Presence Of Invasive Cancer Research Articles

Total versus Partial Pancreatectomy in Patients with Pancreatic Cancer Arising from Multifocal or Diffuse Intraductal Papillary Mucinous Neoplasia - A Multicenter Observational Study.

To investigate the impact of total pancreatectomy (TP) on oncological outcomes for patients at high-risk of local recurrence or secondary progression in the remnant gland after partial pancreatectomy (PP) for IPMN-associated cancer. Major risk factors for invasive progression in the remnant gland include multifocality, diffuse main duct dilation, and the presence of invasive cancer. In these high-risk patients, a TP may be oncologically beneficial. However, current guidelines discourage TP, especially in elderly patients. This international multicenter study compares TP versus PP in patients with adenocarcinoma arising from multifocal or diffuse IPMN (2002-2022). Log-rank test and multivariable Cox-analysis with interaction analysis was performed to assess overall survival (OS), disease-free survival (DFS), and local-DFS. Of 359 included patients, 162 (45%) were treated with TP, whereas 197 (55%) underwent PP. Despite TP and PP having similar R0-rates (59% vs. 58%, P=0.866), patients undergoing a TP had significantly longer local-DFS compared to PP (P=0.039). However, no difference in OS was observed between the two surgical approaches (P=0.487). In a multivariable analysis, young age (optimal cut-off ≤63.6yrs) was associated with an OS benefit derived from TP (HR:0.44, 95%CI:0.22-0.89), whereas no significant difference was observed in elderly patients (HR:1.24, 95%CI:0.92-1.67, Pinteraction=0.007). Since overall, patients with diffuse or multifocal IPMN with an invasive component do not benefit from TP in terms of OS, the indication for TP may be individualized to young patients who have sufficient life expectancy to benefit from the prevention of secondary progression or local recurrence.

Role of Intraoperative Frozen Section Assessment of Proximal Bile Duct Margins and the Impact of Additional Re-Resection in Perihilar Cholangiocarcinomas.

Intraoperative frozen section (FS) analysis to assess the bile duct margin status is commonly used to assess the completeness of resection during surgery for perihilar cholangiocarcinoma (pCCA) resection. However, the impact of additional re-section on the long-term outcome after obtaining an initial positive margin remains unclear. Patients diagnosed as pCCA on preoperative imaging and subjected to curative intent surgery from May 2013 to June 2021 with a minimum follow-up of 2years were included. Intraoperative FS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of invasive cancer. Out of the 62 patients with a preoperative diagnosis of pCCA on imaging, 35 patients were included for final analyses after excluding patients with inoperable disease (on staging laparoscopy or local exploration) and other/benign pathology on the final histopathology report. Out of the 35 patients, patients with postoperative 90-day mortality were excluded from the final survival analysis. FS analysis revealed an initial positive margin in 10 (28.5%) patients. Among 10 patients who underwent re-resection to achieve negative proximal margins, only 5 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes. Median disease-free survival (DFS) and overall survival (OS) were 16 and 19.6months for patients with an initial positive margin, but 36 and 58.2months for patients with an initial negative margin, respectively (p = 0.012). The median DFS and OS were significantly lower for those with secondary R0 as compared to primary R0 (16 vs. 36months for DFS, p = 0.117 and 19.6 vs. 58.2months for OS, p = 0.027, respectively). An intraoperative FS positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable pCCA. Additional resection has a questionable benefit on survival, when a secondary negative margin is achieved.

How Well Does Non-mass Enhancement Correlate With DCIS/Invasive Cancer?

Contiguous non-mass enhancement (NME) often coexists with a solid tumor component on MRI, but it can be challenging to predict whether NME represents invasive breast cancer, ductal carcinoma in situ (DCIS), benign disease, or biopsy site reaction. The purpose of this study was to determine the association between the size/extent of NME and the presence of invasive cancer and/or DCIS on final pathology. This was a single institution retrospective analysis of a prospectively maintained breast cancer registry (2010-2020). Female patients who underwent surgical resection were included if they had a diagnosis of invasive breast cancer (with or without DCIS) and had an MRI showing both a solid mass and contiguous NME. The size of NME on MRI was compared with the size of invasive cancer and/or DCIS on the final pathology. From a total of 3443 patients, 225 patients were included. 86.2% had invasive ductal carcinoma (IDC), and 12.0% had invasive lobular carcinoma 76.9% were ER+, 16.4% were HER2+, and 13.3% were triple negative breast cancer (TNBC). 18.7% received neoadjuvant chemotherapy (NCT) of whom 31% achieved a complete radiographic/pathologic response. Pearson correlation coefficients (r) between the size of NME and invasive cancer/DCIS showed a strong and positive correlation of MRI NME with DCIS on pathology in patients without NCT. Subgroup analysis showed the strongest correlations for NME and DCIS among non-white (r = .70) and HER2 + patients (r = .74) who did not receive NCT. Strong correlations between NME and DCIS were found for HER2 + disease and non-white patients, but only modest correlations were found for other patient/disease characteristics. These correlations may impact decisions in surgical approach.

