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Vaccine Delays Recurrence in Ovarian Cancer: In a phase II open-label clinical trial, maintenance therapy with Vigil, an autologous tumor cell vaccine, resulted in a delay in disease progression in late-stage ovarian cancer patients. Bevacizumab Added to Chemotherapy Improves Progression-Free Survival in Ovarian Cancer: The Gynecologic Oncology Group 213 trial demonstrated that adding bevacizumab to paclitaxel and carboplatin improved progression-free survival in 674 women with recurrent, platinum-sensitive ovarian cancer.
Olaparib Beneficial in Heavily Pretreated Advanced Ovarian Cancer Patients With BRCA Mutations: A pooled analysis from six prospective clinical trials found that patients with relapsed ovarian, fallopian tube, or peritoneal cancer with germline BRCA mutations had a 36% overall response rate with olaparib monotherapy. Varying Ovarian Cancer Survival Outcomes Among Asian and Caucasian Patients: Asians enrolled in phase III epithelial ovarian cancer clinical trials had prolonged survival compared with Caucasian patients. High Pretreatment Circulating Tumor Cell (CTC) Count Associated With Higher Survival in Cervical Cancer: Advanced cervical cancer patients who had higher numbers of CTCs prior to treatment with chemotherapy plus bevacizumab in the Gynecologic Oncology Group 240 phase III clinical trial had higher overall survival. This journal is a member of and subscribes to the principles of the Committee on Publication Ethics. The good news is that nearly all women diagnosed with this early-stage breast cancer can be cured.
Carcinoma in-situ is a condition of the breast milk ducts and lobules where malignant (cancer) cells of varying differentiation (grade) are present, but do not break through the wall of the duct or lobule.
The 2010 American Joint Committee on Cancer (AJCC) and the International Union for Cancer Control (UICC) gives carcinoma in-situ the designation of Tis and Stage O (TisNoMo). Lobular carcinoma in-situ (LCIS) (or ‘lobular neoplasia’) is often grouped with ductal carcinoma in situ (DCIS) as a non-invasive breast cancer.
The 2012 World Health Organization (WHO) classification of breast tumors lists both DCIS and LCIS (‘lobular neoplasia’) as precursor lesions for breast cancer, but emphasizes their different clinical behavior. It is important for the Pathologist to distinguish between ductal carcinoma in-situ (DCIS) and lobular carcinoma in-situ (LCIS) on the breast tissue biopsy or excisional biopsy specimen. Very simply then, ductal carcinoma forms in the lining of a milk duct and lobular begins in the lobules which are connected to the ducts and produce breast milk.
An abnormality detected by mammography may be assessed by core needle biopsy (CNB), incision biopsy or local excision. Sentinel lymph node (SLN) dissection is not indicated in the evaluation of the patient with confirmed DCIS undergoing breast-conserving surgery (BCS).
Ductal carcinoma in-situ (DCIS) is not a life-threatening condition, but the diagnosis can be alarming.
In 2006, the European Organisation for Research and Treatment of Cancer (EORTC) Trial 10853, reported a 10-year cancer-specific survival for DCIS of more than 97% (Bijker et al., 2006).
DCIS is believed to progress inevitably to invasive ductal carcinoma and so it is considered to be a true ‘pre-malignant’ condition. This is why, ladies, it is so important to attend regular screening tests for breast cancer. Magnetic resonance imaging (MRI) is no better than mammography for distinguishing between DCIS and benign, atypical proliferative breast lesions or micro-invasion. What is known is that the grade, or degree of differentiation, of the cells that make up the DCIS are important.
Ductal carcinoma in-situ (DCIS) lesions are classified based upon the growth pattern and cytological appearances of the atypical cells within the ducts.
The micro-papillary type of DCIS: small tufts of cells, oriented perpendicular to the basement membrane and projecting into the duct lumena.
The papillary type of DCIS: intraluminal projections of tumor cells that do have fibrovascular cores. The solid type of DCIS: tumor cells completely fill and distend the involved duct spaces, without necrosis, fenestrations or papillary projections. High-grade DCIS lacks estrogen recept and progesterone receptors, has a high proliferative rate, over-expresses the HER2 oncogene, has mutations of the p53 oncogene and is associated with angiogenesis in the surrounding breast stroma. When a diagnosis of ductal carcinoma in-situ (DCIS) has been made, without invasion, there is no risk of metastatic spread to other sites in the body (infiltrating ductal carcinoma). For women having mastectomy as a treatment option, the risk of local recurrence of DCIS is less than 2 %.
