scholarly journals The effect of smoking on biological change of recurrent breast cancer

2020 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Rika Kouhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Growth Factor Receptor ◽  
Cancer Recurrence ◽  
Smoking History ◽  
Her2 Expression ◽  
Recurrent Tumors ◽  
Recurrent Breast

Abstract Background: The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence.Methods: This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined.Results: When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p=0.024).Conclusions: Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.

scholarly journals The effect of smoking on biological change of recurrent breast cancer

2020 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Rika Kouhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Growth Factor Receptor ◽  
Cancer Recurrence ◽  
Smoking History ◽  
Her2 Expression ◽  
Recurrent Tumors ◽  
Recurrent Breast

Abstract Background The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence. Methods This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined. Results When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p=0.024). Conclusions Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.

scholarly journals RIPK3 upregulation confers robust proliferation and collateral cystine-dependence on breast cancer recurrence

2019 ◽  
Author(s):  
Chao-Chieh Lin ◽  
Nathaniel Mabe ◽  
Yi-Tzu Lin ◽  
Wen-Hsuan Yang ◽  
Xiaohu Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Tumor Recurrence ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Recurrent Tumor ◽  
Breast Tumor Cells ◽  
Recurrent Tumors ◽  
Recurrent Breast

AbstractThe molecular and genetic basis of tumor recurrence is complex and poorly understood. RIPK3 is a key effector in programmed necrotic cell death and, therefore, its expression is frequently suppressed in primary tumors. In a transcriptome profiling between primary and recurrent breast tumor cells from a murine model of breast cancer recurrence, we found that RIPK3, while absent in primary tumor cells, is dramatically re-expressed in recurrent breast tumor cells by an epigenetic mechanism. Unexpectedly, we found that RIPK3 knockdown in recurrent tumor cells reduced clonogenic growth, causing cytokinesis failure, p53 stabilization, and repressed the activities of YAP/TAZ. These data uncover a surprising role of the pro-necroptotic RIPK3 kinase in enabling productive cell cycle during tumor recurrence. Remarkably, high RIPK3 expression also rendered recurrent tumor cells exquisitely dependent on extracellular cystine and undergo programmed necrosis upon cystine deprivation. The induction of RIPK3 in recurrent tumors unravels an unexpected mechanism that paradoxically confers on tumors both growth advantage and necrotic vulnerability, providing potential strategies to eradicate recurrent tumors.

NRF2-dependent metabolic reprogramming is required for tumor recurrence following oncogene inhibition

2019 ◽  
Author(s):  
Douglas B. Fox ◽  
Ryan Lupo ◽  
Laura C. Noteware ◽  
Rachel Newcomb ◽  
Juan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Residual Disease ◽  
Cancer Recurrence ◽  
Cellular Metabolism ◽  
Metabolic Reprogramming ◽  
Oncogenic Signaling ◽  
Recurrent Tumors ◽  
Recurrent Breast

SummaryOncogenic signaling pathways both directly and indirectly regulate anabolic metabolism, and this is required for tumor growth. Targeted therapies that inhibit oncogenic signaling have dramatic impacts on cellular metabolism. However, it is not known whether the acquisition of resistance to these therapies is associated with – or driven by – alterations in cellular metabolism. To address this, we used a conditional mouse model of Her2-driven breast cancer to study metabolic adaptations following Her2 inhibition, during residual disease, and after tumor recurrence. We found that Her2 downregulation caused widespread changes in cellular metabolism, culminating in oxidative stress. Tumor cells adapted to this metabolic stress by upregulation of the antioxidant transcription factor, NRF2. Constitutive NRF2 expression persisted during residual disease and tumor recurrence, and NRF2 was both sufficient to promote tumor recurrence, and necessary for recurrent tumor growth. These results are supported by clinical data showing that the NRF2 transcriptional program is activated in recurrent breast tumors, and that NRF2 is associated with poor prognosis in patients with breast cancer. Mechanistically, NRF2 signaling in recurrent tumors induced metabolic reprogramming to re-establish redox homeostasis and upregulate de novo nucleotide synthesis. Finally, this NRF2-driven metabolic state rendered recurrent tumor cells sensitive to glutaminase inhibition, suggesting that NRF2-high recurrent tumors can be therapeutically targeted. Together, these data provide evidence that NRF2-driven metabolic reprogramming is required for breast cancer recurrence following oncogene inhibition.SignificanceAlthough tumor recurrence is the leading cause of mortality in breast cancer, the cellular properties that allow tumor cells to evade therapy and form recurrent tumors remain largely uncharacterized. Similarly, very little is known about how tumor metabolism changes following therapy, or whether alterations in cellular metabolism drive tumor recurrence. In this study, we identify the antioxidant transcription factor NRF2 as a critical positive regulator of breast cancer recurrence. We find that NRF2-dependent metabolic reprogramming is both sufficient and required to promote tumor recurrence. Additionally, we demonstrate that the NRF2-driven metabolic state renders recurrent tumors sensitive to glutaminase inhibitors, suggesting a novel therapeutic approach for the treatment of recurrent breast cancer.

