The answer is 2, study of hormone receptors and HER2. This is because no study of first-degree relatives is appropriate, as it does not appear to be hereditary breast cancer since there is no family history of neoplasia. On the other hand, there is no indication for BRCA 1-2 study.

The answer is [HIDDEN], study of hormone receptors and HER2. This is because no study of first-degree relatives is appropriate, as it does not appear to be hereditary breast cancer since there is no family history of neoplasia. On the other hand, there is no indication for BRCA 1-2 study.

A 67-year-old woman diagnosed with infiltrating ductal carcinoma of the breast with no family history of neoplasia. What additional studies should be performed on the tumor because of its clinical and therapeutic implications?

Complete phenotypic study by flow cytometry.

Study of hormone receptors, e-cadherin and study of first degree relatives.

Study of BRCA 1-2 and study of first-degree relatives.

The significance of family history for patients with carcinoma of the breast.

Since the risk of carcinoma of the breast is increased in women with a family history of the disease, new primary carcinomas of the breast may be increased after treatment. Women with several relatives with carcinoma of the breast are thought to be at higher risk of having a second primary carcinoma of the breast develop and mastectomy is more frequently recommended. The computerized registry of the Mount Sinai Medical Center Breast Service was used to identify 1,337 patients with complete information concerning family history. Three hundred fifty-nine patients with a family history of carcinoma of the breast were compared with women with no family history. Compared with patients with no family history of carcinoma of the breast, patients with a family history of carcinoma of the breast were significantly younger (54.0 versus 55.8 years of age, p < 0.01), were significantly more likely to have used oral contraceptives (26 versus 13 percent, p < 0.001), had significantly more ductal carcinoma in situ (10 versus 4 percent, p < 0.01), and were significantly more often treated with breast conservation (42 versus 31 percent, p < 0.001). Simultaneous contralateral carcinoma of the breast was diagnosed more frequently in patients with a family history (3 versus 1 percent, p < 0.025), but metachronous contralateral carcinomas were not increased. In comparing the two groups, there were no significant differences in proportion premenopausal, parity, use of postmenopausal hormones, tumor size, tumor differentiation, nodal involvement, TNM stage, estrogen receptor status, or use of adjuvant radiation, chemotherapy, or tamoxifen. Complete five-year follow-up evaluation for 748 patients, 179 with a family history, found no differences in local, distant, or disease-free survival rates for mastectomy or breast conservation in relation to family history. Outcome for patients with first-degree affected relatives and those with more than one affected relative was the same as those with no family history. These results indicate that women with a family history of carcinoma of the breast should be treated no differently than women with no family history.

BRCA mutation

Relative indications for testing for a mutation in BRCA1 or BRCA2 for newly diagnosed or family members include a family history among 1st (FDR), 2nd (SDR), or 3rd(TDR) degree relatives usually on the same side of the family but not limited: A known mutation (BRCA1 or BRCA2) in a cancer susceptibility gene within the family Women affected with any breast cancer diagnosed under the age of 30 Women affected with triple negative breast cancer (TNBC) (estrogen receptor negative, progesterone receptor negative, and HER2/neu negative) under the age of 50 Two relatives (FDR/SDR) diagnosed under the age of 45 Three relatives (FDR/SDR) diagnosed with average age of 50 or less Four relatives at any ages Ovarian cancer with either an additional diagnosed relative or a relative with male breast cancer A single family member with both breast and ovarian cancer Male breast cancer Pancreatic cancer with breast or ovarian cancer in the same individual or on the same side of the family

Influence of young age at diagnosis and family history of breast or ovarian cancer on breast cancer outcomes in a population-based cohort study.

The objective of this study was to examine the association of: (i) diagnosis at age </=35, (ii) first-degree family history of breast or ovarian cancer (BOC) and (iii) a research based definition of genetic risk, with tumor characteristics, treatment and survival in breast cancer (BC). Consenting female participants in the population-based Ontario Familial Breast Cancer Registry diagnosed with primary invasive BC between 1996 and 1998 were followed prospectively until 2005. Among 967 women, 105 were </=35 years old at diagnosis and 686 were classified as genetic risk cases, including 349 with a first-degree family history. Individuals diagnosed at age </=35 were more likely to self-detect tumors, to present with inflammatory BC, to have invasive ductal carcinoma of no special type, high T stage, and tumors with lymphovascular invasion (LVI), high grade and negative estrogen receptors. Younger women were more likely to receive chemotherapy and less likely to receive hormonal therapy. Diagnosis </=35 years old was associated with significantly reduced distant recurrence free survival, an effect that did not persist after adjustment for tumor and treatment related variables. Poor outcomes were restricted to younger women with hormone responsive BC. Family history was associated with increased rates of mammographic detection of BC, lower tumor stage and less frequent inflammatory BC, but had no association with BC outcomes. Women diagnosed with BC at age </=35 have more aggressive tumors; these adverse tumor characteristics, rather than age, lead to poor outcomes. Family history was not associated with survival.

