Diagnosis Of Lobular Carcinoma In Situ Research Articles

Abstract ED02-02: The Challenges of Lobular Carcinoma

Abstract Infiltrating lobular carcinoma (ILC) and lobular carcinoma in situ (LCIS) were first described in the1940s by two Memorial Hospital pathologists, Foote and Stewart. They were most intrigued by the infiltrative appearance of these lobular cancers which they described as demonstrating large numbers of isolated, loose or dyscohesive cells of rather uniform size but of varying shape. We now recognize that this dyscohesive growth pattern is the result of loss of a functional e-cadherin protein; a distinguishing feature between ILC and invasive ductal carcinoma (IDC). Several studies comparing clinical features and outcomes between ILC and IDC have generated consistent findings. Lobular cancers are more likely to be ER+, larger, lower grade, less likely to be detected on MMG and more likely to have positive margins at breast conserving surgery (BCS), or to require mastectomy. Yet importantly, if BCS is successful, local recurrence and rates of contralateral breast cancer are equal for ILC and IDC. Although lobular cancers represents only 5-15% of all breast cancer, numerically, if ILC was an independent cancer in women, it would rank as the 6th most common cancer in women. Notably the incidence of ILC rose sharply in the late 80s throughout the 90s, and it has become clear that there is a strong relationship between ILC and hormone replacement therapy. Perhaps the “strongest” risk factor for ILC, is LCIS. Classic LCIS is an incidental finding – there are no pathnogmonic features on breast imaging or gross examination of tissue. On microscopic examination it is often multicentric and bilateral. Although originally considered a precursor to ILC and treated with mastectomy, over the years it was realized that rates of ipsilateral cancer in women who were not treated for LCIS were lower than expected and were quite similar to rates of contralateral breast cancer – and this combined with the fact that only 50% of the cancers were of the lobular phenotype led to a movement to consider LCIS as a high risk lesion. Contemporary data continue to support this management approach as rates of cancer development in women with a diagnosis of LCIS are consistently reported at 1-2% per year and the risk is conferred bilaterally, with a slightly higher representation of ILC in the ipsilateral breast. In this presentation we will review areas of clinical controversy, including the use of MRI, the safety of breast conservation, the role of neoadjuvant chemotherapy and the utility of genomic assays in patients with ILC. Citation Format: T. King. The Challenges of Lobular Carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED02-02.

Immediate and delayed risk of breast cancer associated with classic lobular carcinoma in situ and its variants.

To determine the risk of breast cancer due to lobular carcinoma in situ (LCIS). This retrospective IRB-approved study identified cases of LCIS after percutaneous breast biopsy from 7/2005 to 7/2022. Excluded were cases with less than 2years of imaging surveillance or a concurrent ipsilateral breast cancer diagnosis within 6months of the LCIS diagnosis. Final outcomes of cancer versus no cancer were determined by pathology at surgical excision or the absence of cancer on imaging surveillance. A total of 116 LCIS lesions were identified. The primary imaging findings targeted for percutaneous biopsy included calcifications (50.0%, 58/116), MR enhancing lesions (25.0%, 29/116), noncalcified mammographic architectural distortions (10.3%, 12/116), or masses (14.7%, 17/116). Surgical excision was performed in 49.1% (57/116) and imaging surveillance was performed in 50.9% (59/116) of LCIS cases. There were 22 cancers of which 11 cancers were discovered at immediate excision [19.3% (11/57) immediate upgrade] and 11 cancers developed later while on imaging surveillance [18.6% (11/59) delayed risk for cancer]. Among all 22 cancers, 63.6% (14/22) occurred at the site of LCIS (11 at immediate excision and 3 at surveillance) and 36.4% (8/22) occurred at a location away from the site of LCIS (6 in a different quadrant and 2 in the contralateral breast). LCIS has both an immediate risk (19.3%) and a delayed risk (18.6%) for cancer with 90.9% occurring in the ipsilateral breast (63.6% at and 27.3% away from the site of LCIS) and 9.1% occurring in the contralateral breast.

Abstract P1-22-07: Surgical outcomes of lobular carcinoma in situ diagnosed on core biopsy in Dutch women between 2011 and 2020

