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1.
Quirine F. Manson Natalie D. ter Hoeve Horst Buerger Cathy B. Moelans Paul J. van Diest 《Targeted oncology》2018,13(6):769-777
Background
Male breast cancer is rare, as it represents less than 1% of all breast cancer cases. In addition, male breast cancer appears to have a different biology than female breast cancer. Programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), seem to have prognostic and predictive values in a variety of cancers, including female breast cancer. However, the role of PD-1 and PD-L1 expression in male breast cancer has not yet been studied.Objectives
To compare PD-1 and PD-L1 expression in male breast cancer to female breast cancer and to evaluate prognostic values in both groups.Patients and Methods
Tissue microarrays from formalin-fixed paraffin-embedded resection material of 247 female and 164 male breast cancer patients were stained for PD-1 and PD-L1 by immunohistochemistry.Results
PD-1 expression on tumor-infiltrating lymphocytes was significantly less frequent in male than in female cancers (48.9 vs. 65.3%, p?=?0.002). In contrast, PD-L1 expression on tumor and immune cells did not differ between the two groups. In male breast cancer, PD-1 and tumor PD-L1 were associated with grade 3 tumors. In female breast cancer, PD-1 and PD-L1 were associated with comparably worse clinicopathological variables. In a survival analysis, no prognostic value was observed for PD-1 and PD-L1 in either male and female breast cancer. In a subgroup analysis, female patients with grade 3/tumor PD-L1-negative or ER-negative/immune PD-L1-negative tumors had worse overall survival.Conclusions
PD-1 seems to be less often expressed in male breast cancer compared to female breast cancer. Although PD-1 and PD-L1 are not definite indicators for good or bad responses, male breast cancer patients may therefore respond differently to checkpoint immunotherapy with PD-1 inhibitors than female patients.2.
Li Liu Bo Yin Zhu Yi XiuJuan Liu ZhiQian Hu WenChao Gao HaiWen Yu QingQuan Li 《Breast cancer (Tokyo, Japan)》2018,25(6):706-716
Background
Cancer stem cells (CSCs) are believed to form metastases. We sought to determine whether CD70?+?subpopulation in human breast cancers represents the CSCs accounting for distant metastasis.Methods
We measured the expression levels of CD70 in breast cancer cell lines and 122 primary breast cancer samples. We characterized the functional roles of CD70?+?subpopulation in distant metastasis of breast cancers.Results
We observed a distinct pattern of CD70 expression in a panel of primary breast carcinoma samples, indicating that CD70 serves as a biomarker of lung-specific metastasis. CD70? and CD70+?cell populations isolated from breast cancer cell lines exhibited epithelial and mesenchymal phenotypes, respectively. CD70+?cells, but not CD70? cells, possessed self-renewal and differentiation potentials. Tumorsphere formation in suspension cultures and in vivo tumorigenicity were significantly greater in CD70+?cells than in CD70? cells. Furthermore, the development of lung metastases induced by orthotopic injection was markedly increased in mice inoculated with CD70?+?cells. CD70 contributed to the promotion of lung metastases by enhancing self-renewal potential of CD70?+?cells.Conclusions
We isolated CSCs from primary human breast cancers and found that CD70?+?subpopulations mediate lung-specific metastasis. These findings might be used to aid in selection of patients for postoperative adjuvant therapy.3.
Purpose of review
This review summarizes current immunotherapies in breast cancer, with an emphasis on immune checkpoint inhibitors and vaccines.Recent findings
Combination immunotherapy with checkpoint inhibitors and cytotoxic therapies have shown promising results. Active clinical trials are ongoing in both early stage and metastatic settings for triple negative, HER2+, and hormone-positive breast cancer patients.Summary
Ongoing challenges remain in defining biomarkers that predict response to immunotherapy, determining the optimal combination immunotherapies, and enhancing the immunogenicity of breast cancer subtypes.4.