Diffusion-weighted Breast MRI in Prediction of Upstaging in Women with Biopsy-proven Ductal Carcinoma in Situ.

Background Accurate preoperative prediction of upstaging in women with biopsy-proven ductal carcinoma in situ (DCIS) is important for surgical planning, but published models using predictive MRI features remain lacking. Purpose To develop and validate a predictive model based on preoperative breast MRI to predict upstaging in women with biopsy-proven DCIS and to select high-risk women who may benefit from sentinel lymph node biopsy at initial surgery. Materials and methods Consecutive women with biopsy-proven DCIS who underwent preoperative 3.0-T breast MRI including dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) and who underwent surgery between June 2019 and March 2020 were retrospectively identified (development set) from an academic medical center. The apparent diffusion coefficients of lesions from DWI, lesion size and morphologic features on DCE MRI scans, mammographic findings, age, symptoms, biopsy method, and DCIS grade at biopsy were collected. The presence of invasive cancer and axillary metastases was determined with surgical pathology. A predictive model for upstaging was developed by using multivariable logistic regression and validated in a subsequent prospective internal validation set recruited between July 2020 and April 2021. Results Fifty-seven (41%) of 140 women (mean age, 53 years ± 11 [SD]) in the development set and 43 (41%) of 105 women (mean age, 53 years ± 10) in the validation set were upstaged after surgery. The predictive model combining DWI and clinical-pathologic factors showed the areas under the receiver operating characteristic curve at 0.87 (95% CI: 0.80, 0.92) in the development set and 0.76 (95% CI: 0.67, 0.84) in the validation set. The predicted probability of invasive cancer showed good interobserver agreement (intraclass correlation coefficient, 0.79); the positive predictive value was 85% (28 of 33), and the negative predictive value was 92% (22 of 24). Conclusion A predictive model based on diffusion-weighted breast MRI identified women at high risk of upstaging. © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Baltzer in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

Spontaneous regression of breast carcinoma: A radio-pathological case report and review of the literature

Spontaneous regression (SR) is defined as complete or partial disappearance of a proven malignant tumor without adequate medical treatment. Although there have been reports on SR of breast cancers, this phenomenon remains rare. We report a case of SR of breast cancer in a 62-year-old woman who presented to our hospital with a few months history of a painless breast lump. Initial radiological investigations reveal a suspicious mass in the left upper outer quadrant. Histopathology confirms the presence of invasive cancer. The patient initially refused any surgical or medical interventional and defaulted follow-up. The patient presented again after four months with consent for surgical treatment. Repeat ultrasound just before the hook wire localization procedure demonstrated the absence of tumor in the region of interest. The subsequent repeat mammogram and MRI also demonstrated complete regression of breast cancer. MRI however, does reveal a suspicious left axillary lymph node, which was also deemed suspicious on PET-CT. In view of these findings, the patient was counsel for surgery. The exact mechanism of SR of cancer remains unclear in our patient. We are unable to identify the exact mechanism triggering and influencing the SR in our patient. Our hypotheses include substance within the herbal remedies or a carcinoma-directed immune response triggered by the biopsy. Further research is needed to determine causes for spontaneous regressions of cancer and towards finding a possible cure for cancer.

Preoperative Magnetic Resonance Imaging Features Associated with Positive Resection Margins in Patients with Invasive Lobular Carcinoma.

ObjectiveTo investigate preoperative magnetic resonance imaging (MRI) findings associated with resection margin status in patients with invasive lobular carcinoma (ILC) who underwent breast-conserving surgery.Materials and MethodsOne hundred and one patients with ILC who underwent preoperative MRI were included. MRI (tumor size, multifocality, type of enhancing lesion, distribution of non-mass enhancement [NME], and degree of background parenchymal enhancement) and clinicopathological features (age, pathologic tumor size, presence of ductal carcinoma in situ [DCIS] or lobular carcinoma in situ, presence of lymph node metastases, and estrogen receptor/progesterone receptor/human epidermal growth factor receptor type 2 status) were analyzed. A positive resection margin was defined as the presence of invasive cancer or DCIS at the inked surface. Logistic regression analysis was performed to determine pre- and postoperative variables associated with positive resection margins.ResultsAmong the 101 patients, 21 (20.8%) showed positive resection margins. In the univariable analysis, NME, multifocality, axillary lymph node metastasis, and pathologic tumor size were associated with positive resection margins. With respect to preoperative MRI findings, multifocality (odds ratio [OR] = 3.977, p = 0.009) and NME (OR = 2.741, p = 0.063) were associated with positive resection margins in the multivariable analysis, although NME showed borderline significance.ConclusionIn patients with ILC, multifocality and the presence of NME on preoperative breast MRI were associated with positive resection margins.