scholarly journals Interaction of MRE11 and Clinicopathologic Characteristics in Recurrence of Breast Cancer: Individual and Cumulated Receiver Operating Characteristic Analyses

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Cheng-Hong Yang ◽  
Sin-Hua Moi ◽  
Li-Yeh Chuang ◽  
Shyng-Shiou F. Yuan ◽  
Ming-Feng Hou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Receiver Operating Characteristic ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Growth Factor Receptor ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Prognostic Indicators ◽  
Clinicopathologic Characteristics ◽  
Receiver Operating

The interaction between the meiotic recombination 11 homolog A (MRE11) oncoprotein and breast cancer recurrence status remains unclear. The aim of this study was to assess the interaction between MRE11 and clinicopathologic variables in breast cancer. A dataset for 254 subjects with breast cancer (220 nonrecurrent and 34 recurrent) was used in individual and cumulated receiver operating characteristic (ROC) analyses of MRE11 and 12 clinicopathologic variables for predicting breast cancer recurrence. In individual ROC analysis, the area under curve (AUC) for each predictor of breast cancer recurrence was smaller than 0.7. In cumulated ROC analysis, however, the AUC value for each predictor improved. Ten relevant variables in breast cancer recurrence were used to find the optimal prognostic indicators. The presence of any six of the following ten variables had a high (79%) sensitivity and a high (70%) specificity for predicting breast cancer recurrence: tumor size ≥ 2.4 cm, tumor stage II/III, therapy other than hormone therapy, age ≥ 52 years, MRE11 positive cells > 50%, body mass index ≥ 24, lymph node metastasis, positivity for progesterone receptor, positivity for epidermal growth factor receptor, and negativity for estrogen receptor. In conclusion, this study revealed that these 10 clinicopathologic variables are the minimum discriminators needed for optimal discriminant effectiveness in predicting breast cancer recurrence.

Postchemotherapy rheumatism.

1993 ◽  
Vol 11 (4) ◽  
pp. 768-770 ◽  
Author(s):  
C L Loprinzi ◽  
J Duffy ◽  
J N Ingle
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Combination Chemotherapy ◽  
Case Reports ◽  
Cancer Recurrence ◽  
Recurrent Breast Cancer ◽  
Rheumatologic Diseases ◽  
Clinical Phenomenon ◽  
Recurrent Breast

PURPOSE This report describes a previously unreported clinical phenomenon that occurs in some patients after completion of combination chemotherapy. METHODS AND RESULTS Eight case reports are presented. Affected patients developed a syndrome of myalgias/arthralgias within several months of completing cyclophosphamide/fluorouracil (5FU)-containing adjuvant combination chemotherapy for breast cancer. These symptoms did not appear to be related to cancer recurrence or any common rheumatologic disorder. The syndrome generally resolved over several months. CONCLUSION Postchemotherapy rheumatism is a syndrome of myalgias/arthralgias that usually develops 1 to 3 months after completion of adjuvant chemotherapy. Recognition of this syndrome can limit the need for extensive work-ups to exclude recurrent breast cancer or inflammatory rheumatologic diseases.

scholarly journals Discordance in Biomarker Expression in Breast Cancer After Metastasis: Single Center Experience in India

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ajay Gogia ◽  
S. V. Suryanarayana Deo ◽  
Dayanand Sharma ◽  
Rakesh K. Phulia ◽  
Sanjay Thulkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Tumor Biology ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Disease Evolution ◽  
Metastatic Recurrence ◽  
Single Center Experience ◽  
7Th Edition ◽  
Treatment Plans

PURPOSE Biomarker—estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/ neu) —discordance plays an essential role in the management and prognosis of patients with metastatic breast cancer. Rates of discordance have been previously reported around 12% to 35%, 30% to 50%, and 5% to 15%, respectively, in Western literature. Data are sparse regarding the same from developing countries, such as India. METHODS We performed an ambispective review of paired biomarker status in patients with breast cancer—stage I, II, and III as per American Joint Committee on Cancer, 7th edition—who developed metastasis at recurrence (N = 103 patients). Biomarker status and clinical and radiologic parameters were documented at baseline and subsequent follow-up. RESULTS Discordance was present in 21.3% for ER, 29.1% for PR, and 15.5% for HER2/ neu receptor. In our cohort, 7.8% had positive to negative ER and 13.6% negative to positive. Whereas 21.4% had positive to negative PR, 7.8% had negative to positive PR. Approximately 6.8% had positive to negative HER2/ neu receptor and 8.7% negative to positive. In our cohort, 41 patients (40%) had single-site metastasis—bone, 15.5%; lung, 11.7%; nonregional lymph node, 7.8%; liver, 3.9%; and brain, 0.97%. More than one site of metastasis was present in 62 patients (60%). The most common sites of metastasis were visceral—lung and liver—followed by bone, nonregional lymph node, skin, and brain. CONCLUSION The current study demonstrated that metastatic disease evolution in breast cancer is characterized by change in the tumor biology, which leads to discordance in receptor status. Repeat biomarker studies at metastatic recurrence is warranted, especially if treatment plans include hormone and targeted therapy.