Background and aim
The concepts of the pathogenesis of epithelial ovarian tumors have significantly changed during the last decade. The aim of this review is to briefly present the current concepts on this topic.Methods
This work is based on a selective PubMed search using the terms “ovarian” cancer and “origin”.Results
Numerous studies have shown that the histological subtypes of ovarian cancer greatly differ in molecular features, etiology, therapy response, and prognosis. Correlations between histopathological and molecular characteristics revealed that serous tubal intraepithelial carcinoma (STIC) is probably the precursor of high grade serous carcinoma, and that endometrioid and clear cell carcinomas arise in ovarian endometriosis cysts. Preliminary data also point to a tubal origin of low grade serous carcinoma while the pathogenesis of rare mucinous neoplasia is currently unclear.Conclusions
The histological subtypes of ovarian cancer should be considered as separate entities. The origin of most epithelial ovarian neoplasia very probably lies in extraovarian organs.5.
Arvids Irmejs Edvins Miklasevics Viktors Boroschenko Andris Gardovskis Andrejs Vanags Inga Melbarde-Gorkusa Marianna Bitina Janina Suchy Janis Gardovskis 《Hereditary cancer in clinical practice》2006,4(1):48-51
Introduction
It has not been established whether CHEK2 and NOD2 variants are present in Latvia and whether inherited variation in these genes influences cancer risk in this population.Aim of the study
To evaluate the role of CHEK2 and NOD2 mutations in breast and colorectal cancers in the population of Latvia.Materials and methods
Peripheral venous blood samples were collected from 185 breast cancer and 235 colorectal cancer consecutive hospital-based cases from 11/2003 to 06/2005. The population control group included blood samples from the clamped distal part of the umbilical cord from 978 consecutive anonymous newborns born between 03/2005 and 08/2005. All cases and controls were tested for the presence of NOD2 3020insC mutation and CHEK2 I157T mutation.Results
NOD2 3020insC was present in 7.7% (18/235) of CRC cancers, in 9.2% (17/185) of breast cancers and in 7.7% (75/974) of controls. CHEK2 I157T variant was found in 7.6% (14/185) of breast cancer cases, 10.2% (24/235) of colon cancer cases and in 6.4% (63/978) of population controls. NOD2 3020insC variant was associated with increased risk of breast cancer (OR = 2.5, p < 0.05) for cases diagnosed at age between 51 and 60 years. CHEK2 I157T variant was associated with increased risk of colorectal cancer (OR = 1.7, p < 0.05) with the highest OR = 2.0 for cases diagnosed at age >70 yrs.Conclusions
NOD2 3020insC, CHEK2 I157T variants may be associated with increased risk of colorectal and breast cancers in Latvia.6.
Yun-Bi Ni Julia Y. S. Tsang Mu-Min Shao Siu-Ki Chan Sai-Yin Cheung Joanna Tong Ka-Fai To Gary M. Tse 《Breast cancer research and treatment》2018,169(1):25-32
Purpose
Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear.Methods
To address these questions, totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23 distant metastases, and 208 lung carcinomas were included. GATA-3 expression was analyzed by immunohistochemistry and compared to other breast markers [gross cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)].Results
GATA-3 was expressed in 82.5% of IBC, predominantly in luminal (93.9%), and lower in non-luminal cancers [59.6% of HER2 overexpressing (HER2-OE) and 38.1% of triple negative breast cancer (TNBC) subtypes]. GATA-3 identified more IBC than GCDFP-15 (23.9%) and MGB (46.6%). However, MGB showed a comparable sensitivity for non-luminal cancers to GATA-3. Combining MGB and GATA-3 improved sensitivity for both HER2-OE (80.8%) and TNBC cases (55.4%). GATA-3 showed a high sensitivity for nodal metastases and distant metastases, with good concordance with primary tumors. GATA-3 was expressed in 1.0% of lung carcinomas, with sensitivity and specificity of 82.5 and 99.0% in differentiating IBC and lung carcinoma.Conclusions
GATA-3 expression was the highest in luminal breast carcinomas, and showed higher sensitivity than GCDFP-15 and MGB. However, in the poorly differentiated IBC, its utility was still limited. One should be aware of the possible GATA-3 expression in lung carcinomas.7.