Abstract Background Lobular carcinoma in situ (LCIS) can be divided into classic LCIS and pleomorphic LCIS. Current treatment guidelines recommend that pleomorphic LCIS should be treated as a ductal carcinoma in situ (DCIS). This is because of the high upgrade rate to DCIS or invasive carcinoma. Classic LCIS, on the contrary, has a low upgrade rate. Active surveillance, such as an annual mammogram, is sufficient. Widely divergent upgrade rates have been published for both classic and pleomorphic LCIS, probably due to selection bias and the limited number of patients included in each study. We report a population based study in patients with a biopsy-based diagnosis of LCIS. Methods In this retrospective nationwide cohort study, patients with a primary diagnosis of LCIS in the period from 2011 to 2020 were identified. Patients with a concurrent high-risk lesion or with a history of a high-risk lesion in the same breast were excluded. Data were received from the Dutch Pathology Registry. In addition to classic LCIS and pleomorphic LCIS, there was a residual group of non-classical LCIS. Results 1185 biopsies from 1183 patients were included in the study. All patients were female. In two patients, the LCIS was bilateral. 1024 biopsies contained classic LCIS, 130 pleomorphic LCIS, and 31 non-classic LCIS. The mean age was 54.7 years for classic LCIS, 60.8 for pleomorphic LCIS, and 60.6 for non-classic LCIS. Of the classic LCIS patients 18.4% underwent surgery. This was 83.1% for pleomorphic LCIS and 83,9% for non-classic LCIS. Of the classic LCIS , 34.0 % had an upgrade to invasive carcinoma or DCIS. This was 31.5 % for pleomorphic LCIS and 30.8 % for non-classic LCIS. A high incidence of invasive lobular cancer (ILC) was found with the invasive cancers being predominantly ER positive and HER2 negative (table). Conclusions Between 2011 and 2020, the incidence of biopsies with LCIS was 119 per year (For comparison, the annual incidence of DCIS biopsies is approximately 2500 per year). Of all biopsies, approximately 11 % were pleomorphic LCIS. Approximately 2.5 % of all biopsies were non-classic LCIS. The upgrade rate for classic LCIS, pleomorphic LCIS, and non-classic LCIS was comparable, however the operation rates were not comparable. In contrast to pleomorphic and non-classic LCIS, only selected cases of classic LCIS were followed up with surgical operation. Surgical outcomeClassic LCISPleomorphic LCISNon-classic LCISTotalP-valueN=188N=108N=26N=322Mean Age (SD)54.4 (9.3)60.6 (8.6)60.4 (6.8)57.0 (9.3)Type surgery N (%)0.269Lumpectomy158 (84.0)83 (76.9)23 (88.5)264 (82.0)Ablation30 (16.0)25 (23.1)3 (11.5)58 (18.0)Upgraded N (%)0.915Yes64 (34.0)34 (31.5)8 (30.8)106 (32.9)No124 (66.0)74 (68.5)18 (69.2)216 (67.1)Type upgrade N0.815DCIS187126classic ILC3623564Pleomorphic ILC0101Invasive carcinoma NST82212Tubular carcinoma1101Papillary carcinoma1001 Citation Format: Pieter J Westenend, Crystal Kerkhoven, Claudia JC Meurs, Sabine Siesling. Surgical outcomes of lobular carcinoma in situ diagnosed on core biopsy in Dutch women between 2011 and 2020 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-07.

Comparison of Outcomes for Classic-Type Lobular Carcinoma In Situ Managed with Surgical Excision After Core Biopsy Versus Observation.

Studies report low upgrade rates following excision for classic-type lobular carcinoma in situ (LCIS) with radiologic-pathologic concordance. Thus, in the absence of other high-risk lesions, observation has become standard. We report long-term outcomes of excision versus observation following a core biopsy diagnosis of classic-type LCIS. Women with LCIS treated from 2013-2020 and managed with excision or observation were identified from a prospective database. Women with cancer upgrade at excision or history of cancer were excluded. We compared rates and characteristics of subsequent breast cancers by clinical management strategy. Of 312 women, 170 (54%) underwent excision and 142 (46%) were managed with observation. Among the excision group, 36 of 170 (21%) had radiologic-pathologic concordant LCIS without other high-risk lesions, mass, or symptoms (concordant LCIS excision group). Overall, at 3.1 years median follow-up, 11 (6.5%) women managed with excision and 11 (7.7%) women managed with observation developed cancer. Cancer development was not associated with management choice (overall excision cohort vs. observation group [p = 0.8]) and did not differ between the concordant LCIS excision and observation groups (p > 0.9). The 5-year cancer development rate was 8.9% (95% confidence interval [CI]: 2.3-31.6%) in the concordant LCIS excision group and 10.3% (95% CI 5.5-18.6%) in the observation group. No difference in breast cancer rates existed among women with a core-biopsy diagnosis of classic-type LCIS managed with excision or observation. These data support management of LCIS as a risk factor, with consideration of chemoprophylaxis, rather than as an indication for surgical excision.

Imaging Spectrum of Lobular Carcinoma In Situ and Correlation with Pathology Findings.

Background Lobular carcinoma in situ (LCIS) is a noninvasive neoplasm that is known to have an increased relative risk for developing subsequent invasive breast carcinoma. Pure LCIS is usually an incidental finding on histopathological examination (HPE) of tissue samples. However, in the recent years, there has been an increasing trend seen in the diagnosis of LCIS. Purpose This article aims to bring out the spectrum of appearances on breast imaging in confirmed cases of pure LCIS on HPE and immunohistochemical. Materials and Methods Cases that were confirmed as pure LCIS on HPE from core or excision biopsy were retrospectively analyzed for abnormalities on breast imaging. Digital breast tomosynthesis mammography was performed with high-resolution ultrasound with elastography for all cases. Magnetic resonance imaging (MRI) was performed in cases wherever indicated, with dynamic postcontrast imaging after injecting intravenous gadolinium. Conclusion LCIS is recognized as an intermediate risk factor for the development of breast cancer. Pure LCIS has varied histology and imaging patterns on mammography, high-resolution ultrasound, and MRI. It is important to recognize the imaging appearances of these lesions to enable the radiologist to detect LCIS early for proper management.