Clinical features and first degree relative breast cancer, their correlation with histological tumor grade: a 5-year retrospective case study of breast cancer in Mizoram, India.

The aim was to assess the association of histological tumor grade with other clinical features and epidemiological factors of women with invasive breast carcinoma. A retrospective study of 103 Mizo breast cancer patients visiting hospitals was made in Aizawl, Mizoram, Northeast India. With a prior consent, information on epidemiological factors and family history in relation to cancer was obtained. Clinical reports were obtained from their medical records. The frequency of distribution was calculated for age at diagnosis and tumor characteristics. Statistical analysis for different variables was done using a chi-square test. p < 0.05 was considered significant. The histological tumor grades in our studies were found to be associated with lymph node invasion (p < 0.021), different subtype of hormone receptor such as ER status (p < 0.004), ER/PR status (p < 0.007), HER2/neu status (p < 0.014), and ER/PR/HER2 status (p < 0.025). A patient with a family history of breast cancer in their 1st degree relative is also seen to have association in determining the tumor grade (p < 0.003). Reproductive history, lifestyle and dietary habits, tobacco, and alcohol consumption were found to have no influence on breast cancer tumor grade. Our results showing significant correlation between status of lymph node, ER, PR, and HER2/neu oncoprotein and family history with 1st degree relative breast cancer are the first time report to target and focus on the possible role of biomarkers for diagnosis among the Mizo tribal breast cancer patients.

Cancer biomarker

Similarly, additional laboratory research has shown that tumor cells undergoing apoptosis can release cellular components such as cytochrome c, nucleosomes, cleaved cytokeratin-18, and E-cadherin. Studies have found that these macromolecules and others can be found in circulation during cancer therapy, providing a potential source of clinical metrics for monitoring treatment. Recurrence Cancer biomarkers can also offer value in predicting or monitoring cancer recurrence. The Oncotype DX® breast cancer assay is one such test used to predict the likelihood of breast cancer recurrence. This test is intended for women with early-stage (Stage I or II), node-negative, estrogen receptor-positive (ER+) invasive breast cancer who will be treated with hormone therapy. Oncotype DX looks at a panel of 21 genes in cells taken during tumor biopsy. The results of the test are given in the form of a recurrence score that indicates likelihood of recurrence at 10 years.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications.

Cancer arising in carriers of mutations in the BRCA1 and BRCA2 genes differs from sporadic breast cancer of age-matched controls and from non-BRCA1/2 familial breast carcinomas in its morphological, immunophenotypic and molecular characteristics. Most BRCA1 carcinomas have the basal cell phenotype, a subtype of high-grade, highly proliferating, estrogen receptor- and HER2-negative breast carcinomas, characterized by the expression of basal or myoepithelial markers such as basal keratins, P-cadherin, epidermal growth factor receptor, etc. This phenotype is rarely found in BRCA2 carcinomas, which are of higher grade than sporadic age-matched controls, but tend to be estrogen receptor- and progesterone receptor-positive. The expression of the cell-cycle proteins cyclins A, B1 and E and SKP2 is associated with a BRCA1 phenotype, whereas cyclin D1 and p27 expression is associated with BRCA2 carcinomas. Recent studies have shown that hereditary carcinomas that are not attributable to BRCA1/2 mutations have phenotypic similarities to BRCA2 tumors, but tend to be of lower grade and proliferation index. Somatic mutations in the BRCA genes are rarely found in hereditary tumors; by contrast, BRCA1 and BRCA2 loss of heterozygosity (LOH) is found in almost all BRCA1 and BRCA2 carcinomas, respectively. Furthermore, all types of hereditary breast carcinomas have a low frequency of HER2 expression. Finally, comparative genomic hybridization studies have revealed differences in chromosomal gains and losses between genotypes. The pathological and molecular features of hereditary breast cancer can drive specific treatments and influence the process of mutation screening. In addition, detecting molecular changes such as BRCA1/2 LOH in nonatypical cells obtained by random fine-needle aspiration, ductal lavage or nipple aspirate fluid may help to earlier identify carrier women who are at an even higher risk of developing breast carcinoma.

