scholarly journals Can surgery provoke the outgrowth of latent breast cancer? A unifying hypothesis

2007 ◽  
Vol 10 (4) ◽  
pp. 1-6 ◽  
Author(s):  
M. W. Retsky ◽  
R. Demicheli ◽  
W. J. M. Hrushesky ◽  
M. Baum ◽  
I. D. Gukas
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Unified Field Theory ◽  
Node Positive ◽  
Unified Field ◽  
Primary Surgery ◽  
Breat Cancer ◽  
Outcome Differences ◽  
High Benefit ◽  
Breast Cancer Growth

AbstractTo explain bimodal relapse patterns, we have previously suggested that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell and avascular micrometastasis phases (with 1 year and 2 year half-lives respectively). We further suggested that primary surgery sometimes initiates growth of distant dormant disease accelerating relapse. These iatrogenic events are common in that they occur in over half of all relapses. Surgery induced angiogenesis is mostly confined to premenopausal node positive patients in which case 20% of patients are so affected. We review here how this hypothesis explains a vairety of previously unrelated breast cancer phenomenon including 1) the mammography paradox for women age 40–49 untreated with adjuvant therapy, 2) the particularly high benefit of adjuvant chemotherapy for premenopausal node positive patients, 3) the heterogeneity of breast cancer, 4) the aggressiveness of cancer in young women, 5) the outcome differences with timing of surgery within the menstrual cycle, 6) the common myths regarding cancer spreading “when the air hits it” and treatment “provoking” the tumor, 7) the excess mortality of blacks over whites, and 8) reports from physicians 2000 years ago. In parallel to physicists who have long sought to explain all of physics with a unified field theory, we now suggest temporary dormancy together with surgery induced tumor growth provides a unifying theory for much of breat cancer.

scholarly journals cPLA2 Blockade Attenuates S100A7-Mediated Breast Tumorigenicity by Inhibiting the Immunosuppressive Tumor Microenvironment

2021 ◽  
Author(s):  
SANJAY MISHRA ◽  
Manish Charan ◽  
Rajni Kant Shukla ◽  
Pranay Agarwal ◽  
Swati Misri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Immunosuppressive Tumor Microenvironment ◽  
Tumor Growth And Metastasis ◽  
Breast Cancer Growth

Abstract Background: Metastasis is the major cause of mortality in breast cancer; however, the molecular mechanisms remain elusive. In our previous study, we demonstrated that S100A7/RAGE mediates breast cancer growth and metastasis by recruitment of tumor-associated macrophages. However, the downstream S100A7-mediated inflammatory oncogenic signaling cascade that enhances breast tumor growth and metastasis by generating the immunosuppressive tumor microenvironment (iTME) has not been studied. In this present study, we aimed to investigate the S100A7 and cPLA2 cross-talk in enhancing tumor growth and metastasis through enhancing the iTME.Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2 titer. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3(1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effect of S100A7/cPLA2 inhibition on the recruitment of various immune cells.Results: S100A7 and cPLA2 are highly expressed and positively correlated in malignant breast cancer patients. S100A7/RAGE upregulates cPLA2/PGE2 axis in aggressive breast cancer cells. Furthermore, S100A7 is positively correlated with PGE2 in breast cancer patients. Moreover, cPLA2 pharmacological inhibition suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models. Mechanistically, S100A7-mediated activation of cPLA2 enhances the recruitment of immunosuppressive myeloid cells by increasing PGE2 to fuel breast cancer growth and its secondary spread. We revealed that cPLA2 inhibitor mitigates S100A7-mediated breast tumorigenicity by suppressing the iTME. Furthermore, CODEX imaging data showed that cPLA2 inhibition increased the infiltration of CD4+/CD8+ T cells in the TME. Analysis of metastatic breast cancer samples revealed a positive correlation between S100A7/cPLA2 with CD163+ tumor-associated M2-macrophages.Conclusions: Our study shows that cross-talk between S100A7 and cPLA2 plays an important role in enhancing breast tumor growth and metastasis by generating an immunosuppressive tumor microenvironment and reducing infiltration of T cells. Furthermore, S100A7 could be used as a novel non-invasive prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing metastatic breast cancer.