Cancer Progress and Priorities: Breast Cancer.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

Abstract PS8-11: Recruitment strategies for enrollment of high-risk women to a randomized controlled trial of web-based decision support tools to increase breast cancer chemoprevention

Abstract Background: Less than 10 % of those identified as eligible for clinical trials are recruited. Recruitment for chemoprevention trials poses challenges as it is often difficult to identify unaffected patients at high risk for cancer. Barriers to recruitment include personal perceptions of the benefits, fear of trials, low recruitment of minorities, language barriers, transportation costs, and complex study designs. In this study, we identified five potential sources of recruitment that could be collectively leveraged to identify women at high risk for breast cancer to improve recruitment yield. Methods: A total of 300 high-risk women and 50 healthcare providers were recruited and randomized to access web-based decision support tools in combination with standard educational materials or standard educational materials alone. Patient inclusion criteria included: 1) women, age 35-75 years; 2) English or Spanish-speaking; 3) no previous breast cancer diagnosis; 4) no prior use of selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Five broad strategies were considered for identification and recruitment of women at high risk for breast cancer: 1) in-person recruitment during routine screening mammography with survey administration for breast cancer risk assessment according to the Gail model; 2) collection of breast cancer risk factors from the electronic health record (EHR) for risk assessment according to the Breast Cancer Surveillance Consortium (BCSC) risk calculator; 3) identification of women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) using ICD-9/10 diagnostic codes from the EHR; 4) high-risk women with clinic appointments and referred by enrolled providers; 5) women who responded to recruitment flyers and online recruitment distributed throughout the medical center and community. Results: A total of 6229 high-risk women were identified using these recruitment sources, of which 3663 were contacted by email, mailed letter, and/or phone for participation in our clinical trial. Of these contacted women, 16.4% were identified through in-person recruitment during screening mammography, 35.8% through breast cancer risk factors in the EHR, 14.5% had a diagnosis of AH or LCIS identified in the EHR, 28.7% had appointments with enrolled providers, and 4.5% responded to recruitment flyers or online recruitment. Women from the different recruitment sources varied by mean age (64.7 years for mammography and 44.9 years for recruitment flyers), race/ethnicity (73.7% non-white from mammography and 45.5% from breast cancer risk factors in the EHR), and mean 5-year breast cancer risk (2.56% identified from the EHR and 1.34% from recruitment flyers). Of 300 consented patients, 44.7% came from provider referrals (12.7% recruitment yield [number consented/number contacted]) and 27.3% from mammography (13.6% recruitment yield). Comparing enrolled to unenrolled patients, there were significant differences in mean age (57.3 vs. 58.7 years, p=0.027), proportion of non-whites (41.5% vs. 54.7%, p<0.001), and mean 5-year breast cancer risk (3.0% vs. 2.2%, p<0.001). Conclusions: We were able to identify a large cohort of women at high risk from breast cancer from multiple different recruitment sources. Our recruitment yield was highest among direct referrals from healthcare providers and in-person recruitment from mammography. Consented patients tended to be younger, include more non-Hispanic whites, and have a higher risk of breast cancer compared to the overall pool of high-risk women identified. We were able to successfully recruit a racially-ethnically diverse study population to a randomized controlled trial of decision support for breast cancer chemoprevention. Citation Format: Gauri Bhatkhande, Thomas Silverman, Jennie Mata, Ashlee Guzman, Ting He, Jill Dimond, Tarsha Jones, Rita Kukafka, Katherine Crew. Recruitment strategies for enrollment of high-risk women to a randomized controlled trial of web-based decision support tools to increase breast cancer chemoprevention [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-11.

Do Body Mass Index and Breast Density Impact Cancer Risk Among Women with Lobular Carcinoma In Situ?

Both body mass index (BMI) and breast density impact breast cancer risk in the general population. Whether obesity and density represent additive risk factors in women with lobular carcinoma in situ (LCIS) is unknown. Patients diagnosed with LCIS from 1988 to 2017 were identified from a prospectively maintained database. BMI was categorized by World Health Organization classification. Density was captured as the mammographic Breast Imaging Reporting and Data System (BIRADS) value. Other covariates included age at LCIS diagnosis, menopausal status, family history, chemoprevention, and prophylactic mastectomy. Cancer-free probability was estimated using the Kaplan-Meier method, and Cox regression models were used for univariable and multivariable analyses. A total of 1222 women with LCIS were identified. At a median follow-up of 7years, 179 women developed breast cancer (121 invasive, 58 ductal carcinoma in situ); 5- and 10-year cumulative incidences of breast cancer were 10% and 17%, respectively. In multivariable analysis, increased breast density (BIRADS C/D vs. A/B) was significantly associated with increased hazard of breast cancer (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.52-3.88), whereas BMI was not. On multivariable analysis, chemoprevention use was associated with a significantly decreased hazard of breast cancer (HR 0.49, 95% CI 0.29-0.84). Exploratory analyses did not demonstrate significant interaction between BMI and menopausal status, BMI and breast density, BMI and chemoprevention use, or breast density and chemoprevention. Breast cancer risk among women with LCIS is impacted by breast density. These results aid in personalizing risk assessment among women with LCIS and highlight the importance of chemoprevention counseling for risk reduction.

