Triple negative breast cancer: Clinical characteristics in the different histological subtypes

PurposeTo investigate the clinical behavior of triple negative breast cancer (TNC), including age distribution, occurrence of LN (lymph node) invasion and prognosis in different histological subtypes.MethodsFor this cohort study we used data on 476 patients with newly diagnosed TNC at the University Hospitals Leuven (Belgium) between 1999 and 2009. Of these, 395 received upfront surgery, 68 neoadjuvant chemotherapy and 21 had metastases at diagnosis.ResultsApocrine and invasive lobular TNC occur more often in older patients compared to IDC-NOS. Of the primarily operated patients with TNC, 35.1% has pathological LN involvement. There were no significant differences in nodal invasion between different histological subtypes, but most subtypes contained few patients. In contrast to previous reports, 6/14 of apocrine TNC had LN involvement. Disease free survival (DFS) was different in different histological subtypes, but group sizes were insufficient to be able to draw firm conclusions. Within the histologically ‘homogeneous’ IDC-NOS group with primary surgery and outcome data (n = 300), DFS with 3.5 year median follow-up decreased with increasing age, but chemotherapy and radiotherapy were much less frequently given with increasing age. In multivariable analysis, lower age, presence of LN involvement, lack of administration of chemotherapy and radiotherapy were significant predictors of relapse.ConclusionTNC is not a uniform disease. Different histological subtypes have different age distribution and behavior. The prognosis of the most common histological subgroup, IDC-NOS, is better in older patients, but this is counterbalanced by significantly decreased use of chemotherapy and radiotherapy.     

microRNA在三阴型乳腺癌中的研究进展

microRNA（miRNA）是一种小分子RNA,对细胞的增殖、分化、凋亡以及应激等生物过程有广泛的调节作用。miRNA通过多种方式参与乳腺癌的发生及进展,笔者就其在三阴型乳腺癌（TNBC）中的研究进展作一综述。     

Triple negative breast cancer: proposals for a pragmatic definition and implications for patient management and trial design

In trials in triple negative breast cancer (TNBC), oestrogen and progesterone receptor negativity should be defined as < 1% positive cells. Negativity is a ratio of <2 between Her2 gene copy number and centromere of chromosome 17 or a copy number of 4 or less. In routine practice, immunohistochemistry is acceptable given stringent quality assurance. Triple negativity emerging after neoadjuvant treatment differs from primary TN and such patients should not enter TNBC trials. Patients relapsing with TN metastases should be eligible even if their primary was positive. Rare TN subtypes such as apocrine, adenoid-cystic and low-grade metaplastic tumours should be excluded. TN and basal-like (BL) signatures overlap but are not equivalent. Since the significance of basal cytokeratin or EGFR overexpression is not known and we lack validated assays, these features should not be used to subclassify TN tumours. Tissue collection in trials is mandatory so the effect on outcome of different tumour phenotypes and BRCA mutation can be explored. No prospective studies have established that TN tumours have particular sensitivity or resistance to any specific chemotherapy agent or radiation. TNBC patients should be treated according to tumour and clinical characteristics.     

Clinical trials in triple negative breast cancer

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease against which targeted therapies that significantly improve the prognosis for hormone receptor-positive and HER2-overexpressing breast cancers are ineffective. This article summarizes our current understanding of the biology of TNBC as it relates to the efficacy of standard and investigational therapies. It reviews promising preliminary results that have been achieved with chemotherapeutic agents including the platinum analogs and agents that inhibit DNA repair by targeting poly ADP-ribose polymerase (PARP), while anti-angiogenic therapies and those that target the epidermal growth factor receptor (EGFR) have had more limited success. Agents that target a number of other pathways which appear to influence the biologic aggressiveness of TNBC, including src and PI3K, are in early stage clinical trials. As we learn more about TNBC, and which of its characteristics determine treatment response and resistance, we should become better able to select appropriate therapies for biologically defined patient subgroups, and reduce the clinical burden of this disease.     