Negative/low HER2 expression alone or combined with E-cadherin positivity is predictive of better prognosis in patients with breast carcinoma.

The loss of E-cadherin expression leads to absence of tissue integrity, an essential step in tumor progression. Methylation of CpG islands in the promoter region of the CDH1 gene coding E-cadherin might be an alternative for gene silencing. In the present study, we investigate the expression of E-cadherin and hormone receptors in invasive ductal breast carcinoma (IDCs). Protein expression was analysed immunohistochemically in 87 cases, including 26 familial tumors. The most interesting results revealed a significantly reduced E-cadherin expression in cases with familial history compared to sporadic tumors (p=0.009), as well as with tumors ≤5 cm (p=0.022). Moreover, HER2 over-expression was associated with distant metastasis (p=0.011) and overall survival (p log rank=0.028). Tumors displaying negative/low HER2 expression combined with E-cadherin positivity confer better patient survival (p=0.052). Triple Negative tumors (TN) were more frequently found in patients with advanced grade (GIII) (p=0.001) and TNM (III+IV) (p=0.018) which supports the aggressive behavior of TN tumors. On the other hand, hypermethylation of CDH1 gene promoter was observed in 46% of hereditary cases and strongly associated with loss of E-cadherin expression (p=0.002). Furthermore, patients with unmethylated CDH1 pattern have a better 5-year disease free survival (p=0.021). In conclusion, in patients with hereditary breast cancer, the CpG methylation event contributes to the loss of E-cadherin expression. On the other hand, HER2 over-expression is predictive of worse prognosis, either alone or combined with loss of E-cadherin expression in Tunisian patients with breast cancer.

Four new cases of double heterozygosity for BRCA1 and BRCA2 gene mutations: clinical, pathological, and family characteristics.

Double heterozygosity (DH) for BRCA1 and BRCA2 mutations is a very rare finding, particularly in non-Ashkenazi individuals, and only a few cases have been reported to date. In addition, little is known on the pathological features of the tumors that occur in DH cases and on their family history of cancer. Four carriers of pathogenic mutations in both BRCA1 and BRCA2 were identified among women who underwent genetic counseling for hereditary susceptibility to breast and ovarian carcinoma at three different Italian institutions. Clinical, pathological, and family history data were collected from medical records and during genetic counseling sessions. All identified DH cases developed breast carcinoma and three of them were also diagnosed with ovarian carcinoma. Mean ages of breast and ovarian cancer diagnosis were 42.7 and 48.6 years, respectively. The majority of breast cancers showed a BRCA1-related phenotype, being negative for hormone receptors and HER2. Two cases reported different gastrointestinal tumors among relatives. Although the individuals described in this study show more severe clinical features in comparison to previously reported BRCA1 and BRCA2 DH cases, our observations support the hypothesis of a non specific phenotype of DH cases in terms of age of disease onset. In addition, our observations indicate that in DH patients breast carcinogenesis appears to be driven mainly by the mutations in BRCA1. The possible association of DH for BRCA gene mutations with gastrointestinal tumors is in keeping with previous reports, but needs to be confirmed by further analyses.

Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk.

Triple-negative breast cancer accounts for less than 20% of breast cancers overall, but is the predominant subtype among carriers of mutations in BRCA1. However, few studies have assessed the association between breast cancer family history and risk of triple-negative breast cancer. We examined the relationship between having a family history of breast cancer in first-degree relatives and risk of triple-negative breast cancer, and risk of two other breast cancer subtypes defined by tumor marker expression. We evaluated data collected by the Breast Cancer Surveillance Consortium from 2,599,946 mammograms on 1,054,466 women, among whom 15% reported a first-degree family history of breast cancer. Using Cox regression in this cohort, we evaluated subtype-specific associations between family history and risk of triple-negative (N = 705), estrogen receptor-positive (ER+, N = 10,026), and hormone receptor-negative/HER2-expressing (ER-/PR-/HER2+, N = 308) breast cancer among women aged 40-84 years. First-degree family history was similarly and significantly associated with an increased risk of all the subtypes [hazard ratio (HR) = 1.73, 95% confidence interval (CI): 1.43-2.09, HR = 1.62, 95% CI: 1.54-1.70, and HR = 1.56, 95% CI: 1.15-2.13, for triple-negative, ER+, and ER-/PR-/HER2+, respectively]. Risk of all the subtypes was most pronounced among women with at least two affected first-degree relatives (versus women with no affected first-degree relatives, HR(triple-negative) = 2.66, 95% CI: 1.66-4.27, HR(ER+) = 2.05, 95% CI: 1.79-2.36, HR(ER)-(/PR)-(/HER2+) = 2.25, 95% CI: 0.99-5.08). Having a first-degree family history of breast cancer was associated with an increased risk of triple-negative breast cancer with a magnitude of association similar to that for the predominant ER+ subtype and ER-/PR-/HER2+ breast cancer.

BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations. A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR). (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p = 1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p = 0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39 years, compared with 46 years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX ≥ 2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p = 0.022), age at diagnosis ≤35 years (OR 0.149, 95% CI 0.023-0.954, p = 0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p = 0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p = 0.459 and p = 0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p = 0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p = 0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR. DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35 years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.

Breast cancer and family history: a multivariate analysis of levels of tumor HER2 protein and family history of cancer in women who have breast cancer.

The HER2 gene, located on the long arm of chromosome 17, codes for a protein with the characteristics of a growth factor receptor. In a preliminary study, we reported that high levels of tumor HER2 (erbB-2/neu) protein are associated with a family history of breast cancer (that is, one or more female blood relatives with breast cancer). We have now collected a larger number of subjects (94) and performed a multivariate analysis of the independent variables family history of breast cancer, tumor estrogen receptor, age, and tumor DNA index. Family history of breast cancer was assessed by questioning the patient, in many cases by telephone. HER2 levels were significantly higher in women with a family history of breast cancer (p = 0.015, two-tailed t-test). The 27 women with family history were predominantly postmenopausal, mean age 61 +/- 2.3 (mean +/- SEM), versus a mean age of 56 +/- 1.7 for the 67 women with no family history. Of the 27 women with a family history of breast cancer, 13 had a first-degree relative (mother or sister) with the disease. The remaining 14 women had other relatives (grandmothers, aunts, cousins, or a niece) with breast cancer. The results of multiple linear regression analysis, with HER2 as the dependent variable, showed that family history of breast cancer was significantly associated with elevated HER2 levels in the tumors (p = 0.0038), after controlling for the effects of age, tumor estrogen receptor, and DNA index. The association of family history of breast cancer and elevated tumor HER2 protein suggests that postmenopausal familial breast cancer may be associated with altered HER2 expression.

Lobular carcinoma in situ

Cells of Lobular Neoplasia (LN), including both Atypical Lobular Hyperplasia and LCIS, and ILC share common genetic alterations, perhaps accounting, in part, for the similarities in histologic appearance. Classic LCIS and invasive lobular lesions are low-grade ER and PR-positive cancers, referring to the positive expression of Estrogen and Progesterone receptors on the neoplastic cells (determined via immunohistochemistry). These entities are also both classically negative for HER2 (human epidermal growth factor receptor 2). These hormone and growth factor receptors are clinically significant, as they represent targets for chemotherapy. Chromosomal alterations have also been consistently observed between LCIS and ILC – namely, loss of 16q and gain of 1q, referring to the loss of the long arm (designated q) of chromosome 16 and an extra copy of the long arm of chromosome 1. Furthermore, e-cadherin, the transmembrane protein mediating epithelial cell adhesion, exhibits loss of

Metaplastic carcinoma

Metaplastic carcinoma, otherwise known as metaplastic carcinoma of the breast (MCB), is a heterogeneous group of cancers that exhibit varied patterns of metaplasia and differentiation along multiple cell lines. This rare and aggressive form of breast cancer is characterized as being composed of a mixed group of neoplasms containing both glandular and non-glandular patterns with epithelial and/or mesenchymal components. It accounts for fewer than 1% of all breast cancer diagnoses. It is most closely associated with invasive ductal carcinoma of no special type. (IDC), and shares similar treatment approaches. Relative to IDC, MCB generally has higher histological grade and larger tumor size at time of diagnosis, with a lower incidence of axillary lymph node involvement. MCB tumors are typically estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER-2) negative, meaning hormone therapy is generally not an effective treatment option, which correlates to

Breast cancer expression of E-cadherin does not differ between patients with positive and negative oncological history.

The question of whether or not non-sporadic breast malignancies have different immunohistochemical features than sporadic malignancies has not been investigated previously. Consequently, the purpose of this study was to compare the expression of E-cadherin (EC) in breast cancer patients with positive and negative oncologic histories. The study included 98 breast cancer patients divided into two groups: 1) without the personal or familial history of previous malignancies, and 2) with the personal history of previous malignancies and/or with the data on cancer episodes in first- and/or second-degree relatives. There were no significant differences in the expression of EC between breast malignancies of the two groups. Moreover, statistical relationships were not observed between the positive or negative oncologic history, the age, and the menopausal status of patients, or histological tumor grade. Although the results of our series revealed no significant differences in the expression of EC between assumed sporadic and assumed non-sporadic malignancies, there is a need for further comparative studies on the immunohistochemistry of both the breast carcinoma types in order to find the other biological markers that could suggest or exclude cancer susceptibility in a given patient. Nevertheless, the results of our study suggest that EC immunohistochemistry cannot be used as a surrogate marker for screening for hereditary breast cancer.