The Tyrer–Cuzick Model Inaccurately Predicts Invasive Breast Cancer Risk in Women With LCIS

The Tyrer-Cuzick model has been shown to overestimate risk in women with atypical hyperplasia, although its accuracy among women with lobular carcinoma in situ (LCIS) is unknown. We evaluated the accuracy of the Tyrer-Cuzick model for predicting invasive breast cancer (IBC) development among women with LCIS. Women with LCIS participating in surveillance from 1987 to 2017 were identified from a prospectively maintained database. Tyrer-Cuzick score (version 7) was calculated near the time of LCIS diagnosis. Patients with prior or concurrentbreast cancer, a BRCA mutation, receiving chemoprevention, or with pleomorphic LCIS were excluded. Invasive cancer-free probability was estimated using the Kaplan-Meier method. A total of 1192 women with a median follow-up of 6years (interquartile range [IQR] 2.5-9.9) were included. Median age at LCIS diagnosis was 49years (IQR 45-55), 88% were white; 37% were postmenopausal, 28% had ≥ 1 first-degree family member with breast cancer, and 13% had ≥ 2 second-degree family members with breast cancer. In total, 128 patients developed an IBC; median age at diagnosis was 54years (IQR 49-61). Five- and 10-year cumulative incidences of invasive cancer were 8% (95% confidence interval [CI] 6-9%) and 14% (95% CI 12-17%), respectively. The median Tyrer-Cuzick 10-year risk score was 20.1 (IQR 17.4-24.3). Discrimination measured by the C-index was 0.493, confirming that the Tyrer-Cuzick model is not well calibrated in this patient population. The Tyrer-Cuzick model is not accurate and may overpredict IBC risk for women with LCIS, and therefore should not be used for breast cancer risk assessment in this high-risk population.

Trends in lobular carcinoma in situ management: endocrine therapy use in California and New Jersey.

The diagnosis of lobular carcinoma in situ (LCIS) is a strong risk factor for breast cancer. Endocrine therapy (ET) for LCIS has been shown to decrease breast cancer risk substantially. The purpose of this study was to evaluate the trends of ET use for LCIS in two large geographic locations. We identified women, ages 18 through 75, with a microscopic diagnosis of LCIS in California (CA) and New Jersey (NJ) from 2004 to 2014. We evaluated trends in unadjusted ET rates during the study period and used logistic regression to evaluate the relationship between patient, tumor, and treatment characteristics, and ET use. We identified 3,129 patients in CA and 2,965 patients in NJ. The overall use of ET during the study period was 14%. For the combined sample, women in NJ were significantly less likely to utilize ET then their counterparts in CA (OR 0.77, CI 0.66-0.90, NJ vs. CA). In addition, patients in the later year period (OR 1.27, CI 1.01-1.59, 2012-2014 vs. 2004-2005) and women who received an excisional biopsy (OR 2.35, CI 1.74-3.17), were more likely to utilize ET. Uninsured women were less likely to receive ET (OR 0.61, CI 0.44-0.84, non-insured vs. insured status). We observed that an increasing proportion of women are using ET for LCIS management, but geographical differences exist. Health insurance status played an important role in the underutilization of ET. Further research is needed to assess patient outcomes given the variations in management of LCIS.

Surgical Management of Lobular Carcinoma In Situ: Analysis of the National Cancer Database.

Current guidelines recommend counseling on risk-reduction strategies, including lifestyle modification, endocrine therapy, and bilateral mastectomy, for patients with classic-type lobular carcinoma in situ (LCIS) detected on core biopsy or surgical excision. Importantly, current diagnosis and treatment guidelines for classic-type LCIS do not include unilateral mastectomy for primary treatment or risk reduction. Prior studies reporting national practice patterns suggest increasing use of mastectomy for management of LCIS, with considerable variation by geographic region. However, these studies did not distinguish between uni- and bilateral mastectomies. This study aimed to investigate national practice patterns and factors associated with unilateral mastectomy. The study used the National Cancer Database to identify women with a diagnosis of LCIS from 2004 to 2013. Descriptive statistics were used to describe surgical treatment, and multinomial logistic regression was used to identify temporal, patient, and facility-level factors associated with receipt of uni- and bilateral mastectomy. The study identified 30,105 women with LCIS. Of these woman, 5.4% received no surgery, 84.8% had surgical excision, 4% underwent unilateral mastectomy, and 5.1% underwent bilateral mastectomy. Adjusted analysis showed that young age, white race, insurance coverage, greater comorbidity, and geographic region (p < 0.001) were associated with receipt of both uni- and bilateral mastectomy. Additionally, more recent year of diagnosis was associated with receipt of bilateral mastectomy. Unilateral mastectomy rates within geographic regions ranged from 2.7% in New England to 8% in the South. Nearly as many patients underwent unilateral (4%) as bilateral mastectomy (5.1%), representing inappropriate care. These findings highlight an opportunity to reduce unnecessary care through improved provider and patient education regarding optimal management of LCIS.