Triple assessment in the diagnosis of breast cancer in Kashmir

Background  

Although the diagnosis of breast cancer is suggested on clinical examination, the degree of suspicion is variable. Currently a combination of three tests, i.e. clinical examination, radiological imaging (mammography, ultrasonography) and pathology called as triple assessment test is used to accurately diagnose all palpable breast lumps. Together they give sensitivity of 99%. The triple assessment is taken as positive if any of the three components is positive and negative only if all of its components are negative for malignancy.     

Management of triple negative breast cancer

Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases. TNBC is an immunohistochemically defined subtype, with significant diversity within the subtype. Generally TNBC occurs in younger women and is marked by high rates of relapse, visceral and CNS metastases, and early death. Current therapy fails to curtail the innate aggressive behaviour of TNBC in the majority of patients. The poor prognosis coupled with a lack of targeted use of therapies is reflected in the high mortality. In a minority of patients with highly chemosensitive disease, no robust clinical evidence exists to guide use of current cytotoxics. Critical to optimal future management are accurate identification of truly triple negative disease and adequately powered prospective TNBC trials to establish treatment efficacy and define predictive biomarkers.     

Neoadjuvant chemotherapy's role in triple negative breast cancer

Neoadjuvant chemotherapy (NC) facilitates breast conservation in women with large tumors, which are common in our inner city breast clinic. We performed this review of our NC breast cancer experience, which includes a disproportionate number of triple negative patients. Patients treated with NC were divided into two groups based on their tumor's receptor status. Patients with tumors negative for estrogen, progesterone, and HER2-neu were considered triple negative (TN) and patients with positive staining for any of these receptors were considered nontriple negative (NTN). Response to NC was considered a complete response (CR) if no residual tumor was detected at surgery, partial response (PR) if the height and width was reduced by at least 50 per cent, and no response (NR) for anything less than a PR. Differences were assessed by χ(2) analysis and Student's t test. We identified 30 patients treated with NC (11 TN and 19 NTN). Twenty-one patients (70%) were African American (11/11 TN and 10/19 NTN; P = 0.01). Age (46.8 ± 6.0 years TN vs 49.5 ± 11.7 years NTN), response rates (18% NR, 55% PR, and 27% CR TN; 37% NR, 42% PR, and 21% CR NTN), and node positivity (64% TN vs 74% NTN) were statistically similar. Two TN (20%) and seven (41%) NTN patients underwent breast conservation therapy. Our results demonstrate the association of African American race and TN breast cancer. TN cancers respond similarly to NC when compared with NTN, allowing for tumor downstaging and possible breast conservation surgery.     

Current treatment options in triple negative breast cancer

Triple negative breast cancer (TNBC) refers to a subgroup of breast carcinomas that do not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor type 2. This heterogeneous group of tumors has significant overlap with both basal-like tumors (defined through gene expression array) and BRCA1 mutation-associated tumors. Due to a lack of well defined clinical targets, chemotherapy is the standard of care treatment for TNBC. When compared with other breast cancer subtypes, TNBC exhibits at least equivalent, or often superior sensitivity to chemotherapy. However, despite this increased chemosensitivity, TNBC has a worse clinical outcome than other breast cancer subtypes. This has led to the investigation of DNA damaging chemotherapy agents, including platinum drugs, angiogenesis inhibitors, poly(ADP-ribose) polymerase inhibitors, novel microtubule inhibitors, and other targeted therapies in an effort to improve the outcome for patients with these high-risk tumors. Treatment decisions for patients with TNBC should be based on the best currently available evidence, which consists mainly of retrospective and prospective subgroup analyses and phase II prospective data. This review summarizes data from select neoadjuvant, adjuvant, and metastatic chemotherapy clinical trials which included analyses of treatment effects and outcomes in TNBC and/or basal-like breast cancer.     

