Invasive Ductal Cancer Research Articles

Abstract P5-22-12: Oncological safety of nipple-areola sparing mastectomy in comparison with skin sparing and total mastectomy: Results from a NCI-designated comprehensive cancer center

Abstract Nipple-areola sparing mastectomy (NSM) may be offered to some women with breast cancer as an alternative to skin sparing (SSM) or total mastectomy (TM) with excellent cosmetic results and acceptable recurrence risk. The aim of this study is to determine the local/regional recurrence rate of NSM in comparison to SSM and TM at our institution and to determine the factors that may be associated with risk of recurrence. Women who underwent NSM (n=148), SSM (n=660) or TM (n=443) at City of Hope National Medical Center between May 2007 and December 2014 for Stage 0-III breast cancer were identified retrospectively. Exclusions were: women with inflammatory breast cancer and those who had mastectomy for recurrent breast cancer. Overall survival (OS) and disease free survival (DFS) were analyzed using Cox regression controlling for age, race/ethnicity, stage, histology, grade, hormone receptor and Her2 receptor status. There were total of 165 NSMs, 704 SSMs and 466 TMs performed for cancer, accounting for the patients with bilateral cancers. The median follow up time was 38, 58 and 55 months for NSM, SSM and TM, respectively. Median (range) age at diagnosis was 49 (23-74) for NSM, 51 (23-90) for SSM and 59 (26-92) for TM. In the NSM group, 76% of patients had invasive ductal cancer (IDC) and 15% had ductal carcinoma in-situ (DCIS); this was comparable to 73% and 13% in the SSM group and 78% and 9% in the TM group, respectively. The majority of patients who underwent NSM had Stage II disease (45%), which was similar to SSM (43%) and TM (44%). Only 3% of NSM patients had Stage III disease compared to 17% of SSM patients and 29% of TM patients. Most of the patients in all 3 surgical groups received adjuvant chemotherapy (NSM 59%; SSM 52%; TM 51%). Of patients who underwent NSM, 20% received neoadjuvant chemotherapy, compared with 29% of SSM patients and 35% of TM patients. The local/regional recurrence rate per breast was 12/165 (7.3%) for NSM, 23/704 (3.3%) for SSM and 11/466 (2.4%) for TM (n=11). Median time to recurrence was 20, 26 and 16 months for NSM, SSM and TM, respectively. Of the NSMs performed only 1 recurrence occurred at the nipple-areolar complex (0.6%), 9 recurrences were at the chest wall (5.5%) and 2 were at the axilla (1.2%). Eight recurrences after NSM had DCIS in addition to IDC at the time of initial diagnosis while 2 had pure DCIS, 1 had pure IDC and 1 had invasive lobular cancer. There were 8 recurrences with estrogen receptor (ER) and progesterone receptor (PR) positivity at the time of initial diagnosis, that converted to ER+, PR-. One third of recurrences after NSM had multifocal disease. There was no significant difference found in adjusted overall survival (p=0.49) and adjusted disease free survival (p=0.10) among NSM, SSM and TM patients. Even though there is higher rate of local/regional recurrence with NSM, there is no difference in overall and disease-free survival at our institution. Presence of DCIS may be an important factor for recurrence. From these data we conclude that NSM is an oncologically acceptable alternative to SSM and TM, with excellent cosmetic results. Citation Format: Bostanci Z, Wang X, Ottesen R, Nikowitz J, Jones VC, Springer L, Lai L, Taylor L, Vito CA, Paz IB, Niland J, Kruper L, Yim JH. Oncological safety of nipple-areola sparing mastectomy in comparison with skin sparing and total mastectomy: Results from a NCI-designated comprehensive cancer center [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 P5-22-12.