MRI surveillance for women with dense breasts and a previous breast cancer and/or high risk lesion

BackgroundThe role of surveillance breast MRI for women with mammographically dense breasts, a personal history of breast cancer (BC), atypical hyperplasia (AH), or lobular carcinoma in situ (LCIS) is unclear. We estimated the performance of annual surveillance MRI in women with a combination of these risk factors. MethodsWe performed a retrospective review of the clinical, radiological, and pathological parameters of women who received annual concurrent surveillance breast MRI and mammography between 04/2013 and 12/2015 and fulfilled all of the following criteria: 1) age <70; 2) prior diagnosis of AH, LCIS or BC; 3) heterogeneously or extremely dense breast(s); and 4) did not qualify for our provincial breast MRI high risk screening program. ResultsThis study included 198 patients (266 MRI exams). MRI detected 15 cancers: 11 invasive stage I and 4 in-situ. All but 1 were mammographically occult and there were no interval cancers. The cancer detection rate (CDR) and false positive (FP) rate were 6.1% and 21% for round one and 4.7% and 12.5% for round two, respectively. Not being on anti-estrogen therapy and having a 1st degree relative with BC significantly increased the likelihood of tumor detection. ConclusionsThe CDR and FP rate of surveillance MRI in this study were comparable to those reported for women with BRCA mutations. The addition of annual MRI to mammography should be considered for surveillance of women with a combination of these risk factors, particularly if they have a family history of BC and are not on anti-estrogen therapy.

Population-Based Analysis of Breast Cancer Incidence and Survival Outcomes in Women Diagnosed with Lobular Carcinoma In Situ.

A diagnosis of lobular carcinoma in situ (LCIS) is associated with an increased risk of developing breast cancer, although little data exist on long-term patient outcomes, including those who develop subsequent breast malignancies. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women with a histological diagnosis of LCIS between 1983 and 2014. The incidence and clinicopathologic features of subsequent malignancies were then examined, and the Kaplan-Meier method and multivariable Cox PH regression used to obtain breast cancer-specific survival (BCSS) estimates and associated hazard ratios. Overall, 19,462 women swith a mean age at LCIS diagnosis of 53.7years, and a 10- and 20-year cumulative incidence of subsequent breast malignancy of 11.3% [95% confidence interval (CI) 10.7-11.9%] and 19.8% (95% CI 18.8-20.9) met the eligibility criteria. At a median follow-up of 8.1years (range 0-30.9) a total of 1837 primary breast cancers were diagnosed, of which 55.2% were diagnosed in the ipsilateral breast. Most breast cancers were of low/intermediate grade, hormone receptor-positive, and diagnosed in early stages. Of subsequent malignancies, invasive ductal carcinoma (IDC) distributed equally across both breasts, whereas invasive lobular carcinoma (ILC) was more likely to present in the ipsilateral breast (69.0% ILC vs. 49.2% IDC; p<0.001). On multivariable analysis, type of surgical treatment for LCIS had no affect on long-term survival (p=0.44). The 10- and 20-year BCSS for women with LCIS was 98.9 and 96.3%, respectively. Women with LCIS who are diagnosed with a subsequent primary breast cancer are often diagnosed in early stages and have excellent BCSS.

Breast cancer prevention strategies in lobular carcinoma in situ: A decision analysis.

Women diagnosed with lobular carcinoma in situ (LCIS) have a 3-fold to 10-fold increased risk of developing invasive breast cancer. The objective of this study was to evaluate the life expectancy (LE) and differences in survival offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy among women with LCIS. A Markov simulation model was constructed to determine average LE and quality-adjusted LE (QALE) gains for hypothetical cohorts of women diagnosed with LCIS at various ages under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, other-cause mortality and the effectiveness of preventive strategies were derived from published studies and from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Assuming a breast cancer incidence from 1.02% to 1.37% per year under active surveillance, a woman aged 50 years diagnosed with LCIS would have a total LE of 32.78 years and would gain 0.13 years (1.6 months) in LE by adding chemoprevention and 0.25 years (3.0 months) in LE by adding bilateral prophylactic mastectomy. After quality adjustment, chemoprevention resulted in the greatest QALE for women ages 40 to 60 years at LCIS diagnosis, whereas surveillance remained the preferred strategy for optimizing QALE among women diagnosed at age 65 years and older. In this model, among women with a diagnosis of LCIS, breast cancer prevention strategies only modestly affected overall survival, whereas chemoprevention was modeled as the preferred management strategy for optimizing invasive disease-free survival while prolonging QALE form women younger than 65 years. Cancer 2017;123:2609-17. © 2017 American Cancer Society.

Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ.

