Search

Background: The FOLFIRINOX regimen recently became the new standard of care for patients with advanced pancreatic cancer. However, FOLFIRINOX hasn’t been widely used in China as the hesitance of oncologists to use FOLFIRINOX due to the toxicity of the regimen and the presumption that Chinese patients could not tolerate FOLFIRINOX. Methods: We retrospectively analyzed the clinical data of ten patients with pancreatic cancer who received the FOLFIRINOX regimen from July 2016 to July 2018. The two woman and eight men enrolled were aged 29 to 76 years. Three, three, and four patients were diagnosed with borderline resectable pancreatic cancer (BRPC), liver-metastatic pancreatic cancer (LMPC), and recurrent pancreatic cancer (RPC), respectively. Seven and three patients received a full or 80% initial dose, according to their Eastern Cooperative Oncology Group performance status. Results: One of the seven patients was administered an 80% dose after the second cycle because of febrile neutropenia (grade >3). The most common adverse event was neutropenia (grade 2). Four patients with BRPC or LMPC successfully underwent surgical resection. Two patients with LMPC achieved partial remission (PR). The levels of the serum carbohydrate antigen 19-9 of three patients with RPC significantly decreased (>60%). Conclusions: The FOLFIRINOX regimen is effective and is tolerated by certain Chinese patients with advanced pancreatic cancer. The dose of the FOLFIRINOX regimen should be individually adjusted to reduce toxicity.

Background Metaplastic breast cancer (MBC), characterized by a mixture of epithelial, squamous or mesenchymal elements and a usually triple-negative (TN) phenotype, accounts for Methods With IRB approval, we identified adult patients diagnosed with MBC at our institution from 2001 to 2011 from our prospective surgical pathology database. Patient, pathology, imaging, treatment and outcome data were obtained from electronic medical record, tumor registry, pathology slide and imaging review. Median follow-up for surviving patients was 66 months. Statistical analyses were performed using JMP 10.0 software. Results We identified 41 MBC patients, median age 60 years (range 33-89 years), with a median tumor size of 2.7 cm; 33 (80%) were TN. 23 patients (56%) had a preoperative axillary ultrasound (AUS): 9 (39%) showed at least one suspicious axillary lymph node (LN) of whom 6 had a preoperative fine needle LN biopsy (FNA) of which 3 were positive for metastasis. 6 patients, including the 3 LN+ on FNA, had neoadjuvant chemotherapy (NAC). Operation included axillary dissection (ALND) in 14, sentinel LN biopsy (SLNB) in 23, and SLNB followed by ALND in 1, while 3 patients had no axillary surgery. 10 patients were LN+ at operation. Among 22 patients who had both an AUS and axillary surgery, AUS had a sensitivity of 100% and specificity of 78%. Patient and tumor variables in association with pathologic LN status are summarized in the table. LN positivity correlated with increasing tumor size, T stage, grade and angiolymphatic invasion. 16 patients recurred, most with distant disease (10/16, 63%), although there was a solitary axillary recurrence 8 months after a negative SLNB in one patient who did not have a preoperative AUS. Thus the accuracy of SLNB was 96% (23/24) overall, but among those without preoperative AUS, 1/7 (14%) SLNBs were falsely negative. 5-year disease-free and breast cancer-specific survival estimates were 49% and 63%. LN- N=28 (74%)LN+ N=10 (26%)p-valueSize, median (IQR), cm2.7 (1.6-4.6)6.6 (2.5-16.5)0.001T stage 0.03T19 (100%)0 (0%) T214 (78%)4 (22%) T33 (60%)2 (40%) T42 (33%)4 (67%) Grade 0.04Low6 (16%)0 (0%) Intermediate/High22 (58%)10 (26%) Estrogen Receptor 0.61Positive (>1%)5 (71%)2 (29%) Negative ( Conclusion Our study is the first to specifically address AUS and SLNB for patients with metaplastic breast cancer. AUS had 100% sensitivity and 78% specificity, while one patient without a preoperative AUS had a falsely negative SLNB. Further, AUS with FNA of suspicious LNs was useful for staging at the time of diagnosis and informing treatment. We recommend this approach for patients with MBC. Citation Format: Murphy BL, Fazzio RT, Hoskin TL, Glazebrook KN, Keeney MG, Habermann EB, Hieken TJ. Management of the axilla in metaplastic breast carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-01.

Variation in the surgical treatment of melanoma occurs despite efforts to standardize care. This may lead to morbidity, inaccurate staging, and poor outcomes, or it may be cost ineffective. The purpose of our study was to evaluate our institutional compliance with National Comprehensive Cancer Network (NCCN) melanoma treatment guidelines. We studied 252 clinically node-negative melanoma patients identified from our cancer registry. Treatment data were confirmed by individual review of pathology and operative reports. Documented margins of excision conformed to NCCN guidelines in 87% of Tis–T1 tumors and 60% of T2–T4 tumors. Lymph node staging was performed in 11% of T1a, 64% of T1b, 74% of T2, 63% of T3, and 47% of T4 patients. Treatment by a surgical oncologist achieved margin and lymph node compliance in 95% and 92% of cases versus other practitioners in 38% and 67%, respectively (P

We investigated the impact of neoadjuvant chemotherapy (NAC) on axillary disease burden in clinically node-negative (cN0) HER-2 positive breast cancer patients.We studied 215 cN0 patients with HER-2 positive tumors. Multivariable logistic regression was used to compare NAC versus primary surgery (PS) with respect to outcome of pathologic nodal disease.Of 215 patients, 42 (20%) received NAC. NAC use correlated with higher clinical T stage (P 0.0001) and younger age (P = 0.03) with no difference in ER/PR status or tumor grade. Despite higher clinical T stage in the NAC group, rate of pathologic positive axillary nodes was non-significantly lower (NAC 5/42 = 11.9%, PS 27/173 = 15.6%, P = 0.54). In multivariable analysis, after adjustment for confounders including clinical T stage, age, and multifocal/multicentric disease, NAC showed significant reduction in odds of pathologic nodal disease (OR 0.26, 95%CI:0.06-0.90, P = 0.03). Further, among those with pathologic nodal disease, the number of positive nodes was lower after NAC (adjusted P = 0.03). Extranodal extension was present in 8/27 (30%) PS patients vs. 1/5 (20%) of the NAC patients (adjusted P = 0.36).NAC in cN0 HER-2 positive breast cancers reduces the rate of pathologic node-positive disease at operation and nodal disease burden and may decrease the need for axillary node dissection.

