A Multi- institutional Prospective Analysis of Impact of CanAssist Breast (Morphometric Immunohistochemistry Based Test) on Adjuvant Chemotherapy Decisions in Early Breast Cancer

Abstract Purpose: CanAssist Breast (CAB) has been validated retrospectively for assessing risk of recurrence and thereby usefulness of chemotherapy in HR+/HER2- breast cancer. The objective of this study is to assess the agreement between physician’s treatment plan and CAB risk stratification and evaluate whether CAB results aid in the physician’s treatment decision.Methods: The data on the physician’s treatment plan before and after the CAB test was collected prospectively between 2016 and 2021 in 249 patients. Changes in treatment recommendations and compliance with CAB reports were analyzed. Results: Based on conventional clinicopathological features physicians planned to treat 46% of patients with endocrine therapy (ET) (low-risk-LR)), 24% with chemoendocrine therapy (CET) (high-risk-HR)) and in 30% physicians were uncertain of prescribing chemotherapy (intermediate-risk-IR)) before CAB testing. The correlation between clinical risk assessment and CAB risk stratification (k=0.2 (0.05-0.35) was nonsignificant. CAB classified 64% as LR, which was 18% (9.3-25, P=0.0001) higher compared to clinical LR. In the clinical IR category, CAB risk proportions were 55:45 (LR: HR). We observed a substantial shift in treatment recommendation from CET to ET in 54% (40.75- 66.84, P<0.0001) of clinical HR and ET to CET in 26% (18.27- 35.01, P<0.0001) of clinical LR patients. Overall CAB lead to change in treatment recommendation in 42% of the cohort.Conclusions: There was a significant impact of CAB on the physician’s treatment decision. CAB provided definite treatment recommendation to IR patients where the physician had dilemma on prescribing chemotherapy and provided precise treatment plan to clinical LR and HR patients.

Download Full-text

Evaluation of the tumor marker Ca27.29 for risk stratification and treatment monitoring in primary breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.11005 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 11005-11005

Author(s):

E. M. Genss ◽

B. Rack ◽

H. L. Sommer ◽

I. Schrader ◽

R. Lorenz ◽

...

Keyword(s):

Breast Cancer ◽

Risk Stratification ◽

Tumor Marker ◽

Primary Breast Cancer ◽

Primary Diagnosis ◽

Over Expression ◽

Before And After ◽

Node Metastases

11005 Background: Several trials have shown an earlier detection of metast. disease in breast cancer pts by the use of TU- markers. Whether this lead time advantage can be translated into improved outcome is discussed controversially. We prospectively evaluated the role of Ca27.29 in breast cancer pts at primary diagnosis and during adjuvant systemic treatment within the German SUCCESS-Trial (n=3658 pts planned). Methods: The SUCCESS-Trial compares sequential chemotherapy with FEC-Docetaxel(Doc) vs. FEC- DocGemcitabine, followed by zoledronate 2 vs. 5 years in primary high risk N0 and N+ breast cancer pts. Ca27.29 levels were assessed using the specific ST AIA-PACK Ca27.29 reagents directed against MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). Cut-off levels for the assay was 24 U/ml. Results: We analyzed 1098 breast cancer pts prospectively before start and after completion of chemotherapy. 21% of pts (n=226; median 17U/ml; range 4–410) had tumor marker elevation = 24 U/ml before and 48% (n=524; median 23U/ml; range 4–198) after completion of chemotherapy. Ca27.29 levels before and after chemo correl. significantly (p<.001). Of those pts who presented with elevated values initially, 14% remained positive, while 84% had normal Ca27.29 after chemo. Those pts with initially negative blood sampling, returned with high Ca27.29 in 38% and normal values in 62% of cases. While Ca27.29 was well balanced between the two treatment arms at primary diagnosis with a rate of 10% with elevated Ca27.29 in each arm, significantly more pts showed high Ca27.29 with FEC-DocGemcitabine compared to FEC-Doc (27% vs. 21%, p<.001). Ca27.29 elevation did not correl. with most conventional prognostic factors such as tumor size (p=.23), histopath. grading (p=.98) or HR-status (p=.46). However, we found a significant correlation of Ca 27.29 with the presence of lymph node metastases (p=.01) and Her2/neu-over-expression of the primary tumor (p=.04). Conclusions: Measurement Ca27.29 in peripheral blood of primary breast cancer is feasible and reproducible. Whether it can be used for risk stratification leading to more tailored treatment approaches and for the monitoring of treatment efficacy in individual pts will show further follow-up of the SUCCESS-Study. No significant financial relationships to disclose.