Somatostatin receptor 2

other components of the endocrine system and nervous system, so it can be drawn that the receptor family has great influence among these systems. The family was first discovered in a segment of a rat's pituitary gland known as the tumor cell line. A cell line is grown as a culture under controlled conditions, so the first discovery was found by culturing these cells in controlled conditions and in an environment outside of its norm. There, researchers found that the tumor cell line expresses a cell dividing inhibitor known as the transforming growth factor beta (TGF-beta) and also acts as an inhibitor to the milk producing hormone in female mammals, prolactin, and growth hormones. Researchers studied the activity of the receptors by conducting an assay with Ligand binding studies, which basically means they were conducting studies to see how prevalent the binding of the receptors occurred. Differences in how prevalently they receptors bonded revealed the existence of multiple

Does family history influence survival in breast cancer cases?

A few studies have suggested a relatively better prognosis for breast cancer (BC) cases reporting a positive family history (FH). We aimed at comparing the survival of patients according to FH in a large hospital-based series of 1,278 BC cases. Information on FH for BC was obtained at diagnosis by interview. All cases reporting a first- or second-degree FH for breast carcinoma were compared with cases without FH. Overall survival was estimated using a product-limit method. Hazard ratios (HRs) and the corresponding 95% confidence intervals (95% CIs), adjusted for confounding factors, were computed using proportional hazard models. Overall, 240 (18.8%) cases reporting, at diagnosis, a positive FH (156 with at least 1 first-degree relative and 84 with at least 1 second-degree relative) were compared with 1,038 patients without FH for BC. No significant differences were found in terms of distribution of age at diagnosis, tumor stage, nodal involvement, receptor status and histology. Cumulative survival rates at 5 years for cases without FH and with first-degree and second-degree FH for BC were 79.8 (95% CI 77.0-83.0), 78.6 (95% CI 70.0-88.0) and 80.2 (95% CI 68.0-92.0), respectively (log-rank test, chi(2) (2) = 0.02, p = 1.0). After adjustment for age, pathologic size and nodal involvement, the HR among cases of invasive cancer with a first-degree FH of BC was 0.91 (95% CI 0.55-1.48); however, the HR for cases with second-degree FH was 1.18 (95% CI 0.62-2.25) compared to cases without FH. Our study, based on a large series of consecutive invasive BC cases, did not find any significant survival differences associated with a positive FH for breast carcinoma, suggesting the existence of a large heterogeneity among BC cases with FH.

Combined small-cell lung carcinoma

Pemetrexed has been shown to improve survival in non-squamous cell NSCLC, and is the first drug to reveal differential survival benefit in large cell lung carcinoma. C-SCLC appear to express female hormone (i.e. estrogen and/or progesterone) receptors in a high (50–67%) proportion of cases, similar to breast carcinomas. However, it is at present unknown whether blockade of these receptors affects the growth of c-SCLC. Prognosis Current consensus is that the long-term prognosis of c-SCLC patients is determined by the SCLC component of their tumor, given that "pure" SCLC seems to have the worst long-term prognosis of all forms of lung cancer. Although data on c-SCLC is very sparse, some studies suggest that survival rates in c-SCLC may be even worse than that of pure SCLC, likely due to the lower rate of complete response to chemoradiation in c-SCLC, although not all studies have shown a significant difference in survival.

Clinical characteristics of breast cancer patients with family history.

This study was conducted to acquire information as to the clinicopathological characteristics of breast cancer patients with family history. Of 583 patients with breast cancer, 60 (10.3%) had family history in at least one relative within the second-degree. The affected family member was most frequently a sister (43%), followed by the mother (23%) and an aunt (20%). Comparison of the data for the patients between with and without family history revealed no significant differences for any of mean age, menopausal status, histological type, histological staging, and estrogen receptor status. Although the sample size was small, neither the survival rate nor the bilaterality of disease was influenced by the family history of breast cancer.