Abstract MS2-2: Understanding the unique biology of ILC

Abstract Invasive lobular breast cancer (ILC) is characterized by distinct etiological, pathological, and clinical features, yet the underlying biology is poorly understood. To extend the molecular determinants of ILC beyond the well-known loss of E-cadherin, we combined a plethora of in silico and wet-bench approaches, and comprehensively characterized ILC tumor models and clinical samples. In support of recent data from The Cancer Genome Atlas on differences in mutations in critical ER co-factors between invasive lobular and ductal cancers, we have identified distinct ER signaling pathways, and mechanisms of endocrine resistance in ILC. These include the acquisition of unique ER target genes, activation of IGF and FGFR signaling, and changes in metabolic pathways. As part of our efforts to elucidate mediators of ILC progression, transcriptomic analysis of primary tissue from patients with and without disease recurrence identified potential genetic drivers, including Cortactin, an actin binding protein with a known role in metastasis. To further identify genes that mediate the unique metastatic properties of ILC cells, we sequenced metastases to the ovary and the gastrointestinal tract, and uncovered pathways that might serve as critical vulnerabilities and therapeutic opportunities. In this lecture, I will review our progress, and discuss the potential clinical significance and implications of these findings. Citation Format: Oesterreich S. Understanding the unique biology of ILC [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 MS2-2.

Early Diagnosis of Breast Cancer: Public Health and Mammographic Screening

Malignant breast tumors are the leading oncological pathology (after skin cancer) in the female population all over the world (more than 20%). According to American Cancer Society, breast cancer is expected to account for 30% of all new cancer cases among women in 2017 (Simon, 2017). The research in the sphere of the timely diagnosis of malignant neoplasms led to the development and further widespread implementation of screening programs, which help to reveal the disease before the onset of symptoms or signs of illness. The paper discusses different scientific approaches to mass screening, various opinions concerning the real impact of screening and contemporary treatment into breast cancer mortality decrease, and presents the results of a breast screening program in the Republic of Tatarstan (Russian Federation). The results showed the effectiveness of this diagnostic method: in 59,000 women aged 50–69 years in total, there were revealed 373 cases of breast cancer (0.63%), in which breast cancer of the I–II stage was 80%. Of the histological forms, 45.4% in the detected malignant neoplasms were presented by invasive ductal cancer, 24.8%—by invasive lobular carcinoma, and the proportion of non-invasive cancer was 4%. Cancer without metastatic involvement of lymphatic nodes (T1–4N0) occurred in 63% of cases. The paper discusses such negative factors of mass mammographic screening as overdiagnosis, false-positive results, and overtreatment. The analyses of existing research all over the world show that since the problem has been actively studied all over the world, the approach to the analysis of screening results has changed to the prevalence of individual approach to each case, the number of cases connected with overdiagnosis is constantly reduced, and the quality of visualization is rapidly improving due to the success of interdisciplinary research and rapid technical progress.

Eligibility of patients for minimally invasive breast cancer therapy based on MRI analysis of tumor proximity to skin and pectoral muscle.

There is growing interest in minimally invasive breast cancer therapy. Eligibility of patients is, however, dependent on several factors related to the tumor and treatment technology. The aim of this study is to assess the proportion of patients eligible for minimally invasive breast cancer therapy for different safety and treatment margins based on breast tumor location. Patients with invasive ductal cancer were selected from the MARGINS cohort. Semiautomatic segmentation of tumor, skin, and pectoral muscle was performed in Magnetic Resonance images. Shortest distances of tumors to critical organs (ie, skin and pectoral muscle) were calculated. Proportions of eligible patients were determined for different safety and treatment margins. Three-hundred-forty-eight patients with 351 tumors were included. If a 10mm safety margin to skin and pectoral muscle is required without treatment margin, 72.3% of patients would be eligible for minimally invasive treatment. This proportion decreases to 45.9% for an additional treatment margin of 5mm. Shortest distances between tumors and critical organs are larger in older patients and in patients with less aggressive tumor subtypes. If a 10mm safety margin to skin and pectoral muscle is required, more than two-thirds of patients would be eligible for minimally invasive breast cancer therapy.

Comparison of clinicopathological features and prognostic factors between advanced invasive lobular cancer and invasive ductal breast cancer

Comparison of clinicopathological features and prognostic factors between advanced invasive lobular cancer and invasive ductal breast cancer

Clinicopathological features and treatment of bilateral asynchronous breast cancer: report of 13 cases

