scholarly journals Should Triple-Negative Breast Cancer (TNBC) Subtype Affect Local-Regional Therapy Decision Making?

2014 ◽  
pp. e32-e36 ◽  
Author(s):  
Meena S. Moran
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Conservation ◽  
Definitive Treatment ◽  
Partial Breast Irradiation ◽  
Breast Irradiation ◽  
Regional Management ◽  
Younger Age ◽  
Tnbc Subtype

The more aggressive biologic characteristics and the current lack of targeted therapy for triple-negative breast cancer (TNBC) make local-regional management decisions challenging for physicians. TNBC is associated with patients of younger age, black race and BRCA1 mutation carriers. Distinctions between BRCA1-associated and sporadic TNBC include increased lifetime risk of ipsilateral and contralateral breast cancer after breast cancer therapy (BCT) for BRCA carriers, which is not shared by sporadic TNBC. However, the presence of a BRCA mutation should not preclude a breast-conservation approach in patients who are otherwise appropriate candidates for BCT. Data suggest that local-regional relapse (LRR) at baseline after BCT appears to be comparable for TNBC and the HER2-positive subgroups, but is about 50% greater than luminal tumors. LRR appears to be similarly increased after mastectomy; thus, TNBC should not be a contra-indication for BCT. Recent hypothesis-generating data suggest less LRR after BCT (where radiation is routinely delivered) than with mastectomy for early-stage TNBC. To date, no specific local-regional guideline recommendations for TNBC exist. Level I outcome data for TNBC using accelerated partial breast irradiation (APBI) and hypofractionated whole-breast irradiation (hWBRT) are lacking. TNBC should be treated with APBI only on clinical trials. Although hWBRT may be considered in TNBC, its association with younger age, advanced disease and use of systemic chemotherapy often precludes its use for this subtype. Until definitive treatment strategies are validated in large datasets and confirmed in randomized trials, TNBC subtype, in and of itself, should not direct local-regional management treatment decisions.

scholarly journals Targeting the Id1-Kif11 Axis in Triple-Negative Breast Cancer Using Combination Therapy

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1295
Author(s):  
Archana P. Thankamony ◽  
Reshma Murali ◽  
Nitheesh Karthikeyan ◽  
Binitha Anu Varghese ◽  
Wee S. Teo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Genomic Analysis ◽  
Aurora Kinase ◽  
Cell Cycle Regulators ◽  
Tumor Models ◽  
Tnbc Subtype

The basic helix-loop-helix (bHLH) transcription factors inhibitor of differentiation 1 (Id1) and inhibitor of differentiation 3 (Id3) (referred to as Id) have an important role in maintaining the cancer stem cell (CSC) phenotype in the triple-negative breast cancer (TNBC) subtype. In this study, we aimed to understand the molecular mechanism underlying Id control of CSC phenotype and exploit it for therapeutic purposes. We used two different TNBC tumor models marked by either Id depletion or Id1 expression in order to identify Id targets using a combinatorial analysis of RNA sequencing and microarray data. Phenotypically, Id protein depletion leads to cell cycle arrest in the G0/G1 phase, which we demonstrate is reversible. In order to understand the molecular underpinning of Id proteins on the cell cycle phenotype, we carried out a large-scale small interfering RNA (siRNA) screen of 61 putative targets identified by using genomic analysis of two Id TNBC tumor models. Kinesin Family Member 11 (Kif11) and Aurora Kinase A (Aurka), which are critical cell cycle regulators, were further validated as Id targets. Interestingly, unlike in Id depletion conditions, Kif11 and Aurka knockdown leads to a G2/M arrest, suggesting a novel Id cell cycle mechanism, which we will explore in further studies. Therapeutic targeting of Kif11 to block the Id1–Kif11 axis was carried out using small molecular inhibitor ispinesib. We finally leveraged our findings to target the Id/Kif11 pathway using the small molecule inhibitor ispinesib in the Id+ CSC results combined with chemotherapy for better response in TNBC subtypes. This work opens up exciting new possibilities of targeting Id targets such as Kif11 in the TNBC subtype, which is currently refractory to chemotherapy. Targeting the Id1–Kif11 molecular pathway in the Id1+ CSCs in combination with chemotherapy and small molecular inhibitor results in more effective debulking of TNBC.