A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx): NSABP B-43.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS657-TPS657
Author(s):  
Melody A. Cobleigh ◽  
Stewart J. Anderson ◽  
Thomas B. Julian ◽  
Kalliopi P. Siziopikou ◽  
Douglas W. Arthur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Tumor Biology ◽  
Cancer Recurrence ◽  
Breast Conserving Surgery ◽  
Molecular Therapy ◽  
Phase Iii ◽  
Fish Analysis ◽  
Ipsilateral Breast ◽  
Hazard Reduction

TPS657 Background: Asignificant amount of DCIS is ER negative and/or overexpresses HER2. This provides an opportunity to test molecular therapy in DCIS. In xenograft models and cell lines, T boosts RT effectiveness. In T-treated HER2+ patients, apoptosis occurs within 1 wk of single agent T use, with T found in ductal aspirates. Ample safety evidence for T exists. T given during whole breast irradiation (WBI) may improve results for Lx-resected HER2+ DCIS. A trial to examine this question will enhance the understanding of breast tumor biology and the prevention of such tumors and could possibly extend breast-conserving surgery benefits for women with DCIS. Methods: After Lx for pure DCIS, each patient’s DCIS lesion is centrally tested for HER2 by IHC analysis. HER2 2+ tumors undergo FISH analysis. HER2 3+ or FISH+ patients can be randomly assigned to 2 doses of T, 3 weeks apart during WBI or to WBI alone. Women ≥18 yrs. with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are and clinically or pathologically node negative are eligible. Centrally tested DCIS must be HER2 +. ER and/or PR status must be known before randomization. Primary aims are to determine if T decreases ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. B-43 will determine if DFS, recurrence-free interval, and OS can be improved with the use of T. 2000 patients will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at163 ipsilateral breast cancer events (7.5 - 8 yrs. after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 ipsilateral breast cancer events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 12-31-11, 763 patients have been randomized. NCT00769379 Grant support: PHS NCI-U10-CA-69651, -12027, and NCI P30-CA-14599 from the US NCI and Genentech, Inc.

scholarly journals Panoptic Overview of Triple-Negative Breast Cancer in Nigeria: Current Challenges and Promising Global Initiatives

2018 ◽  
pp. 1-20
Author(s):  
Nikita Wright ◽  
Padmashree Rida ◽  
Emad Rakha ◽  
Ayodeji Agboola ◽  
Ritu Aneja
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Resource Constraints ◽  
African Ancestry ◽  
Expression Patterns ◽  
Tumor Biology ◽  
The United States ◽  
Nigerian Women

PurposeTriple-negative breast cancer (TNBC) is the most deadly form of breast cancer (BC) today. TNBC treatment is fraught with challenges because of the extensive interpatient heterogeneity in clinical behavior and scarcity of stratifying biomarkers and actionable targets. Women of African ancestry face a disproportionate burden resulting from this disease, which affects them earlier and more aggressively and has a higher propensity to spread and resist conventional treatments. A much higher proportion of Nigerian patients with BC have TNBC compared with patients with BC in the United States and Europe.MethodsThis article spotlights Nigeria as an example of a nation wherein genetic and nongenetic spheres of influence intersect to affect the prevalence of this disease, the scale of its challenge, and its toll.ResultsStudies have illuminated the inherently different tumor biology of Nigerian TNBCs, which show distinct genetic variants and gene expression patterns compared with European or European-American TNBCs. Parallels are apparent between TNBC phenotypes among African Americans and Nigerians, implicating the common thread of shared genetic ancestry between these populations. Reproductive, lifestyle, socioeconomic, and cultural factors also shape TNBC outcomes in Nigeria, as do resource constraints in Nigerian health care and research sectors.ConclusionIncreasing our understanding of how these factors contribute to poorer outcomes among Nigerian women may uncover valuable insights and strategies in alleviating the TNBC burden in many countries of the world and help reduce the racial disparity in BC-related outcomes here in the United States. Importantly, this review also highlights collaborative global and local initiatives that converge expertise and resources to advance research on effective management of TNBC in diverse populations.

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