Type Of Invasive Breast Cancer Research Articles

Abstract P6-01-03: Invasive Micropapillary Carcinoma (IMPC) of the Breast: An Uncommon but Aggressive Special Type of Breast Cancer

Abstract IMPC is an uncommon type of invasive breast cancer. However, in comparison to invasive ductal carcinoma of no special type (IDC), it is reported to have a more aggressive behavior. Our objective was to compare and contrast IMPC with IDC in terms of clinicopathologic features and outcome. One hundred-thirty-one IMPC cases were compared to 1295 IDC and 189 invasive lobular carcinoma (ILC). Medical records and pathology slides were reviewed for traditional factors (tumor grade, lymphatic invasion [LVI], lymph node [LN] status, stage, receptor status, treatment) and specific tumor features (extent of retraction artifact [RA]). Clinicopathologic features between groups were compared and clinical outcome of IMPC was recorded. All patients were women with a median age of 57.6 yrs (range 22-93) for IMPC, 56.3 yrs (range 22-96) for IDC and 60.7 (range35-85) for ILC, respectively (P<0.0001). There were no differences noted for family history, race, or presentation (symptomatic vs. screening). Surgical treatment was partial mastectomy in 770 (47.7%) and mastectomy in 845 (52.3%). All patients had axillary lymph node biopsy. The median tumor size was 2.2 (range 0.3-15.2) cm for IMPC, 2.0 (range 0.05-11.0) cm for ILC and 1.7 (range 0.05-19.0) cm for IDC, respectively (P<0.). The extent of micropapillary features in IMPC ranged from 3% to 100% with a median value of 20%. LVI was more likely to be present in IMPC (67.9%) compared to IDC (28.3%) and ILC (6.9%) (P<0.0001). Axillary LN metastases were seen in 71.8% of IMPC compared to 44.1 % of IDC and 54.5% of ILC (P<0.0001). IMPC and ILC was significantly more frequently ER and PR positive (P<0.0001 each) compared to IDC, while ILC was significantly less frequently HER2 positive (2.8%) compared to IDC (17.9%) and IMPC (8.2%). The mean percent of tumors showing retraction artifact (RA) was 60.2% in IMPC compared to 25.4% in IDC and 3.8% in ILC (P<0.0001). During a median follow-up of 24.3 months 19 (14.5%) and 17 (13.0%) IMPC patients developed local and distant recurrence, respectively. IMPC is an uncommon special type of invasive breast cancer but it is more aggressive in reference to IDC and ILC based on larger tumor size and more frequent the presence of LVI and LN metastases. The presence of IMPC features in breast cancers, even if present focally, should alert the clinician for the high likelihood of lymphatic tumor spread and an adverse biologic behavior. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-03.

Risk factors for ductal and lobular breast cancer: results from the nurses' health study

IntroductionDuctal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses' Health Study.MethodsMultivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes.ResultsThe associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het < 0.001) and postmenopausal hormone use (P-het < 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het ≥ 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors.ConclusionsThese data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology.

Alcohol Consumption and Risk of Postmenopausal Breast Cancer by Subtype: The Women's Health Initiative Observational Study

Alcohol consumption is a well-established risk factor for breast cancer. This association is thought to be largely hormonally driven, so alcohol use may be more strongly associated with hormonally sensitive breast cancers. Few studies have evaluated how alcohol-related risk varies by breast cancer subtype. We assessed the relationship between self-reported alcohol consumption and postmenopausal breast cancer risk among 87 724 women in the Women's Health Initiative Observational Study prospective cohort from 1993 through 1998. Multivariable adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. A total of 2944 invasive breast cancer patients were diagnosed during follow-up through September 15, 2005. In multivariable adjusted analyses, alcohol consumption was positively related to risk of invasive breast cancer overall, invasive lobular carcinoma, and hormone receptor-positive tumors (all P(trend) ≤ .022). However, alcohol consumption was more strongly related to risk of certain types of invasive breast cancer compared with others. Compared with never drinkers, women who consumed seven or more alcoholic beverages per week had an almost twofold increased risk of hormone receptor-positive invasive lobular carcinoma (HR = 1.82; 95% CI = 1.18 to 2.81) but not a statistically significant increased risk of hormone receptor-positive invasive ductal carcinoma (HR = 1.14; 95% CI = 0.87 to 1.50; difference in HRs per drink per day among current drinkers = 1.15; 95% CI = 1.01 to 1.32, P = .042). The absolute rates of hormone receptor-positive lobular cancer among never drinkers and current drinkers were, 5.2 and 8.5 per 10 000 person-years, respectively, whereas for hormne receptor-positive ductal cancer they were 15.2 and 17.9 per 10 000 person-years, respectively. Alcohol use may be more strongly associated with risk of hormone-sensitive breast cancers than hormone-insensitive subtypes, suggesting distinct etiologic pathways for these two breast cancer subtypes.