Purpose of Review
One in eight women in the USA will develop breast cancer in her lifetime. Despite established efficacy, the use of pharmacotherapy for breast cancer prevention is limited by concerns over toxicities that may negatively influence quality of life. Additional interventions for breast cancer prevention are needed.Recent Findings
There is emerging evidence from observational studies that obesity, physical inactivity, sedentary behavior, and dietary patterns are associated with breast cancer risk. Randomized trials are necessary to provide unbiased efficacy estimates of lifestyle changes on breast cancer risk, but such trials require a large sample size, long-term follow-up, and substantial financial investment. One approach to manage these barriers is to leverage recent advances in precision prevention to identify high-risk study participants to reduce sample size or shorten length of follow-up.Summary
Precision prevention approaches may accelerate the translation of epidemiologic discoveries into proven population-based breast cancer prevention interventions.8.
Nora K. Horick Ariela Muzikansky Hilda L. Gutierrez Kristina L. Boyd Dianne M. Finkelstein 《Journal of cancer survivorship》2018,12(6):835-842
Purpose
Advances in cancer detection and treatment have resulted in a growing population of long-term survivors, but even years after treatment has concluded, many survivors report physical symptoms that interfere with daily living. While there are studies of late effects following common cancers, less is known about these complications in rare cancers. This study focuses on the physical symptoms reported by long-term survivors enrolled in the NIH-sponsored Rare Cancer Genetics Registry.Methods
The Rotterdam Symptom Checklist-Modified was administered to evaluate the severity of physical symptoms commonly reported by long-term cancer survivors. Logistic regression was used to assess association between symptoms and demographic and clinical factors.Results
In 309 subjects with a median time of 7.6 years from a diagnosis of one or more rare cancers, the median number of symptoms present per participant was 7. The most prevalent symptom reported was tiredness/lack of energy, which was present/very bothersome in 70%/25% of registrants. Women, non-whites, current smokers, and upper GI cancer survivors are particularly affected. Overall, symptom prevalence was similar across rare cancer types, time since diagnosis, and type of treatment.Conclusions
Rare cancer survivors continue to experience troublesome symptoms many years after diagnosis, regardless of cancer type or treatment modality.Implications for Cancer Survivors
There is a need for continued emphasis on smoking cessation in cancer survivors as well as enhanced monitoring of long-term complications in female, non-white, and upper GI cancer survivors.9.
Aim
To explore information-seeking behaviors on links between cancers and environment.Method
Focus groups and individual semi-structured interviews realized, respectively, with individuals without and with personal cancer experience.Results
The majority of respondents reported informationscanning behaviors. Only half cancer patients searched for information regarding the links between cancers and environment.Conclusion
Little information is sought on links between cancers and environment.10.
Background
Ubiquitin-associated protein 2-like (UBAP2L) contains a ubiquitin-associated domain near its N-terminus, which has been demonstrated to be overexpressed in multiple tumors, including hepatocellular carcinoma and colorectal carcinoma but its role has not been well studied in breast cancer. Thus, this study was designed to evaluate whether UBAP2L can serve as a potential molecular target for breast cancer therapy.Methods
The expression of UBAP2L was determined in breast cancer tissues and cell lines by Western blotting and Oncomine database mining. Then the expression of UBAP2L was silenced using RNA interference and the effects of UBAP2L knockdown on breast cancer cell proliferation and cell cycle progression by MTT and colony formation assay, and Flow cytometry, respectively.Results
We found the expression of UBAP2L was significantly up-regulated in breast cancer tissues and cell lines. Knockdown of UBAP2L suppressed cell proliferation, impaired colony formation ability and induced cell cycle arrest at G2/M phase. At molecular levels, knockdown of UBAP2L increased p21 expression, but decreased the expression of CDK1 and Cyclin B1 in breast cancer cells.Conclusion
Our findings suggest that UBAP2L plays an important role in breast cancer cell proliferation and might serve as a potential target for breast cancer treatment.11.