Women with benign breast disease (BBD) have an increased risk of developing breast cancer (BC). Nearly 30% of all BCs develop in women with prior BBD. Information regarding features of the expected number of BCs after BBD would enhance individualized surveillance and prevention strategies for these women. In the current study, the authors sought to characterize BCs developing in a large cohort of women with BBD.The current study cohort included 13,485 women who underwent breast biopsy for mammographic or palpable concerns between 1967 and 2001. Biopsy slides were reviewed and classified as nonproliferative disease, proliferative disease without atypia, or atypical hyperplasia. BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed.With median follow-up of 15.8 years, 1273 women developed BC. The majority of BCs were invasive (81%), of which 61% were ductal, 13% were mixed ductal/lobular, and 14% were lobular. Approximately two-thirds of the BC cases were intermediate or high grade, and 29% were lymph node positive. Cancer characteristics were similar across the 3 histologic categories of BBD, with a similar frequency of ductal carcinoma in situ, invasive disease, tumor size, time to invasive BC, histologic type of BC, lymph node positivity, and human epidermal growth factor receptor 2 positivity. Women with atypical hyperplasia were found to have a higher frequency of estrogen receptor-positive BC (91%) compared with women with proliferative disease without atypia (80%) or nonproliferative disease (85%) (P = .02).A substantial percentage of all BCs develop in women with prior BBD. The majority of BCs after BBD are invasive tumors of ductal type, with a substantial number demonstrating lymph node positivity. Of all the BCs in the current study, 84% were estrogen receptor positive. Prevention therapy should be strongly encouraged in higher-risk women with BBD.

Rates of contralateral prophylactic mastectomy (CPM) have been increasing nationally. The goal of this study was to evaluate recent trends in rates of CPM and immediate breast reconstruction (IBR).After institutional review board approval, we evaluated all surgical procedures for women with newly diagnosed unilateral stages 0-III breast cancer from January 2009 to December 2014. Patients opting for therapeutic mastectomy were classified as either unilateral mastectomy or bilateral mastectomy, if CPM was performed, and according to whether or not they underwent IBR. Analysis was performed using trend tests for univariate associations and both binary and multinomial logistic regression for multivariate analysis.There were 3,195 women who underwent surgery for breast cancer--51% lumpectomy, 49% therapeutic mastectomy. Of the 1,571 patients undergoing therapeutic mastectomy, 829 (53%) underwent bilateral mastectomy. The rates of therapeutic mastectomy did not change over the study period (P = .92), but the use of IBR among patients undergoing therapeutic mastectomy increased from 37% in 2009 to 68% in 2014 (P.0001). The use of bilateral mastectomy with IBR increased from 26% in 2009 to 46% in 2014 (P.0001), whereas conversely the use of bilateral mastectomy without IBR decreased from 22% to 12% (P.0001). IBR was associated with bilateral mastectomy; 69% of patients opting for IBR also underwent bilateral mastectomy compared with 38% choosing bilateral mastectomy in the group without IBR (adjusted odds ratio, 2.7; 95% CI, 2.1-3.5; P.0001).Over recent years, rates of bilateral mastectomy have remained high. The use of IBR increased substantially for women undergoing therapeutic mastectomy and women undergoing IBR were significantly more likely to opt for bilateral mastectomy. The availability of IBR may influence patients' decisions to pursue bilateral mastectomy.

Several approaches to minimize postoperative pain, nausea, and enhance recovery are available for patients undergoing mastectomy with immediate tissue expander (TE) reconstruction. We compared the effectiveness of intraoperative local infiltration of liposomal bupivacaine (LB) to preoperative paravertebral block (PVB). We retrospectively reviewed patients who underwent mastectomy with immediate TE reconstruction between May 2012 and October 2014 and compared patients with preoperative ultrasound-guided PVB to those with intraoperative LB infiltration. Fifty-three patients (54.6 %) received LB and 44 received PVB. LB was associated with less opioid use in the recovery room (p

Estrogen receptor (ER) β is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967–1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P < 0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ERβ expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low–moderate ERβ expression (P = 0.0008). High ERβ expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ERβ may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction. Cancer Prev Res; 8(11); 1084–92. ©2015 AACR.

Demand for nipple-sparing mastectomy (NSM) has increased. The authors’ initial NSM guidelines included risk reduction and cancers 2 cm or smaller located more than 2 cm from the nipple. The relative contraindications included obesity, large and/or ptotic breasts, and prior radiation. This study aimed to evaluate changes over time in NSM indications, surgical approach, and early outcomes. After institutional review board approval, the study identified 354 patients scheduled for 588 NSMs, 341 (96 %) of whom underwent 566 NSMs. Changes across time [early (2009–2010), mid (2011–2012), and recent (2013–6/2014)] were assessed using tests for linear trend. For patients undergoing reconstruction, NSMs increased from 24 % (early) to 40 % (recent) (p = 0.004). Among the NSM patients, average body mass index, proportion with bra cup sizes of C or larger, and prior radiation increased significantly over time. Performance of NSM for tumors 2 cm or less from the nipple increased from 5 to 18 %, and after neoadjuvant therapy, from 8 to 21.5 % (p = 0.02). Use of inframammary, radial, and reduction-type incisions increased over time, together with intraoperative laser angiography (both p

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 woman's breast cancer risk after a benign biopsy than the BCRAT.

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.

6531 Background: Annual mammography is recommended to screen residual breast tissue for new cancers and recurrent disease after treatment for early stage breast cancer. This study aimed to assess mammography rates over time in breast cancer survivors. Methods: We used administrative claims data from a large U.S. commercial insurance database, OptumLabs, to retrospectively identify privately- and Medicare Advantage-insured women with operable breast cancer who had residual breast tissue after definitive breast surgery between 2006 and 2015. We required coverage for at least 13 months following surgery. For each subsequent 13-month time period, we only included women without a loss of coverage, bilateral mastectomy, metastatic breast cancer diagnosis, or non-breast cancer diagnosis. We calculated the proportion of patients who had a mammogram during each 13-month period following breast surgery. We used multivariable logistic regression to test for factors associated with mammography in the first 13 months. Results: The cohort included 26,011 women followed for a median of 2.9 years (IQR 1.9-4.6) after surgery; 63.1% were less than 65 years of age, and 74.4% were white. In their first year of follow-up, 86% underwent mammography, but by year 7, this decreased to 73%. Fewer than 1% underwent MRI instead of mammography. In multivariable analysis, mammograms were less likely during the first year after surgery among women aged < 50 years (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.6 to 0.8), African Americans (OR, 0.7; 95% CI, 0.7 to 0.8), patients who underwent mastectomy (OR, 0.7; 95% CI, 0.6 to 0.7), and patients residing in the Western part of the country (OR, 0.9; 95% CI, 0.7 to 0.9). Those with 1-2 comorbidities were more likely (OR, 1.1; 95% CI 1.1-1.2) than those with none to have a mammogram during that period. Mammography use did not differ significantly by year of diagnosis (2006-2015). Conclusions: Even in an insured cohort, a substantial proportion of breast cancer survivors do not undergo annual surveillance mammography. Mammography use falls as the time from the early stage breast cancer diagnosis increases. Understanding factors associated with lack of mammographic screening may help improve survivorship care.