Natural history of cervical intraepithelial neoplasia in pregnancy: postpartum histo-pathologic outcome and review of the literature.

BackgroundTo study the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy and to compare the rates of persistence, progression and regression of CIN by colposcopically guided biopsy (CGB) during pregnancy with outcome in non-pregnant-women.MethodsA retrospective analysis of all pregnant women diagnosed with CIN at our outpatient clinic between 2005 and 2010 was performed. A CGB for histo-pathological analysis was obtained in all participants and observational management was performed. The histo-pathologic findings of initial and postpartum visits were collected. Rates of persistence, progression and regression of CIN were assessed. Results were compared to a matched control group of non-pregnant women where observational management was performed for at least three months. In addition a review of the literature and pooled analysis of published data was performed.ResultsA total of 51 pregnant women with CIN were included into analysis. CIN 1, 2, and 3 was diagnosed by CGB in 33.3, 13.7 and 52.9 % of all pregnant women, respectively. The postpartum histo-pathologic evaluation of the pregnant cohort revealed a significantly higher tendency to spontaneous regression (56.9 versus 31.4 %, p = 0.010) and a considerably, but not significantly higher complete remission rate (41.2 versus 27.5 %, p = 0.144) when compared to the non-pregnant cohort. In addition, we observed a significantly lower CIN persistence rate than in the non-pregnant cohort (39.2 versus 58.8 %, p = 0.048). The progression rate was notably low in the pregnant cohort (3.9 %) and no progression to invasive cancer was observed.ConclusionsCIN lesions show considerably high spontaneous regression rates postpartum. Once presence of invasive cancer is ruled out definitive treatment can be deferred to the postpartum period.

Abstract P2-12-22: Atypical ductal hyperplasia and breast cancers - A ten year clinical and pathological review on core biopsy, lumpectomy and mastectomy specimens

Abstract Introduction Atypical ductal hyperplasia (ADH) is known to be associated with underlying pre-malignant or malignant breast conditions. Here we report our 10-year data on ADH found in core biopsy, lumpectomy and mastectomy specimens Methods From 1st January 2005 to 31st December 2014, a total of 104 core needle biopsy specimens and 218 lumpectomy / mastectomy specimens were found to contain ADH. Clinical, radiological and pathology data were retrieved and analysed from a prospectively-maintained database. Results Out of the 104 patients with core biopsy showing ADH, 101 patients received excision and 3 refused operation. 34 patients turned out to have ductal carcinoma in-situ (DCIS) on excision, while 6 had invasive ductal carcinoma (IDC), 1 had lobular carcinoma in-situ (LCIS) and 1 had angiosarcoma resulting in an upstaging rate of 40.4% (42/104). The remaining patients had benign lesions including papillary lesions, fibrocystic disease, or ADH alone. Multivariate analysis found that the only correlating factor for the presence of DCIS or IDC was suspicious mammographic features (BIRADS 4 or above) (P = 0.008 and 0.02 respectively) but not other parameters such as extent of micro-calcifications (P = 0.12) or age (P = 0.11). Histopathological diagnosis after excision of lesions containing ADH on core biopsyExcisional Biopsy ResultNumber (%)DCIS34 (32.7%)ADH32 (30.8%)Benign27 (26%)IDC6 (5.8%)LCIS1 (0.9%)Angiosarcoma1 (0.9%)Refuse operation3 (2.9%) 218 lumpectomy or mastectomy specimens were found to harbor ADH. 62 (28.4%) had co-existing pre-malignant or malignant breast diseases. The only determining factor for the presence of malignant or pre-malignant condition was suspicious breast imaging features (BIRADS 4 or above) after multivariate analysis (P = 0.0003). Co-existing conditions in the lumpectomy / mastectomy specimens with ADHCo-existing Patholog(ies)Number (%)Atypical Ductal Hyperplasia alone97 (44.4%)Fibroadenoma / Fibrocystic disease31 (14.2%)Intraductal papilloma22 (10%)Phyllodes tumor6 (2.8%)Ductal carcinoma in-situ36 (16.5%)Invasive ductal carcinoma23 (10.6%)Lobular carcinoma in-situ1 (0.5%)Invasive lobular carcinoma1 (0.5%)Malignant phyllodes tumor1 (0.5%) Conclusion ADH is closely related to the presence of invasive cancer or DCIS especially when suspicious breast imaging features are present. The upstaging rate is still high in patients where initial biopsy was ADH. Citation Format: Co M, Kwong A. Atypical ductal hyperplasia and breast cancers - A ten year clinical and pathological review on core biopsy, lumpectomy and mastectomy specimens. [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 P2-12-22.