Purpose of Review
Bone-modifying agents have an important role in the treatment of patients with bone mineral density loss, early-stage breast cancer to reduce risk of recurrence, and metastatic breast cancer with bone involvement. Here we review mechanisms of action of these agents and clinical indications for their use.Recent Findings
The meta-analysis undertaken by the Early Breast Cancer Trialists’ Collaborative Group showed that the use of bisphosphonates was associated with a decreased risk of breast cancer recurrence.Summary
The effect of bisphosphonates and receptor activator of nuclear factor kappa-B ligand inhibitors on bone health provides an opportunity to decrease the incidence of skeletal-related events and improve cancer outcomes in certain subsets of patients.12.
Michiyo Saimura Kenichiro Koga Keisei Anan Shoshu Mitsuyama Sadafumi Tamiya 《Breast cancer (Tokyo, Japan)》2018,25(4):470-478
Background
Breast carcinoma arising in a benign fibroepithelial tumor is rare, and is usually discovered incidentally during examination of the breast mass.Methods
We evaluated the clinicopathological features, treatment, and prognosis of seven women with breast carcinomas within benign fibroepithelial tumors, diagnosed and treated at a single institution between 2011 and 2015.Results
Seven women, aged 21–64 years, visited our hospital complaining of a breast mass detected by self-checking or screening examination. All patients had well-demarcated movable breast masses. Ultrasonography showed circumscribed masses suggesting benign tumors in all cases, and mammography revealed well-defined, high-density masses, with or without calcification. The masses progressed in two patients. A preoperative histological diagnosis of carcinoma was made following needle biopsy in four patients. Tumorectomy, breast-conserving surgery, and mastectomy were performed in three, two, and two patients, respectively. One patient underwent lymph node dissection and another underwent sentinel node biopsy. Histologically, the masses were diagnosed as invasive ductal carcinoma, ductal carcinoma in situ or lobular carcinoma in situ, arising in a benign phyllodes tumor, fibroadenoma, or fibroadenomatoid mastopathy. Lymph node metastasis was detected in two patients. There was no recurrence in any of the patients.Conclusions
Although a carcinoma within a preexisting benign fibroepithelial tumor is extremely rare, it is important to be aware of the possibility of invasive and metastatic disease.13.
Purpose of Review
Breast cancer treatment continues to evolve as targeted therapeutic strategies are developed for the various molecular subtypes of breast cancer. The PARP inhibitors represent a novel targeted therapy for tumors with defective homologous recombination DNA repair. These agents may become standard new treatment options for patients harboring BRCA1/2 mutations and show promise in BRCA1/2 wild-type patients with triple-negative breast cancers, which are treated predominantly with traditional cytotoxic chemotherapy. This review will discuss the results of clinical trials of these agents in breast cancer as well as important ongoing and anticipated trials.Recent Findings
Recent reports support the use of olaparib monotherapy in BRCA1/2-mutated metastatic cancer. Results of PARP inhibitor combinations with chemotherapy have been mixed. The addition of veliparib failed to improve pathological complete response rates in patients with early-stage triple-negative breast cancer treated with carboplatin (AUC6) and paclitaxel followed by doxorubicin plus cyclophosphamide in a phase 3 trial. The PARP inhibitors talazoparib and olaparib are currently being tested in the neoadjuvant and adjuvant settings but impact on survival measures will likely take years prior to reporting in these early-stage breast cancer studies.Summary
While data from the first phase 3 trials of PARP inhibitors in breast cancers are encouraging in patients with germline deleterious BRCA1/2 mutations, continued work is needed to elucidate their utility beyond the BRCA1/2-mutated population as has been possible in ovarian cancer. Additionally, defining the ideal population and setting for combination treatment remains a challenge and has been limited by synergistic toxicities.14.