Objective To analyze the clinicaopathological features and treatment of bilateral asynchronous breast cancer. Methods The clinical and pathological data of 13 patients with bilateral asynchronous breast cancer admitted in our hospital from 2010 to 2016 were retrospectively reviewed. Results The bilateral asynchronous breast cancer accounted for 1.7% of all breast cancer patients admitted in the same period (13/782). The median age of patients at first onset was 47. The modified radical operation was the main surgical modality (12/13 for the first cancer; 8/13 for the second cancer). The clinical stage Ⅱ was predominant in all patients (10/13 of the first cancer; 9/13 of the second cancer). Invasive ductal cancer was the most common pathologic type (in 11/13 of the first cancer; 11/13 of the second cancer). Hormone receptors were highly expressed in most of the cases (9/13 of the first cancer; 7/13 of the second cancer). The disease-free interval was more than 10 years in most cases (8/13). Among 13 cases local recurrence was detected in 1 case, distant metastases in 2 cases, and 1 case died from distant metastasis. Conclusion The bilateral asynchronous breast cancer has a low incidence; however, a close follow up is necessary for early detection and treatment of the second carcinoma. Key words: Breast neoplasms; Neoplasms, multiple primary; Pathology conditions, signs and symptoms; Treatment outcome

In support of the Choosing Wisely campaign: Perceived higher risk leads to unnecessary imaging in accelerated partial breast irradiation?

Accelerated partial breast irradiation (APBI) is an increasingly utilized modality for early stage breast cancer as part of breast conservation therapy (BCT). There remains concern regarding local recurrence, requiring more frequent post-radiation surveillance imaging. The purpose of this study is to determine clinical significance of frequent surveillance in this perceived higher risk population. Patients treated at a community academic medical center from 2005 to 2013 with partial breast radiation were retrospectively identified. All patients were treated with lumpectomy followed by balloon based APBI. Diagnostic, clinical, radiographic, and outcomes data were collected. One hundred and sixty-nine patients were identified. Median age at time of diagnosis was 63. Stage was 0, I, and II in 27%, 64%, and 9%, respectively. Most patients had pure invasive ductal cancer. Ninety-two percent and 99% of patients had imaging performed by 6 and 12 months (± 3 months) respectively. Median interval between end of radiation and first image, and subsequent 3 images were 6, 6, 9, and 12 months, respectively. Median follow-up was 49 months for all patients (range 7-106). Six patients experienced local recurrence: 4 invasive, all clinically detected, and none within the first 2 years. One patient had mammographically detected recurrent ductal carcinoma in situ. No mammographic images within the first year lead to diagnosis of recurrent cancer. APBI via balloon base brachytherapy offered women excellent locoregional control rates. Frequent mammographic surveillance did not result in increased detection of early recurrent disease. The result of our study are in line with the Choosing Wisely campaign recommendations to perform no more than annual follow-up for women who have completed radiation as part of BCT, with first imaging done at 6-12 months. We recommend mammographic surveillance be performed no more frequently than annually, with first image after BCT to be done 12 months from completion of radiation.

Breast Cancer Case Using Tamoxifen during Pregnancy: A Case Report and Literature Review

<p>This is a case of 32 years old nulliparous female who was diagnosed in November 2004 as a case of carcinoma of the right breast , luminal A , (Estrogen Receptor positive Progesterone receptor negative, Her 2 negative, Ki67 10 %), poorly differentiated invasive ductal cancer, TNM stage,T2 N0 MO. She had a wide local excision and axillary clearance. As she is a case of low risk early stage luminal A breast cancer; she was not given chemotherapy, instead she had a course of external irradiation and was put on Tamoxifen (Astra Zeneca, 20 mg daily), and was advised not to get pregnant during this treatment,but she got pregnant and delivered normally a healthy infant, although Tamoxifen is potentially teratogenic.</p>

Sonographic Phenotypes of Molecular Subtypes of Invasive Ductal Cancer in Automated 3-D Breast Ultrasound

Our aim was to investigate whether Breast Imaging Reporting and Data System—Ultrasound (BI-RADS-US) lexicon descriptors can be used as imaging biomarkers to differentiate molecular subtypes (MS) of invasive ductal carcinoma (IDC) in automated breast ultrasound (ABUS). We included 125 IDCs diagnosed between 2010 and 2014 and imaged with ABUS at two institutes retrospectively. IDCs were classified as luminal A or B, HER2 enriched or triple negative based on reports of histopathologic analysis of surgical specimens. Two breast radiologists characterized all IDCs using the BI-RADS-US lexicon and specific ABUS features. Univariate and multivariate analyses were performed. A multinomial logistic regression model was built to predict the MSs from the imaging characteristics. BI-RADS-US descriptor margins and the retraction phenomenon are significantly associated with MSs (both p < 0.001) in both univariate and multivariate analysis. Posterior acoustic features and spiculation pattern severity were only significantly associated in univariate analysis (p < 0.001). Luminal A IDCs tend to have more prominent retraction patterns than luminal B IDCs. HER2-enriched and triple-negative IDCs present significantly less retraction than the luminal subtypes. The mean accuracy of MS prediction was 0.406. Overall, several BI-RADS-US descriptors and the coronal retraction phenomenon and spiculation pattern are associated with MSs, but prediction of MSs on ABUS is limited.