Risk factors for postoperative recurrence of intraductal papillary mucinous neoplasms of the pancreas based on a long-term follow-up study: proposals for follow-up strategies.

The aim of this study was to examine the associations between postoperative clinicopathological features of intraductal papillary mucinous neoplasm (IPMN) and recurrence over a long follow-up period. We retrospectively assessed 153 IPMN patients who underwent resection. The resected tumors showed low/intermediate-grade dysplasia (LGD/IGD), high-grade dysplasia (HGD), T1a (stromal invasion ≤5 mm), and invasive intraductal papillary mucinous carcinoma (IPMC), in 54.9%, 22.2%, 4.6%, and 18.3% of patients, respectively. The median follow-up period after surgery was 46.4 (6.0-216.3) months, with an overall recurrence rate of 17.0%; the recurrence rates by histological type were 6.0%, 5.9%, 42.9%, and 57.1% for LGD/IGD, HGD, T1a, and invasive IPMC, respectively. Multivariate analysis revealed that recurrences related with tumor location, mural nodule size, presence of invasive cancer, lymph node metastasis, IPMN in the remnant pancreas, and main pancreatic duct dilatation after surgery. Recurrence occurred within the remnant pancreas in all LGD-T1a patients and as extrapancreatic metastasis in all patients with invasive IPMC. Of the total recurrences, 15.4% occurred over 5 years postoperatively. The postoperative follow-up protocol for patients with LGD-T1a should be similar to non-resected IPMN, and that for invasive IPMC should be the same as for pancreatic ductal adenocarcinoma patients.

Preoperatively diagnosed ductal cancers in situ of the breast presenting as even small masses are of high risk for the invasive cancer foci in postoperative specimen.

BackgroundIn ductal carcinoma in situ of the breast (DCIS), histologic diagnosis obtained before the definitive treatment is related to the risk of underestimation if the presence of invasive cancer is found postoperatively. These patients need a second operation to assess the nodal status. We evaluated the upstaging rate in patients with mass-forming DCIS.MethodsSixty-three women with pure DCIS presenting as sonographic mass lesion underwent vacuum-assisted or core-needle biopsy and subsequent surgery. Rates of postoperative upstaging to invasive cancer were calculated and compared with clinical character and size of DCIS.ResultsMedian age of patients (range) was 63 years (27–88) while median diameter of DCIS was 11 mm (6–60). Fifty-six percent of DCIS were upstaged. Patient age did not differ significantly between groups with and without final invasion (median, mean, SD): 63, 61.4, 12.5 vs 62, 61.2, 10.6 years, respectively (P = 0.659). The difference of DCIS size between these groups was statistically important (median, mean, SD): 13, 17.3, 11.4 vs 9.5, 9.8, 3.2 mm, respectively (P = 0.0003). Mass size and palpability were significant risk factors (P < 0.001 and P < 0.01, respectively). Rate of underestimation for mass with diameter ≤10 mm, 10–20 mm and >20 mm was 37, 64 and 91 %, respectively.ConclusionsDCIS diagnosed on minimal-invasive biopsy of even small sonographic mass is of high risk for the upstaging to invasive cancer after final surgical excision. In these patients, subsequent intervention is needed for nodal status assessment. They are good candidates for the sentinel node biopsy during the breast operation to avoid multi-step surgery.

Abstract P1-15-02: Utilization of hypofractionated radiation therapy for early stage breast cancer in women over 50 years of age