The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden of mammographically diagnosed cancers, and with a global trend towards more population-based screening, the incidence of these lesions will continue to rise. Because outcomes following treatment for DCIS and LCIS are excellent, there is emerging controversy about what extent of treatment is optimal for both diseases. Here we review the current approaches to the diagnosis and treatment of both DCIS and LCIS. In addition, we will consider potential directions for future management of these lesions.

Abstract P5-17-11: Trends in incidence, patient characteristics, and management of lobular carcinoma in situ

Abstract Introduction: Lobular carcinoma in situ (LCIS) is a rare lesion accounting for only 5% of total breast cancer diagnosis; however, the incidence has continued to increase, albeit at a slower rate than was seen in the 1980s and 1990s. Current National Comprehensive Cancer Network (NCCN) guidelines recommend surgical excision of the breast tissue containing LCIS due to risk of concomitant malignancy, but wide variations in treatment exist. Using the Surveillance, Epidemiology, and End Results (SEER) and National Cancer Database (NCDB) participant user files, an extensive survey of women with LCIS breast cancer was completed. Our aim was to identify patient and facility characteristics that are associated with aggressive treatment (mastectomy) or under-treatment (no surgical excision) following LCIS diagnosis. Methods: Women with a diagnosis of LCIS from 1998 to 2011 within the SEER and NCDB databases were identified. Incidence data was gathered from SEER while all other characteristics (patient, facility, and treatment factors) were obtained from the NCDB. A logistic regression model was created to examine factors associated LCIS treatment modalities recorded in the NCDB. Results: The incidence of LCIS increased from 3.85 to 4.46 / 100,000 women between 2000 and 2011. 62,923 female patients with LCIS were identified within the NCDB. The majority of women diagnosed with LCIS were between the ages of 40 and 59 years (66.8%, N=42,044), white (87.4%, N=55,022), and non-Hispanic (86.9%, N=54,679). Following a diagnosis of LCIS, most women underwent surgical excision (71.1%, N=44,731), with an additional 20.7% undergoing mastectomy (N=13,039) or opting for no surgery (8.0%, N=5,023). Logistic regression analysis demonstrated that age over 60 years was associated with no surgical intervention (OR 1.49, p&amp;lt;0.001), while age 40 to 59 were associated with aggressive therapy (OR 1.19, p&amp;lt;0.001). Economic factors associated with no surgical intervention following LCIS diagnosis include: no insurance (OR 1.24, p&amp;lt;0.001), government sponsored insurance (OR 1.48, p&amp;lt;0.001), live in areas with median income less than $63,000 per year (OR 0.744, p&amp;lt;0.001), and live in an area with higher rates of the population lacking high school education (OR 1.19, p&amp;lt;0.001). Patients undergoing aggressive treatment were more likely to be white (OR 1.57, p&amp;lt;0.001) and carry private insurance (OR 1.87, p&amp;lt;0.001). Patients receiving care at an academic center were more likely to receive aggressive treatment (OR 1.22, p&amp;lt;0.001). Living farther from treatment center was associated with increased odds of aggressive therapy, but not under-treatment (p&amp;lt;0.001 vs p=0.906, respectively). Conclusion: Despite being a rare cancer, the incidence of LCIS continues to rise. LCIS is predominantly a cancer diagnosed in white, non-hispanic women. Advanced age, poverty, lack of insurance, low high school graduation rates were factors significantly associated with under-treatment of LCIS. Conversely, white women between 40-59 yo with private insurance and treated at a cancer center were more likely to undergo aggressive treatment. Citation Format: Johnson AT, Guo X, Nygaard RM, Zera RT. Trends in incidence, patient characteristics, and management of lobular carcinoma in situ. [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 P5-17-11.