Tumor biologic characteristics and clinical outcomes in geriatric patients with breast cancer.

e21526 Background: The probability of dying from breast cancer increases from 0.2% to 2% annually for women once they reach 70 years of age. However there is limited age-related information available about tumor biologic characteristics (TBCs) and clinical outcomes among elderly patients (pts). The purpose of this study was to analyze the impact of TBCs on clinical outcomes in a single institution's geriatric breast cancer pts. Methods: An institutional database of a total of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 years or older at the time of diagnosis was reviewed in an IRB approved fashion. Tumors were assessed for Nottingham grade, stage, ER/PR status, HER-2 status, tumor histology, lymphovascular invasion and nodal status. Kaplan-Meyer and Cox proportional hazards methods were used to calculate overall survival (OS). Results: Breast cancer was seen equally in both breasts: left n = 130 (48.3%), right n = 132 (49.1%). Most tumors were located in the upper outer quadrant (n = 122, 45.35%). TNM clinical stage Tlc was identified in 79 pts (29.36%), Tlb in 55 pts (20.44%), T2 in 54 pts (20.07%) and no nodal involvement in 146 pts (54.27%). Nottingham Grade 2 (n = 120, 44.60%) and invasive ductal carcinomas (n = 152, 56.50%) were diagnosed most often. Tumors were more frequently ER+ (n = 237, 88.10%), PR+ (n = 210, 78.06%), and HER2-negative (n = 219, 81.41%). There was no statistically significant increase in OS based on location of tumor (P = 0.9796) and tumor histology (invasive ductal vs invasive lobular cancers, P = 0.1143). Node negative breast cancers were associated with increased OS (P = 0.0014). Grade 2 tumors were associated with increased OS compared to Grade 3 tumors (P = 0.0112). ER+ and PR-negative tumors were associated with decreased OS in both short term and long term follow up (P = 0.0083 &amp; P = 0.0254). Conclusions: In pts 65 years of age or older with newly diagnosed breast cancer, lack of nodal involvement is associated with increased OS. Prognosis for ER+ and PR-negative tumors is worse compared to ER+ and PR+ tumors. Nottingham Grade 2 tumors have better OS compared to Grade 3 tumors. Location of tumor and tumor histology are not associated with increased OS.

Interval breast cancer characteristics before, during and after the transition from screen-film to full-field digital screening mammography

BackgroundTo determine the proportion of “true” interval cancers and tumor characteristics of interval breast cancers prior to, during and after the transition from screen-film mammography screening (SFM) to full-field digital mammography screening (FFDM).MethodsWe included all women with interval cancers detected between January 2006 and January 2014. Breast imaging reports, biopsy results and breast surgery reports of all women recalled at screening mammography and of all women with interval breast cancers were collected. Two experienced screening radiologists reviewed the diagnostic mammograms, on which the interval cancers were diagnosed, as well as the prior screening mammograms and determined whether or not the interval cancer had been missed on the most recent screening mammogram. If not missed, the cancer was considered an occult (“true”) interval cancer.ResultsA total of 442 interval cancers had been diagnosed, of which 144 at SFM with a prior SFM (SFM-SFM), 159 at FFDM with a prior SFM (FFDM-SFM) and 139 at FFDM with a prior FFDM (FFDM-FFDM). The transition from SFM to FFDM screening resulted in the diagnosis of more occult (“true”) interval cancers at FFDM-SFM than at SFM-SFM (65.4% (104/159) versus 49.3% (71/144), P < 0.01), but this increase was no longer statistically significant in women who had been screened digitally for the second time (57.6% (80/139) at FFDM-FFDM versus 49.3% (71/144) at SFM-SFM). Tumor characteristics were comparable for the three interval cancer cohorts, except of a lower porportion (75.7 and 78.0% versus 67.2% af FFDM-FFDM, P < 0.05) of invasive ductal cancers at FFDM with prior FFDM.ConclusionsAn increase in the proportion of occult interval cancers is observed during the transition from SFM to FFDM screening mammography. However, this increase seems temporary and is no longer detectable after the second round of digital screening. Tumor characteristics and type of surgery are comparable for interval cancers detected prior to, during and after the transition from SFM to FFDM screening mammography, except of a lower proportion of invasive ductal cancers after the transition.