Male Breast Cancer -- Etiology

Similarly to women, males have a higher risk of breast cancer if they have a first- or second-degree relative with breast cancer. Studies have shown that an affected sibling or parent of either gender may increase the risk of breast cancer in either the males or females in the family. Bevier et al. (2012) noted in their study that the relative risk (RR) of breast cancer was similar in either offspring when the father or mother was affected (RR = 1.73 and 1.74, respectively), but the risk was slightly higher in the females when the brother is affected as opposed to when the sister is affected (RR = 2.48 and 1.39, respectively). [3] Also, in addition to a family history of breast cancer, males with a BRCA mutation appear to have increased risk for breast cancer as well. Although rare for a male to have a BRCA mutation, those with BRCA2 carrier mutation have a 6% increased risk and BRCA1 with a 4% risk of developing the disease. [4] Other genetic disorders have been implicated in increasing the risk of MBC, including Klinefelter syndrome (47, XXY), Cowden syndrome ( PTEN tumor suppressor gene), Li-Fraumeni syndrome ( TP53 ), Lynch syndrome ( PALB2 and mismatch repair genes). [2] [4]

Selective estrogen receptor modulator

Tamoxifen is a first-line hormonal treatment of ER-positive metastatic breast cancer. It is used for breast cancer risk reduction in women at high risk, and as adjuvant treatment of axillary node-negative and node-positive, ductal carcinoma in situ. Tamoxifen treatment is also useful in the treatment of bone density and blood lipids in postmenopausal women. Adverse effects include hot flushes and more serious is two to three times higher relative risk of developing endometrial cancer compared to women of an age-matched population. Toremifene, a chlorinated tamoxifen derivative, causes fewer DNA adducts in liver than seen with tamoxifen in preclinical studies and was developed to avoid hepatic carcinomas. It is used as endocrine therapy in women with ER/PR-positive stage 4 or recurrent metastatic breast cancer and has demonstrated similar efficacy compared to tamoxifen as adjuvant treatment of breast cancer and in the treatment of metastatic breast cancer.

Parathyroid hormone 1 receptor

Interactions Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2 and Sodium-hydrogen antiporter 3 regulator 1. Model organisms Model organisms have been used in the study of PTH1R function. A conditional knockout mouse line called Pth1rtm1a(EUCOMM)Hmgu was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping See also Parathyroid hormone receptor References Further reading External links G protein-coupled receptors

Prognosis of breast cancer patients with familial history classified according to their menopausal status.

Breast cancer patients were classified in the family history positive (FHP) group when they had at least one second-degree relative who was a breast cancer patient. The results of a comparative study with patients classified in the family history negative (FHN) group showed the prognosis of the FHP group was significantly better than that of the FHN group. However, when those patients were classified according to their menopausal status at onset, there were no significant differences in survival rates between the FHP and FHN groups with onset before menopause, whereas the survival rate of the FHP group was significantly higher than that of the FHN group with onset after menopause. The same results were found when the FHP group was subgrouped into the FHP group with first-degree relatives and the FHP group with second-degree relatives. Further investigations on background factors revealed that the patients with onset before menopause showed no significant differences between the FHP and FHN groups in age at surgery, diameter of the tumor, histologic grade, the number of metastatic lymph nodes, body weight, estrogen receptor (ER) status, and the values of CEA and CA15-3 before surgery. On the other hand, the FHP patients with onset after menopause showed significantly lower numbers of metastatic lymph nodes and trends showing higher ER values and lower CA15-3-values. Therefore the favorable prognosis in the FHP group seems to be attributable to the higher survival rate of the FHP patients with onset after menopause.

Karen E. Knudsen

Research Knudsen is an oncology researcher whose studies are focused on precision medicine in advanced prostate cancer, with an emphasis on understanding therapeutic relapse and designing new means of clinical intervention. Her translational studies have resulted in new clinical trials targeting DNA repair, cell cycle, and hormonal regulation pathways in patients with advanced disease. Knudsen and her colleagues discovered the mechanisms by which androgen signaling impacts cancer cell proliferation and DNA repair processes, and identified novel strategies for therapeutic intervention. Notable discoveries include identification of RB tumor suppressor loss as a major mechanism of therapeutic bypass, discovery of the androgen-DNA repair axis, and elucidation of androgen receptor function in the mitotic cell cycle. Her discoveries were amongst the first to propose utilization of PARP 1/2 inhibitors for advanced disease, now an FDA-approved agent for selected prostate cancers.

A clinicopathological analysis of breast cancer in patients with a family history.