Triple negative invasive lobular carcinoma of the breast presents as small bowel obstruction

Metastasis from breast carcinoma to the gastrointestinal tract (GIT) is very uncommon. To date, only a few cases have been described worldwide. Of those which do metastasize to the GIT, only estrogen receptor (ER), progesterone receptor (PR) and HER2-neu receptor positive cancers have been reported and none have been mentioned in the U.S. We report a case of a 70-year-old white female with history of triple negative lobular carcinoma eight years earlier who presented with solitary jejunal mass causing obstruction.     

Sentinel node biopsy in breast cancer patients: Triple technique as a routine procedure

Since its introduction in the early 1990s, the sentinel node (SN) concept in breast cancer has been validated by many studies. Because SN biopsy in breast cancer enables the identification of node-negative axillae, the potential morbidity of an axillary lymph node dissection (ALND) can be avoided. The SN procedure is still surrounded by many variables and uncertainties, such as the clinical relevance of micrometastases. However, the main goal is to avoid unnecessary ALND in node-negative breast cancer patients. Sufficient clinical data are available to achieve this goal by incorporating the SN procedure into routine clinical practice. The ultimate safety of the applied technique will be determined by the number of axillary recurrences during long-term follow-up. Preoperative lymphoscintigraphy and intraoperative use of both blue dye and a hand-held gamma probe—the triple technique—has been applied at our institute since early 1994.     

Oncoplastic surgery: the evolution of breast cancer treatment

Oncoplastic surgery is an establish approach that combines conserving treatment for breast cancer and plastic surgery techniques. It allows wide excisions and prevents breast deformities by immediate reconstruction of large resection defects. The procedures are mostly useful for resection of 20-40% of the breast - a group of patients normally treated by mastectomy in the past. Four features are integral to oncoplastic breast surgery: (i) Appropriate surgery for cancer excision. (ii) Partial reconstruction to correct wide excision defects. (iii) Immediate reconstruction with the full range of available techniques. (iv) Correction of volume and shape asymmetries relative to the contra-lateral healthy breast. There are two fundamentally different approaches: (i) volume-replacement procedures, which combine resection with immediate reconstruction by using local flaps (glandular, fasciocutaneous, and latissimus dorsi mini-flaps), and (ii) volume-displacement procedures, which combine resection with a variety of different breast reduction and reshaping techniques, according to the location of the tumor. Oncoplastic surgery increases the oncological safety of breast-conserving treatment because a much larger breast volume can be excised and wider surgical margins can be achieved. Moreover, a "surgical screening" of the contra-lateral breast allows the diagnosis of occult cancers. Among oncoplastic approaches, a very unique technique is the possibility of implant use (augmentation mammaplasty) in case of quadrantectomy and simultaneous delivery of intraoperative radiotherapy to the tumor bed.     

三阴性乳腺癌的临床病理特征分析

目的:探讨三阴性乳腺癌(triple negative breast cancer,TNBC)的临床病理特点,以及TNBC中突变型p53的表达及其意义。方法:回顾性分析195例乳腺癌病例,按雌激素受体、孕激素受体、人表皮生长因子受体2的表达分为TNBC组34例和对照组161例。检测TNBC组织中突变型p53的表达,分析其与TNBC临床病理特征及预后的关系。结果:TNBC组病人的复发转移率较高(29.4%比1.2%,P0.001)、无病生存率显著低于对照组(52.9%比90.7%,P0.001)。TNBC组突变型p53阳性表达率明显高于对照组(47.1%比22.4%,P0.01),且突变型p53阳性表达与TNBC腋窝淋巴结转移有关(77.8%比36.0%,P0.05)。结论:TNBC乳腺癌复发转移率高,无病生存率较低,预后较差。TNBC组织中突变型p53表达上调,其可作为TNBC重要的预后指标。     

微小RNA在三阴性乳腺癌中的研究进展

三阴性乳腺癌(triple-negative breast cancer,TNBC)是指免疫组织指标ER、PR、HER2三者均为阴性的一种乳腺癌分子亚型,也是一种高度异质性的疾病.TNBC与其他乳腺癌分子亚型相比,生物学行为上表现侵袭性强、易复发和内脏转移,易产生耐药性,预后不良.miRNA是一种很有前景的生物标志物和...