Protein Expression Er (Estrogen Receptor) in Breast Cancer Degree of Malignancy Mild, Moderate, and Severe

Introduction: Mammary carcinoma is the most common malignancy and main mortality cause in women. Hormonal status (ER and PR expression) was long used as patient suitability for hormonal therapy. However, lately there have been many patients with ER and PR negative. This study wanted to prove the relevance of protein expression of ER (estrogen receptor) with the histopathological degree of malignancy of breast invasive ductal cancer and the prognosis of breast cancer with ER protein expression of positive and negative.Methods: In this retrospective and cross sectional analytical study retrieved data about hormonal status (ER expression) and histopathological grading of infiltrating ductal carcinoma patients. This study consisted of 201 patients with mammary carcinoma who referred to medical records Department Pathology Anatomic of Faculty Medicine Airlangga University/Dr. Soetomo General Hospital Surabaya on 1 January 2010–31 December 2010 and their medical record suitable with inclusion criterias. The data was categorized into several groups based on the ER expression result.Results: Most of the sample was in 41–50 year age group (37.31%), and 54,7% of them were in poor expression. The relationship of estrogen receptor (ER) with the degree of histopathology infiltrating ductal carcinoma patients, obtained p-value = 0.001 (p &lt; 0.5) and the 2 × 2 table is only moderate and severe degrees compared with the results of ER expression results obtained p = 0.001 (p &lt; 0.5) and odds ratio of 0.362 (CI: 0194-0675).Conclusion: This study found significant correlation between ER expression with histopathological grading of infiltrating ductal carcinoma patients.

Histogram analysis of volume-based apparent diffusion coefficient in breast cancer.

Background Breast cancer is a heterogeneous disease. Recent studies showed that apparent diffusion coefficient (ADC) values have various association with tumor aggressiveness and prognosis. Purpose To evaluate the value of histogram analysis of ADC values obtained from the whole tumor volume in invasive ductal cancer (IDC) and ductal carcinoma in situ (DCIS). Material and Methods This retrospective study included 201 patients with confirmed DCIS (n = 37) and IDC (n = 164). The IDC group was divided into two groups based on the presence of a DCIS component: IDC-DCIS (n = 76) and pure IDC (n = 88). All patients underwent preoperative breast magnetic resonance imaging (MRI) with diffusion-weighted images at 3.0 T. Histogram parameters of cumulative ADC values, skewness, and kurtosis were calculated and statistically analyzed. Results The differences between DCIS, IDC-DCIS, and pure IDC were significant in all percentiles of ADC values, in descending order of DCIS, IDC-DCIS, and pure IDC. IDC showed significantly lower ADC values than DCIS, and ADC50 was the best indicator for discriminating IDC from DCIS, with a threshold of 1.185 × 10-3 mm2/s (sensitivity of 82.9%, specificity of 75.7%). However, multivariate analysis of obtained ADC values showed no significant differences between DCIS, IDC-DCIS, and pure IDC ( P > 0.05). Conclusion Volume-based ADC values showed association with heterogeneity of breast cancer. However, there was no additional diagnostic performance in histogram analysis for differentiating between DCIS, IDC-DCIS, and pure IDC.