A study was conducted to investigate the clinical and pathological characteristics of breast cancer in patients with a family history (FH). Among 4,481 primary breast cancer patients, 394 (8.8%) had families which included two or more breast cancer patients within three generations (FH(+)group). This group was compared with the remaining 3,969 patients (FH(-) group) with the following results: (1) The tumor diameter in the FH(+) group was slightly less than that in the FH(-) group [not significant (NS)], with fewer lymph node metastases (P < 0.05); (2) the positive rates for the estrogen receptor were 52% (138/266) and 49% (1,216/2,481), respectively (NS); (3) expression of the c-erbB-2 protein was observed in 14 out of 40 (35%) and 32 out of 100 cases (32%), respectively (NS); (4) the relative risk of bilateral occurrence in the FH(+) group was 1.4, with a 95% confidence interval of 0.9-2.4; (5) the 15-year survival rate was 72% and 60%, respectively, suggesting a better prognosis for the FH(+) group (P < 0.01); and (6) multivariate analysis showed that the contribution of FH to postoperative survival was marginal (P = 0.07). Factors related to the hormonal environment such as age at menarche (P = 0.08) and age at menopause (P = 0.08) made a greater but non-significant contribution to the prognosis of the FH(+) group than to that of the FH(-) group. However, further genetic and molecular biological analyses of familial breast cancer are needed in order to clarify the mechanisms of cancer accumulation within families.

Abemaciclib

As of early 2016, abemaciclib was involved in 3 Phase III clinical trials: The JUNIPER Study is comparing abemaciclib against erlotinib in patients with stage IV non-small-cell lung carcinoma Due to collect data until September 2017. The MONARCH 2 study is investigating the effectiveness of abemaciclib in combination with fulvestrant for women with breast cancer. It is due to end in Feb 2017. In March 2017, Eli Lilly announced that it had met its primary endpoint of superior progression-free survival (PFS) over placebo plus fulvestrant in patients with estrogen receptor positive and HER2 negative advanced or metastatic breast cancer. This result led to the September 2017 FDA approval. The MONARCH 3 study is investigating the effectiveness of abemaciclib, plus either anastrozole or letrozole, as a first-line treatment for women with breast cancer. The trial is expected to end in June 2017.

Dynamic angiothermography

DATG is able to detect changes in blood flow that are indicative of breast cancer, may be used for younger patients, is completely non-invasive (no need for radiation or contrast agent, no need for compression of the breast) and is lower cost than alternatives requiring minimal facilities. This technology, performed quickly (5–6 minutes for visit) and very precise, is useful for screening and is also able to detect precancerous lesions. Studies have been conducted that have shown how it is possible, by means of this methodology, to diagnose invasive ductal carcinoma and infiltrating lobular carcinoma with the same accuracy. DATG can be strategic for young patients, or patients with dense breasts where the contrastive performance of mammography is challenged. Another application of DATG is the monitoring of at-risk patients with increased changes of breast cancer who take hormone replacement therapy (sometimes taken to reduce menopause symptoms) and participate in in-vitro

Family history of cancer other than breast or ovarian cancer in first-degree relatives is associated with poor breast cancer prognosis.

Whether a first-degree family history of others cancers (FHOC) than breast or ovarian cancer (BOC) is associated with breast cancer prognosis remains unknown. Thus, the aim of the present study was to clarify this issue. Women who were diagnosed with invasive breast cancer at the Renmin Hospital of Wuhan University from 2010 to 2013 were included in the study. The demographic and clinicopathological characteristics of these patients were extracted. FHOC was considered positive for any patient who had a relative who had been diagnosed with cancer other than BOC. Disease-free survival (DFS) was calculated based on the date of diagnosis. DFS was analyzed using the Cox proportional hazards model. A total of 434 breast cancer patients were included in this study. Among these patients, 61 (14.06%) had a positive FHOC in first-degree relatives. Patients with a positive FHOC tended to have HER2-positive breast cancer (p = 0.03). In the survival analysis, FHOC was associated with poor DFS in both univariate (HR = 2.21 (1.28-3.83), 95% CI: 1.28-3.83, p < 0.01) and multivariate (HR = 2.50, 95% CI: 1.24-5.04, p = 0.01) analyses, especially in patients with luminal A subtypes. The results demonstrated an increased risk of recurrence in breast cancer patients with FHOC, especially in patients with luminal A subtype.

Linking Histopathology and Family History in Breast Cancer.