494 Clinical significance of lymphangiogenesis in molecular types of invasive breast cancer

Vascular endothelial growth factor-C (VEGF-C) is the quintessential lymphangiogenic growth factor that is required for the development of the lymphatic system and is capable of stimulating lymphangiogenesis in adults by activating its receptor, VEGFR-3. Although VEGF-C is a major candidate molecule for the development of prolymphangiogenic therapy for defective lymphatic vessels in lymphedema, the stability of lymph vessels generated by exogenous VEGF-C administration is not currently known. We studied VEGF-C-stimulated lymphangiogenesis in inducible transgenic mouse models in which growth factor expression can be spatially and temporally controlled without side effects, such as inflammation. VEGF-C induction in adult mouse skin for 1 to 2 weeks caused robust lymphatic hyperplasia that persisted for at least 6 months. VEGF-C induced lymphangiogenesis in numerous tissues and organs when expressed in the vascular endothelium in either neonates or adult mice. Very few or no effects were observed in either blood vessels or collecting lymph vessels. Additionally, VEGF-C stimulated lymphangiogenesis in embryos after the onset of lymphatic vessel development. Strikingly, a strong angiogenic effect was observed after VEGF-C induction in vascular endothelium at any point before embryonic day 16.5. Our results indicate that blood vessels can undergo VEGF-C-induced angiogenesis even after down-regulation of VEGFR-3 in embryos; however, transient VEGF-C expression in adults can induce long-lasting lymphatic hyperplasia with no obvious side effects on the blood vasculature.

Clinical and Prognostic Features of Infiltrating Lobular Carcinoma of the Breast in a Korean Series.

Abstract Introduction: Infiltrating lobular carcinoma (ILC) is the second most common histological type of invasive breast cancer (IBC) and accounts for 10% of all IBCs. ILC differs from IDC in many respects including age of patients, tumor size and increased frequency of multifocality and bilaterality. But, the outcome of ILC remains unclear. Therefore, we studied the clinical features and prognosis of patients with ILC and infiltrating ductal carcinoma (IDC). Methods: We analyzed data from 3716 breast cancer pts who were were treated at the Yonsei University Health System between 1984 and 2005. Median follow time is 74 months. The patients were categorized as having ILC or IDC. Results: 95(2.3%) tumors were classified as ILC, 3621 (89.4%) as IDC. In analysis there were no differences of age, tumor size, nodal status and stage between ILC and IDC. However, patients with ILC were significantly more likely to have estrogen positive (79.7% for ILC vs 62.6% for IDC, p=0.003) and HER-2 negative tumors (83.6% for ILC vs 70.8% for IDC, p=0.038) compared to patients with IDC. The frequency of bilateral breast cancers was higher for patients with ILC than for patients with IDC (ILC: 6.8% vs. IDC: 3.5%, p=0.013). The systemic recurrence and local recurrence rates for ILC were similar to IDC. However, the sites of systemic recurrence were different. IDC more commonly metastasized lung than IDC (36.5% for IDC vs 9.1% for ILC). ILC more commonly metastasized to bone and the ovaries than IDC (bone: 72.7% for ILC vs 36.5 % for IDC, ovary: 18.2% for ILC vs 0% for IDC). there were no statistically significant differences in DFS and OS between ILC and IDC. The 5-year DFS was 87.6% for ILC and 78.7% for IDC.(p=0.174) The 5-year OS was 93.6% for ILC and 85.5% for IDC.(p=0.104) Conclusion: In the results of this study, the incidence of ILC was quite low in Korean breast cancer patients. ILC showed different histologic features as bilateral involvement, ER positivity, HER-2 negativity and systemic recurrence sites compared to IDC. But the prognosis of ILC was similar to that of IDC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3036.