Despite decreasing rates of subsequent contralateral breast cancer after diagnosis of unilateral primary breast cancer, the proportion of patients electing contralateral prophylactic mastectomy (CPM) is increasing. Our aim was to identify risk factors associated with the identification of occult malignancy (OM) or high-risk lesion (HRL) in CPM to facilitate patient counseling and operative planning. We identified patients undergoing CPM in addition to mastectomy for index breast cancer between October 2008 and June 2013. Patient and tumor factors were analyzed to identify associations with OM or HRL in CPM. Among 740 CPM patients, an OM was identified in 4.1 % and an HRL was identified in 10.5 %. On multivariable analysis, factors associated with either occult finding included older age [odds ratio (OR) 1.37, per 10-year increase], invasive lobular index tumor histology (OR 2.60), progesterone receptor (PR)-positive index tumor (OR 1.79), and neoadjuvant therapy (OR 0.55). Overall, 244 patients (33 %) underwent BRCA testing, and 38 (16 %) had a deleterious mutation; 494 patients (67 %) had a preoperative breast MRI. Neither absence of a deleterious BRCA mutation nor a negative preoperative MRI decreased the likelihood of an occult finding in CPM. Although invasive cancer was identified infrequently in CPM specimens, the rate of HRL or OM in our study was 14.6 %. Older age and infiltrating lobular and PR-positive index breast cancers were associated with a higher risk of OM in CPM, while neoadjuvant therapy diminished the risk. BRCA testing and preoperative MRI were not associated with HRL or OM. This information is valuable for patient counseling and surgical planning.

Background Among older melanoma patients, lymphatic mapping failure, lower rates of SLN positivity and poor prognosis are reported reasons for omission of sentinel lymph node biopsy (SLNB). We investigated reasons for non-compliance with guidelines, sensitivity and prognostic significance of SLNB and completion lymphadenectomy (CLND) for elderly melanoma patients. Methods Retrospective review of patients ≥65 years with ≥1 mm thick melanoma treated at a single Institution. Wilcoxon, chi-square and Fisher's exact tests were used for analysis as appropriate. Univariable and multivariable Cox regressions were used to analyze time-to-event variables. Results 72 of 358 patients (20%) did not undergo SLNB. Reasons for omission included selective neck dissection in 26 (7%), patient refusal in 11 (3%), physician recommendation in 15 (4%) and significant comorbidities in 8 (2%). Of the 286 patients undergoing SLNB, only 5 (1.7%) had lymphatic mapping failures. 76 patients (26.6%) were SLN-positive. The sensitivity of SLNB was 90.5%, the negative predictive value was 96.3% and the false negative rate was 3.8%. Sixty-seven (88%) SLN-positive patients underwent CLND and 10 (15%) had positive non-SLNs. Reasons for omission of CLND included patient refusal in 3 (4%), surgeon recommendation in 5 (7%) and postoperative complication in 1 (1%). SLN and non-SLN status were independently associated with disease-free survival. SLN status was independently associated with melanoma-specific survival. Conclusions SLNB was successful in 98.7% of elderly patients with high sensitivity and a low false negative rate. Only 2% of our elderly patients appeared too frail for SLNB. Age alone should not be a contraindication to SLNB and CLND for melanoma.

Malignant phyllodes tumors are rare fibroepithelial breast neoplasms. Appropriate surgical management remains a subject of debate. The purpose of our study was to define optimal surgical treatment and to identify factors associated with outcome.After confirmatory pathology review, we identified 67 patients with borderline (n = 15) and malignant (n = 52) phyllodes tumors treated at our institution between 1971 and 2008. We used Cox proportional hazards models to evaluate associations between treatment, patient and tumor characteristics, and disease-free (DFS) and cancer-specific survival (CSS).Median patient age was 47 years. For 32 patients, definitive surgical treatment was wide local excision (WLE): 27 with margins ≥1 cm and 5 with margins1 cm. Thirty-five underwent mastectomy. Two patients received radiotherapy after WLE and two after mastectomy with microscopically positive margins. After 10 years median follow-up, 16 patients (24 %) recurred locally (8 postmastectomy and 8 after WLE). Treatment type and margin extent did not impact local recurrence. Fifteen patients (22 %) developed distant disease. Overall 5-year DFS was 67.9 % and CSS 80.1 %. Tumor size5 cm, mitotic rate ≥10/10 HPF, stromal overgrowth and cellularity (all p0.05) predicted DFS, whereas CSS was associated with the latter three variables. CSS was diminished for mastectomy patients who were significantly more likely to harbor tumors with adverse features.With long-term follow-up, extent of surgical resection did not affect DFS for patients with borderline and malignant phyllodes tumors. Tumor features, most notably stromal overgrowth, were predictive of recurrence and survival, suggesting these high-risk patients may benefit from additional therapeutic strategies.

BackgroundIn this 2-site randomized trial, we investigated the effect of antiseptic drain care on bacterial colonization of surgical drains and infection after immediate prosthetic breast reconstruction.MethodsWith IRB approval, we randomized patients undergoing bilateral mastectomy and reconstruction to drain antisepsis (treatment) for one side, with standard drain care (control) for the other. Antisepsis care included both: chlorhexidine disc dressing at drain exit site(s) and irrigation of drain bulbs twice daily with dilute sodium hypochlorite solution. Cultures were obtained from bulb fluid at 1 week and at drain removal, and from the subcutaneous drain tubing at removal. Positive cultures were defined as ≥1+ growth for fluid and >50 CFU for tubing.ResultsCultures of drain bulb fluid at 1 week (the primary endpoint) were positive in 9.9 % of treatment sides (10 of 101) versus 20.8 % (21 of 101) of control sides (p = 0.02). Drain tubing cultures were positive in 0 treated drains versus 6.2 % (6 of 97) of control drains (p = 0.03). Surgical site infection occurred within 30 days in 0 antisepsis sides versus 3.8 % (4 of 104) of control sides (p = 0.13), and within 1 year in three of 104 (2.9 %) of antisepsis sides versus 6 of 104 (5.8 %) of control sides (p = 0.45). Clinical infection occurred within 1 year in 9.7 % (6 of 62) of colonized sides (tubing or fluid) versus 1.5 % (2 of 136) of noncolonized sides (p = 0.03).ConclusionsSimple and inexpensive local antiseptic interventions with a chlorhexidine disc and hypochlorite solution reduce bacterial colonization of drains, and reduced drain colonization was associated with fewer infections.

Obesity affects 36 % of American women and is a well-documented breast cancer risk factor. Preoperative axillary ultrasound (AUS) is used routinely for axillary staging in newly diagnosed breast cancer patients; However, the impact of obesity on the usefulness of AUS is unknown. Our aim was to evaluate the effect of body mass index (BMI) on the performance of AUS. From our prospective breast surgery database, we identified 1,510 consecutive invasive breast cancers in patients undergoing primary surgery, including axillary operation, from January 2010 to July 2013. Preoperative AUS was performed in 1,375 cases (91 %). We analyzed patient, pathology and imaging data. Median BMI was 27.4 and 479 patients (36 %) were classified as obese (BMI ≥ 30). Most tumors were T1 (71 %) and estrogen receptor-positive (87 %). AUS was suspicious in 401 (29 %) patients, of whom 374 had ultrasound-guided lymph node fine-needle aspiration (FNA). Overall, 124 patients (33.2 %) were FNA positive. FNA identified disease preoperatively in 35.8 % of node-positive obese patients. For all BMI categories (normal, overweight, obese), AUS was predictive of pathologic nodal status (p

Background: With the increasing use of neoadjuvant and minimally invasive therapy, the accuracy of preoperative determination of breast tumor size becomes important. Therefore, we undertook this study to compare mammography and ultrasonography (US). Methods: A total of 180 invasive breast cancer patients were prospectively examined by mammography and US; 146 eligible patients had tumors visualized by both modalities. Results: In 69% of cases, US was better than or equivalent to mammography in determining tumor size. Both underestimated tumor size; mean (median) underestimation was 3.8 ± 0.7 mm (1.7 mm) by US and 3.5 ± 0.9 mm (2 mm) by mammogram. Maximal tumor dimension was accurate within 5 mm in 65% of cases by mammography and 75% of cases by US. For mammographically determined size (versus pathologic size) correlation, r, was 0.4 and for US it was 0.63 and improved for only T1 and T2 tumors. Conclusions: These data suggest that US is more accurate than mammography in assessing breast cancer size.