Download Full-text

Genomics of HER2+ breast cancer in young women before and after exposure to chemotherapy (chemo) plus trastuzumab (H).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.554 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 554-554

Author(s):

Adrienne Gropper Waks ◽

Esha Jain ◽

Laura C. Collins ◽

Shoshana M. Rosenberg ◽

Kathryn Jean Ruddy ◽

...

Keyword(s):

Breast Cancer ◽

Young Women ◽

Evolutionary Analysis ◽

Mechanisms Of Resistance ◽

Her2 Breast Cancer ◽

Whole Exome ◽

Activating Mutation ◽

Before And After ◽

Myc Gene ◽

Large Prospective Cohort

554 Background: HER2+ breast cancer (BC) is particularly common in young women. Genomic features of HER2+ tumors before and after H-based therapy have not been described in a population of young women and may point to clinically targetable mechanisms of resistance. Methods: From a large prospective cohort of women diagnosed with BC age ≤40 years, we identified those with HER2+ BC and tumor tissue available for sequencing before and after chemo+H. Whole exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. Evolutionary analysis was performed for patients with both pre- and post-treatment (tx) samples. Results: 22 women had successful WES samples from at least one timepoint; 13 of these had paired sequencing results both before and after chemo+H. For the majority of women, post-tx sample was following neoadjuvant chemo + H, though post-tx timepoint for other women represented locoregional or distant metastasis (Table). TP53 was the only gene that was significantly recurrently mutated in both pre- and post-tx samples. Comparison of matched pre-tx and post-tx samples demonstrated that large changes in HER2 CN over the course of tx were uncommon, only 2/13 pts had > 2-fold change in HER2 CN. Other clonal and subclonal genomic alterations were found to be acquired in the post-tx sample compared to the pre-tx sample. One patient acquired a putative activating mutation in ERBB2. Another patient acquired a clonal hotpsot mutation in TP53. MYC gene amplification was observed in 4 post-tx tumors. NOTCH2 alterations were found in post-tx biopsies from 2 different patients, and mutations in STIL were also found in post-tx biopsies from 2 patients, though the function of these mutations is not known. Conclusions: HER2+ breast tumors in young women display genomic evolution following tx with chemo+H. HER2 CN changes are uncommon, but we identified several genes that warrant exploration as potential mechanisms of resistance to therapy in this population.[Table: see text]

Download Full-text

P238 EndoPredict-based treatment decision can reduce chemotherapy usage in ER+, HER2− breast cancer

The Breast ◽

10.1016/s0960-9776(15)70270-5 ◽

2015 ◽

Vol 24 ◽

pp. S107 ◽

Cited By ~ 3

Author(s):

G. Schlake ◽

R. Kronenwett ◽

F. Tiecke ◽

K. Kastrup ◽

N. Bleuel ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Decision ◽

Her2 Breast Cancer

Download Full-text

Gene-expression signatures to inform neoadjuvant treatment decision in HR+/HER2− breast cancer: Available evidence and clinical implications

Cancer Treatment Reviews ◽

10.1016/j.ctrv.2021.102323 ◽

2022 ◽

Vol 102 ◽

pp. 102323

Author(s):

Gaia Griguolo ◽

Michele Bottosso ◽

Grazia Vernaci ◽

Federica Miglietta ◽

Maria Vittoria Dieci ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Neoadjuvant Treatment ◽

Treatment Decision ◽

Clinical Implications ◽

Her2 Breast Cancer ◽

Gene Expression Signatures

Download Full-text

Need for systematic de-escalation of care in HER2+ breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12657 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12657-e12657

Author(s):

