scholarly journals Expected Monetary Impact of Oncotype DX Score-Concordant Systemic Breast Cancer Therapy Based on the TAILORx Trial

2019 ◽  
Vol 112 (2) ◽  
pp. 154-160 ◽  
Author(s):  
Angela Mariotto ◽  
Jinani Jayasekerea ◽  
Valentina Petkov ◽  
Clyde B Schechter ◽  
Lindsey Enewold ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oncotype Dx ◽  
Sensitivity Analyses ◽  
Estimation Methods ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Initial Care ◽  
Personalized Cancer ◽  
The Impact ◽  
Care Costs

Abstract Background TAILORx demonstrated that women with node-negative, hormone receptor-positive, HER2-negative breast cancers and Oncotype DX recurrence scores (RS) of 0–25 had similar 9-year outcomes with endocrine vs chemo-endocrine therapy; evidence for women aged 50 years and younger and RS 16–25 was less clear. We estimated how expected changes in practice following the trial might affect US costs in the initial 12 months of care (initial costs). Methods Data from Surveillance, Epidemiology, and End Results (SEER), SEER-Medicare, and SEER-Genomic Health Inc datasets were used to estimate Oncotype DX testing and chemotherapy rates and mean initial costs pre- and post-TAILORx (in 2018 dollars), assuming all women received Oncotype DX testing and score-suggested therapy posttrial. Sensitivity analyses tested the impact on costs of assumptions about compliance with testing and score-suggested treatment and estimation methods. Results Pretrial mean initial costs were $2.816 billion. Posttrial, Oncotype DX testing costs were projected to increase from $115 to $231 million and chemotherapy use to decrease from 25% to 17%, resulting in initial care costs of $2.766 billion, or a net savings of $49 million (1.8% decrease). A small net savings was seen under most assumptions. The one exception was if all women aged 50 years and younger with tumors with RS 16–25 elected to receive chemotherapy, initial care costs could increase by $105 million (4% increase). Conclusions Personalizing breast cancer treatment based on tumor genetic profiles could result in small cost decreases in the initial 12 months of care. Studies are needed to evaluate the long-term costs and nonmonetary benefits of personalized cancer care.

Using tumor genomic profile testing and comorbidity level to personalize chemotherapy decisions among older patients with early-stage breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12055-e12055
Author(s):  
Young Chandler ◽  
Claudine Isaacs ◽  
Jinani Jayasekera ◽  
Clyde B. Schechter ◽  
Christopher Cadham ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Older Women ◽  
Early Stage ◽  
Breast Cancer Mortality ◽  
Oncotype Dx ◽  
Sensitivity Analyses ◽  
Breast Cancers ◽  
Life Years ◽  
The Impact

e12055 Background: Under-representation of women ages 65+ (“older”) in the trials may limit clinical translation of results to this growing population. We used simulation modeling to estimate chemotherapy outcomes by age and comorbidity level among older women with early stage, estrogen-receptor+/HER2- breast cancers with an Oncotype DX score of 26+. Methods: A discrete-time stochastic state-transition model synthesized data from population studies and clinical trials to estimate outcomes over a 25-year horizon for subgroups of women based on age (65-69, 70-74, 75-79, and 80-89) and comorbidity levels (no/low, moderate, and severe). Age-, comorbidity-specific non-cancer survival was derived from a random 5% sample of women enrolled in the Medicare Part A and B program from 1992 to 2005 and included in the SEER areas. Outcomes included life years (LYs), quality-adjusted life years (QALYs), and breast cancer and other-cause mortality with chemoendocrine therapy or endocrine therapy alone. Sensitivity analysis tested the impact on outcomes of varying values of uncertain parameters. Results: Women with life expectancies of ≥ 7 years had net gains of 0.17 to 0.45 LYs (2.0-5.4 months) with chemotherapy; this group was mainly women aged 65-69 and 70-74 with no/low or moderate comorbidity. Women destined to develop distant recurrence gained between 4.2-10.4 months. LYs were reduced by chemotherapy toxicity. The majority of women died of other causes, ranging from 59% to 98% across all age groups and comorbidity levels, but chemotherapy reduced breast cancer mortality by 14.5% and 25.7% among women ages 65-69 and 70-74 with no/low comorbidity, respectively. Results were robust in sensitivity analyses, and chemotherapy improved all outcomes as treatment efficacy increased, assuming no change in toxicity. Conclusions: Older women with early stage, estrogen-receptor+/HER2- breast cancers with Oncotype DX scores of 26+ may benefit from chemotherapy, when both conditions of age <75 and comorbidity at no/low or moderate level can be met. Personalized treatment decisions for older women will ultimately depend on comorbidity-specific lifespan and individual preferences for the balance of benefits and harms of chemotherapy.