Abstract P6-06-02: Germline CDH1 mutations in lobular carcinoma in situ

Abstract BACKGROUND: Germline CDH1 mutations are responsible for the increased risk of both gastric cancer and invasive lobular breast cancer (ILC) in families with hereditary diffuse gastric cancer syndrome; yet germline CDH1 mutations in women with ILC without a family history (FH) of gastric cancer are rare. Lobular carcinoma in situ (LCIS) is both a risk factor and non-obligate precursor of ILC and recent data suggest that germline CDH1 mutations may be present in up to 8% of patients with bilateral LCIS +/- ILC; raising questions about the role of genetic testing in this context. The purpose of this study was to determine the frequency of germline CDH1 mutations in a large prospectively followed cohort of patients with pathologically confirmed bilateral LCIS. METHODS: Patients with a biopsy proven history of LCIS, entering surveillance or presenting for surgery (prophylactic or therapeutic mastectomy), between 2005 and 2013 were prospectively identified and enrolled in IRB approved protocols at Memorial Sloan-Kettering Cancer Center for the collection of tissue and/or germline DNA (IRB 01-135, 99-030). All biopsies were reviewed to confirm LCIS and mastectomy specimens were subject to extensive sampling of all quadrants. Cases with confirmed bilateral LCIS were chosen for the primary analysis. Cases where bilateral mastectomy tissue sampling confirmed only unilateral LCIS were included for comparison. Germline DNA was anonymized and analyzed for CDH1 mutations using targeted capture sequencing with baits for all exons of CDH1 on HiSeq2000. Germline single nucleotide variants were called using GATK HaplotypeCaller and insertions/deletions by Varscan and Scalpel. Mutations were manually inspected using the Integrative Genomics Viewer (IGV). Clinical data were abstracted prior to anonymization. RESULTS: Germline DNA was available for 114 patients; 78 underwent bilateral mastectomy for breast cancer (BC), 8 chose prophylactic mastectomy and 28 patients with biopsy proven bilateral LCIS were identified in surveillance. Following mastectomy, tissue sampling confirmed bilateral LCIS in 67/86 (78%) patients, and ruled out bilateral LCIS in 19 patients; yielding 95 patients with bilateral LCIS for the primary analysis. Median age at LCIS diagnosis for bilateral and unilateral cases respectively was 48yrs (range 36-70) and 44 yrs (range 38-63). One patient with bilateral LCIS also reported a FH of gastric cancer. Pathogenic germline CDH1 mutations (D72N (missense) and E35* (nonsense)) were identified in 2/95 (2%) patients with bilateral LCIS, one of whom also had invasive breast cancer (ILC). A germline CDH1 mutation was not identified in the patient with bilateral LCIS and a FH of gastric cancer, nor were CDH1 mutations identified among the 19 patients with unilateral LCIS. CONCLUSIONS: In this cohort of 95 patients with pathologically documented bilateral LCIS +/- BC, the overall frequency of CDH1 germline mutations was 2%; considerably lower than previously reported. To our knowledge this is the largest series to address this question and these findings do not support germline testing for CDH1 mutations in women with bilateral LCIS. Citation Format: Reyes SA, Sakr RA, Schizas M, Towers R, Park AY, Ng CKY, Weigelt B, Reis-Filho JS, King TA. Germline CDH1 mutations in lobular carcinoma in situ. [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 P6-06-02.

Long term clinical follow-up of atypical ductal hyperplasia and lobular carcinoma in situ in breast core needle biopsies

Atypical ductal hyperplasia (ADH) and lobular carcinoma in situ (LCIS) may be associated with a relatively high incidence of invasive carcinoma and ductal carcinoma in situ (DCIS) on immediate excision when found on core needle biopsy of the breast. However, the long term significance of ADH and LCIS in a breast core needle biopsy is not as well characterised. We reviewed the results of all breast core needle biopsies with a diagnosis of ADH or LCIS and immediate excision from the years 2000-2004, and correlated the results with long term clinical follow-up. Of 175 biopsies with ADH, 53 (30.3%) had carcinoma (8 invasive, and 45 DCIS) at the time of immediate re-excision. Of 69 biopsies with LCIS, three (4.3%) had carcinoma (2 invasive, and 1 DCIS) at the time of immediate re-excision. A total of 14 (11.5%) patients with ADH and benign re-excisions developed invasive carcinoma (12) or DCIS (2) on follow-up. A total of 17 (25.8%) patients with LCIS and benign re-excisions developed invasive carcinoma (13) or DCIS (4) on follow-up. The risk of invasive carcinoma or DCIS on immediate re-excision was significantly higher for women with ADH than LCIS (p<0.001). Women with LCIS developed significantly more invasive carcinomas and DCIS than women with ADH on long term follow-up (p=0.01). Compared to women with fibrocystic changes (FCC) on core needle biopsy, the risk of developing invasive carcinoma or DCIS was significantly higher for women with ADH and benign initial re-excisions (95% CI 1.092-7.297, p=0.03), and women with LCIS and benign re-excisions (95% CI 3.028-18.657, p<0.001). Overall, 67/175 (38.3%) women with ADH and 20/69 (29.0%) women with LCIS on core needle biopsy either had carcinoma at the time of the biopsy or later developed carcinoma. Significantly more women with LCIS developed invasive carcinoma or DCIS than women with ADH on long term follow-up. The relative risk for ADH and LCIS on core biopsy with a negative excision compared with FCC was similar to that reported in the literature (ADH 1-7×, LCIS 3-19×).

Abstract P6-13-02: The extent of lobular carcinoma in situ (LCIS) at surgical excision predicts for the development of subsequent breast cancer