Routine laparoscopy and laparoscopic ultrasound (LUS) for staging intra-abdominal malignancies remains controversial. Thus, we undertook a prospective study to assess the value of preoperative laparoscopy with LUS for patients with intra-abdominal tumors judged resectable by preoperative studies. Laparoscopy was successfully performed in 76 of 77 patients, and 60 underwent LUS. Of 33 patients with presumed pancreatic cancer, laparoscopic findings changed the operative management of 11 patients, and LUS altered the management of an additional 6 patients. Laparotomy was avoided in 9 patients (27%). Among 14 patients with hepatobiliary tumors, laparotomy was avoided in 9 patients in whom laparoscopy and/or LUS revealed either benign or advanced disease. Operative management was altered in 4 of 18 patients with gastric or esophageal cancer by laparoscopic findings. LUS did not add to the management of these patients. Of 12 patients with presumed intra-abdominal lymphoma, 9 were diagnosed with lymphoma and 3 with benign disease, without laparotomy in all but 1 case. Laparoscopy and LUS are valuable tools for evaluating the resectability of pancreatic and hepatobiliary tumors. Laparoscopy, and to a lesser degree LUS, greatly facilitates diagnosing patients with intra-abdominal lymphomas and spares an occasional patient with esophagogastric carcinoma from undergoing laparotomy.

BACKGROUND The limitations of morphologic criteria alone in determining the prognosis for a patient with a particular intermediate-thickness primary melanoma have prompted efforts to identify other markers. METHODS In this study, the authors analyzed expression of p53, β1 integrin, and β3 integrin in primary tumors from 111 patients with intermediate-thickness malignant melanoma. RESULTS Eighty-nine (80%) had detectable p53 protein, 58 (52%) expressed β1 integrin, and 71 (64%) expressed β3 integrin. Patients with β3 positive melanomas were more likely to die of their disease (32 of 71 patients, 45%) than those with β3 negative tumors (3 of 40 patients, 8%) (P < 0.0001). The number of involved lymph nodes, Clark's level, β1 integrin expression, thickness, and mitotic rate also had prognostic significance. β3 integrin was associated with subsequent lung metastases and β1 integrin with lymph node involvement. CONCLUSIONS Integrin expression, along with histopathologic criteria, is a prognostic marker for intermediate-thickness malignant melanoma and may indicate the site of subsequent metastasis. These observations may have clinical utility and suggest areas for future investigation. Cancer 1999;85:375–82. © 1999 American Cancer Society.

Mastectomy with immediate tissue expander reconstruction is associated with postoperative pain, nausea, and vomiting. Various techniques of perioperative and postoperative pain control have been described. Our standard of care for postsurgical pain management in patients undergoing mastectomy with immediate tissue expander reconstruction has been preoperative ultrasound-guided paravertebral block. Recent literature demonstrating the opioid-sparing benefits of liposomal bupivacaine has directed two of our plastic surgeons to pilot its use in immediate tissue expander reconstruction. In the accompanying video, we present our technique of intraoperative local infiltration of liposomal bupivacaine into the base of mastectomy skin flaps, serratus fascia, and periaxillary tissue after completion of the mastectomy and before tissue expander placement into the reconstruction pocket.

Purpose To investigate the feasibility of utilizing carbon fiducials to increase localization accuracy of lumpectomy cavity for partial breast irradiation (PBI). Methods Carbon fiducials were placed intraoperatively in the lumpectomy cavity following resection of breast cancer in 11 patients. The patients were scheduled to receive whole breast irradiation (WBI) with a boost or 3D-conformal PBI. WBI patients were initially setup to skin tattoos using lasers, followed by orthogonal kV on-board-imaging (OBI) matching to bone per clinical practice. Cone beam CT (CBCT) was acquired weekly for offline review. For the boost component of WBI and PBI, patients were setup with lasers, followed by OBI matching to fiducials, with final alignment by CBCT matching to fiducials. Using carbon fiducials as a surrogate for the lumpectomy cavity and CBCT matching to fiducials as the gold standard, setup uncertainties to lasers, OBI bone, OBI fiducials, and CBCT breast were compared. Results Minimal imaging artifacts were introduced by fiducials on the planning CT and CBCT. The fiducials were sufficiently visible on OBI for online localization. The mean magnitude and standard deviation of setup errors were 8.4mm ± 5.3 mm (n=84), 7.3mm ± 3.7mm (n=87), 2.2mm ± 1.6mm (n=40) and 4.8mm ± 2.6mm (n=87), for lasers,more » OBI bone, OBI fiducials and CBCT breast tissue, respectively. Significant migration occurred in one of 39 implanted fiducials in a patient with a large postoperative seroma. Conclusion OBI carbon fiducial-based setup can improve localization accuracy with minimal imaging artifacts. With increased localization accuracy, setup uncertainties can be reduced from 8mm using OBI bone matching to 3mm using OBI fiducial matching for PBI treatment. This work demonstrates the feasibility of utilizing carbon fiducials to increase localization accuracy to the lumpectomy cavity for PBI. This may be particularly attractive for localization in the setting of proton therapy and other scenarios in which metal clips are contraindicated.« less

Breast surgical oncologists have rapidly and successfully transitioned from the routine use of axillary lymph node dissection (ALND) to sentinel lymph node (SLN) biopsy for staging the axilla in clinically node negative patients. This approach limits the use of ALND to those patients with pathologically-proven axillary lymph node metastases and has prompted great current interest in whether or not all SLN-positive patients benefit from a completion ALND. Analysis of population-based data shows a decades-long trend towards omitting ALND in patients with low volume axillary disease. Thus, even prior to publication of the results of the ACOSOG Z0011 study and the IBCSG 23-01 study, completion ALND was being performed less frequently for selected patients with nodal micrometastases. Herein we review the contribution of the recently published IBCSG 23-01 study which provides additional data to confirm that for selected patients, mainly those with small, estrogen receptor-positive tumors with low nodal disease burden undergoing breast conservation with radiation and adjuvant systemic therapy, ALND might be avoided safely. This trial, which included small numbers of patients treated by mastectomy without radiation, and lumpectomy with partial breast irradiation, suggests interest in further clinical trials investigating these important patient populations. The study’s short median follow-up however, cautions us to be clear in discussion, especially with younger patients who have otherwise biologically favorable tumors, that the long-term outcomes of SLN biopsy alone for low volume axillary disease remains unknown.