Eboneé N. Butler Chiu-Kit Tse Mary Elizabeth Bell Kathleen Conway Andrew F. Olshan Melissa A. Troester 《Cancer causes & control : CCC》2016,27(6):775-786
Purpose
Growing evidence suggests an association between active cigarette smoking and increased breast cancer risk. However, the weak magnitude of association and conflicting results have yielded uncertainty and it is unknown whether associations differ by breast cancer subtype.Methods
Using population-based case–control data from phases I and II of the Carolina Breast Cancer Study, we examined associations between self-reported measures of smoking and risk of Luminal and Basal-like breast cancers. We used logistic regression models to estimate case–control odds ratios (OR) and 95 % confidence intervals (CI).Results
Ever smoking (current and former) was associated with a weakly increased risk of Luminal breast cancer (OR 1.12, 95 % CI 0.92–1.36) and was not associated with risk of Basal-like breast cancer (OR 0.96, 95 % CI 0.69–1.32). Similarly, smoking duration of more than 20 years was associated with increased risk of Luminal (OR 1.51, 95 % CI 1.19–1.93), but not Basal-like breast cancer (OR 0.90, 95 % CI 0.57–1.43). When stratified by race, elevated odds ratios between smoking and Luminal breast cancer risk were found among black women across multiple exposure measures (ever smoking, duration, and dose); conversely, among white women odds ratios were attenuated or null.Conclusions
Results from our study demonstrate a positive association between smoking and Luminal breast cancer risk, particularly among black women and women with long smoking histories. Addressing breast cancer heterogeneity in studies of smoking and breast cancer risk may elucidate associations masked in prior studies.15.
Dejan Nikolić Miroslav Granić Nebojša Ivanović Darko Zdravković Aleksandra Nikolić Violeta Stanimirović Marija Zdravković Srdjan Dikić Marko Nikolić Miroslav Djordjević 《Breast cancer research and treatment》2018,171(3):565-569
Introduction
Lesbian, gay, and bisexuals have unique healthcare needs. Breast cancer is leading cancer in women, worldwide, accounting for 25% of all cases. Annual incidence rates increased significantly in all countries and age groups. The occurrence of breast cancer is rare in transgender population. As they have very limited access to medical care, it is much less likely to pursue breast cancer screening than in other individuals not identified as transgender.Review of the cases from literature
Up to date, only 13 cases of the breast cancer transsexuals (female to male) have been reported in six published papers worldwide. Histological examination of the breast tumor in female-to-male transgender showed progesterone/estrogen-positive invasive ductal carcinoma.Discussion
Gender identity describes a person’s inherent sense of being a woman, man, or of neither gender, whereas sexual orientation refers to how people identify their physical and emotional attraction to others. Gender reassignment surgery, as series of complex surgical genital and non-genital procedures, is recognized as the most effective treatment for patients with gender dysphoria. The two main principles of hormone therapy for transgender patients are to reduce endogenous hormone levels and their associated sex characteristics and replace them with hormones of the preferred sex. Breast cancer infrequently occurs in transgender patients. Even breast core biopsies can be difficult for interpreting after changes in breast tissue in female-to-male transsexuals following gender reassignment.Conclusion
Reviewing the literature, so many different data concerning probability of breast cancer in sexual minority can be found. Breast cancer screening program should be offered to all transgender individuals according to national guidelines. Very important is to take into consideration a transgender person’s natal and surgical anatomy, unique clinical concerns for depression and anxiety, risk of suicide together with risk factors including experiences of harassment or physical or sexual violence, low education level, and unemployment. Understanding the need for mammography in these often marginalized groups is very important in addressing breast cancer disparities despite differences in insurance coverage in some countries and greater concern for the cancer of the breast in residual breast tissue. The best screening rule, ever, for breast cancer in male transsexuals and other similar population should be, besides surgical history and hormonal status, “Screen Now, Screen Regularly and Screen What You Have.”16.
Kelly A Metcalfe William D Foulkes Henry T Lynch Parviz Ghadirian Nadine Tung Ivo A Olivotto Ellen Warner Olufunmilayo Olopade Andrea Eisen Barbara Weber Jane McLennan Ping Sun Steven A Narod 《Hereditary cancer in clinical practice》2005,3(2):53-57
Purpose
To compare the presentation of invasive breast cancer in BRCA1 and BRCA2 mutation carriers with and without prior bilateral oophorectomy.Patients and methods
Women with a BRCA1 or BRCA2 mutation with the diagnosis of invasive breast cancer were identified from ten cancer genetics clinics. The medical history, medical treatment records and pathology reports for the breast cancers were reviewed. Information was abstracted from medical charts, including history (and date) of oophorectomy, date of breast cancer diagnosis, stage of disease, and pathologic characteristics of the breast cancer. Women with prior bilateral oophorectomy were matched by age, year of diagnosis, and mutation with one or more women who had two intact ovaries at the time of breast cancer diagnosis. Characteristics of the breast tumours were compared between the two groups.Results
Women with prior bilateral oophorectomy presented with smaller tumours on average compared to women without prior oophorectomy (mean size 1.50 cm vs. 1.95 cm; p = 0.01). Additionally, although not statistically significant, women with intact ovaries were more likely to have high-grade tumour (70% vs. 54%: p = 0.10) and to have positive lymph nodes (34% vs. 18%; p = 0.11) compared to women with prior bilateral oophorectomy.Conclusions
Bilateral oophorectomy prior to breast cancer appears to favourably influence the biological presentation of breast cancer in BRCA1 and BRCA2 mutation carriers.17.