Abstract Purpose: Hypofractionated whole breast irradiation (HF-WBI) following breast conserving surgery for early stage breast cancer is now recommended for women over 50 years of age by the American Society for Radiation Oncology (ASTRO). Herein, we explored the rate of HF-WBI utilization and its associated patterns of care using the National Cancer Data Base (NCDB), a comprehensive oncology outcomes database which captures 70% of all newly diagnosed cancer patients in the US. Methods: We utilized NCDB to identify women aged ≥50 diagnosed with T1N0/T1Nx invasive breast cancer or Tis (DCIS) who underwent breast conserving surgery and adjuvant whole breast external beam radiation therapy. HF-WBI was defined when a definitive radiation dose (≥40 Gy) was delivered in ≤23 fractions. We evaluated factors associated with the use of HF-WBI through exploratory univariate and multivariable analyses. Results: A total of 311,071 patients from 1998-2011 met inclusion criteria. The commonest HF-WBI regimen was 42.56 Gy in 16 fractions. The rate of HF-WBI utilization increased over time from 0.4% in 1998 to 16.5% in 2011 (p&amp;lt;0.001). HF-WBI was delivered more often for women of advancing age. In 2011, HF-WBI was delivered in 10.0%, 14.2%, 24.2% and 35.6% of women in their 50’s, 60’s, 70’s and 80+ (p&amp;lt;0.001). Multivariable analysis correlated significantly increased use of HF-WBI with (in order of association): later year of diagnosis, advancing age (decade), treatment in academic center, regional location in US, lower grade of disease, white race, residence in a higher income area (p&amp;lt;0.001), greater comorbidity score (p&amp;lt;0.03), presence of invasive cancer (p&amp;lt;0.01), right-sided disease (p&amp;lt;0.01), and greater distance from reporting facility (p&amp;lt;0.001). Factors Associated with Increased Use of HF-WBIAssociation with HF-WBIOdds Ratio of HF-WBI Use (95% confidence interval)Year of Diagnosis (2011 vs. prior to 2009)7.14 (6.85-7.52)Age (Decade, 80+ years)6.45 (6.06-6.90)Facility Type: Academic4.00 (3.69-4.33)Location (Mountain Region)1.82 (1.68-1.97)Grade 11.40 (1.33-1.47)Race: White1.38 (1.25-1.53)Income Quartile 4 (&amp;gt;$46K/year)1.30 (1.21-1.40)Comorbidity Index (High, 2)1.15 (1.02-1.31)Invasive Cancer1.09 (1.04-1.14)Laterality (Right Side)1.05 (1.02-1.09)Distance from Treatment Facility1.002 per mile (1.002-1.002) Conclusions: This comprehensive patterns of care study of HF-WBI in women ≥50 years old with early stage breast cancer from a national database identified a substantial increase in the utilization of this technique with time. Advancing patient age and treatment at academic facility were also strong predictors of delivery of HF-WBI. Disparities in utilization of HF-WBI and overall employment of this technique, even in later years, remain suboptimal. Strategies to identify and break barriers to the adoption of HF-WBI should be explored. Citation Format: Malolan S Rajagopalan, Craig Lehocky, John C Flickinger, Dwight E Heron, Paniti Sukumvanich, Joseph L Kelley, Gretchen M Ahrendt, Sushil Beriwal. Utilization of hypofractionated radiation therapy for early stage breast cancer in women over 50 years of age [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 P1-15-02.

For "difficult" benign colorectal lesions referred to surgical resection a second opinion by an experienced endoscopist is mandatory: A single centre experience.

To assess how many patients with benign "difficult" colorectal lesions (DCRLs) referred to surgical resection, may be treated with endoscopic resection (ER) rather than surgical resection. The prospectively collected colonoscopy database of our Endoscopic Unit was reviewed to identify all consecutive patients who, between July 2011 and August 2013, underwent an endoscopic re-evaluation before surgical resection due to the presence of DCRLs with a histological confirmation of benignancy on forceps biopsy. ER was attempted when the lesion did not have definite features of deeply invasive cancer. The "nonlifting sign" excluded ER only in naive lesions without a prior attempted resection. Lesions were classified, using the Kyoto-Paris classification for mucosal neoplasia. For sessile and non-polypoid lesions the "inject and cut" resection technique was used. Pedunculated and semi-pedunculated lesions were transected at the stalk just below the polyps head and before or after resection, metal clips or a loop were applied on the stalk to prevent bleeding. The lesions were histologically classified according to the Vienna criteria and for the pedunculated lesions the Haggitt classification was used. Eighty-two patients (42 females, mean age 62 years) with 82 lesions (mean size 37 mm) were included in the study. Sixty-nine (84%) lesions were endoscopically resected, while 13 underwent surgical resection since ER was deemed unsuitable. On histology, cancer was found in 21/69 lesions (14 intra-mucosal, 7 sub-mucosal) and was associated with the size (P < 0.001) and with type 0-IIa +Is (P = 0.011) and 0-IIa + IIc (P < 0.001) lesions. All patients with sub-mucosal cancer, underwent surgical resection. Complications occurred in 11/69 patients (7 bleedings, 2 transmural burn syndromes, 2 perforations), all managed endoscopically or conservatively, and were associated with presence of invasive cancer (P = 0.021). During follow-up recurrence/residual tissue was found in 14/51 sessile or non-polypoid lesions (13 treated endoscopically, 1 underwent surgical resection) and was associated with type 0-IIa + Is lesions (P = 0.001), piecemeal resections (P = 0.01) and with lesion size (P = 0.004). Overall, 74% of patients avoided surgery. Surgical resection was significantly associated with type 0-IIa + Is (P = 0.01) and 0-IIa + IIc (P = 0.001) lesions, with sub-mucosal invasion on histology (P < 0.001), with presence of the "nonlifting sign" (P < 0.001), and related to the dimension of the lesions (P = 0.001). In the logistic regression analysis, the only independent predictor for surgical resection was the dimension of the lesions (P = 0.002). Before submitting patients to surgical resection for a benign DCRL, a second opinion by an experienced endoscopist is mandatory to avoid unnecessary surgery.