Although surgical management of the breast after neoadjuvant chemotherapy (NAC) may be governed by treatment response, axillary management continues to be determined by stage at presentation. Axillary ultrasound (AUS) with fine-needle aspiration (FNA) is used to detect lymph node (LN) metastases for pre-NAC staging, but imaging assessment of treatment response in the axilla remains undefined. We evaluated post-NAC axillary imaging and surgical pathology to understand how imaging might direct axillary surgery.We evaluated pre- and post-NAC axillary imaging and clinicopathologic data in 272 patients who received NAC for primary breast cancer and underwent operation at our institution from 2010 to 2012. Treatment response on imaging was categorized as complete (CR), partial (PR), and none/progression (NR).Pre-NAC axillary staging classified patients as AUS negative/no FNA (n = 61), FNA/LN negative (n = 42), and FNA/LN positive (n = 169). Post-NAC axillary imaging included AUS (n = 146), MRI (n = 139), and PET-CT (n = 38). At operation, 128 of 272 patients (47 %) were LN positive: 23.3 % (24 of 103) of cN0 and 61.5 % (104 of 169) of cN1-AUS/FNA-positive patients at presentation. Of the 65 cN1-ypN0 patients, 58.1 % (25 of 43) had an imaging CR by US, 58.6 % (17 of 29) by MRI, and 84.6 % (11 of 13) by PET-CT. The sensitivity of post-NAC axillary imaging in detecting persistent LN metastases for cN1-AUS/FNA-positive patients was 69.8 % for US, 61.0 % for MRI, and 63.2 % for PET-CT.Performance characteristics of AUS, MRI, and PET-CT, while informative, were inadequate to preclude surgical axillary staging of in breast cancer patients after NAC. Whether this information might be used to tailor surgical and postsurgical treatment requires further investigation.

Tumor-infiltrating lymphocytes (TILs) and regression are manifestations of the host immune response to tumor, but their influence on outcome remains undefined. There is a paucity of data on the elderly who represent a growing proportion of melanoma patients. The aim of this study was to evaluate the influence of TILs and regression as an indirect measure of immunity on outcome in elderly patients with melanoma. From a prospective database, we identified 250 consecutive cutaneous melanoma patients aged at least 65 years at the time of diagnosis. Data were verified by record review. Within the primary melanoma, a brisk TIL response was present in 66 (31%), nonbrisk TILs in 36 (17%), and absent in 111 (52%). The presence of a brisk infiltrate conferred a three-fold increased risk of sentinel lymph node (SLN) metastasis (P=0.02). Despite this, nonbrisk or absent TILs were associated with a five-fold increased risk of recurrence (P=0.0001). In multivariate analysis, nonbrisk or absent TILs were independently associated with recurrence (P0.0001), diminished 5-year disease-free survival (76 vs. 91%, P=0.0006), and 5-year melanoma-specific survival (82 vs. 95%, P=0.0008). Regression was not an independent predictor of SLN metastasis, disease-free survival, or melanoma-specific survival. Our study demonstrates that an active antitumor immune response exists in elderly melanoma patients that, paradoxically, predicts both SLN metastasis and improved melanoma-specific outcomes. Further investigation to characterize this lymphocytic infiltrate and to confirm its clinical significance as a predictor of nodal status, patient outcome, and response to immunotherapy in elderly melanoma patients appears warranted.

Background Although sentinel lymph node biopsy has been accepted as a useful procedure for certain breast cancer patients, the value of this procedure in the elderly remains unknown. We undertook this study to evaluate changes in adjuvant treatment attributable to sentinel lymph node biopsy. Methods A total of 104 patients ≥65 years underwent sentinel lymph node biopsy plus lumpectomy or mastectomy for the treatment of clinically node-negative invasive breast cancer. Demographic, pathologic, and treatment data were evaluated using an SAS software package (SAS, Cary, North Carolina). Results Twenty-nine of 104 patients (28%) had metastatic disease in ≥1 sentinel lymph node. Nonsurgical treatment was modified in 38% of patients because of sentinel lymph node biopsy results. Changes included adjuvant chemotherapy and/or hormonal therapy, adjuvant axillary radiotherapy, and decisions against adjuvant therapy. Conclusions These data suggest that sentinel lymph node biopsy in elderly breast cancer patients is beneficial.

As a result of bioassay-guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma-specific cytotoxic agent. In follow-up studies conducted with athymic mice carrying human melanomas, tumour growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumour activity was mediated by the induction of apoptosis. Betulinic acid is inexpensive and available in abundant supply from common natural sources, notably the bark of white birch trees. The compound is currently undergoing preclinical development for the treatment or prevention of malignant melanoma.

Background ER+ BC is associated with activated CDK4/6. The CDK4/6 inhibitor palbociclib (P) markedly improves time to progression in advanced ER+HER2- BC. We conducted a neoadjuvant phase II trial to determine the activity of P in primary breast cancer as a prelude to adjuvant studies. Methods To assess molecular changes induced by anastrozole (A) or P+A, patients (pts) were treated initially with A alone (1mg PO daily) for 28 days in cycle 0 (C0) before the addition of P (125mg PO daily on D1-21 each cycle) on C1D1. P+A was administered for 4 28-day cycles followed by C5 with A alone for 2-4 weeks (wks) before surgery. P was added in C5 for 10-12 days immediately prior to surgery in the last 20 pts enrolled to assess molecular changes induced by A, either alone or in combination with P immediately prior to surgery, in resected tumor. Goserelin was added in premenopausal pts. Research tumor biopsies were obtained at baseline, C1D1, and C1D15. Central Ki67 analysis was performed at all timepoints, those with Ki67 >10% at C1D15 went off study treatment. The primary endpoint was complete cell cycle arrest (CCA), defined as Ki67 50% improvement over A in CCA rate on C1D15 biopsy (44% with A alone based on historical data, vs 66% with P+A, power = 0.8, alpha=0.05). The primary endpoint is met if >20 pts achieved CCA in this cohort. Correlative endpoints included assessment of markers of proliferation, apoptosis, senescence, Rb, gene expression microarray, intrinsic subtype, and next generation sequencing of 83-gene panels, which will be reported at the meeting. Results Between 4/23/2013 and 4/24/2015, 50 pts (33 PIK3CA WT, 11 PIK3CA Mut, 2 pending, 4 tissue quantity or quality not sufficient for sequencing (QNS)) were enrolled to the study. Median age was 57.5 (range: 34.1–79.6) years. Four pts, all with WT PIK3CA, went off study due to Ki67 >10% on C1D15 biopsy, 26 pts completed treatment and surgery, 1 refused surgery, 3 withdrew study treatment in C1, and 16 continued to receive study drug (2 in C0, 3 in C1, 4 in C2, 5 in C3, 1 in C4, and 1 in C5). Among the 40 pts currently evaluable for the primary endpoint (C1D15 Ki67), CCA occurred in 34 (85%) pts, including 9 of 9 (100%) PIK3CA Mut, 22 of 28 (78.5%) WT, and 3 of 3 QNS pts. Preliminary analysis of available data indicated a significantly lower Ki67 value after 2 wks of P+A (C1D15) compared to that on A alone (C1D1) (p=0.034, n=18). Conclusion This study met the primary endpoint demonstrating that P+A is a highly effective anti-proliferative combination. The sequential biopsy design clearly demonstrated that P+A increased cell cycle control over A alone. P+A was effective regardless of PIK3CA mutation status and these results support the evaluation of this combination in the adjuvant setting for ER+HER2- BC. Citation Format: Ma CX, Gao F, Northfelt D, Goetz M, Forero A, Naughton M, Ademuyiwa F, Suresh R, Anderson KS, Margenthaler J, Aft R, Hobday T, Moynihan T, Gillanders W, Cyr A, Eberlein TJ, Hieken T, Krontiras H, Hoog J, Han J, Guo Z, Vij K, Mardis E, Al-Kateb H, Sanati S, Ellis MJ. A phase II trial of neoadjuvant palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with anastrozole for clinical stage 2 or 3 estrogen receptor positive HER2 negative (ER+HER2-) breast cancer (BC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S6-05.

