Homologous recombination deficiency (HRD) status predicts response to standard neoadjuvant chemotherapy in patients with triple-negative or BRCA1/2 mutation-associated breast cancer

Telli, Melinda L.; Hellyer, Jessica A.; Audeh, William; Jensen, Kristin C.; Bose, Shikha; Timms, Kirsten M.; Gutin, Alexander; Abkevich, Victor; Peterson, Rebecca N.; Neff, Chris; Hughes, Elisha; Sangale, Zaina; Jones, Joshua T.; Hartman, Anne Renee; Chang, Pei Jen; Vinayak, Shaveta; Wenstrup, Richard J.; Ford, James M.

doi:10.1007/s10549-017-4624-7

Cited by 97 publications

(78 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…45 In multivariable analyses of breast cancers, HRD score was able to detect significant BRCA1/2 deficiency not captured by the any single score. 43 The predictive effects of HRD score and/or HR deficiency in early-stage TNBC have been illustrated by recent studies, [45][46][47] as shown in Table 2. But in metastatic setting, the dichotomized HRD score was not found to be associated with sensitivity to carboplatin and the reason may be that nonmutated HRD-high cancers frequently reverse the homologous repair defect in metastatic setting.…”

Section: Biomarkers Associated With Genomic Instabilitymentioning

confidence: 93%

“…Telli(2015) 46 Phase II Neoadjuvant HRD score, BRCA1/2 mutation status HRD score 42 and BRCA1/2 mutation GeparSixto/Von Minckwitz (2015) 66 and Denkert(2015) 61 Phase II Neoadjuvant HRD score, Stromal TILs, mRNA expression of immunoactivating factors (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21), immunosuppressive factors (IDO1, PD-1, PD-L1, CTLA4, FOXP3) HRD score 42, Increased levels of stromal TILs and all 12 immune mRNA markers Tutt(2015) 69 Phase III First line BRCA1/2 mutation status,HRD score BRCA1/2 mutation Sharma(2015) 57 Prospective Neoadjuvant Hematological toxicity Thrombocytopenia ORR: overall response rate. PFS: progression-free survival.…”

Section: Platinum Salts In Early-stage Tnbcmentioning

confidence: 99%

See 1 more Smart Citation

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Jin

Zhang

et al. 2017

Cancer Biology & Therapy

View full text Add to dashboard Cite

Treatment of triple negative breast cancer (TNBC) has been a big challenge since it is defined. To date, platinum-based chemotherapy has played a significant role in the treatment of TNBC patients. However, some patients do not respond to platinum salts or gradually develop chemoresistance, resulting in little effect, or even some adverse effects. Here, we review numerous preclinical and clinical investigations to summarize possible mechanisms and potential predictive biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD) resulting from the loss of BRCA function is the main rationale of platinum efficacy in TNBC. BRCA mutation and methylation have been demonstrated to be important potential biomarkers. Based on genome-wide effects, BRCA-like classifier can identify the functional loss of BRCA and work as the predictor. HRD score that is able to identify the "BRCAness" and predict the sensitivity of platinum is increasingly considered. Taken together, all findings suggest that HR deficiency profile encompassed by BRCA mutation and high HRD score could predict response to platinum, even to other DNA-damage inducing agents. p53 family members and molecular subtypes of TNBC are also important alternative considerations for predicting platinum response based on the preclinical trials. Currently, tumor infiltrating lymphocyte level and thrombocytopenia are emerging as predictive biomarkers.

show abstract

Section: Biomarkers Associated With Genomic Instabilitymentioning

confidence: 93%

Section: Platinum Salts In Early-stage Tnbcmentioning

confidence: 99%

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Jin

Zhang

et al. 2017

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…Aromatase inhibitor hormone therapy is administered only in postmenopausal women to treat ER + early and/or late stage breast cancer [22]. It acts on the aromatase enzyme that still produces estrogen hormone in fat tissue of post-menopausal women or women without active ovaries.…”

Section: Hormone Therapy or Endocrine Therapymentioning

confidence: 99%

“…This accounted for approximately 15% of all cancer deaths among women globally [1]. In 2018, the highest numbers of breast cancer cases were reported from Asia (9,11,014) followed by Europe (5,22,512), North America (2,62,347), Latin America and Caribbean (199,734), Africa (1,68,690) and Oceania (24,551) [1]. Although very common in women, breast cancer rarely occurs in men [2].…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, trastuzumab (herceptin) is mostly recommended to the HER2+ breast cancer patients [20]. TNBC patients are difficult to treat, with unfavorable prognosis and are generally administered with the standard chemotherapy along with the PARP inhibitors or the DNAtargeting platinum drug (carboplatin) [21,22]. Another strategy is based on the holistic approach of patient recovery i.e.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Drug repurposing for breast cancer therapy: Old weapon for new battle

Aggarwal

Verma

Aggarwal

et al. 2021

Seminars in Cancer Biology

104

View full text Add to dashboard Cite

Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed. Current breast cancer therapyUnlike a decade ago, clinicians today have multiple choices for breast cancer treatment depending on the size, stage, grade, metastatic behavior, aggressiveness and intrinsic molecular subtyping of tumor, age, menopausal status, overall health, comorbidities, and preferences of the patient [9-13]. Chemotherapy, hormone therapy, immunotherapy, radiotherapy, and surgery are the common modalities for breast cancer [10,14]. Primary choice of treatment usually includes surgery with the aim of complete resection of the major tumor mass on the first hand. Breast conserving (lumpectomy) and breast reconstruction surgeries, mastectomy or lymph node dissections are performed initially in the breast cancer patients [15]. Surgery may be preceded with the systemic neoadjuvant therapies in order to shrink the tumor for effective surgery and to maximize breast conservation. For example, in HER2+ cases, Trastuzumab (Herceptin) and Pertuzumab (Perjeta)

show abstract

Development in Drug Repurposing for the Treatment of Acute Leukemia Complicating Metastatic Breast Cancer

Shaikh

Adimule²,

Nandi

2023

Drug and Therapy Development for Triple Negative Breast Cancer

View full text Add to dashboard Cite

Homologous recombination deficiency (HRD) status predicts response to standard neoadjuvant chemotherapy in patients with triple-negative or BRCA1/2 mutation-associated breast cancer

Abstract: HR deficiency status is significantly associated with response to standard neoadjuvant chemotherapy in TNBC. This observation is consistent with the mechanisms of action of doxorubicin and cyclophosphamide as DNA damaging agents.

Cited by 97 publications

References 19 publications

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Drug repurposing for breast cancer therapy: Old weapon for new battle

Development in Drug Repurposing for the Treatment of Acute Leukemia Complicating Metastatic Breast Cancer

Contact Info

Product

Resources

About