Abstract P5-16-30: Feasibility trial for identification of patients for eliminating breast cancer surgery following neoadjuvant systemic therapy

Abstract P5-16-30: Feasibility trial for identification of patients for eliminating breast cancer surgery following neoadjuvant systemic therapy

Breast MRI increases the number of mastectomies for ductal cancers, but decreases them for lobular cancers

PurposeIn this retrospective population-based cohort study, we analyzed breast MRI use and its impact on type of surgery, surgical margin involvement, and the diagnosis of contralateral breast cancer.MethodsAll Dutch patients with cT1–4N0–3M0 breast cancer diagnosed in 2011–2013 and treated with primary surgery were eligible for inclusion. Using multivariable analyses, we analyzed in different categories whether MRI use was related to surgery type, margin involvement, and diagnosis of contralateral breast cancer (CBC).ResultsMRI was performed in 10,740 out of 36,050 patients (29.8%). Patients with invasive ductal cancer undergoing MRI were more likely to undergo primary mastectomy than those without MRI (OR 1.30, 95% confidence interval (CI) 1.22–1.39, p < 0.0001). Patients with invasive lobular cancer undergoing MRI were less likely to undergo primary mastectomy than those without MRI (OR 0.86, 95% CI 0.76–0.99, p = 0.0303). A significantly lower risk of positive surgical margins after breast-conserving surgery was only seen in patients with lobular cancer who had undergone MRI as compared to those without MRI (OR 0.59, 95% CI 0.44–0.79, p = 0.0003) and, consequently, a lower risk of secondary mastectomy (OR 0.61, 95% CI 0.42–0.88, p = 0.0088). Patients who underwent MRI were almost four times more likely to be diagnosed with CBC (OR 3.55, 95% CI 3.01–4.17, p < 0.0001).ConclusionsBreast MRI use was associated with a reduced number of mastectomies and less positive surgical margins in invasive lobular cancer, but with an increased number of mastectomies in ductal cancers. Breast MRI use was associated with a fourfold higher incidence of CBC.

Non-mass breast lesions on ultrasound: final outcomes and predictors of malignancy

Background Breast cancer can present as non-mass lesions (NMLs) on ultrasound. However, knowledge of and understanding about NMLs are scarce. Purpose To retrospectively investigate the final outcomes of sonographic breast NMLs and determine the clinical and radiologic variables associated with malignancy Material and Methods In our radiologic database of breast ultrasound examinations between 2011 and 2014, we found 119 women with 121 NMLs with available histopathologic or sonographic follow-up (over 2 years) data. We collected the clinical variables (patient's age, symptoms, and mammographic density) and histopathologic data as well as radiologic variables (mammographic and ultrasound findings) after retrospective review by two radiologists, the authors of the current paper, in consensus. We classified the ultrasound findings according to distribution (focal, linear or segmental, and regional) and associated features (calcification, architectural distortion, and ductal changes) and analyzed the associations between variables and malignancy using the t test and χ2 test. Results Of the 121 NMLs, 88 (72.7%) were benign and 33 (27.3%) were malignant. Ductal carcinoma in situ (DCIS) (17/33, 51.5%) and invasive ductal cancer with or without DCIS (13/33, 39.4%) comprised the main malignancies, and malignancy was significantly associated with palpability ( P = 0.000). Mammographic findings and sonographic distribution and associated features were significantly different between benign and malignant lesions ( P = 0.000, P = 0.004, and P = 0.001, respectively). Malignant lesions showed more frequent calcifications combined with asymmetry ( P = 0.000) on mammography and linear-segmental distributions ( P = 0.001) and associated calcifications ( P = 0.019) or architectural distortions ( P = 0.015) on ultrasound. Conclusion Breast NMLs on ultrasound showed high risk of malignancy. Symptoms and mammographic and ultrasound findings can be possible predictors of malignancy in NMLs.

Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer.

Breast cancer is the most common malignant tumor in women worldwide, and accounts for an estimated 29% of new cases and 15% of cancer-associated mortalities each year. Invasive ductal carcinoma represents 70-80% of all breast cancer cases, which are responsible for the majority of breast cancer fatalities. Though great progress has been made in understanding the tumorigenesis and development of breast cancer, problems surrounding treatment persist. It was previously reported that carcinoma-associated fibroblasts (CAFs) may be closely associated with chemotherapy resistance. In the present study, primary-cultured CAFs from surgically resected breast invasive ductal cancer tissues were prepared and tested to clarify the change of gene expression profile following treatment with 20 ng/ml Taxotere® for 24 h through microarray analysis. In addition, quantitative polymerase chain reaction and western blotting were performed to compare the gene and protein expression of the candidate gene in CAFs prior to and following Taxotere treatment. Based on the obtained data, 35 differentially expressed genes were identified, including ACTA2, ACTC1, ACTG, ALDH1B1, AMY1A, C5orf13, CNN1, CXCR7, DDAH1, FGF1, PDLIM3, MAMLD1, MYH11, OXTR, PDLIM5, RARRES1, SERPINA3, TRIL, C14orf43, C1orf51, CXCL12, CXCL2, EGR2, EGR3, IER3, interleukin (IL)8, IRF1, JUNB, MMP1, NAV2, NFKBIA, NFKBIZ, TRIB1, WNT16 and ZC3H12A. It was observed that the expression of the candidate gene IL8 in the CAFs of breast invasive cancer following treatment with Taxotere was increased (P<0.05). Overall, elevated expression of IL8 induced by Taxotere in CAFs potentially supports the association between IL8 and chemotherapy response.

