Cctg MA.39 tailor RT: A randomized trial of regional radiotherapy in biomarker low-risk node-positive breast cancer (NCT03488693).

TPS602 Background: Biomarker low risk, ER positive (+), HER2 negative (-) breast cancer with low burden nodal involvement may be associated with good outcomes (Woodward 2016, Mamounas 2017). There is conflicting data regarding the efficacy of regional radiotherapy after breast conserving surgery (BCS) or mastectomy in these patients (Kyndi 2008, Whelan 2015, Poortmans 2015, Liu 2015). Our hypothesis is that the risk of recurrence in patients with biomarker low risk, ER+, Her2- breast cancer and involvement of 1-3 lymph nodes where regional RT is omitted will not be inferior to the risk of recurrence in patients treated with regional RT. Methods: MA39 is a Canadian Cancer Trials Group led, NCTN sponsored, randomized phase III study comparing breast cancer recurrence free interval (BCRFI) in patients with ER+, Her2-, LN 1-3+ breast cancer that is low risk as defined by Oncotype Dx Recurrence Score < 18. Secondary objectives include a comparison of DFS, breast cancer mortality, OS, locoregional and distant recurrence free intervals, toxicity, arm volume and mobility measurements, patient reported outcomes and cost effectiveness. Key eligibility criteria include: age ≥ 40 years; BCS or mastectomy with axillary dissection and 1-3 positive axillary nodes; BCS and SLNB alone and 1-2 positive axillary nodes; mastectomy and SLNB alone and only 1 positive axillary node; planned endocrine therapy ≥ 5 years; adjuvant chemotherapy allowed. Statistical design: The primary analysis will be a test of non-inferiority (NI) in the intention to treat population. If the upper bound of a one-sided 95% interval for the hazard ratio for BCRFI is < 1.4, NI will be declared. Using a one-sided α of 0.05 and a power of 87%, it is anticipated that 278 events are required. With an expected 5 years of accrual and 4.5 years of follow-up, 2140 patients are needed for the final sample size. Conduct to Date: Study activation May 30 2018. Participation as of February 2019: Registrations 64 Randomizations 26. CIRB approval for continuation of MA.39 was received on January 11 2019. Clinical trial information: NCT03488693.

Download Full-text

Oncotype DX testing in early-stage node-positive breast cancer and impact on chemotherapy use at a comprehensive cancer center.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.549 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 549-549

Author(s):

Katya Losk ◽

Rachel A. Freedman ◽

Elizabeth A. Mittendorf ◽

Zhenying Tan-Wasielewski ◽

Lorenzo Trippa ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Multinomial Logistic Regression ◽

Recurrence Score ◽

Low Risk ◽

Oncotype Dx ◽

Comprehensive Cancer Center ◽

Factors Associated ◽

Node Positive ◽

Her2 Breast Cancer

549 Background: The 21-gene Oncotype DX Recurrence Score (RS) is widely used to guide adjuvant chemotherapy decisions in hormone receptor positive (HR+), HER2-negtive (HER2-), lymph node negative (LN-) breast cancer. It’s adoption in lymph node positive (LN+) disease remains controversial. In 2016, we implemented ‘reflex’ RS testing for patients ≤65 years with HR+/HER2- breast cancer including T1/T2 N1 (grade 1 or 2) tumors. Providers can also order Oncotype DX outside of reflex criteria. We sought to assess RS distribution and factors associated with chemotherapy use in HR+/HER2-/LN+ breast cancer patients at our center. Methods: Patients with non-metastatic HR+/HER2-/LN+ breast cancer who underwent primary surgery at our center were identified from our prospective database. We examined the distribution of low (RS < 18), intermediate (RS 18-30) and high (RS > 30) RS and identified characteristics for those who did not meet reflex criteria. A multinomial logistic regression model was performed to identify factors associated with chemotherapy receipt among all LN+ patients. Results: From 1/2016-3/2018, we identified 296 consecutive patients with HR+/HER2-/LN+ breast cancer. 200 (68%) patients had RS testing and 128 (64%) met reflex criteria. Reasons for not meeting RS reflex criteria included age > 65 (n = 35), grade III disease (n = 35) and N2/N3 tumors (n = 10). Among the 200 patients with RS, 122 (61%) had RS < 18, 67 (34%) had RS 18-30, and 11 (6%) had RS > 30. Only 68/200 (34%) patients with RS received chemotherapy as compared to 54/96 (56%) patients without RS (p = 0.0004). Compared to patients without RS testing, the odds of receiving chemotherapy were less with RS < 18 (OR = 0.46). The odds of receiving chemotherapy were greater with ≥3 positive LNs versus 1 positive LN (OR = 3.40). Conclusions: The majority of HR+/HER2-/LN+ patients undergoing upfront surgery at our center receive RS testing (200/296), with 122 (61%) resulting in low risk RS. Patients with low risk scores (RS < 18) were less likely to receive chemotherapy. While nodal involvement remains a common driver of chemotherapy use, our study demonstrates that RS testing provides clinically useful information in this population.