Predictive biomarkers of invasive carcinoma on excision in patients with a diagnosis of ductal carcinoma in situ of the breast by needle biopsy.

e12029 Background: DCIS diagnosed on needle biopsy may underestimate the presence of invasive cancer identified on subsequent excision. This study aims to identify clinicopathologic factors from pr...

Abstract P5-16-04: Predictive biomarkers for invasion on final pathology in patients with preoperative diagnosis of ductal carcinoma in situ of the breast by needle biopsy

Abstract Background Predictors of synchronous invasive breast cancer in patients diagnosed with only ductal carcinoma in situ (DCIS) in pre-operative needle biopsies have not been well-defined. Establishing such predictors of invasion has potential to significantly alter management by identifying those patients for whom surgery may be avoidable en lieu of conservative management. This study aims to identify clinicopathologic factors from pre-operative needle biopsies that are predictive of invasive cancer on subsequent surgical excision. Methods The study population consisted of 69 breasts from 67 patients initially diagnosed with only DCIS on needle biopsy (core needle or mammotome) at St. Luke's International Hospital, Japan from 2006 until 2008. Parameters analyzed included presenting clinical features, DCIS nuclear grade and morphologic pattern, and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor-2 (HER2), Ki-67 antigen, p16, p53 and cyclooxygenase-2 (COX2) in biopsy specimens. These immunohistochemical markers were previously identified to foretell invasive carcinoma subsequent to DCIS (Kerlikowske, JNCI 2010). Associations between clinical, pathological, and immunohistochemical findings in initial biopsy specimens and the presence of invasive cancer on subsequent excision were analyzed for significance using univariate and multivariate analysis. Results Of 69 breasts with only DCIS on initial needle biopsy, subsequent surgical excision revealed pure DCIS in 46 (66.7%), microinvasive carcinoma in 4 (5.8%), and invasive carcinoma in 19 (27.5%) cases. Sentinel node biopsy was performed in 57 (82.6%) of 69 cases, and 53 (93.0%) of these showed no evidence of lymph node metastases. All 4 cases with lymph node metastases revealed invasive carcinoma in surgical excisions. By univariate analysis, pre-operative factors significantly associated with invasion on surgical excision included detection of a lump by palpation (p&amp;lt;0.05), sampling by core needle biopsy rather than mammotome (p&amp;lt;0.01), p53 positivity (p&amp;lt;0.01), and lack of ER expression (p&amp;lt;0.05) in needle biopsy samples. Combined absence of p16 and COX2 with low Ki-67 expression in needle biopsies was associated with pure DCIS (and absence of invasive cancer) in surgical excisions (p&amp;lt;0.05). Multivariate analysis using all five significant univariate variables revealed two independent pre-operative predictors of invasive cancer on final pathology, namely sampling by core needle biopsy (odds ratio 7.0; 95% CI 1.2-41.7; p&amp;lt;0.05) and p53 positivity (odds ratio 7.1; 95% CI 1.1-44.9; p&amp;lt;0.05). Conclusion If confirmed in a larger sample, predictive clinical and biomarker parameters can help identify those patients diagnosed with only DCIS in needle biopsy who are at high risk of harboring unsampled invasive cancer on final pathology. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-16-04.

Features of Occult Invasion in Biopsy-Proven DCIS at Breast MRI

The purpose of this study is to determine if MRI BI-RADS criteria or radiologist perception correlate with presence of invasive cancer after initial core biopsy of ductal carcinoma in situ (DCIS). Retrospective search spanning 2000-2007 identified all core-biopsy diagnoses of pure DCIS that coincided with preoperative MRI. Two radiologists fellowship-trained in breast imaging categorized lesions according to ACR MRI BI-RADS lexicon and estimated likelihood of occult invasion. Semiquantitative signal enhancement ratio (SER) kinetic analysis was also performed. Results were compared with histopathology. 51 consecutive patients with primary core biopsy-proven DCIS and concurrent MRI were identified. Of these, 13 patients (25%) had invasion at excision. Invasion correlated significantly with presence of a mass for both readers (p = 0.012 and 0.001), rapid initial enhancement for Reader 1 (p = 0.001), and washout kinetics for Reader 2 (p = 0.012). Significant correlation between washout and invasion was confirmed by SER (p = 0.006) when threshold percent enhancement was sufficiently high (130%), corresponding to rapidly enhancing portions of the lesion. Radiologist perception of occult invasion was strongly correlated with true presence of invasion. These results provide evidence that certain BI-RADS MRI criteria, as well as radiologist perception, correlate with occult invasion after an initial core biopsy of DCIS.