Outcomes and feasibility of nipple-sparing mastectomy for node-positive breast cancer patients.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 60-60 ◽  
Author(s):  
Brittany L. Murphy ◽  
Tanya L. Hoskin ◽  
Judy Caroline Boughey ◽  
Amy C. Degnim ◽  
James W. Jakub ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Oncologic Outcomes ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Primary Surgery ◽  
Nipple Sparing Mastectomy ◽  
Nipple Sparing

60 Background: Indications for nipple-sparing mastectomy (NSM) with immediate reconstruction have expanded. For cancer patients, NSM is thought best-suited for early stage patients, with nodal involvement initially viewed as a relative contraindication. We undertook this study to evaluate the use and early outcomes of NSM in node-positive (LN+) breast cancer. Methods: We identified 240 cancers in 226 patients (14 bilateral) scheduled for NSM and operated on at our institution 1/2009-6/2014. Data on intraoperative conversion from NSM, recurrence and follow-up was abstracted from the medical record. Chi-square and long-rank tests were used for statistical analysis. P-values < 0.05 were considered significant. Results: Of 240 cancers, 182 were LN- and 58 were LN+. More LN+ patients had T2/T3 tumors (27/58, 47%) than LN- patients (31/182, 17%), p < 0.0001, but ER and HER2 status was similar. Of 58 LN+ cases, 19 (33%) were cN1 confirmed by positive LN cytology and 39 (67%) were cN0 but LN+ at operation. 10 patients LN+ at diagnosis received neoadjuvant therapy (NT) followed by operation (at which 6 were pLN+ and 4 rendered ypN0); 39 cN0 (4 NT, 35 primary surgery) and 9 cN1 primary surgery patients were pLN+ at operation with a median of 1 LN+. NSM was successful in 13/14 LN+ NT patients (93%) and 39/44 LN+ primary surgery patients (89%), p = 0.64. Six LN+ patients (10%) were converted to skin-sparing mastectomy (SSM) at initial operation based on frozen section pathology (n = 5) or at a second operation (n = 1) vs 13/182 LN- patients (7%), p = 0.44. Among cancer patients treated with NSM, 7 locoregional recurrences (5 in LN+, 2 in LN- patients) occurred at 25 mos median follow-up. 3-year locoregional disease-free estimates were 87% (95% CI 75-100%) for LN+ vs 99% (95% CI 97-100%) for LN- patients, p = 0.007. One nipple-areolar recurrence occurred, in a LN- patient. 3-year breast cancer-specific survival was 97% (95% CI 92-100%) in LN+ vs 99% (95% CI 98-100%) in LN- patients, p = 0.40. Conclusions: Conversion from planned NSM to SSM did not differ significantly between LN+ and LN- patients. Short-term oncologic outcomes were satisfactory. These data suggest that NSM may be appropriate for carefully selected LN+ breast cancer patients.

scholarly journals Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth

2017 ◽  
Vol 16 (3) ◽  
pp. 494-505 ◽  
Author(s):  
Marilena Tauro ◽  
Gemma Shay ◽  
Samer S. Sansil ◽  
Antonio Laghezza ◽  
Paolo Tortorella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Metastatic Breast ◽  
Matrix Metalloproteinase 2 ◽  
Cancer Growth ◽  
Breast Cancer Growth

scholarly journals The interactions of Bcl9/Bcl9L with β-catenin and Pygopus promote breast cancer growth, invasion, and metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Vida Vafaizadeh ◽  
David Buechel ◽  
Natalia Rubinstein ◽  
Ravi K. R. Kalathur ◽  
Lorenzo Bazzani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Progression ◽  
Transcriptional Response ◽  
Metastatic Breast ◽  
Conditional Knockout ◽  
Cancer Growth ◽  
Tumor Cell Death ◽  
Breast Cancer Growth ◽  
Canonical Wnt