Rare histological types of invasive breast cancer

Rare histological types of invasive breast cancer

Clinicopathological Characteristics of Invasive Lobular Carcinoma of the Breast

The clinical features of invasive lobular carcinoma (ILC) of the breast have remained unclear due to the rarity of such cases. This study investigated the clinical and pathological features of ILC. The medical records of 413 patients with invasive breast cancer who underwent surgery in our department were reviewed. These cases included 13 patients with ILC (3.1%). The age of the patients ranged from 36 to 77 years old (mean, 56). The tumour size was evaluated as T1 in five patients, T2-4 in 8. The lymph node metastasis was diagnosed as negative in six patients, positive in six. In this patient population, 11 (85%) and nine (69%) patients were positive for oestrogen and progesterone receptors, respectively. The 5-year survival rate was 76.2%, which was not significantly different from other types of invasive breast cancer. Extensive intraperitoneal metastasis was observed in two of the three patients. Two patients had bilateral carcinoma and one patient had a multicentric lesion in the ipsilateral breast. Multicentric development of breast cancer and intraperitoneal metastasis were one of clinical characteristics of ILC. The prognosis of ILC was not significantly different from other types of invasive breast carcinoma.

Proteomics of Grade 3 infiltrating ductal carcinoma in Malaysian Chinese breast cancer patients

Breast cancer is the leading cause of cancer-related mortality and morbidity among women worldwide and IDC (infiltrating ductal carcinoma) is the most common type of invasive breast cancer. The changes in the biological behaviour of cancer tissue can be predicted by measuring the differential protein expression of normal and cancerous tissues. Using a combination of SDS/PAGE and LC (liquid chromatography)-MS/MS (tandem MS), we identified 82 common and differentially expressed proteins from normal and cancerous breast tissues in 20 Malaysian Chinese patients with IDC. These proteins are extracted from the normal and cancerous tissue of patients and therefore represent the actual proteins involved in cancer development. Proteins identified possibly have significant roles in the development of breast cancer in Malaysian Chinese patients in view of their consistent expression in most of the patients, although some of the proteins had not been detected in earlier studies that were mostly carried out in Western countries. This observation suggests that molecular mechanisms leading to breast cancer development in this region may not be identical with those leading to IDC in Western regions.

An investigational rapid RT-PCR assay for the detection of metastasis in sentinel lymph nodes shows improved performance over frozen section H&amp;E: Analysis by primary tumor characteristics

10561 Background: In order for a RT-PCR test to accurately diagnose the metastatic status of sentinel lymph nodes the test must perform well across all primary tumor types. Methods: A prospective study was conducted at 11 clinical sites to evaluate a real- time RT-PCR assay (investigational GeneSearch™ Breast Lymph Node Assay, Veridex, LLC, Warren, NJ, USA) for the detection of sentinel lymph node metastasis in patients with invasive breast cancer. Detection limits were pre-set to detect only metastases that are clinically relevant (&gt; 0.2 mm). Tumor information such as tumor stage, size, type and other molecular characteristics were collected. RT-PCR assay was then compared against permanent section H&amp;E and IHC for final performance calculations. A total of 416 patients’ results were analyzed for overall assay performance: sensitivity 87.6% and specificity 94.2%. The assay was then evaluated within each primary tumor characteristics category. Results: Overall RT-PCR sensitivity is an improvement (p= 0.039) over that of current intra-operative methods (frozen section H&amp;E), while specificity is similar (p=0.054). For the various tumor sub-types, in a matched dataset, the RT-PCR assay has up to 35.7% (Invasive Lobular) higher sensitivity compared to frozen section H&amp;E. Conclusions: The data suggest that the RT-PCR assay performs well and has higher sensitivity than frozen section H&amp;E regardless of primary tumor characteristics and, therefore, can be used to detect metastasis for all types of invasive breast cancer. [Table: see text] No significant financial relationships to disclose.

Relationship between Established Breast Cancer Risk Factors and Risk of Seven Different Histologic Types of Invasive Breast Cancer

Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types. Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression. Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma. Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer.