Abstract P4-14-10: Atypical Ductal Hyperplasia diagnosed on directional vacuum-assisted biopsy: is surgical excision mandatory?

Abstract Background: The incidence of atypical ductal hyperplasia (ADH) is increasing due to mass screening. Because of the underestimation risk of malignancy, the management remains controversial. Our goal was to analyze clinicopathologic features of patients with ADH diagnosed on directional vacuum-assisted biopsy (DVAB). The objectives of this continuous retrospective study were to evaluate the underestimation rate of malignancy and to identify predictors of upgrade to carcinoma. Methods: Between 2003 and 2010, 3159 patients underwent stereotactic DVAB in our institute. We retrospectively evaluate clinical, mammographic and pathological features of 298 cases of ADH who underwent surgical excision in our center (93.1%). Patients with concurrent history of breast cancer, intraductal carcinoma (DCIS) associated, or with no follow-up or surgical excision on place were excluded. Histological scar of macrobiopsy was systematically searched in surgical specimens. A pathologic upgrade was defined by presence of invasive cancer or DCIS on surgical specimen. Statistical tests used were the chi-square or Fisher's exact test. Results: Among the 298 studied DVAB, 224 ADH were isolated (75.2%), 46 associated to flat epithelial atypia (15.4%) and 28 to lobular neoplasia (9.4%). 98.4% patients presented microcalcifications at diagnosis. In 52 cases, lesions were upgraded to DCIS (n = 38) or invasive cancer (n = 14). The underestimated rate was 17.5%. In 67.3% cases, upgrade lesions were low or intermediate grade DCIS. Only the history of contralateral breast cancer was significantly correlated with the underestimated rate (p = 0.04). There was no statistical difference between these 52 cases and the 246 others for: family history, size of calcification, sampling number, histological lesion, and quality of calcifications removal. Conclusions: In this study, DVAB may not be considered a therapeutic procedure in case of ADH, even in the case of complete removal of microcalcifications. It is still challenging to identify a subgroup of ADH cases with a low upgrade rate. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-10.

Abstract 1757: Patterns of clonal chromosomal aberrations in invasive breast cancer compared to adjacent DCIS lesions detected by a ten-probe FISH panel

Abstract Ductal carcinoma in situ (DCIS) refers to lesions with malignant epithelial cells that have not invaded the surrounding stroma. These lesions are confined to the ducts of the breast. It is thought that DCIS represents a stage that precedes invasive ductal carcinoma (IDC). However the linkage between these two lesions is still obscure. In order to analyze the patterns of genetic alterations as an approach to understand the correlation between DCIS and IDC, we developed four panels of FISH probes consisting of a total of eight gene specific probes and two centromeric probes and conducted a systematic FISH evaluation of breast tumor specimens containing both lesions. The gene probes tested for oncogenes and tumor suppressor genes specific for breast tumorigenesis while the centromeric probes were included to reflect and adjust for the ploidy of the cells. Objectives Determine gain and loss patterns of the oncogene and tumor suppressor gene probes within DCIS and IDC Compare similarities in the genetic make-up of DCIS and corresponding IDC lesions from the same case Characterize clonal evolution from DCIS lesions to IDC The database of the “Breast Susceptibility Study” conducted at the Naval Medical Center, Bethesda, Maryland was searched for patients whose pathology reports were positive for breast carcinoma with neighboring DCIS. Archived paraffin blocks were analyzed by a pathologist for the presence of invasive cancer and DCIS. Representative areas were marked on thick sections. The material was micro-dissected and disintegrated using the Hedley method. The resulting single cell suspensions were cytospun onto slides. The best cytospin for each lesion was. hybridized with four FISH probe panels subsequently. An Imaging relocation software allowed us to assess the same cells for all four sets of probes. For each lesion, manual counting of 150-200 nuclei was performed and tabulated into an excel spreadsheet to allow analysis of signal patterns. In collaboration with NCBI, algorithms were developed to compare clonal patterns. Preliminary data show that there are often major clones both in the DCIS and the IDC that present strong similarities to each other. However, the clones can differ in specific gains or losses of the oncogenes and tumor suppressor genes tested. The signals depicted in the table represent an attempt to delineate major clones within the DCIS and IDC populations. This study will improve our understanding of the molecular events that are involved in the progression from pre-invasive to invasive cancer and may lead to the development of prognostic biomarkers that can predict this transition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1757.

The impact of preoperative magnetic resonance imaging on surgical planning for women with ductal carcinoma in situ.