AbstractCanonical Wnt/β-catenin signaling is an established regulator of cellular state and its critical contributions to tumor initiation, malignant tumor progression and metastasis formation have been demonstrated in various cancer types. Here, we investigated how the binding of β-catenin to the transcriptional coactivators B-cell CLL/lymphoma 9 (Bcl9) and Bcl9-Like (Bcl9L) affected mammary gland carcinogenesis in the MMTV-PyMT transgenic mouse model of metastatic breast cancer. Conditional knockout of both Bcl9 and Bcl9L resulted into tumor cell death. In contrast, disrupting the interaction of Bcl9/Bcl9L with β-catenin, either by deletion of their HD2 domains or by a point mutation in the N-terminal domain of β-catenin (D164A), diminished primary tumor growth and tumor cell proliferation and reduced tumor cell invasion and lung metastasis. In comparison, the disruption of HD1 domain-mediated binding of Bcl9/Bcl9L to Pygopus had only moderate effects. Interestingly, interfering with the β-catenin-Bcl9/Bcl9L-Pygo chain of adapters only partially impaired the transcriptional response of mammary tumor cells to Wnt3a and TGFβ treatments. Together, the results indicate that Bcl9/Bcl9L modulate but are not critically required for canonical Wnt signaling in its contribution to breast cancer growth and malignant progression, a notion consistent with the “just-right” hypothesis of Wnt-driven tumor progression.

A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer.

1988 ◽  
Vol 6 (9) ◽  
pp. 1377-1387 ◽  
Author(s):  
I F Tannock ◽  
N F Boyd ◽  
G DeBoer ◽  
C Erlichman ◽  
S Fine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Metastatic Breast ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Primary Surgery ◽  
Dose Levels

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.

Primary surgery versus no surgery in synchronous metastastic breast cancer: Patient-reported outcomes of the ABCSG 28 Posytive trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1074-1074
Author(s):  
Vesna Bjelic-Radisic ◽  
Florian Fitzal ◽  
Guenther G. Steger ◽  
Christian Marth ◽  
Marija Balic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Physical Functioning ◽  
Systemic Therapy ◽  
Metastatic Breast ◽  
Primary Systemic Therapy ◽  
Primary Surgery ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

1074 Background: The ABCSG 28 Posytive trial compared primary surgery versus primary systemic therapy without surgery in synchronous metastatic breast cancer. The primary aim of the study was to investigate whether immediate resection of the primary tumor followed by standard systemic therapy improves median survival compared with no surgical resection (NCT01015625). This report describes quality-of-life (QoL) results. Methods: Patients were randomized between 2011 and 2015. Patients completed the EORTC QLQ-C30 and EORTC QLQ-BR 23 before treatment and every 6 months during follow-up. Results: 90 patients (45 with surgery, 45 with primary systemic therapy without surgery) from 15 centers were included in the QoL analysis. At 6 months patients after surgery reported more insomnia, breast symptoms and arm symptoms than patients without surgery, but these differences were no longer present at later follow-up visits. In the univariate and multivariate analysis the global health status and physical functioning scales of EORTC QLQ C30 were statistically significant predictors for OS and TTP (p < 0.05). Over a 24-month follow-up, patients > 60 years showed more QoL impairments than those < 60 years, independent of treatment. Patients < 60 years had better physical functioning and less fatigue, appetite loss, constipation and breast symptoms than older patients. There were no differences in QoL between patients with bone metastases vs those with visceral ± bone metastases. Conclusions: In patients with primary metastatic breast cancer primary surgery does not appear to improve QoL. Global health status and physical functioning scales of EORTC QLQ-C30 appears to be a predictive factor for OS and TTP. Clinical trial information: NCT01015625.

Sign in / Sign up

Export Citation Format

Share Document