Accelerated Partial Breast Irradiation in Early-Stage Breast Cancer

2007 ◽  
Vol 25 (8) ◽  
pp. 996-1002 ◽  
Author(s):  
Mary Ella Sanders ◽  
Troy Scroggins ◽  
Federico L. Ampil ◽  
Benjamin D. Li
Keyword(s):  
Breast Cancer ◽  
Time Course ◽  
Treatment Time ◽  
Early Stage ◽  
Breast Conservation ◽  
Intraoperative Radiotherapy ◽  
Accelerated Partial Breast Irradiation ◽  
Intracavitary Brachytherapy ◽  
Partial Breast Irradiation ◽  
Breast Irradiation

Whole-breast irradiation, as part of breast-conservation therapy (BCT), has well-established results, good cosmesis, and low toxicity. Results from the BCT trials suggest that the risk for ipsilateral breast cancer recurrence resides within close proximity to the original tumor site. This leads investigators to consider the role of an accelerated and more tumor bed–focused course of radiotherapy. Accelerated partial-breast irradiation (APBI) involves treating a limited volume of breast tissue, with dose of irradiation per fraction increased and the treatment time course decreased. Four currently available methods of APBI are interstitial brachytherapy, intracavitary brachytherapy, intraoperative radiotherapy, and three-dimensional conformal external-beam radiotherapy. Patient selection is critical. This review article presents some preliminary clinical observations and limitations that suggest a potential role for APBI as a more user-friendly mode for delivering radiotherapy after lumpectomy for early breast cancer.

scholarly journals Intraoperative Radiotherapy for Breast Cancer: The Lasting Effects of a Fleeting Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Harriet B. Eldredge-Hindy ◽  
Anne L. Rosenberg ◽  
Nicole L. Simone
Keyword(s):  
Breast Cancer ◽  
Patient Satisfaction ◽  
Early Stage ◽  
External Beam Radiotherapy ◽  
Breast Conservation ◽  
Intraoperative Radiotherapy ◽  
Ipsilateral Breast Tumor Recurrence ◽  
Partial Breast Irradiation ◽  
Breast Irradiation ◽  
Breast Radiotherapy

In well-selected patients who choose to pursue breast conservation therapy (BCT) for early-stage breast cancer, partial breast irradiation (PBI) delivered externally or intraoperatively, may be a viable alternative to conventional whole breast irradiation. Two large, contemporary randomized trials have demonstrated breast intraoperative radiotherapy (IORT) to be noninferior to whole breast external beam radiotherapy (EBRT) when assessing for ipsilateral breast tumor recurrence in select patients. Additionally, IORT and other PBI techniques are likely to be more widely adopted in the future because they improve patient convenience by offering an accelerated course of treatment. Coupled with these novel techniques for breast radiotherapy (RT) are distinct toxicity profiles and unique cosmetic alterations that differ from conventional breast EBRT and have the potential to impact disease surveillance and patient satisfaction. This paper will review the level-one evidence for treatment efficacy as well as important secondary endpoints like RT toxicity, breast cosmesis, quality of life, patient satisfaction, and surveillance mammography following BCT with IORT.

Breast Conservation Versus Mastectomy in Triple-Negative Breast Cancer: Two Steps Forward, One Step Back?

2011 ◽  
Vol 29 (35) ◽  
pp. 4722-4723 ◽  
Author(s):  
Alison H. Trainer ◽  
Paul A. James ◽  
G. Bruce Mann ◽  
Geoffrey J. Lindeman
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Conservation ◽  
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