In order to assess the prognostic value of family history (FH) of malignancies in patients afflicted with breast cancer (BC), we examined FH and histopathologic characteristics of 542 Iranian primary BC patients. Cases with distant metastasis at the time of diagnosis were excluded. Mean age of the studied population was 49 and the most common presenting stage was stage IIA followed by stage IIB. Data on a total of 6089 relatives (1st to 4th generations with the assumption of probands as the 3rd generation) were gathered. FH of BC and other malignancies (OM) was positive in 29 and 54% of cases, respectively. The most common OM's were gastric (67), lung (52) and uterus (47) cancers. We found that a FH of BC does not have any significant correlation with proven prognostic factors but a history of BC among relatives at or before the age of 36 is associated with more aggressive tumours. On the other hand, although FH of OM was associated with an older age of the probands (which is generally associated with a favourable prognosis), tumours of the cases with FH of OM had higher grades, lymphatic invasion being detected more frequently. Also we noted that the younger the age of the relatives diagnosed with cancer, the higher the stage of the probands themselves. All together our study indicates the possibility of a relation between FH of BC and OM, and histopathologic characteristics of the probands' tumours which would put forward FH as a prognostic factor rather than a simple risk factor in BC.

Retrospective analysis of clinicopathological characteristics and family history data of early-onset breast cancer: a single-institutional study of Hungarian patients.

Patients at young age (≤ 35 years) diagnosed with breast cancer (BC) are considered to have poor prognosis. The aim of the present study was to retrospectively analyse clinicopathological characteristics and prognosis in a group of young BC patients. We included women diagnosed with invasive breast carcinoma younger than/or at the age of 35 years. Between 1999 and 2009, 107 women with early-onset BC were selected from the database of the 2nd Department of Pathology at Semmelweis University. For clinicopathological comparison, 55 women (36-45 years), 214 women (46-65 years), 110 women (66-75 years) and 58 women (76 ≤ years) were also included in the analysis. Family history, clinicopathological and follow-up data were analysed. The tissue specimens were reviewed for histological type, nuclear grade, and estrogen receptor (ER), progesterone receptor (PgR), Ki67 and HER2 status (IHC4). The mean age in the study group was 31.6 years at the time of diagnosis. Histology showed a high incidence of grade III tumours in this group of patients (67.9 %), while only four cases (3.8 %) were considered grade I. According to the immunohistochemical results, 35.3 % of the study cases were considered as Luminal B (LumB: either being higly proliferative or co-expressing HER2) and 33.3 % as triple negative breast carcinomas (TNBC). The detailed questionnaire related to family history was completed and received in 49/107 cases (45.8 %). Analysis of these data revealed an affected family history of breast or ovarian carcinoma in first and second degree relatives in 51.0 %. A high proportion (52.0 %) of TNBC was observed among young women with a family history of the disease. Survival analysis of the 107 patients showed that 25 (23.3 %) women died until 31 December 2012. No significant difference in survival was detectable considering the regimen of systemic treatment (p = 0.188). Regarding clinicopathological parameters, the immunophenotypes, grade, pT and pN values differred substantially between the age groups (p = 0.001, for all), and the shortest relapse-free survival was seen among the youngest BC patients. This analysis illustrates that breast cancer arising in young women is characterized by the presence of less favorable subtypes such as LumB and TNBC. The increased proportion of TNBC was especially remarquable in the group of patients presenting with family history of the disease. The fact that a high rate of death occurred and no significant difference in OS were notable regarding the scheme of systemic therapies (neoadjuvant vs. adjuvant) highlight the necessity of the development of new treatment strategies.

CDH1 (gene)

Clinical significance Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues. E-cadherin is also used by pathologists to diagnose different kinds of breast cancer. When compared with invasive ductal carcinoma, E-cadherin expression is markedly reduced or absent in the great majority of invasive lobular carcinomas when studied by immunohistochemistry. E-cadherin and N-cadherin temporal-spatial expression are tightly regulated during cranial suture fusion in craniofacial development. Interactions CDH1 (gene) has been shown to interact with CBLL1, CDC27, CDON, CDH3, C-Met, CTNND1, CTNNB1, CTNNA1 FOXM1, HDAC1, HDAC2, IQGAP1, FYN, NEDD9, Plakoglobin, Vinculin, PTPmu(PTPRM) PTPrho(PTPRT)

Family History and Risk of Second Primary Breast Cancer after <i>In Situ</i> Breast Carcinoma.

<bBackground:</b Incidence rates of <iin situ</i breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with <iin situ</i breast cancer later develop second primary breast cancers.<bMethods:</b In this population-based nested case-control study among <iin situ</i breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer.<bResults:</b First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous <iin situ</i breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05-1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status.<bConclusions:</b Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous <iin situ</i breast cancer.<bImpact:</b Given the growing population of <iin situ</i breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. <iCancer Epidemiol Biomarkers Prev; 27(3); 315-20. ©2018 AACR</i.