Women who are treated with hormonal therapy, such as tamoxifen, after surgery, have a further reduction in risk of recurrence by 50%.
It is known that the history of DCIS in one breast may be associated with a small increased risk for breast cancer in the other breast (as a new primary cancer), so careful follow-up monitoring of both breasts is advised.
In 2011, clinical trials from the Surveillance, Epidemiology, and End Results (SEER) study of 8,466 cases of DCIS reported an equivalent long-term survival regardless of local treatment (Schonberg et al. These are only general statistics and each case is individual and each year brings new potential. Overall survival for women aged 67 years or older was similar to women not diagnosed with breast cancer.

Mortality risk from breast cancer was estimated to be 1.9 % within ten years, based on the SEER data (Schonberg et al. Women aged 67 years or older were more likely to die of unrelated causes, such as cardiovascular disease. The Van Nuys Prognostic Index (VNPI) is a scoring system used to predict the likelihood of local recurrence following wide excision alone in patients with DCIS. These malignant, but non-invasive ductal cells may travel along the lactiferous ducts to involve the nipple and the skin of the nipple. Paget’s disease of the breast can be associated with ulceration and thickening of the nipple. Lobular carcinoma in-situ (LCIS) is associated with a 7- to 11-fold increased risk of subsequent development of breast cancer in either breast. All this information must be so hard to digest if you’ve just found out you have breast cancer.
Lobular carcinoma in-situ (LCIS) is distinguished from atypical lobular hyperplasia (ALH) histologically. There is little evidence that high-grade features of LCIS (cellular pleomorphism, necrosis and solid involvement of ducts) is predictive of a higher subsequent risk of invasive breast cancer. There are no clinical recommendations for the complete excision of either ALH or LCIS or the pleomorphic variant of LCIS (PLCIS). LCIS is an indolent lesion with very low malignant potential, but it does convey a risk for ipsilateral as well as contralateral invasive breast cancer (lobular carcinoma).
The relative risk of developing an invasive cancer in women with LCIS is approximately twice that of women without LCIS.
LCIS is found in association with an invasive carcinoma in approximately 5 % of breast cancer specimens.
The presence of LCIS in association with an invasive cancer is not a contraindication to breast-conserving therapy.
When lobular carcinoma in-situ (LCIS) is identified in the histology from a core needle biopsy (CNB), an excision biopsy will then be performed to exclude an associated invasive malignancy (see Section 8) and possibly a lymph node biopsy. Studies have identified either DCIS or an invasive cancer in between 15 % to 38 % of patients with LCIS.
If LCIS is diagnosed on histology of an excision breast biopsy, no further surgery is required.
If an invasive carcinoma is detected on histology, appropriate management should be initiated. In 1990, Bradley and colleagues published a meta-analysis of published data, including 389 women diagnosed with LCIS, followed for a mean of 10.9 years.
Most clinical experts consider prophylactic bilateral mastectomy to be a very drastic approach for the moderate level of risk associated with LCIS in the absence of other contributory risk factors. While women with LCIS have a significantly higher risk for developing invasive breast cancer compared with the general population, most will not develop invasive cancer.
The presence of LCIS in association with an invasive cancer is not a contraindication to breast-conserving therapy (BCT). Variants of classic LCIS exist and include forms with marked distension and comedo-type necrosis, as well as pleomorphic and apocrine pleomorphic LCIS.
Classic LCIS is managed as a marker of increased breast cancer risk rather than as a precursor lesion for invasive cancer; the exception is pleomorphic LCIS (PLCIS).
PLCIS consists of larger cells that demonstrate marked nuclear pleomorphism, cytologic dyscohesion and intracytoplasmic inclusions. Recognition of the pleomorphic subtype is important because the nuclear features, necrosis, and calcifications can make the differentiation from DCIS challenging. Patients who are diagnosed with PLCIS by a core biopsy are advised to undergo a surgical excision of the lesion. Remember, laughter is the best medicine, but if you’re laughing without any reason you need medicine! 20% of breast carcinomas are of special type and the majority of these are lobular carcinomas.
