%) developed bilateral breast cancer. Compared with women who had BC-NPM, those who had BC-HL were younger (43 vs 60 years; P < .001) and were less likely to present with ductal carcinoma in situ (8.4% vs 14.9%; P = .001). On multivariable analysis that included adjustment for age, invasive BC-HL was associated with smaller (≤2 cm) tumor size (odds ratio, 1.64; 95% CI, 1.25-2.15) and upper outer quadrant tumors (odds ratio, 1.37; 95% CI, 1.04-1.81) compared with BC-NPM. In a subset analysis of 102 women who had HER2/neu status available, the distribution of biologic subtype was not significantly different between BC-HL and BC-NPM (P = .16). CONCLUSIONS: Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation. LAY SUMMARY: Women who have had radiation therapy for Hodgkin lymphoma at a young age are at increased risk of developing early onset breast cancer; however, most of these breast cancers are sensitive to hormones (estrogen receptor-positive) and are diagnosed at early stages. Because these breast tumors are estrogen receptor-positive, medications that prevent breast cancer by blocking the effect of or lowering hormone levels (also termed endocrine prevention) may be useful in this group of high-risk women.

A systematic review of clinically available gene expression profiling assays for stage II colorectal cancer: initial steps toward genetic staging.

BACKGROUND: In recent years, increasingly accessible and novel genetic technologies have spurred keen interest in the application of cancer genetics in predicting prognosis and response to treatment. In particular, investigators have eagerly sought to establish and validate genetic signatures that might improve the identification of patients with stage II colorectal cancer (CRC) who are at highest risk of recurrence. To better understand the evidence for incorporation of genetic assays into clinical practice, we have systematically reviewed those assays that have been validated and are available for clinical use in stage II CRC. METHODS: A systematic review was performed using PubMed, Web of Science and Scopus databases. The GRADE system was used to evaluate level of evidence and strength of recommendations. RESULTS: After duplicates were removed and exclusion criteria were applied, there were 13 articles for review. CONCLUSION: Identifying high-risk patients with stage II CRC using molecular profiling has been the primary aim of many investigators, and the approach is translating into clinical utility.

Quality and safety in obesity surgery-15 years of Roux-en-Y gastric bypass outcomes from a longitudinal database.

BACKGROUND: Most population-based studies lack long-term data, making the reporting of true mortality and outcome rates difficult. An accurate estimate of these rates in a high-risk population is critical for obtaining informed consent, especially for an elective procedure such as Roux-en-Y gastric bypass (RYGB). OBJECTIVES: To examine the longitudinal outcomes of RYGB. SETTING: The California Office of Statewide Health Planning and Development (OSHPD) longitudinal database. METHODS: The OSHPD longitudinal database was queried for patients who underwent RYGB between 1995 and 2009. The primary outcome was mortality rates at 1, 5, and 10 years. Secondary outcomes were marginal ulcer and reoperation. The Cox hazard proportional analysis was used to determine adjusted survival and long-term outcomes for laparoscopic RYGB compared with open RYGB. RESULTS: The study included 129,432 RYGB patients. Rates of laparoscopy increased from 3% to 35% from 1995 to 2004 and then steeply increased to 80% in 2005 and to 93% in 2009. Overall mortality rate at 1, 5, and 10 years was 2.2%, 4.4%, and 8.1%, respectively; the rates of marginal ulcer were .3%, .7%, and 1%, respectively; and the reoperation rates were .3%, .8%, and 1.2%, respectively. Predictors of poor outcomes were male gender, age, smoking, alcohol, Medicare, Medi-Cal insurance, and Asian or Native American race. The laparoscopic approach was protective against death (hazard ratio [HR] 95% confidence interval [95%CI]: .63[.58-.69]) and long-term complications (HR .78[.72-.85]). CONCLUSIONS: This longitudinal population study showed high rates of mortality following RYGB, with improved long-term outcomes when the laparoscopic approach was used.

Concomitant cholecystectomy should be routinely performed with laparoscopic Roux-en-Y gastric bypass.

INTRODUCTION: As the popularity of a laparoscopic Roux-en-Y Gastric Bypass (RYGB) surpassed that of an open approach, practice of concomitant cholecystectomy declined. Low rates of gallbladder disease following RYGB and high complication rates of concomitant cholecystectomy have been published, but these population-based studies have lacked long-term outcomes and survival data. STUDY DESIGN: The California Office of Statewide Health Planning and Development longitudinal database was queried for patients who underwent RYGB with or without cholecystectomy between 1995 and 2009. Additionally, patients who underwent cholecystectomy after RYGB were compared to all cholecystectomy patients. Primary outcome was survival; secondary long-term outcomes included cholangitis, common duct stones, dumping syndrome, metabolic derangements, ventral hernia, any hernia, marginal ulcers, and reoperation. Cox proportional hazard analysis was performed to determine adjusted survival and outcomes. RESULTS: Of 134,584 RYGB patients, 21,022 underwent concomitant cholecystectomy. Concomitant cholecystectomy improved both survival (HR[95 % CI] 0.51[.48-.54]) and long-term outcomes (HR 0.84[.77-.91]). Incidence of gallbladder disease following RYGB was 6.8 and 15.2 % at 1 and 5 years. In subsequent analysis of 829,333 cholecystectomy patients, 7,099 underwent prior RYGB with higher risk of conversion to open (HR 1.58[1.41-1.78]), post-operative complication (HR 1.47[1.36-1.6]) and death (HR 1.32[1.17-1.5]). CONCLUSIONS: Concomitant cholecystectomy is safe for RYGB patients. Given high rates of gallbladder disease and increased risk when cholecystectomy is performed following RYGB, cholecystectomy should be considered at the time of RYGB.