Premalignant and In Situ Breast Disease: Biology and Clinical Implications

Most types of invasive breast cancer are thought to evolve over long periods from specific preexisting benign lesions. Of the many types of benign entities found in the human breast, only a few have clinically significant premalignant potential. Currently, the best-characterized premalignant lesions are atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ. Ductal carcinoma in situ is considered to be a preinvasive malignant lesion. Two additional lesions, unfolded lobules and usual ductal hyperplasia, are sometimes considered to be very early premalignant epithelial abnormalities. Premalignant lesions are currently defined by their histologic features, and not all necessarily progress to invasive cancer. This suggests that although lesions within specific categories look alike, they must possess underlying genetic differences that cause some to remain stable and others to advance. The development of modern molecular genetic techniques has allowed breast cancer researchers to clarify the multistep model of breast carcinogenesis. Recent studies indicate that cancer evolves by highly diverse genetic mechanisms, and research into these altered pathways may identify specific early defects that might be targeted to prevent progression of premalignant lesions to invasive cancer. Current clinical management is heterogeneous and depends on histologic examination and individual patient factors. Options for breast cancer risk reduction and prevention are available.

Secretory breast carcinoma—case report and review of the medical literature

Secretory breast carcinoma (SBC) is a rare type of invasive breast cancer. Since little is known about the biology of this rare tumour, it is useful to report every such case, in order to make as much information as possible available in the medical literature. We present the case of an 18-year-old woman with a SBC treated by mastectomy (Madden) and axillary node dissection (stage pT3N1M0) 1 1 American Joint Commission on Cancer (1997). followed by chemotherapy (FEC 2 2 FEC—5-fluorouracil (5-FU)+epirubicin+cyclophosphamide. regimen) and radiotherapy. The patient has meanwhile completed 4 years of follow-up with no evidence of recurrence. The authors review the literature and summarize relevant findings concerning definition, pathology, clinical picture, treatment, and follow-up.

Special types of invasive breast cancer, with clinical implications.

Analysis of invasive breast cancers by histopathology has generally revolved around the analysis of individual characteristics such as nuclear pleomorphism and/or gland formation (grading) or categorization by specific histologic patterns (special type carcinomas). Recognition of special types of invasive breast carcinoma allows for the identification of women with an extremely good prognosis often approaching or equaling that of the general population of the same age (with unique problems for medullary). The distinguishing features of special types of breast cancer are present in complete or classic form in the pure examples of these cases, and the features recognizing these types may be present in lesser degrees in many carcinomas of no special type or not otherwise specified in which they often have important clinical correlates other than strong indicators of survival, such as recognizing the diffusely invasive feature of lobular and lobular-like cancers. Many other features have been noted as contenders for types of breast cancer (such as squamous, cystic, clear cell, histiocytoid, and lipid rich). These terms are not discussed here because they have no special clinical correlates relevant to diagnosis or prognosis. It should be reemphasized here that combined histologic grade (Nottingham system favored) with nuclear, glandular, and mitotic evaluation is expected by most authorities for clarification of diagnosis in all but rare, pure medullary cancers. (5, 13, 14, 27) The Nottingham grade 11 interacts with nodal status to produce a very strong prognostic index. The mitotic count may be the most important part of the grading system, certainly for prognosis within 5 years of diagnosis. (22, 26)

Integrated decision support system/image archive for histological typing of breast cancer using a relation oriented inference system.

Histological typing of invasive breast cancer according to the World Health Organisation criteria is prognostically relevant, because some histological subtypes have a markedly better prognosis. However, reproducibility of histological typing is not high because of the absence of strict typing criteria, variations in the application of the typing criteria and the usually limited illustration of the relevant criteria. The aim of this study was to develop an expert system based on highly structured histological typing criteria, integrated with high-quality microscope images to illustrate the typing criteria. This system should be useful as a decision support system in the diagnosis of breast cancers and should increase the reproducibility of histological typing. Criteria for typing were extracted from textbooks and, based on experience, these criteria were structured and implemented in the Relation Oriented Inference System (ROIS), in which information can be structured by defining relations. Illustrative black and white images were digitized and integrated into the shell. The performance of the resulting decision support system was evaluated by a group of six pathologists using a set of slides covering the spectrum of the most frequently occurring histological types of invasive breast cancer. The pathologists first assessed histological type according to standard morphological procedures. The cases were then reassessed with the decision support system available for consultation. The use of the decision support system appeared to influence the previously assessed histological type in about half of the cases. Using the decision support system, histological typing was more uniform and more in accord with a 'gold standard' set by two experts.(ABSTRACT TRUNCATED AT 250 WORDS)