Tushar Pandey ◽

Tyler M Earnest ◽

John A Cole ◽

Eduardo Braun

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Cancer Patients ◽

In Silico ◽

Treatment Plan ◽

Standard Of Care ◽

Her2 Status ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Her2 Breast Cancer

e12657 Background: Over the last decade, there has been incredible progress in HER2-positive breast cancer patients with the adoption of targeted therapies like Trastuzumab and Pertuzumab to complement existing chemotherapies. Increasingly neoadjuvant therapy is the preferred method of therapy as it is better able to predict prognosis via pCR as well as guide adjuvant therapeutic strategy in cases with residual tumor. There are now a variety of combination therapies recommended for HER2-positive patients. As new therapies are developed, the standard-of-care shifts towards the regimen with highest pCR rate. The latest regimen being TCHP which produced pCR rates over 60% in clinical trials. While the improvement in pCR rates at a population level is encouraging, there is a growing sentiment among physicians that we may be over treating patients impacting both costs and resulting toxicity. Methods: We performed an analysis of Breast Cancer trials with pCR as the primary end point and stratification available based on HER2+ status. The cost (median insurance reimbursement) was also referenced from a recent ASCO observational study as a proxy for direct costs of drugs. Toxicities were referenced and each regimen scored (TS) from NCCN Evidence Blocks and adverse events from clinical trials. Potential savings were evaluated if a clinician had the ability to individualize regimen choice by patient. We utilized the SimBioSys TumorScope platform to perform in silico simulations to predict response to alternate therapies as it had previously used to analyze potential deescalate between AC-T vs TC in a HER2- cohort. Results: The following regimens were evaluated HP (pCR:17%,TS:1), TH (pCR: 29%,TS: 2) THP (pCR: 46%, TS: 3), TCH (pCR: 43%, TS: 4), TCHP (pCR: 64%, TS: 5), AC-TH (pCR: 43%, TS: 6), AC-THP(pCR: 55%, TS: 7). Based on an in-silico analysis and selection (where pCR was likely with multiple regimens), the lowest cost & toxicity regimen was selected. The estimated average saving per case of over $100,000 for the overall treatment plan . The calculated toxicity score was also reduced by this method to under 4 from the TCHP(5) standard of care. Conclusions: While the results above are estimates and perfection in such individualization may not be possible, an in-silico approach provides a promising solution.

Download Full-text

Australian Women’s Prediagnostic Decision-Making Styles, Relating to Treatment Choices for Early Breast Cancer Treatment

Research and Theory for Nursing Practice ◽

10.1891/rtnp.17.2.117.53178 ◽

2003 ◽

Vol 17 (2) ◽

pp. 117-136 ◽

Cited By ~ 10

Author(s):

Lea M. Budden ◽

Penny F. Pierce ◽

Barbara A. Hayes ◽

Petra G. Buettner

Keyword(s):

Breast Cancer ◽

Decision Making ◽

Decision Support ◽

Medical Treatment ◽

Early Breast Cancer ◽

Information Seeking ◽

Treatment Plan ◽

Treatment Decision ◽

Treatment Choices ◽

Decision Styles

Women diagnosed with early breast cancer are now asked by their doctors to choose from a range of options for their preferred medical treatment plan. Little information is known about women’s treatment decision-making and therefore nurses do not have evidence to guide this decision support. The aim of this descriptive survey was to investigate the prediagnostic decision-making behavior of a sample (N= 377) of Australian women, regarding their treatment choices for early breast cancer. The data were collected using the Pre-Decision Portfolio Questionnaire (PDPQ) by Pierce (1996), which includes the Michigan Assessment of Decision Styles (MADS). Of 366 participating women, 19.9% strongly agreed to all three items of the MADS factor Deferring Responsibility; 0.3% strongly agreed to all four factors of Avoidance; 32.7% strongly agreed on all four items of Information Seeking; and 63.4% strongly agreed to all five items of Deliberation. Women showed a variety of preferred decision styles, depending on age, education, occupation and employment status. Only 36% of women indicated it was critically important to “get the treatment over as soon as possible;” 55% to “participate in selecting treatment;” and 53% to “read a lot of information.” The understanding of factors that are important to women when they are making decisions for medical treatment is a mandatory step in designing customized evidence-based decision support, which can be delivered by nurses to help women during this distressing experience.

