HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast CancerRead the full article
International Journal of Breast Cancer provides a forum for scientists, clinicians, and health care professionals working in breast cancer research and management. Research includes molecular pathology, genomics, genetic predisposition etc.
International Journal of Breast Cancer maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.
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Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer
Although immune-based therapies have made remarkable inroads in cancer treatment, they usually must be combined with standard treatment modalities, including cytotoxic drugs, to achieve maximal clinical benefits. As immunotherapies are further advanced and refined, considerable efforts will be required to identify combination therapies that will maximize clinical responses while simultaneously decreasing the unpleasant and sometimes life-threatening side effects of standard therapy. Over the last two decades, evidence has emerged that Th1 cytokines can play a central role in protective antitumor immunity and that combinations of Th1 cytokines can induce senescence and apoptosis in cancer cells. To explore the possibility of combining targeted drugs with Th1-polarizing vaccines, we undertook a study to examine the impact of combining Th1 cytokines with the relatively broad-spectrum receptor tyrosine kinase antagonist, sunitinib. We found that when a panel of five phenotypically diverse human breast cancer cell lines was subjected to treatment with sunitinib plus recombinant Th1 cytokines IFN-γ and TNF-α, synergistic effects were observed across a number of parameters including different aspects of apoptotic cell death. Interestingly, sunitinib was found to have a profoundly suppressive effect of T cell’s capacity to secrete IFN-γ, indicating that in vivo use of this drug may hinder robust Th1 responses. Nonetheless, this suppression was circumvented in a mouse model of HER-2pos breast disease by supplying recombinant interferon-gamma to achieve a combination therapy significantly more potent than either agent.
Clinicopathological and Molecular Characteristics of Pleomorphic Invasive Lobular Carcinoma
Pleomorphic invasive lobular carcinoma (PILC) is a distinct morphological and biologically aggressive variant of invasive lobular carcinoma (ILC). We hypothesized that was due to de novo activation of PI3K/Akt/mTOR pathway in PILC resulting in higher proliferation rate and markers of cell cycle activation. We identified PILC and ILC tumors and tested for PI3K/Akt/mTOR pathway activation by immunohistochemistry (PTEN and pS6K1) and gene expression analysis (by Nanostring nCounter system). Proliferation index (Ki67) was elevated in 85% of PILCs compared to 20% of ILCs (). PTEN expression was high in all while pS6K1 was high in 8/9 PILCs compared to 3/9 ILCs (). Gene expression analysis shows that PILCs have overexpression of genes involved in cell cycle proliferation, cellular proliferation, DNA damage, and repair genes but no difference in PI3K/Akt/mTOR pathway genes. PILCs are a biologically distinct group of ILC, and clinicopathological characteristics suggest they would have a more clinically aggressive behavior. In addition, our results indicate that PI3k/Akt/mTOR pathway and cell cycle proliferation are activated in majority of these tumors. Further studies are needed to investigate these mechanisms as there are approved therapies available that may benefit PILCs.
Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives
Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for 15%–20% of all breast cancers and is associated with an aggressive evolution and poor outcomes with the majority of recurrences and deaths occurring in the first 5 years. Chemotherapy remains the mainstay of treatment in the absence of effective targets, but the good understanding of immune tumor microenvironment, the identification of immune-related targets, and the role of tumor-infiltrating lymphocytes (TILs) in TNBC has allowed to develop promising immunotherapeutic strategies for this unique subset of breast cancer. Recently, immunotherapy is being extensively explored in TNBC and clinical trials have shown promising results. In this article, we tried to explain the rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a new standard of care in TNBC in addition to ongoing trials and future directions in the next decade.
Male Breast Cancer in Togo: Imaging and Clinicopathological Findings
Background. Breast cancer in men is a rare condition, often diagnosed late. The purpose of this study was to describe its epidemiological, histopathological, and radiographic aspects in Togo. Materials and Methods. This was a descriptive retrospective study on cases of breast cancer in humans diagnosed histologically at the Laboratory of Anatomy Pathological and Imagery of the University Hospital in Lomé, over a period of 25 years (1995 to 2019). The parameters studied were epidemiological, anatomopathological, and imaging. Results. Eighty-two (82) cases were diagnosed, an annual frequency of 3.28 cases. The mean age was ; the range was 27-63 years. The family history of 47 patients (57.32%) was known. Carcinomas represented the predominant histological group with predominantly nonspecific invasive carcinoma (87.5%). These cancers were diagnosed at late stages (75.71% grade II). They were mainly of luminal B profile (38.75%) and associated with mutations of the BRCA2 and BRCA1 genes in 14.63% of the cases. The lesions were classified ACR 5 in 61.5% (11/18). Two cases of breast angiosarcoma were diagnosed by the identification of CD31 markers and factor VIII in immunohistochemistry. Hormone therapy such as tamoxifen was prescribed in all luminal patients (43 patients). Radiotherapy was administered to 15 patients (18.3%), with acute toxicity in 20% of the cases. After a median follow-up of 36 months, the evolution was complete remission in 27 patients (32.93%). Conclusion. Breast cancer in men is rare, often diagnosed late with a poor prognosis.
A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer
PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA-mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2– advanced (locally unresectable) or metastatic disease (HR+/HER2– mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2– mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2– mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2– mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status.
Breast Cancer Survival and Incidence: 10 Years Cancer Registry Data in the Northwest, Iran
Background and Aim. Breast cancer is the most frequent cancer in women and the second most common cancer across the globe. The aim of this study was to report the survival data and trend analysis of breast cancer between 2007 and 2016 in a northwest region in Iran. Methods. Data were obtained from East Azerbaijan cancer registry database for the 10-year period between 2007 and 2016. Survival analysis was performed to calculate the breast cancer-specific survival proportions and mortality rates. Joinpoint trend analysis was performed to estimate the incidence trend of the cancer. Results. A total number of 4989 patients were recorded with primary diagnosis of breast cancer. Of them, we collected follow-up data for 1335 (1309 female and 26 male). The 10-year crude mortality rate was 3.34 (per 100,000). The one-, two-, three-, five-, and ten-year breast cancer-specific survival proportions were 0.92 (95% CI 0.91-0.93), 0.88 (95% CI 0.86-0.90), 0.84 (95% CI 0.83-0.86), 0.77 (95% CI 0.74-0.80), and 0.65 (95% CI 0.60-0.70), respectively. Over the study period, the age-standardized incidence rates increased from 21.68 to 36.99 (per 100,000) with an annual percentage change of 5.5 percent. Older individuals and males patients had significantly worse survival, and patients with high-grade tumors had significantly higher risk of mortality. Conclusion. A relatively better survival for breast cancer in East Azerbaijan, Iran, was observed compared to the overall breast cancer-specific survival proportions and mortality rates in the country. However, it is still poor compared to the developed countries indicating that inappropriate treatment modalities might have played a role on this.