To assess national practice patterns regarding use of perioperative antibiotics by surgeons performing breast operations requiring drainage tubes. The members of the American Society of Breast Surgeons (ASBrS) were surveyed regarding use of perioperative antibiotics for breast operations requiring drains, with or without immediate tissue expander or implant reconstruction. Of 2,857 ASBrS members contacted, 917 (32 %) responded; all self-identified as surgeons. Of 905 evaluable respondents, most described themselves as general surgeons (46 %) or breast surgeons (46 %). For cases in which drains are anticipated, most respondents (86 %) reported routine use of preoperative prophylactic antibiotics, with 99 % selecting cephalosporins. Use of antibiotic >24 h postoperatively varied by whether or not reconstruction was performed. In nonreconstruction cases, the majority (76 %) reported “never/almost never” prescribing antibiotics beyond the 24-h postoperative period, but 16 % reported “always/almost always.” In reconstruction cases, the majority (58 %) reported routine antibiotic use beyond 24 h, and the primary driver of the decision to use antibiotics was reported to be the plastic surgeon (83 %). Among those reporting use at >24 h, the duration recommended for nonreconstruction cases was “up to 1 week” in 38 % and “until drains removed” in 39 %; this was similar for reconstruction cases. Cephalosporins are utilized uniformly as preoperative antibiotic prophylaxis in breast operations requiring drains. However, use of postoperative antibiotic prophylaxis is strongly dependent on the presence of immediate breast reconstruction. Consensus is lacking on the role of postoperative antibiotic prophylaxis in breast operations utilizing drains.

The purpose of this study was to determine whether surgical excision of benign solitary intraductal papillomas (BSIP) diagnosed by core needle biopsy (CNBx) without an associated high-risk lesion and concordant with imaging is justified.A review of all papillary lesions diagnosed by CNBx from January 2003 to June 2010 was performed. Available histologic and radiologic materials were evaluated in a blinded fashion by three pathologists and three dedicated breast radiologists, respectively, to assess for concordance. The papillary lesions were designated as benign, atypical, or malignant. There were 16 BSIPs excluded because of an adjacent high-risk lesion or same-quadrant ipsilateral cancer. All immediate and delayed excisional specimens were reviewed. Clinical and radiologic data were recorded.A total of 299 papillary lesions diagnosed on CNBx and concordant with imaging were identified. Of these, 240 (80 %) were classified as benign, 49 (16 %) atypical, and 10 (3 %) malignant. After exclusions, 77 of 224 women in our study cohort (34 %) underwent surgical excision with no atypical or malignant upgrades. Of the remaining 147 women diagnosed with a BSIP on CNBx, 47 (32 %) were lost to follow-up and 100 (68 %) were observed. All 100 observed patients had stable imaging findings at follow-up (4.8-93.8 months, mean 36.0 months).The likelihood of diagnosing atypia or malignancy after surgical excision of a BSIP diagnosed on CNBx without associated high-risk lesion or ipsilateral quadrant malignancy is extremely low. For this distinct subset of patients with a BSIP, these data justify close imaging follow-up, rather than surgical excision.

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.

Background Core needle biopsy (CNB) is used increasingly not only to diagnose breast cancer, but to determine tumor histology, grade and marker expression, select neoadjuvant therapy, and predict sentinel lymph node status. Thus, we undertook this study to evaluate the accuracy of CNB as a predictor of breast cancer histology and marker expression. Methods We identified 209 Breast Cancer Registry cases with a preoperative CNB and reviewed all clinicopathologic data for accuracy. Statistical analysis was performed with statistical software. Results CNB unequivocally showed cancer in 93%. Exact tumor histology concordance was 86%. Ductal carcinoma in situ on CNB was upgraded to invasive cancer in 23%. Concordance was substantial for estrogen receptor expression (88%, κ = .71), but kappa values were less than .6 for tumor grade, mitotic rate, progesterone receptor (PR), Ki-67, HER-2/neu, and p53 expression. Conclusions Reliance on CNB grade and marker expression for critical decision making may be inadvisable. Further study is warranted to optimize breast cancer patient care.

Clinical practice guidelines have been developed to improve melanoma patient care. However, it is unclear whether failure to comply with these standards (either excessive or inadequate treatment) increases morbidity or relapse rates. Therefore, we undertook this study to evaluate the effect of variance from National Comprehensive Cancer Network (NCCN) recommendations on postoperative complication rates and disease recurrence. We retrospectively reviewed our institutional cancer registry data on 327 clinically node-negative melanoma patients and assessed compliance with NCCN guidelines, complication rates, and outcome. Data were confirmed by chart, pathology report, and operative note review. Statistical analysis was performed by using the SAS statistical software package. Postoperative complications were documented in 17% of patients and were 3.4-fold higher for patients treated in a margin-noncompliant fashion and 2.4-fold higher for patients treated in a lymph-node-noncompliant manner (P

Background The incidence of ductal carcinoma in situ (DCIS) of the breast is increasing. Optimal treatment remains controversial and, because of a long natural history, may not be evident for many years. We undertook this study to identify markers of disease recurrence. Methods We studied 131 pure DCIS patients with a 100-month mean follow-up. We performed a complete histologic review, immunohistochemical staining for p53 and vascular endothelial growth factor expression, and enumerated microvessel density/mm2 using factor VIII-Ab. Statistical analysis was performed by using an SAS software package (Cary, NC). Results Eleven patients (8%) developed ipsilateral recurrence at a mean of 55 months (11–137 months) after initial treatment. Three were DCIS, and 8 were invasive cancer. Recurrence was significantly predicted by p53 overexpression (in 55% of tumors that recurred versus 22% of those that did not, P = .02) but not other factors. Conclusions These data suggest that biologic factors may have an important role in predicting recurrence in DCIS patients.

2 Background: Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but accurate personalized risk prediction is desirable to facilitate individual clinical management decisions. Currently used models provide poor BC risk prediction for women with AH. Our goal was to develop and validate an improved risk prediction model for women with AH. Methods: From a cohort of 13,538 women with benign breast disease from 1967-2001, pathology review confirmed 699 with AH. Clinical risk factors and histologic features of the tissue biopsy were recorded, and BC events were ascertained from study questionnaires, tumor registry, and review of medical records. Using a lasso approach, 23 variables were assessed for model inclusion. Lasso-identified features were then fit in a Cox regression model to estimate BC risk. Model discrimination was assessed with C-statistics in the model-building set and in a separate external validation set. Calibration was assessed by comparing observed to predicted breast cancer counts. Results: The model-building set comprised 699 women with 142 BC events (median follow-up 8.1 years), and the external validation set comprised 461 women with 114 BC events (median follow-up 11.4 years). The final model included three covariates: age at biopsy, age squared, and number of foci of AH. Model performance was good, with a C-statistic of 0.622 (SE = 0.027) in the model-building set and 0.594 (SE = 0.029) in the external validation set. The model is well-calibrated, with observed to expected numbers of BCs nearly equal across all post-biopsy follow-up years. Conclusions: We propose a new model for predicting BC risk in women with AH based on age at biopsy and number of foci of atypia. This model provides absolute risk estimates for women with AH, has good discriminatory ability, is well-calibrated, and validates in an external cohort.