It is recommended that special types of carcinoma are graded using the same criteria as no specicial type cancers.
These tumours, in their classical form, are characterised by a single file infiltrating pattern. As general guidance if you think the tumour is morphologically lobular report it as such whatever the E cadherin status unless it is really strong when you should look at the H&E again!
Invasive lobular carcinoma showing aberrant E Cadherin staining and cytoplasmic 'Golgi' pattern beta catenin staining - note the normal pattern of beta catenin staining in the duct on the left.

The trial included 31 patients who either received the vaccine (n = 20) or did not (n = 11).
The 273 patients included in the analysis had all been previously treated with chemotherapy. It is important that the patient is aware of what the differences in terminologybetween a DCIS diagnosis and a LCIS diagnosis mean. Axillary nodes are rarely positive for metastatic disease, even with extensive multi-focal, high-grade DCIS.
It is uncommon in women younger than 30 and is as high as 88 per 100,000 in women aged 50 to 64 years. The pattern of micro-calcification can be characteristic; fine granular calcifications are associated with low-grade DCIS and linear branching or segmental types of pleomorphic micro-calcifications are associated with high-grade DCIS.
All patients with suspected DCIS should have a diagnostic bilateral mammogram with magnification views to assess the morphology and extent of any micro-calcifications. The classification of DCIS or the different descriptive types of DCIS may just be a reflection of the grade of the component epithelial cells and how rapidly they divide. The epithelial cells in this subtype are typically small- to medium-sized, with uniform, dark cell nuclei. They’re just classifications based on the type, structure and growth patterns of the abnormal cells in the breast ducts. These features include the size or extent of the DCIS, cell polarization, the presence and location of micro-calcifications (with DCIS with normal tissues) and the presence and type of necrosis. When the diagnosis of DCIS has been made, it is advised to maintain a screening schedule to monitor for any local recurrence in the original breast and also to monitor the healthy breast.
For women having local excision of the DCIS lesion with radiation therapy, the risk of local recurrence ranges from 5% to 15%.
For ductal carcinoma of the breast, the AJCC staging classification is Tis (DCIS) (see Section 7). The distension of more than half of the acini of the lobular unit by uniform, but non-cohesive, small, atypical epithelial cells is diagnostic for LCIS. Treatment of lobular carcinoma in-situ (LCIS) should be based upon the individual patient and their clinical situation. Women with an invasive cancer and LCIS in the specimen may be at greater risk of disease recurrence than those without LCIS. But there are no randomized trials addressing the comparative efficacy of surveillance versus prophylactic mastectomy in a population of high-risk women. In this analysis, breast cancer-specific mortality was 2.8 % among women who had initial excision followed by surveillance and mastectomy for recurrence. The clinical significance of these variants, and the appropriate management is uncertain at the present time. In order to make a diagnosis of a special type of carcinoma >90% of the tumour is required to show the particular pattern in question. You may be offered a sentinel lymph node biopsy to ascertain if the cancer has spread to the lymph nodes, usually in DCIS the cancer cells are contained within the ducts. A risk of breast cancer-related death in women with DCIS is low, estimated at 1.9 % within ten years. These micro-calcifications may be detected mammographically, as linear or branching calcifications.
Your multidisciplinary care team will guide and advise you on the decision-making process for treatment options.
Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: Ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III Trial 10853—A study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: twelve-year observations concerning lobular carcinoma in situ. Within the group of patients treated with bevacizumab, the hazard ratio (HR) for death for pre-treatment CTC counts was 0.9. The case of hysterectomy at risk-reducing salpingo-oophorectomy was cervical cancer stage IAI (BRCA1). A phase III randomized controlled clinical trial of carboplatin and paclitaxel alone or in combination with bevacizumab followed by bevacizumab and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian, peritoneal primary and fallopian tube cancer (Gynecologic Oncology Group 0213). Differences in presentation and survival of Asians versus Caucasians with ovarian cancer: A Gynecologic Oncology Group ancillary study of 7914 patients.

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