Abstract Introduction LCIS is considered both a risk indicator and a non-obligate precursor of invasive breast cancer. A diagnosis of LCIS confers a risk that is 8-10x higher than that of the general population; yet we remain unable to predict risk of progression and hence lack the tools to make personalized treatment recommendations. Here we examine the relationship between pathologic features and extent of LCIS at surgical excision with risk of subsequent breast cancer. Methods From a prospective database of 1032 patients with LCIS diagnosed from 1980-2009, we identified patients with and without a subsequent cancer diagnosis and created a nested case-control cohort study. A case was defined as a breast cancer diagnosis ≥6 months after LCIS diagnosis. All cases were matched to ≥1 control (cancer free) based on age at diagnosis of LCIS +/- 5 yrs and length of follow up. All H&amp;E slides from the first diagnosis of LCIS were requested for central pathology review. Comparisons between cases and controls were done using conditional logistic regression analysis. Results At median followup of 79 mos (2-368mos) 156 pts (15%) in the parent database have developed breast cancer. Case-control matching resulted in a study cohort of 72 cases and 274 controls for which the original LCIS diagnostic slides were available. There were no significant differences in clinical characteristics between the study cohort and the parent population. Median time to cancer among cases was 3.6 yrs (0.5-12.7yrs). Median cancer-free follow up for controls was 9.9 yrs (1.1-19.8yrs). No significant differences in any of the features examined were observed between cases and controls (Table). Although the median number of slides with LCIS did not differ, the ratio of the total number of slides with LCIS over the total number of slides reviewed was significantly associated with case-control status. Cases had a significantly higher ratio (median 0.5, (0.3-1.0)) than controls (median 0.3, (0-1); p=0.003). On conditional logistic regression analysis, a ratio of &amp;gt;0.5 was associated with a 2.7 (95%CI, 1.4-4.9) greater odds for cancer development when compared to a ratio of &amp;lt;0.25 (p=0.008). Conclusion In this nested case-control study, the quantity of LCIS at excision, as measured by the ratio of the number of slides with LCIS over the total number of slides reviewed, was found to be a significant predictor of subsequent breast cancer. Patients with LCIS in &amp;gt;50% of slides reviewed had a 2.7 increased odds for cancer; suggesting that the extent of LCIS in a biopsy specimen should be considered when counseling patients about future risk and risk reducing options. Table 1 Cases n=72Controls n=274p-valueBilateral LCIS at diagnosis2 (3%)6 (2%)0.81Multicentric LCIS at diagnosis7 (10%)25 (9%)0.68Recurrent LCIS over time9 (13%)24 (9%)0.30Median # slides with LCIS4 (1-19)3 (1-41)0.42Median # TDLU with LCIS11 (1-129)6 (1-342)0.40Cell Type[br]A[br]A/B[br]B24 (33%)[br]45 (63%)[br]3 (4%)99 (36%)[br]145 (53%)[br]30 (11%)0.70Nuclear Grade[br]1[br]2[br]314 (19%)[br]54 (75%)[br]4 (6%)58 (21%)[br]189 (69%)[br]27 (10%)0.54Necrosis06 (2%)NACalcifications27 (38%)114 (42%)0.57Ductal Extension60 (83%)249 (91%)0.09ALH12 (17%)31 (11%)0.19 Citation Format: Jessica C Gooch, Elena Guerini-Rocco, Sujata Patil, Starr B Koslow, Marina De Brot, Anna Y Park, Camilla A Boafo, Jorge S Reis-Filho, Tari A King. The extent of lobular carcinoma in situ (LCIS) at surgical excision predicts for the development of subsequent breast cancer [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 P6-13-02.

Surgical outcome of lobular neoplasia diagnosed in core biopsy: Prospective study of 316 cases.

4 Background: Recommendations for management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) diagnosed in core biopsy specimens (CB) are controversial. The aim of our prospective study is to identify subset of patients with LN diagnosed in CB who do not require subsequent surgical excision (SE). Methods: All patients with a diagnosis of ALH or LCIS on CB were referred for SE. Cases with coexistent DCIS or invasive breast carcinoma were excluded. Cases with coexistent ductal atypia including FEA or ADH (LN-DA) and LCIS variants including pleomorphic or necrotic LCIS (LN-V) were separated from classic LN (LN-C). Dedicated breast pathologists and radiologists reviewed all cases with careful imaging/pathology (IP) correlation. Results: From June 2008 to December 2013, 13,772 percutaneous breast CB procedures were performed. A total of 370 patients with LN diagnosed on CB were referred to SE. 302 (82%) patients with 316 lesions underwent SE within 2 months after initial diagnosis. Average age was 55.3, 27% had positive family history and 4% had previous breast carcinoma. After patients with synchronous ipsilateral CB showing cancer were excluded (20 patients) from upgrade analysis, the diagnostic groups included 228 LN-C, 15 LN-V and 53 LN-DA. In the LN-C group I/P discordance represented 6/228 cases (2.6%). Upgrade to carcinoma of LN-C varied between discordant (6/6) and concordant cases (8/222=3.6%). In comparison, upgrades were seen in 26.7% LN-V (4/15), and 28.3% LN-DA (15/53). For concordant LN-C, the imaging target was calcifications in 176/222 cases (81%); 7 were associated with upgrade (3.9%). Upgrades were rare for MRI targeted lesions (0/14) and mass lesions (1/32). Overall, upgrades were similar for ALH and LCIS (3.4% vs. 4.5 %). Conclusions: While LN with nonclassic morphology or with associated ductal atypia requires SE, this can be avoided in classic LN diagnosed on CB targeting calcifications when careful imaging/pathology correlation is applied; the likelihood of unsuspected cancer diagnosis is minimal and limited to coincidental cases. Until larger numbers are studied, excising classic LN diagnosed as masses or MRI detected lesions may be prudent.