Download Full-text

Abstract GS3-00: First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder)

10.1158/1538-7445.sabcs20-gs3-00 ◽

2021 ◽

Author(s):

Kevin Kalinsky ◽

William E Barlow ◽

Funda Meric-Bernstam ◽

Julie R Gralow ◽

Kathy S Albain ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Randomized Clinical Trial ◽

Endocrine Therapy ◽

Hormone Receptor ◽

Recurrence Score ◽

Phase Iii ◽

Hormone Receptor Positive ◽

Her2 Breast Cancer ◽

First Results

Download Full-text

Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®

npj Breast Cancer ◽

10.1038/s41523-021-00216-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Richard Buus ◽

Zsolt Szijgyarto ◽

Eugene F. Schuster ◽

Hui Xiao ◽

Ben P. Haynes ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Early Stage ◽

Recurrence Score ◽

Distant Recurrence ◽

Research Assessment ◽

Expression Data ◽

Her2 Breast Cancer ◽

Validation Set ◽

Development And Validation

AbstractMulti-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2− breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (rc(RS) = 0.96, 95% CI 0.93–0.97 with level of agreement (LoA) of −7.69 to 8.12; rc(EP) = 0.97, 95% CI 0.96–0.98 with LoA of −0.64 to 1.26 and rc(ROR) = 0.97 (95% CI 0.94–0.98) with LoA of −8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data.

Download Full-text

Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay—Results From the SAFIA Phase III Trial

JCO Global Oncology ◽

10.1200/go.20.00575 ◽

2021 ◽

pp. 811-819

Author(s):

Khalid AlSaleh ◽

Heba Al Zahwahry ◽

Adda Bounedjar ◽

Mohammed Oukkal ◽

Ahmed Saadeddine ◽

...

Keyword(s):

Breast Cancer ◽

Epidermal Growth Factor Receptor ◽

Interim Analysis ◽

Growth Factor Receptor ◽

Recurrence Score ◽

Phase Iii ◽

Phase Iii Trial ◽

Hormone Sensitivity ◽

Epidermal Growth ◽

Breast Recurrence

PURPOSE Luminal, human epidermal growth factor receptor 2–negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2–negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate ( P = .05). CONCLUSION The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Download Full-text

87P Patient-reported and cancer-specific health-related quality of life among patients with early stage HR+/HER2- breast cancer (BC)

Annals of Oncology ◽

10.1016/j.annonc.2020.03.027 ◽

2020 ◽

Vol 31 ◽

pp. S44-S45

Author(s):

C. Criscitiello ◽

D. Spurden ◽

A. Rider ◽

R. Williams ◽

M. Corsaro ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Early Stage ◽

Health Related Quality ◽

Her2 Breast Cancer ◽

Patient Reported ◽

Related Quality ◽

Health Related ◽

Specific Health

Download Full-text

PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

Journal of Global Oncology ◽

10.1200/jgo.2016.008318 ◽

2017 ◽

Vol 3 (4) ◽

pp. 289-303 ◽

Cited By ~ 39

Author(s):

Hiroji Iwata ◽

Seock-Ah Im ◽

Norikazu Masuda ◽

Young-Hyuck Im ◽

Kenichi Inoue ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Phase Iii ◽

Asian Patients ◽

Hormone Receptor Positive ◽

Patient Reported ◽

Epidermal Growth

Purpose To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. Results This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

Download Full-text