Oncotype DX 21‑gene test has a low recurrence score in both pure and mixed mucinous breast carcinoma

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.

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Adjuvante Therapie beim nodalpositiven Brustkrebs

Onkologische Welt ◽

10.1055/a-1347-9746 ◽

2021 ◽

Vol 12 (01) ◽

pp. 25-26

Author(s):

Katharina Arnheim

Keyword(s):

Adjuvante Therapie ◽

Recurrence Score ◽

Adjuvante Chemotherapie ◽

Oncotype Dx ◽

Oncotype Dx Recurrence Score

Gemäß Interimsanalyse der Studie RxPONDER kann bei postmenopausalen Frauen mit frühem Hormonrezeptor- (HR) positivem Brustkrebs und positivem Nodalstatus unabhängig von ihrem Oncotype DX Recurrence Score (RS) auf eine adjuvante Chemotherapie verzichtet werden. Prämenopausale Frauen dagegen profitieren von der Chemotherapie mit einer Verbesserung des invasiven krankheitsfreien (iDFS) und Gesamtüberlebens (OS).

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Correlation of manual semi-quantitative and automated quantitative Ki-67 proliferative index with OncotypeDXTM recurrence score in invasive breast carcinoma

Breast Disease ◽

10.3233/bd-201011 ◽

2021 ◽

pp. 1-11

Author(s):

Brian S. Finkelman ◽

Amanda Meindl ◽

Carissa LaBoy ◽

Brannan Griffin ◽

Suguna Narayan ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Hot Spot ◽

Recurrence Score ◽

Invasive Breast Carcinoma ◽

Chemotherapy Response ◽

Scoring Method ◽

Cancer Proliferation ◽

Ki 67 ◽

Breast Cancer Chemotherapy

BACKGROUND: Ki-67 immunohistochemistry (IHC) staining is a widely used cancer proliferation assay; however, its limitations could be improved with automated scoring. The OncotypeDXTM Recurrence Score (ORS), which primarily evaluates cancer proliferation genes, is a prognostic indicator for breast cancer chemotherapy response; however, it is more expensive and slower than Ki-67. OBJECTIVE: To compare manual Ki-67 (mKi-67) with automated Ki-67 (aKi-67) algorithm results based on manually selected Ki-67 “hot spots” in breast cancer, and correlate both with ORS. METHODS: 105 invasive breast carcinoma cases from 100 patients at our institution (2011–2013) with available ORS were evaluated. Concordance was assessed via Cohen’s Kappa (κ). RESULTS: 57/105 cases showed agreement between mKi-67 and aKi-67 (κ 0.31, 95% CI 0.18–0.45), with 41 cases overestimated by aKi-67. Concordance was higher when estimated on the same image (κ 0.53, 95% CI 0.37–0.69). Concordance between mKi-67 score and ORS was fair (κ 0.27, 95% CI 0.11–0.42), and concordance between aKi-67 and ORS was poor (κ 0.10, 95% CI −0.03–0.23). CONCLUSIONS: These results highlight the limits of Ki-67 algorithms that use manual “hot spot” selection. Due to suboptimal concordance, Ki-67 is likely most useful as a complement to, rather than a surrogate for ORS, regardless of scoring method.

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