Introduction: Estrogen receptor beta (ERβ), which is highly expressed in benign breast epithelium, is postulated to function as a tumor suppressor of breast cancer. Atypias of the breast increase the lifetime risk of breast cancer four-fold. However, little is known about ERβ expression in association with atypias or whether ERβ plays a role in mitigating breast cancer risk in high-risk individuals. We therefore undertook this study to examine the relationship of ERβ expression in atypias and adjacent normal lobules with the risk of subsequent breast cancer. Methods: We studied women in a well-characterized benign breast disease cohort with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) diagnosed from 1967 to 1991. Nuclear and cytoplasmic ERβ expression was assessed via immunohistochemistry in both the atypical hyperplasia epithelium (atypia) and background normal lobules for percent (scores 0-4 for 75%, respectively) and intensity (scores 0-3 for negative, weak, intermediate, strong, respectively) using a highly specific ERβ monoclonal antibody (PPG5/10). For nuclear staining, an ERβ sum score (percent + intensity, range 0-7) was created and grouped as low (0-2), moderate (3-5) or high (6-7). Competing risks regression was used to assess the association of ERβ expression with future breast cancer risk while also accounting for the competing risk of death from other causes. Results: 171 women, median age 56, were studied (79 ADH and 92 ALH). Median follow-up was 15 years overall, and 36 women developed breast cancer at a median of 13 years after their atypia biopsy. ERβ expression was lower in the atypia versus normal lobules whether evaluated by nuclear percent stained, nuclear intensity or cytoplasmic intensity (all p < 0.001). For nuclear staining specifically, ERβ expression in the atypia was low in 44 (26%), moderate in 117 (68%) and high in only 10 (6%) based on the sum score. In contrast, ERβ was higher in the normal lobules with a majority showing high expression (n = 96, 56%), moderate expression in 74 (43%) and low expression in only 1 (0.6%). Lower ERβ nuclear expression in the atypia was associated with increased breast cancer risk, whether evaluated by percent staining, intensity or sum score; the same was true for ERβ nuclear expression in the background normal lobules. Low ERβ expression in the atypia (sum score 0-2) was associated with a 2-fold increased risk of subsequent breast cancer compared to atypia with moderate-high expression (sum score 3-7), HR 2.0, 95% CI: 1.02-3.8, p = 0.04. Lower ERβ expression in the normal lobules was also associated with an increased risk of future breast cancer: HR = 2.5 (95% CI: 1.3-5.1, p = 0.009) for low-moderate versus high expression. Conclusions: Increased ERβ expression in normal and atypical lobules was associated with a significantly decreased risk of breast cancer in our high-risk patient cohort. These data suggest that in women with atypical hyperplasia, ERβ expression is protective against the future development of breast cancer. ERβ may serve as a useful biomarker to further stratify breast cancer risk in women with benign breast disease. Citation Format: Tina J. Hieken, Jodi M. Carter, John R. Hawse, IV, Tanya L. Hoskin, Marlene Frost, Lynn C. Hartmann, Derek C. Radisky, Daniel W. Visscher, Vernon S. Pankratz, Amy C. Degnim. ERβ expression and breast cancer risk prediction for women with atypias. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A03.

60 Background: Indications for nipple-sparing mastectomy (NSM) with immediate reconstruction have expanded. For cancer patients, NSM is thought best-suited for early stage patients, with nodal involvement initially viewed as a relative contraindication. We undertook this study to evaluate the use and early outcomes of NSM in node-positive (LN+) breast cancer. Methods: We identified 240 cancers in 226 patients (14 bilateral) scheduled for NSM and operated on at our institution 1/2009-6/2014. Data on intraoperative conversion from NSM, recurrence and follow-up was abstracted from the medical record. Chi-square and long-rank tests were used for statistical analysis. P-values < 0.05 were considered significant. Results: Of 240 cancers, 182 were LN- and 58 were LN+. More LN+ patients had T2/T3 tumors (27/58, 47%) than LN- patients (31/182, 17%), p < 0.0001, but ER and HER2 status was similar. Of 58 LN+ cases, 19 (33%) were cN1 confirmed by positive LN cytology and 39 (67%) were cN0 but LN+ at operation. 10 patients LN+ at diagnosis received neoadjuvant therapy (NT) followed by operation (at which 6 were pLN+ and 4 rendered ypN0); 39 cN0 (4 NT, 35 primary surgery) and 9 cN1 primary surgery patients were pLN+ at operation with a median of 1 LN+. NSM was successful in 13/14 LN+ NT patients (93%) and 39/44 LN+ primary surgery patients (89%), p = 0.64. Six LN+ patients (10%) were converted to skin-sparing mastectomy (SSM) at initial operation based on frozen section pathology (n = 5) or at a second operation (n = 1) vs 13/182 LN- patients (7%), p = 0.44. Among cancer patients treated with NSM, 7 locoregional recurrences (5 in LN+, 2 in LN- patients) occurred at 25 mos median follow-up. 3-year locoregional disease-free estimates were 87% (95% CI 75-100%) for LN+ vs 99% (95% CI 97-100%) for LN- patients, p = 0.007. One nipple-areolar recurrence occurred, in a LN- patient. 3-year breast cancer-specific survival was 97% (95% CI 92-100%) in LN+ vs 99% (95% CI 98-100%) in LN- patients, p = 0.40. Conclusions: Conversion from planned NSM to SSM did not differ significantly between LN+ and LN- patients. Short-term oncologic outcomes were satisfactory. These data suggest that NSM may be appropriate for carefully selected LN+ breast cancer patients.