Somaira Nowsheen Paul V Viscuse Ciara C. O’Sullivan Nicole P. Sandhu Tufia C. Haddad Anne Blaes Jennifer Klemp Lara Nhola Joerg Herrmann Kathryn J. Ruddy 《Current breast cancer reports》2017,9(3):173-182
Purpose of Review
Treatment with trastuzumab is a cornerstone of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treatment, but carries an unfortunate risk of toxicity to the cardiovascular system. Here, we review recent findings on trastuzumab-associated cardiotoxicity, focusing on its incidence, diagnosis, and treatment.Recent Findings
Screening with multigated acquisition scan (MUGA) or echocardiogram (ECHO) is recommended to assess cardiac function prior to and during trastuzumab therapy. Because trastuzumab-induced cardiotoxicity is typically reversible, cessation of trastuzumab and/or administration of first-line heart failure agents effectively restores cardiac function in most cases. Severe trastuzumab-induced cardiotoxicity is rare enough that the risk-benefit ratio still weighs in favor of its use in the vast majority of patients with HER2+ breast cancer.Summary
An improved understanding of the pathophysiology underlying trastuzumab-induced cardiotoxicity and the identification of patients at highest risk will allow us to continue to safely administer trastuzumab in patients with breast cancer.18.
Purpose of Review
As adjuvant therapy for early-stage, hormone receptor-positive breast cancer has improved, late recurrences have become a significant issue. Endocrine therapies such as tamoxifen and aromatase inhibitors play a central role in reducing the risk of recurrence of hormone-positive breast cancers. However, the continued risk of breast cancer recurrence even with 5 years of adjuvant AI therapy has led to interest in extended therapy. This review intends to discuss and analyze recent trials that have reported results with extending AI therapy beyond 5 years of treatment.Recent Findings
The IDEAL, DATA, and NSABP B-42 were unable to demonstrate a significant benefit in disease-free survival for extending aromatase inhibitor therapy beyond 5 years. They collectively demonstrate a decreased risk for contralateral breast cancers, as well as an increased risk for bone-related and cardiovascular toxicity.Summary
There continues to be a lack of definitive evidence on the ideal length of adjuvant AI therapy. As certain subgroups may benefit more and experience less toxicity, selecting future patients based on clinicopathologic and genomic factors may maximize the benefit of extended adjuvant aromatase inhibitor therapy while minimizing harms.19.
Purpose of Review
This review article seeks to summarize the existent literature regarding the use of anthracyclines (specifically doxorubicin) in the treatment of early-stage breast cancers, reviewing the clinically significant side effects of said therapy, and discussing new tools to risk stratify patients.Recent Findings
The 2010 Early Breast Cancer Trialists’ Cooperative Group meta-analysis again found anthracycline-containing regimens to improve outcomes, while the ABC Trials have shown the superiority of regimens including doxorubicin versus regimens with docetaxel and cyclophosphamide alone in early-stage breast cancer. New risk stratification tools—such as Oncotype DX®—are helping oncologists decide which patients may be able to avoid chemotherapy.Summary
Sequential doxorubicin/cyclophosphamide therapy, followed by treatment with docetaxel, improves outcomes in nearly all early-stage breast cancer, with the notable exception of Her2+ disease. Newer risk stratification tools allow better risk/reward calculations in which patients may be able to avoid anthracycline-based chemotherapy and its significant side effects.20.