Abstract Abstract #1163 Background: Ductal carcinoma in situ (DCIS) accounts for about 20% of all female breast cancers and is now diagnosed 10 times more frequently than prior to the use of increased screening mammography. Although magnetic resonance imaging (MRI) has proven to be a useful imaging modality for invasive cancer, its role and impact in preoperative surgical planning for DCIS is unclear. Our aim is to determine if women diagnosed with pure DCIS on core-biopsy who have preoperative MRI are more likely to undergo mastectomy and sentinel lymph node biopsy (SLNB). Methods: Retrospective survey of women diagnosed with pure DCIS on stereotactic core biopsy between 2000-2007 at an academic tertiary referral center. All women underwent definitive surgical treatment for DCIS. Patient characteristics, surgical planning and surgical outcomes were compared between patients who underwent preoperative MRI and those without MRI. Continuous variables among the two groups were compared using the t-test. Differences in dichotomous variables between groups were compared using the chi-square test. Significance was determined if p&amp;lt;0.05. Results: Of 137 women diagnosed with DCIS, 39 underwent preoperative MRI. Mean age, DCIS size and grade, and presence of invasive cancer on surgical specimen were compared between the two groups. The only significant difference between the two groups was younger mean age in the group with preoperative MRI (51 vs 59 yrs, p=0.001). On univariate analysis, mastectomy and SLNB were more commonly employed in the MRI group. The mastectomy rate was 55% for women who had preoperative MRI and 17% for those who did not (p&amp;lt;0.0001). The SLNB rate was 46% for women had preoperative MRI and 23% for those who did not (p=0.009). Number of re-excisions, margin status and size were compared between the two groups. Preoperative MRI was not significantly associated with wider surgical margins or higher proportion of patients with negative margins. However, the mean number of re-excisions was lower in women who underwent preoperative MRI (0.7 vs. 1.2, p=0.003). The only independent factor associated with likelihood of preoperative MRI in the setting of DCIS was patient age. On multivariate analysis, use of SLNB was independently associated with mastectomy, DCIS size and DCIS grade (p=0.0001, p=0.011, p=0.024, respectively). In contrast, independent predictors of mastectomy were DCIS size and use of MRI (OR 5.1, 95% CI 2.0-13.2)). Conclusion: Women who underwent preoperative MRI for DCIS were younger and more likely to undergo mastectomy. However, women who had preoperative MRI required a lower number of re-excisions to obtain negative margins. Our study cannot address whether the strong association between preoperative MRI and mastectomy is a causal one. Nevertheless our data support a critical need for future studies to further define the benefit as well as consequences of the use of MRI for DCIS evaluation and treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1163.

Sonographic lesion size of ductal carcinoma in situ as a preoperative predictor for the presence of an invasive focus

To investigate the preoperative factors associated with upstage to invasive cancer in patients with core needle biopsy (CNB) diagnosis of ductal carcinoma in situ (DCIS) by ultrasound guidance alone. Between 2000 and 2007, 201 patients with DCIS diagnosed at 11- or 14-gauge CNB by ultrasound guidance alone were examined. Preoperative factors were all analyzed to correlate with the presence of invasive cancer after definitive resection. The Pearson chi-square test and stratified analysis with the Mantel-Haenszel chi-squire test were used to assess the association between the preoperative factors and upstage to invasive cancer. Compared with the overall underestimation rate (84 of 201, 41.8%), 47 (60.3%) of 78 patients with abnormal breast palpation, 46 (55.4%) of 83 patients with mammographic finding of a mass lesion, and 38 (67.9%) of 56 patients with a sonographic lesion size >20 mm had invasive cancer components on the final pathology review (Odds ratio [OR] = 2.45; P = 0.04, OR = 3.66; P = 0.002, and OR = 4.13; P = 0.002 respectively). A sonographic lesion size >20 mm can be used as another guideline for surgeons to consider sentinel lymph node biopsy in patients with DCIS diagnosed by a sonographically guided CNB.

Is early postradiation dysplasia almost associated with poor prognosis? A case report and review of the literature

Following radiotherapy for cervical carcinoma, abnormal cytologic changes have been reported in a number of publications. These reactions occur at varying periods of time following irradiation and do not necessarily reflect the presence of invasive cancer. On the basis of cytologic and histopathologic features, these reactions were determined as postradiation dysplasia (PRD). PRD has been reported to occur in 18.7-26% of patients treated by radiotherapy for cervical cancer. In the literature, it was reported that patients diagnosed with PRD less than 3 years after the initial diagnosis of cervical cancer had a mean survival rate of 33.8% as compared with a 100% 5-year survival rate in patients with a delayed (>3 years) onset of period. We present a case of stage IIIB cervical squamous cell carcinoma with PRD detected 6 months after radiotherapy. The patient is still tumor free 8 years after radiotherapy. In the light of this patient, we review the literature and discuss the relationship of PRD with survival in the cervical carcinomas.