Background: Many newly diagnosed breast cancer patients undergo preoperative breast MRI which includes visualization of some degree of the axilla. The impact of patient characteristics and tumor biology on the fidelity of MRI imaging of the axilla in these cases is not well-studied. We sought to examine the correlation between nodal findings on breast MRI and pathologic nodal status in newly diagnosed breast cancer patients. Methods: With IRB approval, we identified 1868 consecutive breasts with invasive cancer in 1803 patients undergoing primary operation with axillary surgery from 1/2010-7/2013. Patients undergoing neoadjuvant chemotherapy (348) were excluded leaving 1510 breasts with cancer in 1455 patients. Preoperative MRI was performed in 763 patients (52%). We evaluated patient, imaging and pathology data. Results: Patients evaluated with MRI were median age 57 years. The majority of tumors were T1 (63%) and T2 (28%). MRI identified suspicious axillary nodes in 240 cases (31%), of which 123 (51%) were node positive at operation. Suspicious axillary findings on MRI predicted both nodal status and pN stage at operation (both p Pathologic Node PositiveSensitivity (95% CI)Specificity (95% CI)NPV (95% CI)PPV (95% CI)Accuracy (95% CI)All Cases (n=763)234 (31%)52.6 (46-59.1)77.9 (74.1-81.3)78.8 (75-82.1)51.3 (44.8-57.7)70.1 (66.7-73.3)Approximated Biologic Subtype (missing=24)ER+/HER2- (n=609)194 (32%)51.0 (43.8-58.2)80.0 (75.8-83.7)77.8 (73.4-81.5)54.4 (46.9-61.7)70.8 (67-74.3)HER2+ (n=69)20 (29%)65.0 (40.9-83.7)71.4 (56.5-83)83.3 (68-92.5)48.1 (29.2-67.6)69.6 (57.2-79.8)ER-/HER2- (n=61)17 (28%)58.8 (33.5-80.6)75.0 (59.4-86.3)82.5 (66.6-92.1)47.6 (26.4-70)70.5 (57.3-81.1)p value0.740.430.330.560.730.98Tumor Grade (missing=5)1 (n=259)58 (22%)32.8 (21.4-46.5)79.6 (73.2-84.8)80.4 (74.1-85.5)31.7 (20.6-45.1)69.1 (63.0-74.6)2 (n=351)124 (35%)55.6 (46.5-64.5)79.7 (73.8-84.6)76.7 (70.7-81.8)60.0 (50.4-68.9)71.2 (66.1-75.9)3 (n=148)51 (34%)66.7 (52.0-79.0)70.1 (59.8-78.8)80.0 (69.6-87.6)54.0 (41.0-66.4)68.9 (60.7-76.1)p value0.0010.00030.110.720.020.93 Diagnostic performance did not vary significantly based on patient body mass index (BMI) or approximated biologic subtype, but specificity was better for patients >age 50 (p=0.007) and sensitivity and PPV both were worse for grade 1 vs grade 2/3 tumors. Node positivity rate at operation was 48% (51/106) for patients with a solitary abnormal node on MRI and 54% (72/134) when >1 suspicious node was seen (p=0.39). However, multiple vs solitary MRI suspicious nodes correlated with ≥3 positive nodes at operation (40 [30%] vs 19 [18%], p=0.03) and pN2/pN3 disease (29 [22%] vs 12 [11%], p=0.03). Conclusion: Axillary lymph node findings on MRI for breast cancer predict nodal status and disease volume in invasive breast cancer patients. Tumor biologic subtype did not affect performance characteristics of preoperative MRI, but tumor grade did influence the sensitivity and PPV of MRI. When MRI is performed in the evaluation of newly diagnosed breast cancer, axillary findings inform pathologic nodal stage at operation regardless of tumor subtype. Citation Format: Sean C Dupont, Judy C Boughey, Tanya L Hoskin, Katrina N Glazebrook, Tina J Hieken. Value of breast MRI for preoperative axillary assessment of breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-03.

The treatment of choice for patients with colorectal hepatic metastases is resection; the other therapies mentioned herein are not substitutes. Resection is undertaken provided certain selected criteria have been met: The patient must be a suitable operative candidate free of serious medical co-morbidities; the patient should be free of local tumor recurrence and extrahepatic disease; and there must be sufficient liver reserve to sustain life after resection. At the time of surgery IOUS is essential and may change the operative approach in a significant number of cases. Five-year survival rates of approximately 30% can be expected following resection. Re-resection can be offered to patients who have failure confined to the liver. Local ablative techniques such as cryotherapy or RFA can be offered to patients whose metastases are not resectable. Intraarterial chemotherapy, as the sole treatment or as an adjunct to resection or cryotherapy, continues to play a role.

86 Background: Phyllodes tumors (PT) are rare breast neoplasms confounding their systematic study and evidence-based management guidelines. There is little data on the sensitivity of preoperative core needle biopsy (CNB) and imaging findings in establishing a correct preoperative diagnosis. We undertook this study to evaluate the sensitivity of CNB histologic findings and imaging findings in preoperatively categorizing tumors as benign or borderline/malignant. Methods: We identified 47 patients who underwent surgical resection of a PT at our institution after a preoperative CNB between 6/2000-3/2012. Statistical analysis utilized Wilcoxon rank-sum, chi-square or Fisher’s exact tests, and 95% confidence intervals (CI) are reported. Results: 30 patients had a final diagnosis of benign and 17 of borderline/malignant PT. The latter were significantly more often palpable (76.5% vs 36.7%, p=0.01). No other clinical or radiologic feature predicted borderline/malignant subtype, although irregular shape on US was suggestive (70.6% vs 44.8%, p= 0.09). CNB diagnosis by tumor type is summarized in the table. No benign PT had ≥10 mitoses, necrosis or marked stromal atypia on CNB. No case with absent mitoses on preoperative CNB was a borderline/malignant PT; however 77% of benign PT did exhibit mitoses on CNB. Sensitivity of CNB for PT overall was 48.9% (95% CI: 35.3-62.8%) while it was 40% (24.6-57.7%) for benign PT and 17.6% (6.2-41.0%) for borderline/malignant PT. Conclusions: Marked stromal atypia, ≥10 mitoses and necrosis were rare on CNB, but suggestive of malignancy. No imaging or histology feature reliably distinguished between tumor types. Over one-third of borderline/malignant PT had a preoperative CNB diagnosis of fibroadenoma or cellular fibroepithelial lesion emphasizing the low sensitivity of CNB and the need for judicious consideration of definitive surgical excision. [Table: see text]

3 Background: Atypical ductal hyperplasia (ADH) is a high-risk breast lesion usually diagnosed with core needle biopsy. Although upgraded to cancer at surgical excision in ~15 to 25% of cases, routine excision is questioned due to cost and overtreatment. We evaluated clinical, imaging, and histologic features associated with cancer upgrade and developed a multivariate model to predict risk of upgrade. Methods: With IRB approval a single institution retrospective review was performed of patients who underwent surgical excision of ADH diagnosed by core biopsy from 06/2005 to 06/2013. Review was performed of electronic records, breast imagin,g and biopsy slides. Multiple imputations were used for missing data. Association of cancer upgrade with various features was assessed with logistic regression. Results: 409 biopsies with ADH on core biopsy, with later surgical excision, were included. The overall upgrade rate was (16.1%, 95% CI:12.9-20.0%); 10 patients had invasive cancer at excision and 56 DCIS only. Features on core biopsy most strongly associated with upgrade were imaging estimated percent of lesion removed (upgrade 9% for 90% removed, 14% for 50 to 75%, and 27% for < 50% removed), individual cell necrosis (upgrade 34% with necrosis vs. 9.5% without), and # foci of ADH (22% for >1 focus vs 8% for 1 focus). A multivariate predictive model (see Table) showed an average C-statistic of 0.77. Women with no necrosis and either 1 focus with ≥ 50% removal or >1 focus with 90% removal (36% of the sample) have low risk of upgrade (5.0%, 95% CI:1.3-8.7%). Conclusions: ADH on core biopsy with low risk of upgrade to cancer is defined by percent of imaging lesion removed, # of foci of ADH, and lack of individual cell necrosis. If findings are validated, women whose biopsies meet low-risk criteria might be considered for chemoprevention and surveillance rather than surgical excision.[Table: see text]