Download Full-text

Prospective Multicenter Study of the Impact of the 21-Gene Recurrence Score Assay on Medical Oncologist and Patient Adjuvant Breast Cancer Treatment Selection

Journal of Clinical Oncology ◽

10.1200/jco.2008.20.2119 ◽

2010 ◽

Vol 28 (10) ◽

pp. 1671-1676 ◽

Cited By ~ 205

Author(s):

Shelly S. Lo ◽

Patricia B. Mumby ◽

John Norton ◽

Karen Rychlik ◽

Jeffrey Smerage ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Treatment ◽

Multicenter Study ◽

Recurrence Score ◽

Treatment Decision ◽

Decisional Conflict ◽

Treatment Recommendation ◽

Patient Anxiety ◽

Medical Oncologist ◽

Medical Oncologists

Purpose The 21-gene Recurrence Score (RS) assay has been validated to quantify the risk of distant recurrence in tamoxifen-treated patients with lymph node–negative, estrogen receptor–positive breast cancer and predict magnitude of chemotherapy benefit. This multicenter study was designed to prospectively examine whether RS affects physician and patient adjuvant treatment selection and satisfaction. Patients and Methods Before and after obtaining the 21-gene RS assay, medical oncologists stated their adjuvant treatment recommendation and confidence in it. Patients also indicated their treatment choice pre- and post-RS assay. Patients completed measures for decisional conflict, anxiety, and quality of life. Results Seventeen medical oncologists at one community and three academic practices consecutively enrolled 89 assessable patients. The medical oncologist treatment recommendation changed for 28 patients (31.%). Twenty-four patients (27%) changed their treatment decision. The largest change after the RS results was conversion from the medical oncologist's pretest recommendation for chemotherapy plus hormonal therapy (CHT) to post-test recommendation for hormone therapy (HT) in 20 cases (22.5%). Nine patients (10.1%) changed their treatment decision from CHT to HT. RS results increased medical oncologist confidence in their treatment recommendation in 68 cases (76%). Patient anxiety and decisional conflict were significantly lower after RS results. Conclusion The results of this study indicate that the RS assay impacts medical oncologist adjuvant treatment recommendations, patient treatment choice, and patient anxiety.

Download Full-text

Estrogen receptor—positive breast cancer survival prediction and analysis of resistance–related genes introduction

PeerJ ◽

10.7717/peerj.12202 ◽

2021 ◽

Vol 9 ◽

pp. e12202

Author(s):

Chen Shuai ◽

Fengyan Yuan ◽

Yu Liu ◽

Chengchen Wang ◽

Jiansong Wang ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Drug Resistance ◽

Risk Stratification ◽

Clinical Decision Making ◽

Survival Prediction ◽

Breast Cancer Dataset ◽

Cancer Dataset ◽

Genetic Characteristics ◽

Her2 Breast Cancer

Background In recent years, ER+ and HER2- breast cancer of adjuvant therapy has made great progress, including chemotherapy and endocrine therapy. We found that the responsiveness of breast cancer treatment was related to the prognosis of patients. However, reliable prognostic signatures based on ER+ and HER2- breast cancer and drug resistance-related prognostic markers have not been well confirmed, This study in amied to establish a drug resistance-related gene signature for risk stratification in ER+ and HER2- breast cancer. Methods We used the data from The Cancer Genoma Atlas (TCGA) breast cancer dataset and gene expression database (Gene Expression Omnibus, GEO), constructed a risk profile based on four drug resistance-related genes, and developed a nomogram to predict the survival of patients with I-III ER+ and HER2- breast cancer. At the same time, we analyzed the relationship between immune infiltration and the expression of these four genes or risk groups. Results Four drug resistance genes (AMIGO2, LGALS3BP, SCUBE2 and WLS) were found to be promising tools for ER+ and HER2- breast cancer risk stratification. Then, the nomogram, which combines genetic characteristics with known risk factors, produced better performance and net benefits in calibration and decision curve analysis. Similar results were validated in three separate GEO cohorts. All of these results showed that the model can be used as a prognostic classifier for clinical decision-making, individual prediction and treatment, as well as follow-up.

Download Full-text