18F-Fluorocholine PET/CT of Incidental Male Breast Cancer

Breast cancer is approximately 100 times less common among men. Estrogen-related receptor α was detected in human prostate cancer tissue, and androgen receptors are expressed in both normal and malignant breast tissue. Thus, prostate cancer hormonal therapy may increase breast cancer risk. A 67-year-old man with prostate cancer history presented with rising prostate-specific antigen level. F-Fluorocholine PET/CT showed intense uptake in his right breast and moderate uptake in right axillary lymph node. Complementary F-FDG PET/CT demonstrated more intense tracer uptakes in both the right breast and axillary lymph node. Breast histological findings were invasive ductal cancer, with axillary lymph node invasion.

Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer

Background/Aims: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. Methods: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. Results: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/β-catenin signaling and inhibited the growth of AR+/ER- breast cancer. Conclusion: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.

Abstract IA21: Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immune-suppressive environment in pancreatic cancer

Abstract Pancreatic cancer is characterized by the accumulation of a fibro-inflammatory stroma. Accumulation of the stroma is already evident surrounding Pancreatic Intraepithelial Neoplasias (PanINs), common precursor lesions to pancreatic cancer (Hezel et al., 2006). The stroma is abundantly infiltrated by immune cells, and myeloid cells are a predominant population (Clark et al., 2007). Different myeloid subsets have been correlated with tumor promotion and unmasking of anti-tumor immunity (Liou et al., 2015; Long et al., 2016; Mitchem et al., 2013; Stromnes et al., 2014). Both PanINs and pancreatic cancer and commonly associated with oncogenic mutations in the Kras gene (Biankin et al., 2012; Jones et al., 2010; Kanda et al., 2012). Expression of oncogenic Kras in the pancreas of genetically engineered mice recapitulates the PanIN to pancreatic cancer progression, including the accumulation of fibrotic stroma (Hingorani et al., 2003). We have described a mouse model that allows inducible and reversible expression of oncogenic Kras in the pancreas, the iKras* mouse. Inactivation of oncogenic Kras during the PanIN stage or in cancer leads to regression of the epithelial lesions as well as to remodeling of the stroma, indicating that the accumulation of the stroma is regulated by signals derived from oncogenic Kras-expressing epithelial cells (Collins et al., 2012a). In the current study, we have investigated the interaction between epithelial cells and myeloid cells that infiltrate the pancreas. For this purpose, we have used a combination of genetically engineered mice (iKras*p53* mice (Collins et al., 2012b)) and transplantation approaches into CD11b-DTR mice (Duffield et al., 2005), that allow depletion of myeloid cells upon administration of Diphtheria Toxin. Our results show that the infiltration and polarization of macrophages in the pancreas depends on signals derived from oncogenic Kras-expressing epithelial cells, either directly or through activation of a pro-inflammatory subset of stromal fibroblasts. Conversely, myeloid cells infiltration is required for the progression of PanINs and pancreatic cancer. Depletion of myeloid cells prevented KrasG12D driven pancreatic cancer initiation. In pre-established tumors, myeloid cell depletion resulted in arrest of growth or tumor regression. We observed that tumor progression was dependent on myeloid cell-mediated blockade of CD8+ T cell anti-tumor activity. Furthermore, myeloid cells regulate the expression of the Programmed death-ligand 1 (PD-L1) in tumor cells in an EGFR/MAPK dependent manner. Our results show that myeloid cells regulate a complex network of signals that ensure immune suppression within the pancreatic cancer microenvironment. Moreover, we show that depletion of the myeloid cell population restores anti-tumor immunity mediated by CD8+ T cells, a finding with implications for the design of immune therapies for pancreatic cancer.