Obesity and Postmenopausal Hormone Receptor-positive Breast Cancer: Epidemiology and Mechanisms

Endocrinology ◽  
2021 ◽  
Author(s):  
Qianying Zuo ◽  
Shoham Band ◽  
Mrinali Kesavadas ◽  
Zeynep Madak Erdogan
Keyword(s):  
Breast Cancer ◽  
Potential Risk ◽  
Cancer Epidemiology ◽  
Breast Cancers ◽  
Breast Carcinogenesis ◽  
Postmenopausal Hormone ◽  
Hormone Receptor Positive ◽  
Breast Cancer Epidemiology ◽  
The Impact ◽  
Positive Breast Cancer

Abstract Obesity is a potential risk for several cancers, including postmenopausal, hormone dependent breast cancers. In this review, we will summarize recent studies on the impact of obesity on postmenopausal women’s health and discuss several mechanisms that were proposed to increase the risk of breast carcinogenesis.

scholarly journals Oncotype Dx Results in Multiple Primary Breast Cancers

2014 ◽  
Vol 8 ◽  
pp. BCBCR.S13727 ◽  
Author(s):  
Michael J. Toole ◽  
Kelley M. Kidwell ◽  
Catherine Van Poznak
Keyword(s):  
Breast Cancer ◽  
Retrospective Chart Review ◽  
Tumor Location ◽  
Positive Lymph Node ◽  
Oncotype Dx ◽  
Genetic Profile ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Node Negative Breast Cancer ◽  
Multiple Primary

Purpose To determine whether multiple primary breast cancers have similar genetic profiles, specifically Oncotype Dx Recurrence Scores, and whether obtaining Oncotype Dx on each primary breast cancer affects chemotherapy recommendations. Methods A database of patients with hormone receptor-positive, lymph node-negative, breast cancer was created for those tumors that were sent for Oncotype Dx testing from the University of Michigan Health System from 1/24/2005 to 2/25/2013. Retrospective chart review abstracted details of tumor location, histopathology, distance between tumors, Oncotype Dx results, and chemotherapy recommendations. Results Six hundred and sixty-six patients for whom Oncotype Dx testing was sent were identified, with 22 patients having multiple breast tumor specimens sent. Of the 22 patients who had multiple samples sent for analysis, chemotherapy recommendations were changed in 6 of 22 patients (27%) based on significant differences in Oncotype Dx Recurrence Scores. Qualitatively, there seems to be a greater difference in genetic profile in tumors appearing simultaneously on different breasts when compared to multiple tumors on the same breast. There was no association between distance between tumors and difference in Oncotype Dx scores for tumors on the same breast. Conclusions Oncotype Dx testing on multiple primary breast cancers altered management in regards to chemotherapy recommendations and should be considered for multiple primary breast cancers.

scholarly journals Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

scholarly journals Top 3 abstracts concerning hormone-receptor-positive early breast cancer

2021 ◽  
Author(s):  
Simon Peter Gampenrieder ◽  
Gabriel Rinnerthaler ◽  
Richard Greil
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Hormone Receptor ◽  
Menopausal Status ◽  
Pathologic Complete Response ◽  
Oncotype Dx ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer

SummaryThe three top abstracts at the 2020 virtual San Antonio Breast Cancer Symposium regarding hormone-receptor-positive early breast cancer, from our point of view, were the long-awaited results from PenelopeB and RxPONDER as well as the data from the ADAPT trial of the West German Study Group. PenelopeB failed to show any benefit by adjuvant palbociclib when added to standard endocrine therapy in patients without pathologic complete response after neoadjuvant chemotherapy. RxPONDER demonstrated that postmenopausal patients with early hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2−) breast cancer, 1–3 positive lymph nodes and an Oncotype DX Recurrence Score of less than 26 can safely be treated with endocrine therapy alone. In contrast, in premenopausal women with positive nodes, adjuvant chemotherapy plays still a role even in case of low genomic risk. Whether the benefit by chemotherapy is mainly an indirect endocrine effect and if ovarian function suppression would be similarly effective, is still a matter of debate. The HR+/HER2− part of the ADAPT umbrella trial investigated the role of a Ki-67 response to a short endocrine therapy before surgery in addition to Oncotype DX—performed on the pretreatment biopsy—to identify low-risk patients who can safely forgo adjuvant chemotherapy irrespective of menopausal status.

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

2008 ◽  
Vol 26 (6) ◽  
pp. 897-906 ◽  
Author(s):  
Marta Guix ◽  
Nara de Matos Granja ◽  
Ingrid Meszoely ◽  
Theresa B. Adkins ◽  
Bobbye M. Wieman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Growth Factor Receptor ◽  
Preoperative Treatment ◽  
Breast Cancers ◽  
Tumor Cell Proliferation ◽  
Hormone Receptor Positive ◽  
Er Positive ◽  
Her 2

Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) –positive but not in human epidermal growth factor receptor 2 (HER-2) –positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor–positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2–positive or triple-negative breast cancers.

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