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. 2024 May;205(1):39-48.
doi: 10.1007/s10549-023-07227-0. Epub 2024 Jan 24.

Real-world use of multigene signatures in early breast cancer: differences to clinical trials

Luca Licata #  1   2 , Rita De Sanctis #  3   4 , Andrea Vingiani  5   6 , Deborah Cosentini  7 , Monica Iorfida  8 , Elena Rota Caremoli  9 , Isabella Sassi  10 , Bethania Fernandes  11 , Andrea Gianatti  12 , Elena Guerini-Rocco  13   14 , Claudia Zambelli  15 , Elisabetta Munzone  8 , Edda Lucia Simoncini  16 , Carlo Tondini  9 , Oreste Davide Gentilini  17   18 , Alberto Zambelli  3   4 , Giancarlo Pruneri  5   6 , Giampaolo Bianchini  19   17
Affiliations

Real-world use of multigene signatures in early breast cancer: differences to clinical trials

Luca Licata et al. Breast Cancer Res Treat. 2024 May.

Abstract

Purpose: In Italy, Lombardy was the first region to reimburse multigene assays (MGAs) for patients otherwise candidates for chemotherapy. This is a real-world experience of MGAs usage in six referral cancer centers in Lombardy.

Methods: Among MGAs, Oncotype DX (RS) was used in 97% of cases. Consecutive patients tested with Oncotype DX from July 2020 to July 2022 were selected. The distribution of clinicopathologic features by RS groups (low RS: 0-25, high RS: 26-100) was assessed using chi-square and compared with those of the TAILORx and RxPONDER trials.

Results: Out of 1,098 patients identified, 73% had low RS. Grade and Ki67 were associated with RS (p < 0.001). In patients with both G3 and Ki67 > 30%, 39% had low RS, while in patients with both G1 and Ki67 < 20%, 7% had high RS. The proportion of low RS in node-positive patients was similar to that in RxPONDER (82% vs 83%), while node-negative patients with low RS were significantly less than in TAILORx (66% vs 86%, p < 0.001). The distribution of Grade was different from registration trials, with more G3 and fewer G1 (38% and 3%) than in TAILORx (18% and 27%) and RxPONDER (10% and 24%) (p < 0.001). Patients ≤ 50 years were overrepresented in this series (41%) than in TAILORx and RxPONDER (31% and 24%, respectively) (p < 0.001) and, among them, 42% were node positive.

Conclusions: In this real-world series, Oncotype DX was the test almost exclusively used. Despite reimbursement being linked to pre-test chemotherapy recommendation, almost 3/4 patients resulted in the low-RS group. The significant proportion of node-positive patients ≤ 50 years tested indicates that oncologists considered Oncotype DX informative also in this population.

Keywords: Adjuvant therapy; ER+/HER2− early breast cancer; Multigene assays; Oncotype DX.

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Conflict of interest statement

LL has served on the advisory boards for: Lilly, Exact Sciences, AstraZeneca, Italfarmaco and Daiichi Sankyo; has received consulting fee from: Exact Sciences, Helsinn and Eisai; honoraria for speakers’ bureaus from: Gilead and Exact Sciences; support for travel, accommodations, expenses from: Lilly and Gilead. RDS has served on the advisory boards for: Novartis, Lilly, Istituto Clinico Gentili, Ipsen, Amgen, EISAI. AV reports honoraria from Roche and Lilly ELS has received consulting fee and served on the advisory boards for: Exact Sciences, Seagen. EM has received consulting fee and served on the advisory boards for: Exact Sciences, EISAI, MSD Oncology, Daiichi Sankyo/Astra Zeneca, Pfizer, Seagen; support for travel, accommodations, expenses from: Roche, Pfizer, Lilly, Novartis. EGR has received advisory fee from AstraZeneca, Exact Sciences, GSK, Novartis, Roche; honoraria from AstraZeneca, GSK, Novartis, Thermo Fisher Scientific; travel accommodation and expenses from AstraZeneca, GSK, LCM Genect, Novartis, Roche, Thermo Fisher Scientific; grants and non-financial support from Thermo Fisher Scientific, Roche. CT has received consulting fee and served on the advisory boards for: Myriad Genetics, MSD Oncology and Amgen; honoraria for speakers’ bureaus from: Amgen; support for travel, accommodations, expenses from: Takeda, Amgen, MSD, Eli Lilly Italia SPA, Roche, Pfizer. AZ has received personal fees and non-financial support from Novartis, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo, MDS (Merck Sharp&Dome), Roche, Seagen, Exact Sciences, Gilaed, Istituto Gentili. GP has served on the advisory boards for: ADS Biotec; has received honoraria for speakers’ bureaus and travel funding from: Lilly, AstraZeneca, Exact Sciences, Novartis. GB has received consulting fee from Roche, AstraZeneca, Novartis, MSD, Sanofi, Daiichi Sankyo, and Exact Sciences; honoraria for speakers’ bureaus from Roche, Pfizer, Astra- Zeneca, Lilly, Novartis, Neopharm Israel, MSD, Chugai, Daiichi Sankyo, EISAI, and Exact Sciences; support for travel, accommodations, expenses from Roche, Pfizer, and AstraZeneca; is co-inventor of ‘European patent Application N. 12195182.6 and 12196177.5 titled “PDL-1 expression in anti-HER2 therapy” -Roche- Issued (no compensation provided); and has served on the advisory boards for Roche, Pfizer, Daiichi Sankyo, Lilly, MSD, Novartis, AstraZeneca, Genomic Health, EISAI, Gilead, and Seagen.

Figures

Fig. 1
Fig. 1
Distribution of Oncotype DX requests according to nodal status and age. Distribution of requests in node-negative (A) and node-positive (B) patients, and in patients ≤ 50 years (C) and > 50 years (D), stratified according to tumor size, grade, and Ki67 levels
Fig. 2
Fig. 2
Correlation between Recurrence Score and clinicopathologic features. Recurrence Score distribution in patients stratified according to age (A), tumor size (B), nodal status (C), tumor grade (D), and Ki67 levels (E)
Fig. 3
Fig. 3
Correlation between Recurrence Score and combined Grade-Ki67. Recurrence Score distribution in Grade 1 (A), Grade 2 (B), and Grade 3 (C) tumors stratified according to Ki67 levels
See this image and copyright information in PMC

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